A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor.
Group of hemorrhagic disorders in which the VON WILLEBRAND FACTOR is either quantitatively or qualitatively abnormal. They are usually inherited as an autosomal dominant trait though rare kindreds are autosomal recessive. Symptoms vary depending on severity and disease type but may include prolonged bleeding time, deficiency of factor VIII, and impaired platelet adhesion.
An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro.
Platelet membrane glycoprotein complex essential for normal platelet adhesion and clot formation at sites of vascular injury. It is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX. Glycoprotein Ib functions as a receptor for von Willebrand factor and for thrombin. Congenital deficiency of the GPIb-IX complex results in Bernard-Soulier syndrome. The platelet glycoprotein GPV associates with GPIb-IX and is also absent in Bernard-Soulier syndrome.
Blood-coagulation factor VIII. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin.
The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.
Endogenous substances, usually proteins, that are involved in the blood coagulation process.
A subtype of von Willebrand disease that results from qualitative deficiencies of VON WILLEBRAND FACTOR. The subtype is divided into several variants with each variant having a distinctive pattern of PLATELET-interaction.
Rod-shaped storage granules for VON WILLEBRAND FACTOR specific to endothelial cells.
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.
A subtype of von Willebrand disease that results from a partial deficiency of VON WILLEBRAND FACTOR.
The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.
A synthetic analog of the pituitary hormone, ARGININE VASOPRESSIN. Its action is mediated by the VASOPRESSIN receptor V2. It has prolonged antidiuretic activity, but little pressor effects. It also modulates levels of circulating FACTOR VIII and VON WILLEBRAND FACTOR.
A family of membrane-anchored glycoproteins that contain a disintegrin and metalloprotease domain. They are responsible for the proteolytic cleavage of many transmembrane proteins and the release of their extracellular domain.
Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function.
Venoms from snakes of the subfamily Crotalinae or pit vipers, found mostly in the Americas. They include the rattlesnake, cottonmouth, fer-de-lance, bushmaster, and American copperhead. Their venoms contain nontoxic proteins, cardio-, hemo-, cyto-, and neurotoxins, and many enzymes, especially phospholipases A. Many of the toxins have been characterized.
The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION.
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
An acquired, congenital, or familial disorder caused by PLATELET AGGREGATION with THROMBOSIS in terminal arterioles and capillaries. Clinical features include THROMBOCYTOPENIA; HEMOLYTIC ANEMIA; AZOTEMIA; FEVER; and thrombotic microangiopathy. The classical form also includes neurological symptoms and end-organ damage, such as RENAL FAILURE.
A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.
A subtype of von Willebrand disease that results from a total or near total deficiency of VON WILLEBRAND FACTOR.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
A familial coagulation disorder characterized by a prolonged bleeding time, unusually large platelets, and impaired prothrombin consumption.
Formation and development of a thrombus or blood clot in the blood vessel.
An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.
A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).
The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage.
Laboratory tests for evaluating the individual's clotting mechanism.
Cell adhesion molecule and CD antigen that mediates the adhesion of neutrophils and monocytes to activated platelets and endothelial cells.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.
Venous vessels in the umbilical cord. They carry oxygenated, nutrient-rich blood from the mother to the FETUS via the PLACENTA. In humans, there is normally one umbilical vein.
A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body.
A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.
Disorders caused by abnormalities in platelet count or function.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.
Proteins prepared by recombinant DNA technology.
The deformation and flow behavior of BLOOD and its elements i.e., PLASMA; ERYTHROCYTES; WHITE BLOOD CELLS; and BLOOD PLATELETS.
A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.
Antibodies produced by a single clone of cells.
A dye which inhibits protein biosynthesis at the initial stages. The ammonium salt (aluminon) is a reagent for the colorimetric estimation of aluminum in water, foods, and tissues.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
A deficiency or absence of FIBRINOGEN in the blood.
Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.
Platelet membrane glycoprotein complex important for platelet adhesion and aggregation. It is an integrin complex containing INTEGRIN ALPHAIIB and INTEGRIN BETA3 which recognizes the arginine-glycine-aspartic acid (RGD) sequence present on several adhesive proteins. As such, it is a receptor for FIBRINOGEN; VON WILLEBRAND FACTOR; FIBRONECTIN; VITRONECTIN; and THROMBOSPONDINS. A deficiency of GPIIb-IIIa results in GLANZMANN THROMBASTHENIA.
A family of related, adhesive glycoproteins which are synthesized, secreted, and incorporated into the extracellular matrix of a variety of cells, including alpha granules of platelets following thrombin activation and endothelial cells. They interact with a number of BLOOD COAGULATION FACTORS and anticoagulant factors. Five distinct forms have been identified, thrombospondin 1, -2, -3, -4, and cartilage oligomeric matrix protein (COMP). They are involved in cell adhesion, platelet aggregation, cell proliferation, angiogenesis, tumor metastasis, VASCULAR SMOOTH MUSCLE growth, and tissue repair.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Agents acting to arrest the flow of blood. Absorbable hemostatics arrest bleeding either by the formation of an artificial clot or by providing a mechanical matrix that facilitates clotting when applied directly to the bleeding surface. These agents function more at the capillary level and are not effective at stemming arterial or venous bleeding under any significant intravascular pressure.
Substances that are recognized by the immune system and induce an immune reaction.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Immunoelectrophoresis in which a second electrophoretic transport is performed on the initially separated antigen fragments into an antibody-containing medium in a direction perpendicular to the first electrophoresis.
Hemorrhagic and thrombotic disorders resulting from abnormalities or deficiencies of coagulation proteins.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Spontaneous or near spontaneous bleeding caused by a defect in clotting mechanisms (BLOOD COAGULATION DISORDERS) or another abnormality causing a structural flaw in the blood vessels (HEMOSTATIC DISORDERS).
The sum of the weight of all the atoms in a molecule.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
The number of PLATELETS per unit volume in a sample of venous BLOOD.
Soluble protein fragments formed by the proteolytic action of plasmin on fibrin or fibrinogen. FDP and their complexes profoundly impair the hemostatic process and are a major cause of hemorrhage in intravascular coagulation and fibrinolysis.
Electrophoresis in which agar or agarose gel is used as the diffusion medium.
Adherence of cells to surfaces or to other cells.
Bleeding or escape of blood from a vessel.
The major human blood type system which depends on the presence or absence of two antigens A and B. Type O occurs when neither A nor B is present and AB when both are present. A and B are genetic factors that determine the presence of enzymes for the synthesis of certain glycoproteins mainly in the red cell membrane.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
An enzyme that oxidizes galactose in the presence of molecular oxygen to D-galacto-hexodialdose. It is a copper protein. EC 1.1.3.9.
Laboratory examination used to monitor and evaluate platelet function in a patient's blood.
Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.
Condensed areas of cellular material that may be bounded by a membrane.
The internal resistance of the BLOOD to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as SICKLE CELL ANEMIA and POLYCYTHEMIA.
An autosomal dominant disorder caused by mutations in a tumor suppressor gene. This syndrome is characterized by abnormal growth of small blood vessels leading to a host of neoplasms. They include HEMANGIOBLASTOMA in the RETINA; CEREBELLUM; and SPINAL CORD; PHEOCHROMOCYTOMA; pancreatic tumors; and renal cell carcinoma (see CARCINOMA, RENAL CELL). Common clinical signs include HYPERTENSION and neurological dysfunctions.
Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.
The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.
Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.
The time required for the appearance of FIBRIN strands following the mixing of PLASMA with phospholipid platelet substitute (e.g., crude cephalins, soybean phosphatides). It is a test of the intrinsic pathway (factors VIII, IX, XI, and XII) and the common pathway (fibrinogen, prothrombin, factors V and X) of BLOOD COAGULATION. It is used as a screening test and to monitor HEPARIN therapy.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The rate dynamics in chemical or physical systems.
The natural enzymatic dissolution of FIBRIN.
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
Collagen receptors are cell surface receptors that modulate signal transduction between cells and the EXTRACELLULAR MATRIX. They are found in many cell types and are involved in the maintenance and regulation of cell shape and behavior, including PLATELET ACTIVATION and aggregation, through many different signaling pathways and differences in their affinities for collagen isoforms. Collagen receptors include discoidin domain receptors, INTEGRINS, and glycoprotein VI.
An integrin alpha subunit that primarily combines with INTEGRIN BETA1 to form the INTEGRIN ALPHA2BETA1 heterodimer. It contains a domain which has homology to collagen-binding domains found in von Willebrand factor.
Protein precursors, also known as proproteins or prohormones, are inactive forms of proteins that undergo post-translational modification, such as cleavage, to produce the active functional protein or peptide hormone.
A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases.
Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
A disorder of HEMOSTASIS in which there is a tendency for the occurrence of THROMBOSIS.
The co-occurrence of pregnancy and a blood disease (HEMATOLOGIC DISEASES) which involves BLOOD CELLS or COAGULATION FACTORS. The hematologic disease may precede or follow FERTILIZATION and it may or may not have a deleterious effect on the pregnant woman or FETUS.
The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and VISCOSITY.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.
The internal resistance of a material to moving some parts of it parallel to a fixed plane, in contrast to stretching (TENSILE STRENGTH) or compression (COMPRESSIVE STRENGTH). Ionic crystals are brittle because, when subjected to shear, ions of the same charge are brought next to each other, which causes repulsion.

Primary haemostasis: sticky fingers cement the relationship. (1/2528)

Platelet aggregation to form a haemostatic plug, or thrombus, plays a key role in preventing bleeding from a wound. Recent studies have provided new insights into how platelet receptors are deployed during the interactions with the vascular subendothelial matrix that lead to haemostatic plug formation.  (+info)

A strategy for enhancing the transcriptional activity of weak cell type-specific promoters. (2/2528)

Cell type- and tissue-specific promoters play an important role in the development of site-selective vectors for gene therapy. A large number of highly specific promoters has been described, but their applicability is often hampered by their inefficient transcriptional activity. In this study, we describe a new strategy for enhancing the activity of weak promoters without loss of specificity. The basic principle of this strategy is to establish a positive feedback loop which is initiated by transcription from a cell type-specific promoter. This was achieved by using a cell type-specific promoter to drive the simultaneous expression of the desired effector/reporter gene product and a strong artificial transcriptional activator which stimulates transcription through appropriate binding sites in the promoter. Using a VP16-LexA chimeric transcription factor, we show that this approach leads to a 14- to > 100-fold enhancement of both the endothelial cell-specific von Willebrand factor promoter and the gastrointestinal-specific sucrase-isomaltase promoter while maintaining approximately 30- to > 100-fold cell type specificity.  (+info)

Glycoprotein (GP) Ib-IX-transfected cells roll on a von Willebrand factor matrix under flow. Importance of the GPib/actin-binding protein (ABP-280) interaction in maintaining adhesion under high shear. (3/2528)

Adhesion of platelets to sites of vascular injury is critical for hemostasis and thrombosis and is dependent on the binding of the vascular adhesive protein von Willebrand factor (vWf) to the glycoprotein (GP) Ib-V-IX complex on the platelet surface. A unique but poorly defined characteristic of this receptor/ligand interaction is its ability to support platelet adhesion under conditions of high shear stress. To examine the structural domains of the GPIb-V-IX complex involved in mediating cell adhesion under flow, we have expressed partial (GPIb-IX), complete (GPIb-V-IX), and mutant (GPIbalpha cytoplasmic tail mutants) receptor complexes on the surface of Chinese hamster ovary (CHO) cells and examined their ability to adhere to a vWf matrix in flow-based adhesion assays. Our studies demonstrate that the partial receptor complex (GPIb-IX) supports CHO cell tethering and rolling on a bovine or human vWf matrix under flow. The adhesion was specifically inhibited by an anti-GPIbalpha blocking antibody (AK2) and was not observed with CHO cells expressing GPIbbeta and GPIX alone. The velocity of rolling was dependent on the level of shear stress, receptor density, and matrix concentration and was not altered by the presence of GPV. In contrast to selectins, which mediate cell rolling under conditions of low shear (20-200 s-1), GPIb-IX was able to support cell rolling at both venous (150 s-1) and arterial (1500-10,500 s-1) shear rates. Studies with a mutant GPIbalpha receptor subunit lacking the binding domain for actin-binding protein demonstrated that the association of the receptor complex with the membrane skeleton is not essential for cell tethering or rolling under low shear conditions, but is critical for maintaining adhesion at high shear rates (3000-6000 s-1). These studies demonstrate that the GPIb-IX complex is sufficient to mediate cell rolling on a vWf matrix at both venous and arterial levels of shear independent of other platelet adhesion receptors. Furthermore, our results suggest that the association between GPIbalpha and actin-binding protein plays an important role in enabling cells to remain tethered to a vWf matrix under conditions of high shear stress.  (+info)

Distinct structural attributes regulating von Willebrand factor A1 domain interaction with platelet glycoprotein Ibalpha under flow. (4/2528)

We have used recombinant von Willebrand factor (vWF) fragments to investigate the properties regulating A1 domain interaction with platelet glycoprotein (GP) Ibalpha. One fragment, rvWF508-704, represented the main portion of domain A1 (mature subunit residues 497-716) within the Cys509-Cys695 disulfide loop. The other, rvWF445-733, included the carboxyl-terminal region of domain D3, preceding A1, and corresponded to the proteolytic fragment originally identified as the GP Ibalpha-binding site (residues 449-728). Conformational changes were induced by reduction and alkylation of the Cys509-Cys695 bond and/or exposure to acidic pH. The cyclic rvWF445-733 fragment exhibited the function of native vWF A1 domain. When immobilized onto a surface, it tethered platelets at shear rates up to 6,300 s-1 mediating low velocity translocation but not stable attachment; in solution, it exhibited limited interaction with GP Ibalpha. In contrast, fragments with perturbed conformation could not tether platelets at high shear rates but promoted stable adhesion at lower shear and bound tightly to GP Ibalpha. Only in the presence of the exogenous modulator, botrocetin, did cyclic rvWF445-733 mediate irreversible adhesion. Thus, conformational transitions in the vWF A1 domain may influence differentially the efficiency of bond formation with GP Ibalpha and the stability of binding.  (+info)

Carbohydrate on human factor VIII/von Willebrand factor. Impairment of function by removal of specific galactose residues. (5/2528)

Human factor VIII/von Willebrand factor protein containing 120 +/- 12 nmol of sialic acid and 135 +/- 13 nmol of galactose/mg of protein was digested with neuraminidase. The affinity of native factor VIII/von Willebrand factor and its asialo form for the hepatic lectin that specifically binds asialoglycoproteins was assessed from in vitro binding experiments. Native factor VIII/von Willebrand factor exhibited negligible affinity while binding of the asialo derivative was comparable to that observed for asialo-alpha1-acid glycoprotein. Incubation of asialo-factor VIII/von Willebrand factor with Streptococcus pneumoniae beta-galactosidase removed only 62% of the galactose but abolished binding to the purified hepatic lectin. When the asialo derivative was incubated with purified beta-D-galactoside alpha2 leads to 6 sialyltransferase and CMP-[14C]NeuAc, only 61% of the galactose incorporated [14C]NeuAc. From the known specificites of these enzymes, it is concluded that galactose residues important in lectin binding are present in a terminal Gal/beta1 leads to 4GlcNAc sequence on asialo-factor VIII/von Willebrand factor. The relative ristocetin-induced platelet aggregating activity of native, asialo-, and agalacto-factor VIII/von Willebrand factor was 100:38:12, respectively, while procoagulant activity was 100:100:103.  (+info)

The crayfish plasma clotting protein: a vitellogenin-related protein responsible for clot formation in crustacean blood. (6/2528)

Coagulation in crayfish blood is based on the transglutaminase-mediated crosslinking of a specific plasma clotting protein. Here we report the cloning of the subunit of this clotting protein from a crayfish hepatopancreas cDNA library. The ORF encodes a protein of 1,721 amino acids, including a signal peptide of 15 amino acids. Sequence analysis reveals that the clotting protein is homologous to vitellogenins, which are proteins found in vitellogenic females of egg-laying animals. The clotting protein and vitellogenins are all lipoproteins and share a limited sequence similarity to certain other lipoproteins (e.g., mammalian apolipoprotein B and microsomal triglyceride transfer protein) and contain a stretch with similarity to the D domain of mammalian von Willebrand factor. The crayfish clotting protein is present in both sexes, unlike the female-specific vitellogenins. Electron microscopy was used to visualize individual clotting protein molecules and to study the transglutaminase-mediated clotting reaction. In the presence of an endogenous transglutaminase, the purified clotting protein molecules rapidly assemble into long, flexible chains that occasionally branch.  (+info)

Conformational changes in the A3 domain of von Willebrand factor modulate the interaction of the A1 domain with platelet glycoprotein Ib. (7/2528)

Bitiscetin has recently been shown to induce von Willebrand factor (vWF)-dependent aggregation of fixed platelets (Hamako J, et al, Biochem Biophys Res Commun 226:273, 1996). We have purified bitiscetin from Bitis arietans venom and investigated the mechanism whereby it promotes a form of vWF that is reactive with platelets. In the presence of bitiscetin, vWF binds to platelets in a dose-dependent and saturable manner. The binding of vWF to platelets involves glycoprotein (GP) Ib because it was totally blocked by monoclonal antibody (MoAb) 6D1 directed towards the vWF-binding site of GPIb. The binding also involves the GPIb-binding site of vWF located on the A1 domain because it was inhibited by MoAb to vWF whose epitopes are within this domain and that block binding of vWF to platelets induced by ristocetin or botrocetin. However, in contrast to ristocetin or botrocetin, the binding site of bitiscetin does not reside within the A1 domain but within the A3 domain of vWF. Thus, among a series of vWF fragments, 125I-bitiscetin only binds to those that overlap the A3 domain, ie, SpIII (amino acid [aa] 1-1365), SpI (aa 911-1365), and rvWF-A3 domain (aa 920-1111). It does not bind to SpII corresponding to the C-terminal part of vWF subunit (aa 1366-2050) nor to the 39/34/kD dispase species (aa 480-718) or T116 (aa 449-728) overlapping the A1 domain. In addition, bitiscetin that does not bind to DeltaA3-rvWF (deleted between aa 910-1113) has no binding site ouside the A3 domain. The localization of the binding site of bitiscetin within the A3 domain was further supported by showing that MoAb to vWF, which are specific for this domain and block the interaction between vWF and collagen, are potent inhibitors of the binding of bitiscetin to vWF and consequently of the bitiscetin-induced binding of vWF to platelets. Thus, our data support the hypothesis that an interaction between the A1 and A3 domains exists that may play a role in the function of vWF by regulating the ability of the A1 domain to bind to platelet GPIb.  (+info)

IL-8 mRNA expression by in situ hybridisation in human pituitary adenomas. (8/2528)

Several cytokines have been shown to be expressed in normal and adenomatous pituitary tissue. Recently, interleukin-8 (IL-8) mRNA was identified by reverse transcription (RT)-PCR in each of a series of 17 pituitary tumours examined. We have investigated further the presence of IL-8 mRNA, using in situ hybridisation in two normal human anterior pituitary specimens and 25 human pituitary adenomas. IL-8 mRNA was not identified in either of the two normal pituitary specimens. Only three of the 25 adenomas were positive for IL-8 mRNA. In these three tumours, which included two null cell adenomas and one gonadotrophinoma, the majority of tumour cells (>90%) were positive for IL-8 mRNA. The remaining 22 adenomas were completely negative. There was no difference in tumour size or type between the IL-8 positive and the IL-8 negative tumours, and immunocytochemistry for von Willebrandt factor showed that the two groups were also similar in their degree of vascularisation. In conclusion, IL-8 mRNA was found in 12% of pituitary adenomas studied and was histologically identified within the tumour cells. In situ hybridisation is a more appropriate technique for assessing cytokine mRNA production by human pituitary tumours because RT-PCR may be too sensitive, identifying very small, possibly pathologically insignificant, quantities of mRNA that could be produced by supporting cells such as fibroblasts, endothelial cells or macrophages.  (+info)

Von Willebrand factor (vWF) is a large multimeric glycoprotein that plays a crucial role in hemostasis, the process which leads to the cessation of bleeding and the formation of a blood clot. It was named after Erik Adolf von Willebrand, a Finnish physician who first described the disorder associated with its deficiency, known as von Willebrand disease (vWD).

The primary functions of vWF include:

1. Platelet adhesion and aggregation: vWF mediates the initial attachment of platelets to damaged blood vessel walls by binding to exposed collagen fibers and then interacting with glycoprotein Ib (GPIb) receptors on the surface of platelets, facilitating platelet adhesion. Subsequently, vWF also promotes platelet-platelet interactions (aggregation) through its interaction with platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptors under high shear stress conditions found in areas of turbulent blood flow, such as arterioles and the capillary bed.

2. Transport and stabilization of coagulation factor VIII: vWF serves as a carrier protein for coagulation factor VIII (FVIII), protecting it from proteolytic degradation and maintaining its stability in circulation. This interaction between vWF and FVIII is essential for the proper functioning of the coagulation cascade, particularly in the context of vWD, where impaired FVIII function can lead to bleeding disorders.

3. Wound healing: vWF contributes to wound healing by promoting platelet adhesion and aggregation at the site of injury, which facilitates the formation of a provisional fibrin-based clot that serves as a scaffold for tissue repair and regeneration.

In summary, von Willebrand factor is a vital hemostatic protein involved in platelet adhesion, aggregation, coagulation factor VIII stabilization, and wound healing. Deficiencies or dysfunctions in vWF can lead to bleeding disorders such as von Willebrand disease.

Von Willebrand disease (vWD) is a genetic bleeding disorder caused by deficiency or dysfunction of the von Willebrand factor (VWF), a protein involved in blood clotting. The VWF plays a crucial role in the formation of a stable platelet plug during the process of hemostasis, which helps to stop bleeding.

There are three main types of vWD:

1. Type 1: This is the most common form, characterized by a partial quantitative deficiency of functional VWF. Bleeding symptoms are usually mild.
2. Type 2: In this type, there is a qualitative defect in the VWF protein leading to various subtypes (2A, 2B, 2M, and 2N) with different bleeding patterns. Symptoms can range from mild to severe.
3. Type 3: This is the most severe form of vWD, characterized by a near or complete absence of functional VWF and Factor VIII. Affected individuals have a high risk of spontaneous and severe bleeding episodes.

The clinical manifestations of vWD include easy bruising, prolonged nosebleeds (epistaxis), heavy menstrual periods in women, and excessive bleeding after dental procedures, surgeries, or trauma. The diagnosis is made based on laboratory tests that assess VWF antigen levels, VWF activity, and Factor VIII coagulant activity. Treatment options include desmopressin (DDAVP) to stimulate the release of VWF from endothelial cells, recombinant VWF, or plasma-derived VWF concentrates, and antifibrinolytic agents like tranexamic acid to reduce bleeding.

Ristocetin is not a medical condition but a type of antibiotic used to treat infections caused by certain Gram-positive bacteria that are resistant to other antibiotics. Ristocetin is an glycopeptide antibiotic, which works by binding to the bacterial cell wall and inhibiting its synthesis, leading to bacterial death. It is not commonly used due to its potential to cause blood disorders, such as thrombocytopenia (low platelet count) and platelet aggregation.

In medical literature, ristocetin is also known for its use in the laboratory setting as a reagent for the platelet function test, called the ristocetin-induced platelet aggregation (RIPA) assay. This test is used to evaluate the ability of platelets to aggregate and form clots in response to ristocetin, which can help diagnose certain bleeding disorders such as Bernard-Soulier syndrome and von Willebrand disease.

The platelet glycoprotein GPIb-IX complex is a crucial receptor on the surface of platelets that plays a vital role in hemostasis and thrombosis. It is a heterotetrameric transmembrane protein complex composed of two disulfide-linked glycoprotein subunits, GPIbα, GPIbβ, GPV (Glycoprotein V), and GPIX (Glycoprotein IX).

The GPIb-IX complex is responsible for the initial interaction between platelets and von Willebrand factor (vWF) in the circulation. When blood vessels are damaged, exposed collagen recruits vWF to the site of injury, where it binds to the GPIbα subunit of the GPIb-IX complex, leading to platelet adhesion and activation. This interaction is critical for primary hemostasis, which helps prevent excessive blood loss from injured vessels.

Genetic mutations or deficiencies in the genes encoding these glycoproteins can lead to bleeding disorders such as Bernard-Soulier syndrome, a rare autosomal recessive disorder characterized by thrombocytopenia and large platelets with impaired vWF binding and platelet adhesion.

Factor VIII is a protein in the blood that is essential for normal blood clotting. It is also known as antihemophilic factor (AHF). Deficiency or dysfunction of this protein results in hemophilia A, a genetic disorder characterized by prolonged bleeding and easy bruising. Factor VIII works together with other proteins to help form a clot and stop bleeding at the site of an injury. It acts as a cofactor for another clotting factor, IX, in the so-called intrinsic pathway of blood coagulation. Intravenous infusions of Factor VIII concentrate are used to treat and prevent bleeding episodes in people with hemophilia A.

Platelet adhesiveness refers to the ability of platelets, which are small blood cells that help your body form clots to prevent excessive bleeding, to stick to other cells or surfaces. This process is crucial in hemostasis, the process of stopping bleeding after injury to a blood vessel.

When the endothelium (the lining of blood vessels) is damaged, subendothelial structures are exposed, which can trigger platelet adhesion. Platelets then change shape and release chemical signals that cause other platelets to clump together, forming a platelet plug. This plug helps to seal the damaged vessel and prevent further bleeding.

Platelet adhesiveness is influenced by several factors, including the presence of von Willebrand factor (vWF), a protein in the blood that helps platelets bind to damaged vessels, and the expression of glycoprotein receptors on the surface of platelets. Abnormalities in platelet adhesiveness can lead to bleeding disorders or thrombotic conditions.

Blood coagulation factors, also known as clotting factors, are a group of proteins that play a crucial role in the blood coagulation process. They are essential for maintaining hemostasis, which is the body's ability to stop bleeding after injury.

There are 13 known blood coagulation factors, and they are designated by Roman numerals I through XIII. These factors are produced in the liver and are normally present in an inactive form in the blood. When there is an injury to a blood vessel, the coagulation process is initiated, leading to the activation of these factors in a specific order.

The coagulation cascade involves two pathways: the intrinsic and extrinsic pathways. The intrinsic pathway is activated when there is damage to the blood vessel itself, while the extrinsic pathway is activated by tissue factor released from damaged tissues. Both pathways converge at the common pathway, leading to the formation of a fibrin clot.

Blood coagulation factors work together in a complex series of reactions that involve activation, binding, and proteolysis. When one factor is activated, it activates the next factor in the cascade, and so on. This process continues until a stable fibrin clot is formed.

Deficiencies or abnormalities in blood coagulation factors can lead to bleeding disorders such as hemophilia or thrombosis. Hemophilia is a genetic disorder that affects one or more of the coagulation factors, leading to excessive bleeding and difficulty forming clots. Thrombosis, on the other hand, occurs when there is an abnormal formation of blood clots in the blood vessels, which can lead to serious complications such as stroke or pulmonary embolism.

Von Willebrand disease (VWD) is a genetic bleeding disorder caused by deficiency or dysfunction of the von Willebrand factor (VWF), a protein involved in blood clotting. There are several types of VWD, and type 2 is further divided into four subtypes (2A, 2B, 2M, and 2N) based on the specific defects in the VWF protein.

Type 2 von Willebrand disease is characterized by qualitative abnormalities in the VWF protein, which affect its ability to function properly. The four subtypes of type 2 VWD are defined as follows:

* Type 2A: This subtype is caused by a decrease in the amount of high molecular weight multimers (HMWM) of VWF, which are essential for effective platelet adhesion and clot formation. The reduction in HMWM leads to a prolonged bleeding time and increased susceptibility to bleeding.
* Type 2B: This subtype is characterized by an increased affinity of VWF for platelets, leading to the formation of large platelet aggregates and a decrease in the amount of circulating VWF. This results in a shortened bleeding time but increased bleeding severity due to the loss of HMWM.
* Type 2M: This subtype is caused by defects in the VWF protein that affect its ability to bind to platelets, leading to a decrease in platelet adhesion and clot formation. The HMWM are present but do not function properly, resulting in a prolonged bleeding time.
* Type 2N: This subtype is characterized by a decreased affinity of VWF for factor VIII, which is necessary for the normal coagulation cascade. This results in a decrease in the half-life of factor VIII and an increased risk of bleeding, particularly during surgery or trauma.

In summary, type 2 von Willebrand disease is a genetic bleeding disorder caused by qualitative abnormalities in the VWF protein, leading to defects in platelet adhesion and clot formation. The four subtypes of type 2 VWD are defined based on specific defects in the VWF protein that affect its ability to bind to platelets, factor VIII, or both.

Weibel-Palade bodies are rod-shaped, membrane-bound organelles found in the cytoplasm of endothelial cells, which line the interior surface of blood vessels. They were first described by Edwin Weibel and George Palade in 1964. These organelles are unique to endothelial cells and serve as storage sites for von Willebrand factor (vWF) and other proteins involved in hemostasis, inflammation, and vasomotor functions.

The main components of Weibel-Palade bodies include:

1. Von Willebrand factor (vWF): A multimeric glycoprotein that plays a crucial role in platelet adhesion and aggregation at the site of vascular injury, as well as mediating the transport of coagulation factors VIII and V.
2. P-selectin: A cell adhesion molecule that facilitates leukocyte rolling and recruitment to sites of inflammation.
3. Endothelial nitric oxide synthase (eNOS): An enzyme responsible for the production of nitric oxide, a potent vasodilator that regulates vascular tone and blood flow.
4. Angiopoietin-2: A growth factor involved in angiogenesis and vascular remodeling.
5. Tissue plasminogen activator (tPA): A serine protease that plays a role in fibrinolysis, the process of breaking down blood clots.

Upon stimulation by various agonists such as thrombin, histamine, or vascular endothelial growth factor (VEGF), Weibel-Palade bodies undergo exocytosis, releasing their contents into the extracellular space. This process contributes to hemostatic responses, inflammatory reactions, and modulation of vascular tone.

Blood platelets, also known as thrombocytes, are small, colorless cell fragments in our blood that play an essential role in normal blood clotting. They are formed in the bone marrow from large cells called megakaryocytes and circulate in the blood in an inactive state until they are needed to help stop bleeding. When a blood vessel is damaged, platelets become activated and change shape, releasing chemicals that attract more platelets to the site of injury. These activated platelets then stick together to form a plug, or clot, that seals the wound and prevents further blood loss. In addition to their role in clotting, platelets also help to promote healing by releasing growth factors that stimulate the growth of new tissue.

Platelet membrane glycoproteins are specialized proteins found on the surface of platelets, which are small blood cells responsible for clotting. These glycoproteins play crucial roles in various processes related to hemostasis and thrombosis, including platelet adhesion, activation, and aggregation.

There are several key platelet membrane glycoproteins, such as:

1. Glycoprotein (GP) Ia/IIa (also known as integrin α2β1): This glycoprotein mediates the binding of platelets to collagen fibers in the extracellular matrix, facilitating platelet adhesion and activation.
2. GP IIb/IIIa (also known as integrin αIIbβ3): This is the most abundant glycoprotein on the platelet surface and functions as a receptor for fibrinogen, von Willebrand factor, and other adhesive proteins. Upon activation, GP IIb/IIIa undergoes conformational changes that enable it to bind these ligands, leading to platelet aggregation and clot formation.
3. GPIb-IX-V: This glycoprotein complex is involved in the initial tethering and adhesion of platelets to von Willebrand factor (vWF) in damaged blood vessels. It consists of four subunits: GPIbα, GPIbβ, GPIX, and GPV.
4. GPVI: This glycoprotein is essential for platelet activation upon contact with collagen. It associates with the Fc receptor γ-chain (FcRγ) to form a signaling complex that triggers intracellular signaling pathways, leading to platelet activation and aggregation.

Abnormalities in these platelet membrane glycoproteins can lead to bleeding disorders or thrombotic conditions. For example, mutations in GPIIb/IIIa can result in Glanzmann's thrombasthenia, a severe bleeding disorder characterized by impaired platelet aggregation. On the other hand, increased expression or activation of these glycoproteins may contribute to the development of arterial thrombosis and cardiovascular diseases.

Von Willebrand disease (VWD) is a genetic bleeding disorder caused by deficiency or abnormality of the von Willebrand factor (VWF), a protein involved in blood clotting. Type 1 VWD is the most common form and is characterized by a partial decrease in the amount of functional VWF in the blood, which can lead to prolonged bleeding times after injury or surgery. The symptoms are usually mild to moderate and may include easy bruising, nosebleeds, heavy menstrual periods, and excessive bleeding following dental work or childbirth. Type 1 VWD is inherited in an autosomal dominant manner, meaning that a person has a 50% chance of inheriting the disorder if one of their parents has it.

Platelet aggregation is the clumping together of platelets (thrombocytes) in the blood, which is an essential step in the process of hemostasis (the stopping of bleeding) after injury to a blood vessel. When the inner lining of a blood vessel is damaged, exposure of subendothelial collagen and tissue factor triggers platelet activation. Activated platelets change shape, become sticky, and release the contents of their granules, which include ADP (adenosine diphosphate).

ADP then acts as a chemical mediator to attract and bind additional platelets to the site of injury, leading to platelet aggregation. This forms a plug that seals the damaged vessel and prevents further blood loss. Platelet aggregation is also a crucial component in the formation of blood clots (thrombosis) within blood vessels, which can have pathological consequences such as heart attacks and strokes if they obstruct blood flow to vital organs.

Desmopressin, also known as 1-deamino-8-D-arginine vasopressin (dDAVP), is a synthetic analogue of the natural hormone arginine vasopressin. It is commonly used in medical practice for the treatment of diabetes insipidus, a condition characterized by excessive thirst and urination due to lack of antidiuretic hormone (ADH).

Desmopressin works by binding to V2 receptors in the kidney, which leads to increased water reabsorption and reduced urine production. It also has some effect on V1 receptors, leading to vasoconstriction and increased blood pressure. However, its primary use is for its antidiuretic effects.

In addition to its use in diabetes insipidus, desmopressin may also be used to treat bleeding disorders such as hemophilia and von Willebrand disease, as it can help to promote platelet aggregation and reduce bleeding times. It is available in various forms, including nasal sprays, injectable solutions, and oral tablets or dissolvable films.

ADAM (A Disintegrin And Metalloprotease) proteins are a family of type I transmembrane proteins that contain several distinct domains, including a prodomain, a metalloprotease domain, a disintegrin-like domain, a cysteine-rich domain, a transmembrane domain, and a cytoplasmic tail. These proteins are involved in various biological processes such as cell adhesion, migration, proteolysis, and signal transduction.

ADAM proteins have been found to play important roles in many physiological and pathological conditions, including fertilization, neurodevelopment, inflammation, and cancer metastasis. For example, ADAM12 is involved in the fusion of myoblasts during muscle development, while ADAM17 (also known as TACE) plays a crucial role in the shedding of membrane-bound proteins such as tumor necrosis factor-alpha and epidermal growth factor receptor ligands.

Abnormalities in ADAM protein function have been implicated in various diseases, including cancer, Alzheimer's disease, and arthritis. Therefore, understanding the structure and function of these proteins has important implications for the development of novel therapeutic strategies.

Bleeding time is a medical test that measures the time it takes for a small blood vessel to stop bleeding after being cut. It's used to evaluate platelet function and the effectiveness of blood clotting. The most common method used to measure bleeding time is the Ivy method, which involves making a standardized incision on the forearm and measuring the time it takes for the bleeding to stop. A normal bleeding time ranges from 2 to 9 minutes, but this can vary depending on the specific method used. Prolonged bleeding time may indicate an impairment in platelet function or clotting factor deficiency.

Crotalid venoms are the toxic secretions produced by the members of the Crotalinae subfamily, also known as pit vipers. This group includes rattlesnakes, cottonmouths (or water moccasins), and copperheads, which are native to the Americas, as well as Old World vipers found in Asia and Europe, such as gaboon vipers and saw-scaled vipers.

Crotalid venoms are complex mixtures of various bioactive molecules, including enzymes, proteins, peptides, and other low molecular weight components. They typically contain a variety of pharmacologically active components, such as hemotoxic and neurotoxic agents, which can cause extensive local tissue damage, coagulopathy, cardiovascular dysfunction, and neuromuscular disorders in the victim.

The composition of crotalid venoms can vary significantly between different species and even among individual specimens within the same species. This variability is influenced by factors such as geographic location, age, sex, diet, and environmental conditions. As a result, the clinical manifestations of crotalid envenomation can be highly variable, ranging from mild local reactions to severe systemic effects that may require intensive medical treatment and supportive care.

Crotalid venoms have been the subject of extensive research in recent years due to their potential therapeutic applications. For example, certain components of crotalid venoms have shown promise as drugs for treating various medical conditions, such as cardiovascular diseases, pain, and inflammation. However, further studies are needed to fully understand the mechanisms of action of these venom components and to develop safe and effective therapies based on them.

Hemostasis is the physiological process that occurs to stop bleeding (bleeding control) when a blood vessel is damaged. This involves the interaction of platelets, vasoconstriction, and blood clotting factors leading to the formation of a clot. The ultimate goal of hemostasis is to maintain the integrity of the vascular system while preventing excessive blood loss.

Fibrinogen is a soluble protein present in plasma, synthesized by the liver. It plays an essential role in blood coagulation. When an injury occurs, fibrinogen gets converted into insoluble fibrin by the action of thrombin, forming a fibrin clot that helps to stop bleeding from the injured site. Therefore, fibrinogen is crucial for hemostasis, which is the process of stopping bleeding and starting the healing process after an injury.

Thrombotic thrombocytopenic purpura (TTP) is a rare but serious blood disorder. It's characterized by the formation of small blood clots throughout the body, which can lead to serious complications such as low platelet count (thrombocytopenia), hemolytic anemia, neurological symptoms, and kidney damage.

The term "purpura" refers to the purple-colored spots on the skin that result from bleeding under the skin. In TTP, these spots are caused by the rupture of red blood cells that have been damaged by the abnormal clotting process.

TTP is often caused by a deficiency or inhibitor of ADAMTS13, a protein in the blood that helps to regulate the formation of blood clots. This deficiency or inhibitor can lead to the formation of large clots called microthrombi, which can block small blood vessels throughout the body and cause tissue damage.

TTP is a medical emergency that requires prompt treatment with plasma exchange therapy, which involves removing and replacing the patient's plasma to restore normal levels of ADAMTS13 and prevent further clotting. Other treatments may include corticosteroids, immunosuppressive drugs, and rituximab.

Platelet activation is the process by which platelets (also known as thrombocytes) become biologically active and change from their inactive discoid shape to a spherical shape with pseudopodia, resulting in the release of chemical mediators that are involved in hemostasis and thrombosis. This process is initiated by various stimuli such as exposure to subendothelial collagen, von Willebrand factor, or thrombin during vascular injury, leading to platelet aggregation and the formation of a platelet plug to stop bleeding. Platelet activation also plays a role in inflammation, immune response, and wound healing.

Von Willebrand disease (VWD) is a genetic bleeding disorder caused by deficiency or abnormality of the von Willebrand factor (VWF), a protein involved in blood clotting. Type 3 is the most severe form of VWD, characterized by extremely low levels or complete absence of VWF and Factor VIII, another clotting factor. This results in a significant impairment of the primary hemostasis, leading to spontaneous and severe bleeding episodes, including mucocutaneous bleeding (nosebleeds, gum bleeding, skin bruising), gastrointestinal bleeding, joint bleeds, and menorrhagia in women. Type 3 VWD is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the abnormal gene, one from each parent, to have the disease.

The endothelium is a thin layer of simple squamous epithelial cells that lines the interior surface of blood vessels, lymphatic vessels, and heart chambers. The vascular endothelium, specifically, refers to the endothelial cells that line the blood vessels. These cells play a crucial role in maintaining vascular homeostasis by regulating vasomotor tone, coagulation, platelet activation, inflammation, and permeability of the vessel wall. They also contribute to the growth and repair of the vascular system and are involved in various pathological processes such as atherosclerosis, hypertension, and diabetes.

Bernard-Soulier Syndrome is a rare autosomal recessive bleeding disorder characterized by a deficiency or dysfunction of the glycoprotein Ib-IX-V complex, which is a crucial component of platelet function. This complex plays a role in the initial adhesion of platelets to the damaged endothelium at the site of blood vessel injury.

The deficiency or dysfunction of this complex leads to abnormalities in platelet aggregation and results in prolonged bleeding times, increased bruising, and excessive blood loss during menstruation, surgery, or trauma. Additionally, individuals with Bernard-Soulier Syndrome often have giant platelets and a decreased platelet count (thrombocytopenia).

The syndrome is named after Jean J. Bernard and Jean-Pierre Soulier, who first described the disorder in 1948. It has an estimated prevalence of about 1 in one million individuals worldwide.

Thrombosis is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. When a clot forms in an artery, it can cut off the supply of oxygen and nutrients to the tissues served by that artery, leading to damage or tissue death. If a thrombus forms in the heart, it can cause a heart attack. If a thrombus breaks off and travels through the bloodstream, it can lodge in a smaller vessel, causing blockage and potentially leading to damage in the organ that the vessel supplies. This is known as an embolism.

Thrombosis can occur due to various factors such as injury to the blood vessel wall, abnormalities in blood flow, or changes in the composition of the blood. Certain medical conditions, medications, and lifestyle factors can increase the risk of thrombosis. Treatment typically involves anticoagulant or thrombolytic therapy to dissolve or prevent further growth of the clot, as well as addressing any underlying causes.

Thrombin is a serine protease enzyme that plays a crucial role in the coagulation cascade, which is a complex series of biochemical reactions that leads to the formation of a blood clot (thrombus) to prevent excessive bleeding during an injury. Thrombin is formed from its precursor protein, prothrombin, through a process called activation, which involves cleavage by another enzyme called factor Xa.

Once activated, thrombin converts fibrinogen, a soluble plasma protein, into fibrin, an insoluble protein that forms the structural framework of a blood clot. Thrombin also activates other components of the coagulation cascade, such as factor XIII, which crosslinks and stabilizes the fibrin network, and platelets, which contribute to the formation and growth of the clot.

Thrombin has several regulatory mechanisms that control its activity, including feedback inhibition by antithrombin III, a plasma protein that inactivates thrombin and other serine proteases, and tissue factor pathway inhibitor (TFPI), which inhibits the activation of factor Xa, thereby preventing further thrombin formation.

Overall, thrombin is an essential enzyme in hemostasis, the process that maintains the balance between bleeding and clotting in the body. However, excessive or uncontrolled thrombin activity can lead to pathological conditions such as thrombosis, atherosclerosis, and disseminated intravascular coagulation (DIC).

Collagen is the most abundant protein in the human body, and it is a major component of connective tissues such as tendons, ligaments, skin, and bones. Collagen provides structure and strength to these tissues and helps them to withstand stretching and tension. It is made up of long chains of amino acids, primarily glycine, proline, and hydroxyproline, which are arranged in a triple helix structure. There are at least 16 different types of collagen found in the body, each with slightly different structures and functions. Collagen is important for maintaining the integrity and health of tissues throughout the body, and it has been studied for its potential therapeutic uses in various medical conditions.

Hemophilia A is a genetic bleeding disorder caused by a deficiency in clotting factor VIII. This results in impaired blood clotting and prolonged bleeding, particularly after injuries or surgeries. Symptoms can range from mild to severe, with the most severe form resulting in spontaneous bleeding into joints and muscles, leading to pain, swelling, and potential joint damage over time. Hemophilia A primarily affects males, as it is an X-linked recessive disorder, and is usually inherited from a carrier mother. However, about one third of cases result from a spontaneous mutation in the gene for factor VIII. Treatment typically involves replacement therapy with infusions of factor VIII concentrates to prevent or control bleeding episodes.

Blood coagulation tests, also known as coagulation studies or clotting tests, are a series of medical tests used to evaluate the blood's ability to clot. These tests measure the functioning of various clotting factors and regulatory proteins involved in the coagulation cascade, which is a complex process that leads to the formation of a blood clot to prevent excessive bleeding.

The most commonly performed coagulation tests include:

1. Prothrombin Time (PT): Measures the time it takes for a sample of plasma to clot after the addition of calcium and tissue factor, which activates the extrinsic pathway of coagulation. The PT is reported in seconds and can be converted to an International Normalized Ratio (INR) to monitor anticoagulant therapy.
2. Activated Partial Thromboplastin Time (aPTT): Measures the time it takes for a sample of plasma to clot after the addition of calcium, phospholipid, and a contact activator, which activates the intrinsic pathway of coagulation. The aPTT is reported in seconds and is used to monitor heparin therapy.
3. Thrombin Time (TT): Measures the time it takes for a sample of plasma to clot after the addition of thrombin, which directly converts fibrinogen to fibrin. The TT is reported in seconds and can be used to detect the presence of fibrin degradation products or abnormalities in fibrinogen function.
4. Fibrinogen Level: Measures the amount of fibrinogen, a protein involved in clot formation, present in the blood. The level is reported in grams per liter (g/L) and can be used to assess bleeding risk or the effectiveness of fibrinogen replacement therapy.
5. D-dimer Level: Measures the amount of D-dimer, a protein fragment produced during the breakdown of a blood clot, present in the blood. The level is reported in micrograms per milliliter (µg/mL) and can be used to diagnose or exclude venous thromboembolism (VTE), such as deep vein thrombosis (DVT) or pulmonary embolism (PE).

These tests are important for the diagnosis, management, and monitoring of various bleeding and clotting disorders. They can help identify the underlying cause of abnormal bleeding or clotting, guide appropriate treatment decisions, and monitor the effectiveness of therapy. It is essential to interpret these test results in conjunction with a patient's clinical presentation and medical history.

P-Selectin is a type of cell adhesion molecule, specifically a member of the selectin family, that is involved in the inflammatory response. It is primarily expressed on the surface of activated platelets and endothelial cells. P-Selectin plays a crucial role in the initial interaction between leukocytes (white blood cells) and the vascular endothelium, which is an essential step in the recruitment of leukocytes to sites of inflammation or injury. This process helps to mediate the rolling and adhesion of leukocytes to the endothelial surface, facilitating their extravasation into the surrounding tissue. P-Selectin's function is regulated by its interaction with specific ligands on the surface of leukocytes, such as PSGL-1 (P-Selectin Glycoprotein Ligand-1).

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Blood coagulation, also known as blood clotting, is a complex process that occurs in the body to prevent excessive bleeding when a blood vessel is damaged. This process involves several different proteins and chemical reactions that ultimately lead to the formation of a clot.

The coagulation cascade is initiated when blood comes into contact with tissue factor, which is exposed after damage to the blood vessel wall. This triggers a series of enzymatic reactions that activate clotting factors, leading to the formation of a fibrin clot. Fibrin is a protein that forms a mesh-like structure that traps platelets and red blood cells to form a stable clot.

Once the bleeding has stopped, the coagulation process is regulated and inhibited to prevent excessive clotting. The fibrinolytic system degrades the clot over time, allowing for the restoration of normal blood flow.

Abnormalities in the blood coagulation process can lead to bleeding disorders or thrombotic disorders such as deep vein thrombosis and pulmonary embolism.

The umbilical veins are blood vessels in the umbilical cord that carry oxygenated and nutrient-rich blood from the mother to the developing fetus during pregnancy. There are typically two umbilical veins, one of which usually degenerates and becomes obliterated, leaving a single functional vein. This remaining vein is known as the larger umbilical vein or the venous duct. It enters the fetal abdomen through the umbilicus and passes through the liver, where it branches off to form the portal sinus. Ultimately, the blood from the umbilical vein mixes with the blood from the inferior vena cava and is pumped to the heart through the right atrium.

It's important to note that after birth, the umbilical veins are no longer needed and undergo involution, becoming the ligamentum teres in the adult.

The endothelium is the thin, delicate tissue that lines the interior surface of blood vessels and lymphatic vessels. It is a single layer of cells called endothelial cells that are in contact with the blood or lymph fluid. The endothelium plays an essential role in maintaining vascular homeostasis by regulating blood flow, coagulation, platelet activation, immune function, and angiogenesis (the formation of new blood vessels). It also acts as a barrier between the vessel wall and the circulating blood or lymph fluid. Dysfunction of the endothelium has been implicated in various cardiovascular diseases, diabetes, inflammation, and cancer.

Mechanical stress, in the context of physiology and medicine, refers to any type of force that is applied to body tissues or organs, which can cause deformation or displacement of those structures. Mechanical stress can be either external, such as forces exerted on the body during physical activity or trauma, or internal, such as the pressure changes that occur within blood vessels or other hollow organs.

Mechanical stress can have a variety of effects on the body, depending on the type, duration, and magnitude of the force applied. For example, prolonged exposure to mechanical stress can lead to tissue damage, inflammation, and chronic pain. Additionally, abnormal or excessive mechanical stress can contribute to the development of various musculoskeletal disorders, such as tendinitis, osteoarthritis, and herniated discs.

In order to mitigate the negative effects of mechanical stress, the body has a number of adaptive responses that help to distribute forces more evenly across tissues and maintain structural integrity. These responses include changes in muscle tone, joint positioning, and connective tissue stiffness, as well as the remodeling of bone and other tissues over time. However, when these adaptive mechanisms are overwhelmed or impaired, mechanical stress can become a significant factor in the development of various pathological conditions.

Blood platelet disorders are conditions that affect the number and/or function of platelets, which are small blood cells that help your body form clots to stop bleeding. Normal platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. A lower-than-normal platelet count is called thrombocytopenia, while a higher-than-normal platelet count is called thrombocytosis.

There are several types of platelet disorders, including:

1. Immune thrombocytopenia (ITP): A condition in which the immune system mistakenly attacks and destroys platelets, leading to a low platelet count. ITP can be acute (lasting less than six months) or chronic (lasting longer than six months).
2. Thrombotic thrombocytopenic purpura (TTP): A rare but serious condition that causes blood clots to form in small blood vessels throughout the body, leading to a low platelet count, anemia, and other symptoms.
3. Hemolytic uremic syndrome (HUS): A condition that is often caused by a bacterial infection, which can lead to the formation of blood clots in the small blood vessels of the kidneys, resulting in kidney damage and a low platelet count.
4. Hereditary platelet disorders: Some people inherit genetic mutations that can affect the number or function of their platelets, leading to bleeding disorders such as von Willebrand disease or Bernard-Soulier syndrome.
5. Medication-induced thrombocytopenia: Certain medications can cause a decrease in platelet count as a side effect.
6. Platelet dysfunction disorders: Some conditions can affect the ability of platelets to function properly, leading to bleeding disorders such as von Willebrand disease or storage pool deficiency.

Symptoms of platelet disorders may include easy bruising, prolonged bleeding from cuts or injuries, nosebleeds, blood in urine or stools, and in severe cases, internal bleeding. Treatment for platelet disorders depends on the underlying cause and may include medications, surgery, or other therapies.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Metalloendopeptidases are a type of enzymes that cleave peptide bonds in proteins, specifically at interior positions within the polypeptide chain. They require metal ions as cofactors for their catalytic activity, typically zinc (Zn2+) or cobalt (Co2+). These enzymes play important roles in various biological processes such as protein degradation, processing, and signaling. Examples of metalloendopeptidases include thermolysin, matrix metalloproteinases (MMPs), and neutrophil elastase.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

Hemorheology is the study of the flow properties of blood and its components, including red blood cells, white blood cells, platelets, and plasma. Specifically, it examines how these components interact with each other and with the walls of blood vessels to affect the flow characteristics of blood under different conditions. Hemorheological factors can influence blood viscosity, which is a major determinant of peripheral vascular resistance and cardiac workload. Abnormalities in hemorheology have been implicated in various diseases such as atherosclerosis, hypertension, diabetes, and sickle cell disease.

Thrombomodulin is a protein that is found on the surface of endothelial cells, which line the interior surface of blood vessels. It plays an important role in the regulation of blood coagulation (clotting) and the activation of natural anticoagulant pathways. Thrombomodulin binds to thrombin, a protein involved in blood clotting, and changes its function from promoting coagulation to inhibiting it. This interaction also activates protein C, an important anticoagulant protein, which helps to prevent the excessive formation of blood clots. Thrombomodulin also has anti-inflammatory properties and is involved in the maintenance of the integrity of the endothelial cell lining.

Monoclonal antibodies are a type of antibody that are identical because they are produced by a single clone of cells. They are laboratory-produced molecules that act like human antibodies in the immune system. They can be designed to attach to specific proteins found on the surface of cancer cells, making them useful for targeting and treating cancer. Monoclonal antibodies can also be used as a therapy for other diseases, such as autoimmune disorders and inflammatory conditions.

Monoclonal antibodies are produced by fusing a single type of immune cell, called a B cell, with a tumor cell to create a hybrid cell, or hybridoma. This hybrid cell is then able to replicate indefinitely, producing a large number of identical copies of the original antibody. These antibodies can be further modified and engineered to enhance their ability to bind to specific targets, increase their stability, and improve their effectiveness as therapeutic agents.

Monoclonal antibodies have several mechanisms of action in cancer therapy. They can directly kill cancer cells by binding to them and triggering an immune response. They can also block the signals that promote cancer growth and survival. Additionally, monoclonal antibodies can be used to deliver drugs or radiation directly to cancer cells, increasing the effectiveness of these treatments while minimizing their side effects on healthy tissues.

Monoclonal antibodies have become an important tool in modern medicine, with several approved for use in cancer therapy and other diseases. They are continuing to be studied and developed as a promising approach to treating a wide range of medical conditions.

Aurintricarboxylic acid (ATA) is a polyphenolic compound with antioxidant and anti-inflammatory properties. Its chemical formula is C14H8O8. It is known to inhibit several enzymes, including lipoxygenases, cyclooxygenases, and phospholipases, and has been studied for its potential therapeutic effects in various diseases such as cancer, neurodegenerative disorders, and cardiovascular diseases. However, more research is needed to fully understand its mechanisms of action and clinical applications.

Macromolecular substances, also known as macromolecules, are large, complex molecules made up of repeating subunits called monomers. These substances are formed through polymerization, a process in which many small molecules combine to form a larger one. Macromolecular substances can be naturally occurring, such as proteins, DNA, and carbohydrates, or synthetic, such as plastics and synthetic fibers.

In the context of medicine, macromolecular substances are often used in the development of drugs and medical devices. For example, some drugs are designed to bind to specific macromolecules in the body, such as proteins or DNA, in order to alter their function and produce a therapeutic effect. Additionally, macromolecular substances may be used in the creation of medical implants, such as artificial joints and heart valves, due to their strength and durability.

It is important for healthcare professionals to have an understanding of macromolecular substances and how they function in the body, as this knowledge can inform the development and use of medical treatments.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

A biological marker, often referred to as a biomarker, is a measurable indicator that reflects the presence or severity of a disease state, or a response to a therapeutic intervention. Biomarkers can be found in various materials such as blood, tissues, or bodily fluids, and they can take many forms, including molecular, histologic, radiographic, or physiological measurements.

In the context of medical research and clinical practice, biomarkers are used for a variety of purposes, such as:

1. Diagnosis: Biomarkers can help diagnose a disease by indicating the presence or absence of a particular condition. For example, prostate-specific antigen (PSA) is a biomarker used to detect prostate cancer.
2. Monitoring: Biomarkers can be used to monitor the progression or regression of a disease over time. For instance, hemoglobin A1c (HbA1c) levels are monitored in diabetes patients to assess long-term blood glucose control.
3. Predicting: Biomarkers can help predict the likelihood of developing a particular disease or the risk of a negative outcome. For example, the presence of certain genetic mutations can indicate an increased risk for breast cancer.
4. Response to treatment: Biomarkers can be used to evaluate the effectiveness of a specific treatment by measuring changes in the biomarker levels before and after the intervention. This is particularly useful in personalized medicine, where treatments are tailored to individual patients based on their unique biomarker profiles.

It's important to note that for a biomarker to be considered clinically valid and useful, it must undergo rigorous validation through well-designed studies, including demonstrating sensitivity, specificity, reproducibility, and clinical relevance.

Afibrinogenemia is a rare genetic disorder characterized by the complete absence or severely decreased levels of fibrinogen, a protein involved in blood clotting. This condition leads to an increased risk of excessive bleeding due to the inability to form proper blood clots. It is caused by mutations in the genes that provide instructions for making the three chains (Aα, Bβ, and γ) that make up the fibrinogen protein. Inheritance is autosomal recessive, meaning an individual must inherit two copies of the defective gene, one from each parent, to have the condition.

Endothelial cells are the type of cells that line the inner surface of blood vessels, lymphatic vessels, and heart chambers. They play a crucial role in maintaining vascular homeostasis by controlling vasomotor tone, coagulation, platelet activation, and inflammation. Endothelial cells also regulate the transport of molecules between the blood and surrounding tissues, and contribute to the maintenance of the structural integrity of the vasculature. They are flat, elongated cells with a unique morphology that allows them to form a continuous, nonthrombogenic lining inside the vessels. Endothelial cells can be isolated from various tissues and cultured in vitro for research purposes.

The platelet glycoprotein GPIIb-IIIa complex, also known as integrin αIIbβ3 or CD41/CD61, is a heterodimeric transmembrane receptor found on the surface of platelets and megakaryocytes. It plays a crucial role in platelet aggregation and thrombus formation during hemostasis and pathological conditions such as arterial thrombosis.

The GPIIb-IIIa complex is composed of two non-covalently associated subunits, GPIIb (αIIb or CD41) and IIIa (β3 or CD61). Upon platelet activation by various agonists like ADP, thrombin, or collagen, the GPIIb-IIIa complex undergoes a conformational change that allows it to bind fibrinogen, von Willebrand factor, and other adhesive proteins. This binding event leads to platelet aggregation and the formation of a hemostatic plug or pathological thrombus.

Inhibition of the GPIIb-IIIa complex has been a target for antiplatelet therapy in the prevention and treatment of arterial thrombosis, such as myocardial infarction and stroke. Several pharmacological agents, including monoclonal antibodies and small molecule antagonists, have been developed to block this complex and reduce platelet aggregation.

Thrombospondins (TSPs) are a family of multifunctional glycoproteins that are involved in various biological processes, including cell adhesion, migration, proliferation, differentiation, and angiogenesis. They were initially identified as calcium-binding proteins that are secreted by platelets during blood clotting (thrombosis), hence the name thrombospondin.

There are five members in the TSP family, designated as TSP-1 to TSP-5, and they share a common structure consisting of several domains, including an N-terminal domain, a series of type 1 repeats, a type 2 (von Willebrand factor C) repeat, a type 3 repeat, and a C-terminal domain.

TSP-1 and TSP-2 are secreted proteins that have been extensively studied for their roles in the regulation of angiogenesis, the process of new blood vessel formation. They bind to various extracellular matrix components, growth factors, and cell surface receptors, and can either promote or inhibit angiogenesis depending on the context.

TSP-3 to TSP-5 are expressed in a variety of tissues and play roles in cell adhesion, migration, and differentiation. They have been implicated in various pathological conditions, including cancer, fibrosis, and neurodegenerative diseases.

Overall, thrombospondins are important regulators of extracellular matrix dynamics and cell-matrix interactions, and their dysregulation has been associated with a variety of diseases.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

Hemostatics are substances or agents that promote bleeding cessation or prevent the spread of bleeding. They can act in various ways, such as by stimulating the body's natural clotting mechanisms, constricting blood vessels to reduce blood flow, or forming a physical barrier to block the bleeding site.

Hemostatics are often used in medical settings to manage wounds, injuries, and surgical procedures. They can be applied directly to the wound as a powder, paste, or gauze, or they can be administered systemically through intravenous injection. Examples of hemostatic agents include fibrin sealants, collagen-based products, thrombin, and oxidized regenerated cellulose.

It's important to note that while hemostatics can be effective in controlling bleeding, they should be used with caution and only under the guidance of a healthcare professional. Inappropriate use or overuse of hemostatic agents can lead to complications such as excessive clotting, thrombosis, or tissue damage.

An antigen is a substance (usually a protein) that is recognized as foreign by the immune system and stimulates an immune response, leading to the production of antibodies or activation of T-cells. Antigens can be derived from various sources, including bacteria, viruses, fungi, parasites, and tumor cells. They can also come from non-living substances such as pollen, dust mites, or chemicals.

Antigens contain epitopes, which are specific regions on the antigen molecule that are recognized by the immune system. The immune system's response to an antigen depends on several factors, including the type of antigen, its size, and its location in the body.

In general, antigens can be classified into two main categories:

1. T-dependent antigens: These require the help of T-cells to stimulate an immune response. They are typically larger, more complex molecules that contain multiple epitopes capable of binding to both MHC class II molecules on antigen-presenting cells and T-cell receptors on CD4+ T-cells.
2. T-independent antigens: These do not require the help of T-cells to stimulate an immune response. They are usually smaller, simpler molecules that contain repetitive epitopes capable of cross-linking B-cell receptors and activating them directly.

Understanding antigens and their properties is crucial for developing vaccines, diagnostic tests, and immunotherapies.

Tertiary protein structure refers to the three-dimensional arrangement of all the elements (polypeptide chains) of a single protein molecule. It is the highest level of structural organization and results from interactions between various side chains (R groups) of the amino acids that make up the protein. These interactions, which include hydrogen bonds, ionic bonds, van der Waals forces, and disulfide bridges, give the protein its unique shape and stability, which in turn determines its function. The tertiary structure of a protein can be stabilized by various factors such as temperature, pH, and the presence of certain ions. Any changes in these factors can lead to denaturation, where the protein loses its tertiary structure and thus its function.

Two-dimensional immunoelectrophoresis (2DE) is a specialized laboratory technique used in the field of clinical pathology and immunology. This technique is a refined version of traditional immunoelectrophoresis that adds an additional electrophoretic separation step, enhancing its resolution and allowing for more detailed analysis of complex protein mixtures.

In two-dimensional immunoelectrophoresis, proteins are first separated based on their isoelectric points (pI) in the initial dimension using isoelectric focusing (IEF). This process involves applying an electric field to a protein mixture contained within a gel matrix, where proteins will migrate and stop migrating once they reach the pH that matches their own isoelectric point.

Following IEF, the separated proteins are then subjected to a second electrophoretic separation in the perpendicular direction (second dimension) based on their molecular weights using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). SDS is a negatively charged molecule that binds to proteins, giving them a uniform negative charge and allowing for separation based solely on size.

Once the two-dimensional separation is complete, the gel is then overlaid with specific antisera to detect and identify proteins of interest. The resulting precipitin arcs formed at the intersection of the antibody and antigen are compared to known standards or patterns to determine the identity and quantity of the separated proteins.

Two-dimensional immunoelectrophoresis is particularly useful in identifying and quantifying proteins in complex mixtures, such as those found in body fluids like serum, urine, or cerebrospinal fluid (CSF). It can be applied to various clinical scenarios, including diagnosis and monitoring of monoclonal gammopathies, autoimmune disorders, and certain infectious diseases.

Coagulation protein disorders are a group of medical conditions that affect the body's ability to form blood clots properly. These disorders can be caused by genetic defects or acquired factors, such as liver disease or vitamin K deficiency.

The coagulation system is a complex process that involves various proteins called clotting factors. When there is an injury to a blood vessel, these clotting factors work together in a specific order to form a clot and prevent excessive bleeding. In coagulation protein disorders, one or more of these clotting factors are missing or not functioning properly, leading to abnormal bleeding or clotting.

There are several types of coagulation protein disorders, including:

1. Hemophilia: This is a genetic disorder that affects the clotting factor VIII or IX. People with hemophilia may experience prolonged bleeding after injuries, surgery, or dental work.
2. Von Willebrand disease: This is another genetic disorder that affects the von Willebrand factor, a protein that helps platelets stick together and form a clot. People with this condition may have nosebleeds, easy bruising, and excessive bleeding during menstruation or after surgery.
3. Factor XI deficiency: This is a rare genetic disorder that affects the clotting factor XI. People with this condition may experience prolonged bleeding after surgery or trauma.
4. Factor VII deficiency: This is a rare genetic disorder that affects the clotting factor VII. People with this condition may have nosebleeds, easy bruising, and excessive bleeding during menstruation or after surgery.
5. Acquired coagulation protein disorders: These are conditions that develop due to other medical factors, such as liver disease, vitamin K deficiency, or the use of certain medications. These disorders can affect one or more clotting factors and may cause abnormal bleeding or clotting.

Treatment for coagulation protein disorders depends on the specific condition and severity of symptoms. In some cases, replacement therapy with the missing clotting factor may be necessary to prevent excessive bleeding. Other treatments may include medications to control bleeding, such as desmopressin or antifibrinolytic agents, and lifestyle changes to reduce the risk of injury and bleeding.

A peptide fragment is a short chain of amino acids that is derived from a larger peptide or protein through various biological or chemical processes. These fragments can result from the natural breakdown of proteins in the body during regular physiological processes, such as digestion, or they can be produced experimentally in a laboratory setting for research or therapeutic purposes.

Peptide fragments are often used in research to map the structure and function of larger peptides and proteins, as well as to study their interactions with other molecules. In some cases, peptide fragments may also have biological activity of their own and can be developed into drugs or diagnostic tools. For example, certain peptide fragments derived from hormones or neurotransmitters may bind to receptors in the body and mimic or block the effects of the full-length molecule.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Hemorrhagic disorders are medical conditions characterized by abnormal bleeding due to impaired blood clotting. This can result from deficiencies in coagulation factors, platelet dysfunction, or the use of medications that interfere with normal clotting processes. Examples include hemophilia, von Willebrand disease, and disseminated intravascular coagulation (DIC). Treatment often involves replacing the missing clotting factor or administering medications to help control bleeding.

Molecular weight, also known as molecular mass, is the mass of a molecule. It is expressed in units of atomic mass units (amu) or daltons (Da). Molecular weight is calculated by adding up the atomic weights of each atom in a molecule. It is a useful property in chemistry and biology, as it can be used to determine the concentration of a substance in a solution, or to calculate the amount of a substance that will react with another in a chemical reaction.

Glycoproteins are complex proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide backbone. These glycans are linked to the protein through asparagine residues (N-linked) or serine/threonine residues (O-linked). Glycoproteins play crucial roles in various biological processes, including cell recognition, cell-cell interactions, cell adhesion, and signal transduction. They are widely distributed in nature and can be found on the outer surface of cell membranes, in extracellular fluids, and as components of the extracellular matrix. The structure and composition of glycoproteins can vary significantly depending on their function and location within an organism.

A platelet count is a laboratory test that measures the number of platelets, also known as thrombocytes, in a sample of blood. Platelets are small, colorless cell fragments that circulate in the blood and play a crucial role in blood clotting. They help to stop bleeding by sticking together to form a plug at the site of an injured blood vessel.

A normal platelet count ranges from 150,000 to 450,000 platelets per microliter (µL) of blood. A lower than normal platelet count is called thrombocytopenia, while a higher than normal platelet count is known as thrombocytosis.

Abnormal platelet counts can be a sign of various medical conditions, including bleeding disorders, infections, certain medications, and some types of cancer. It is important to consult with a healthcare provider if you have any concerns about your platelet count or if you experience symptoms such as easy bruising, prolonged bleeding, or excessive menstrual flow.

Fibrin(ogen) degradation products (FDPs) are a group of proteins that result from the breakdown of fibrinogen and fibrin, which are key components of blood clots. This process occurs during the normal physiological process of fibrinolysis, where clots are dissolved to maintain blood flow.

FDPs can be measured in the blood as a marker for the activation of the coagulation and fibrinolytic systems. Elevated levels of FDPs may indicate the presence of a disorder that causes abnormal clotting or bleeding, such as disseminated intravascular coagulation (DIC), deep vein thrombosis (DVT), pulmonary embolism (PE), or certain types of cancer.

It is important to note that FDPs are not specific to any particular disorder and their measurement should be interpreted in conjunction with other clinical and laboratory findings.

Electrophoresis, Agar Gel is a laboratory technique used to separate and analyze DNA, RNA, or proteins based on their size and electrical charge. In this method, the sample is mixed with agarose gel, a gelatinous substance derived from seaweed, and then solidified in a horizontal slab-like format. An electric field is applied to the gel, causing the negatively charged DNA or RNA molecules to migrate towards the positive electrode. The smaller molecules move faster through the gel than the larger ones, resulting in their separation based on size. This technique is widely used in molecular biology and genetics research, as well as in diagnostic testing for various genetic disorders.

Cell adhesion refers to the binding of cells to extracellular matrices or to other cells, a process that is fundamental to the development, function, and maintenance of multicellular organisms. Cell adhesion is mediated by various cell surface receptors, such as integrins, cadherins, and immunoglobulin-like cell adhesion molecules (Ig-CAMs), which interact with specific ligands in the extracellular environment. These interactions lead to the formation of specialized junctions, such as tight junctions, adherens junctions, and desmosomes, that help to maintain tissue architecture and regulate various cellular processes, including proliferation, differentiation, migration, and survival. Disruptions in cell adhesion can contribute to a variety of diseases, including cancer, inflammation, and degenerative disorders.

Hemorrhage is defined in the medical context as an excessive loss of blood from the circulatory system, which can occur due to various reasons such as injury, surgery, or underlying health conditions that affect blood clotting or the integrity of blood vessels. The bleeding may be internal, external, visible, or concealed, and it can vary in severity from minor to life-threatening, depending on the location and extent of the bleeding. Hemorrhage is a serious medical emergency that requires immediate attention and treatment to prevent further blood loss, organ damage, and potential death.

The ABO blood-group system is a classification system used in blood transfusion medicine to determine the compatibility of donated blood with a recipient's blood. It is based on the presence or absence of two antigens, A and B, on the surface of red blood cells (RBCs), as well as the corresponding antibodies present in the plasma.

There are four main blood types in the ABO system:

1. Type A: These individuals have A antigens on their RBCs and anti-B antibodies in their plasma.
2. Type B: They have B antigens on their RBCs and anti-A antibodies in their plasma.
3. Type AB: They have both A and B antigens on their RBCs but no natural antibodies against either A or B antigens.
4. Type O: They do not have any A or B antigens on their RBCs, but they have both anti-A and anti-B antibodies in their plasma.

Transfusing blood from a donor with incompatible ABO antigens can lead to an immune response, causing the destruction of donated RBCs and potentially life-threatening complications such as acute hemolytic transfusion reaction. Therefore, it is crucial to match the ABO blood type between donors and recipients before performing a blood transfusion.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Electrophoresis, polyacrylamide gel (EPG) is a laboratory technique used to separate and analyze complex mixtures of proteins or nucleic acids (DNA or RNA) based on their size and electrical charge. This technique utilizes a matrix made of cross-linked polyacrylamide, a type of gel, which provides a stable and uniform environment for the separation of molecules.

In this process:

1. The polyacrylamide gel is prepared by mixing acrylamide monomers with a cross-linking agent (bis-acrylamide) and a catalyst (ammonium persulfate) in the presence of a buffer solution.
2. The gel is then poured into a mold and allowed to polymerize, forming a solid matrix with uniform pore sizes that depend on the concentration of acrylamide used. Higher concentrations result in smaller pores, providing better resolution for separating smaller molecules.
3. Once the gel has set, it is placed in an electrophoresis apparatus containing a buffer solution. Samples containing the mixture of proteins or nucleic acids are loaded into wells on the top of the gel.
4. An electric field is applied across the gel, causing the negatively charged molecules to migrate towards the positive electrode (anode) while positively charged molecules move toward the negative electrode (cathode). The rate of migration depends on the size, charge, and shape of the molecules.
5. Smaller molecules move faster through the gel matrix and will migrate farther from the origin compared to larger molecules, resulting in separation based on size. Proteins and nucleic acids can be selectively stained after electrophoresis to visualize the separated bands.

EPG is widely used in various research fields, including molecular biology, genetics, proteomics, and forensic science, for applications such as protein characterization, DNA fragment analysis, cloning, mutation detection, and quality control of nucleic acid or protein samples.

Galactose oxidase is an enzyme with the systematic name D-galactose:oxygen oxidoreductase. It is found in certain fungi and bacteria, and it catalyzes the following reaction:

D-galactose + O2 -> D-galacto-hexodialdose + H2O2

In this reaction, the enzyme oxidizes the hydroxyl group (-OH) on the sixth carbon atom of D-galactose to an aldehyde group (-CHO), forming D-galacto-hexodialdose. At the same time, it reduces molecular oxygen (O2) to hydrogen peroxide (H2O2).

Galactose oxidase is a copper-containing enzyme and requires the cofactor molybdenum for its activity. It has potential applications in various industrial processes, such as the production of D-galacto-hexodialdose and other sugar derivatives, as well as in biosensors for detecting glucose levels in biological samples.

Platelet function tests are laboratory tests that measure how well platelets, which are small blood cells responsible for clotting, function in preventing or stopping bleeding. These tests are often used to investigate the cause of abnormal bleeding or bruising, or to monitor the effectiveness of antiplatelet therapy in patients with certain medical conditions such as heart disease or stroke.

There are several types of platelet function tests available, including:

1. Platelet count: This test measures the number of platelets present in a sample of blood. A low platelet count can increase the risk of bleeding.
2. Bleeding time: This test measures how long it takes for a small cut to stop bleeding. It is used less frequently than other tests due to its invasiveness and variability.
3. Platelet aggregation tests: These tests measure how well platelets clump together (aggregate) in response to various agents that promote platelet activation, such as adenosine diphosphate (ADP), collagen, or epinephrine.
4. Platelet function analyzer (PFA): This test measures the time it takes for a blood sample to clot under shear stress, simulating the conditions in an injured blood vessel. The PFA can provide information about the overall platelet function and the effectiveness of antiplatelet therapy.
5. Thromboelastography (TEG) or rotational thromboelastometry (ROTEM): These tests measure the kinetics of clot formation, strength, and dissolution in whole blood samples. They provide information about both platelet function and coagulation factors.

These tests can help healthcare providers diagnose bleeding disorders, assess the risk of bleeding during surgery or other invasive procedures, monitor antiplatelet therapy, and guide treatment decisions for patients with abnormal platelet function.

Thrombotic microangiopathies (TMAs) are a group of disorders characterized by the formation of blood clots in small blood vessels, causing damage to the end organs. This process leads to a constellation of clinical symptoms including thrombocytopenia (low platelet count), microangiopathic hemolytic anemia (breakdown of red blood cells leading to anemia), and organ dysfunction such as renal failure, neurological impairment, or cardiac involvement.

TMAs can be primary or secondary. Primary TMAs are caused by genetic mutations affecting the complement system, coagulation cascade, or other regulatory proteins involved in vascular homeostasis. Examples of primary TMAs include atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP), and complement-mediated TMA.

Secondary TMAs are caused by various underlying conditions or exposures, such as infections, autoimmune diseases, malignancies, drugs, pregnancy-related complications, or other systemic disorders. The pathogenesis of secondary TMAs is often multifactorial and may involve endothelial injury, complement activation, and platelet aggregation.

The diagnosis of TMAs requires a combination of clinical, laboratory, and sometimes histopathological findings. Treatment depends on the underlying cause and may include supportive care, plasma exchange, immunosuppressive therapy, or targeted therapies such as complement inhibitors.

Cytoplasmic granules are small, membrane-bound organelles or inclusions found within the cytoplasm of cells. They contain various substances such as proteins, lipids, carbohydrates, and genetic material. Cytoplasmic granules have diverse functions depending on their specific composition and cellular location. Some examples include:

1. Secretory granules: These are found in secretory cells and store hormones, neurotransmitters, or enzymes before they are released by exocytosis.
2. Lysosomes: These are membrane-bound organelles that contain hydrolytic enzymes for intracellular digestion of waste materials, foreign substances, and damaged organelles.
3. Melanosomes: Found in melanocytes, these granules produce and store the pigment melanin, which is responsible for skin, hair, and eye color.
4. Weibel-Palade bodies: These are found in endothelial cells and store von Willebrand factor and P-selectin, which play roles in hemostasis and inflammation.
5. Peroxisomes: These are single-membrane organelles that contain enzymes for various metabolic processes, such as β-oxidation of fatty acids and detoxification of harmful substances.
6. Lipid bodies (also called lipid droplets): These are cytoplasmic granules that store neutral lipids, such as triglycerides and cholesteryl esters. They play a role in energy metabolism and intracellular signaling.
7. Glycogen granules: These are cytoplasmic inclusions that store glycogen, a polysaccharide used for energy storage in animals.
8. Protein bodies: Found in plants, these granules store excess proteins and help regulate protein homeostasis within the cell.
9. Electron-dense granules: These are found in certain immune cells, such as mast cells and basophils, and release mediators like histamine during an allergic response.
10. Granules of unknown composition or function may also be present in various cell types.

Blood viscosity is a measure of the thickness or flow resistance of blood. It is defined as the ratio of shear stress to shear rate within the flowing blood, which reflects the internal friction or resistance to flow. Blood viscosity is primarily determined by the concentration and size of red blood cells (hematocrit), plasma proteins, and other blood constituents. An increase in any of these components can raise blood viscosity, leading to impaired blood flow, reduced oxygen delivery to tissues, and potential cardiovascular complications if not managed appropriately.

Von Hippel-Lindau (VHL) disease is a rare genetic disorder characterized by the development of tumors and cysts in various parts of the body. It is caused by mutations in the VHL gene, which leads to the abnormal growth of blood vessels, resulting in the formation of these tumors.

The tumors associated with VHL disease can develop in several organs, including the eyes (in the form of retinal hemangioblastomas), the brain and spinal cord (in the form of cerebellar hemangioblastomas and spinal cord hemangioblastomas), the adrenal glands (in the form of pheochromocytomas or paragangliomas), the kidneys (in the form of clear cell renal cell carcinomas), and the pancreas (in the form of serous cystadenomas or neuroendocrine tumors).

Individuals with VHL disease are at risk for developing multiple tumors over their lifetime, and the severity of the disease can vary widely from person to person. The diagnosis of VHL disease is typically made through genetic testing, family history, and imaging studies to detect the presence of tumors. Treatment may involve surgical removal of the tumors, radiation therapy, or other interventions depending on the location and size of the tumors. Regular monitoring and follow-up are essential for individuals with VHL disease to manage their condition effectively.

Megakaryocytes are large, specialized bone marrow cells that are responsible for the production and release of platelets (also known as thrombocytes) into the bloodstream. Platelets play an essential role in blood clotting and hemostasis, helping to prevent excessive bleeding during injuries or trauma.

Megakaryocytes have a unique structure with multilobed nuclei and abundant cytoplasm rich in organelles called alpha-granules and dense granules, which store various proteins, growth factors, and enzymes necessary for platelet function. As megakaryocytes mature, they extend long cytoplasmic processes called proplatelets into the bone marrow sinuses, where these extensions fragment into individual platelets that are released into circulation.

Abnormalities in megakaryocyte number, size, or function can lead to various hematological disorders, such as thrombocytopenia (low platelet count), thrombocytosis (high platelet count), and certain types of leukemia.

Protein multimerization refers to the process where multiple protein subunits assemble together to form a complex, repetitive structure called a multimer or oligomer. This can involve the association of identical or similar protein subunits through non-covalent interactions such as hydrogen bonding, ionic bonding, and van der Waals forces. The resulting multimeric structures can have various shapes, sizes, and functions, including enzymatic activity, transport, or structural support. Protein multimerization plays a crucial role in many biological processes and is often necessary for the proper functioning of proteins within cells.

Disulfides are a type of organic compound that contains a sulfur-sulfur bond. In the context of biochemistry and medicine, disulfide bonds are often found in proteins, where they play a crucial role in maintaining their three-dimensional structure and function. These bonds form when two sulfhydryl groups (-SH) on cysteine residues within a protein molecule react with each other, releasing a molecule of water and creating a disulfide bond (-S-S-) between the two cysteines. Disulfide bonds can be reduced back to sulfhydryl groups by various reducing agents, which is an important process in many biological reactions. The formation and reduction of disulfide bonds are critical for the proper folding, stability, and activity of many proteins, including those involved in various physiological processes and diseases.

Partial Thromboplastin Time (PTT) is a medical laboratory test that measures the time it takes for blood to clot. It's more specifically a measure of the intrinsic and common pathways of the coagulation cascade, which are the series of chemical reactions that lead to the formation of a clot.

The test involves adding a partial thromboplastin reagent (an activator of the intrinsic pathway) and calcium to plasma, and then measuring the time it takes for a fibrin clot to form. This is compared to a control sample, and the ratio of the two times is calculated.

The PTT test is often used to help diagnose bleeding disorders or abnormal blood clotting, such as hemophilia or disseminated intravascular coagulation (DIC). It can also be used to monitor the effectiveness of anticoagulant therapy, such as heparin. Prolonged PTT results may indicate a bleeding disorder or an increased risk of bleeding, while shortened PTT results may indicate a hypercoagulable state and an increased risk of thrombosis.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Fibrinolysis is the natural process in the body that leads to the dissolution of blood clots. It is a vital part of hemostasis, the process that regulates bleeding and wound healing. Fibrinolysis occurs when plasminogen activators convert plasminogen to plasmin, an enzyme that breaks down fibrin, the insoluble protein mesh that forms the structure of a blood clot. This process helps to prevent excessive clotting and maintains the fluidity of the blood. In medical settings, fibrinolysis can also refer to the therapeutic use of drugs that stimulate this process to dissolve unwanted or harmful blood clots, such as those that cause deep vein thrombosis or pulmonary embolism.

A point mutation is a type of genetic mutation where a single nucleotide base (A, T, C, or G) in DNA is altered, deleted, or substituted with another nucleotide. Point mutations can have various effects on the organism, depending on the location of the mutation and whether it affects the function of any genes. Some point mutations may not have any noticeable effect, while others might lead to changes in the amino acids that make up proteins, potentially causing diseases or altering traits. Point mutations can occur spontaneously due to errors during DNA replication or be inherited from parents.

Collagen receptors are a type of cell surface receptor that bind to collagen molecules, which are the most abundant proteins in the extracellular matrix (ECM) of connective tissues. These receptors play important roles in various biological processes, including cell adhesion, migration, differentiation, and survival.

Collagen receptors can be classified into two major groups: integrins and discoidin domain receptors (DDRs). Integrins are heterodimeric transmembrane proteins that consist of an alpha and a beta subunit. They bind to collagens via their arginine-glycine-aspartic acid (RGD) motif, which is located in the triple-helical domain of collagen molecules. Integrins mediate cell-collagen interactions by clustering and forming focal adhesions, which are large protein complexes that connect the ECM to the cytoskeleton.

DDRs are receptor tyrosine kinases (RTKs) that contain a discoidin domain in their extracellular region, which is responsible for collagen binding. DDRs bind to collagens via their non-RGD motifs and induce intracellular signaling pathways that regulate cell behavior.

Abnormalities in collagen receptor function have been implicated in various diseases, including fibrosis, cancer, and inflammation. Therefore, understanding the structure and function of collagen receptors is crucial for developing novel therapeutic strategies to treat these conditions.

Integrin alpha2, also known as CD49b or ITGA2, is a type I transmembrane glycoprotein that forms a heterodimer with integrin beta1 to create the collagen receptor very late antigen-2 (VLA-2) or α2β1 integrin. This integrin plays crucial roles in various cellular processes such as adhesion, migration, and signaling during embryonic development, hemostasis, and tissue repair. It specifically binds to collagen types I, II, and IV, contributing to the regulation of cell-matrix interactions in several tissues, including bone, cartilage, and vascular systems. Integrin alpha2 also participates in immune responses by mediating lymphocyte adhesion and activation.

Protein precursors, also known as proproteins or prohormones, are inactive forms of proteins that undergo post-translational modification to become active. These modifications typically include cleavage of the precursor protein by specific enzymes, resulting in the release of the active protein. This process allows for the regulation and control of protein activity within the body. Protein precursors can be found in various biological processes, including the endocrine system where they serve as inactive hormones that can be converted into their active forms when needed.

Tissue Plasminogen Activator (tPA) is a thrombolytic enzyme, which means it dissolves blood clots. It is naturally produced by the endothelial cells that line the interior surface of blood vessels. tPA activates plasminogen, a zymogen, to convert it into plasmin, a protease that breaks down fibrin, the structural protein in blood clots. This enzyme is used medically as a thrombolytic drug under various brand names, such as Activase and Alteplase, to treat conditions like acute ischemic stroke, pulmonary embolism, and deep vein thrombosis by dissolving the clots and restoring blood flow.

Blood coagulation disorders, also known as bleeding disorders or clotting disorders, refer to a group of medical conditions that affect the body's ability to form blood clots properly. Normally, when a blood vessel is injured, the body's coagulation system works to form a clot to stop the bleeding and promote healing.

In blood coagulation disorders, there can be either an increased tendency to bleed due to problems with the formation of clots (hemorrhagic disorder), or an increased tendency for clots to form inappropriately even without injury, leading to blockages in the blood vessels (thrombotic disorder).

Examples of hemorrhagic disorders include:

1. Hemophilia - a genetic disorder that affects the ability to form clots due to deficiencies in clotting factors VIII or IX.
2. Von Willebrand disease - another genetic disorder caused by a deficiency or abnormality of the von Willebrand factor, which helps platelets stick together to form a clot.
3. Liver diseases - can lead to decreased production of coagulation factors, increasing the risk of bleeding.
4. Disseminated intravascular coagulation (DIC) - a serious condition where clotting and bleeding occur simultaneously due to widespread activation of the coagulation system.

Examples of thrombotic disorders include:

1. Factor V Leiden mutation - a genetic disorder that increases the risk of inappropriate blood clot formation.
2. Antithrombin III deficiency - a genetic disorder that impairs the body's ability to break down clots, increasing the risk of thrombosis.
3. Protein C or S deficiencies - genetic disorders that lead to an increased risk of thrombosis due to impaired regulation of the coagulation system.
4. Antiphospholipid syndrome (APS) - an autoimmune disorder where the body produces antibodies against its own clotting factors, increasing the risk of thrombosis.

Treatment for blood coagulation disorders depends on the specific diagnosis and may include medications to manage bleeding or prevent clots, as well as lifestyle changes and monitoring to reduce the risk of complications.

An Enzyme-Linked Immunosorbent Assay (ELISA) is a type of analytical biochemistry assay used to detect and quantify the presence of a substance, typically a protein or peptide, in a liquid sample. It takes its name from the enzyme-linked antibodies used in the assay.

In an ELISA, the sample is added to a well containing a surface that has been treated to capture the target substance. If the target substance is present in the sample, it will bind to the surface. Next, an enzyme-linked antibody specific to the target substance is added. This antibody will bind to the captured target substance if it is present. After washing away any unbound material, a substrate for the enzyme is added. If the enzyme is present due to its linkage to the antibody, it will catalyze a reaction that produces a detectable signal, such as a color change or fluorescence. The intensity of this signal is proportional to the amount of target substance present in the sample, allowing for quantification.

ELISAs are widely used in research and clinical settings to detect and measure various substances, including hormones, viruses, and bacteria. They offer high sensitivity, specificity, and reproducibility, making them a reliable choice for many applications.

Cricetinae is a subfamily of rodents that includes hamsters, gerbils, and relatives. These small mammals are characterized by having short limbs, compact bodies, and cheek pouches for storing food. They are native to various parts of the world, particularly in Europe, Asia, and Africa. Some species are popular pets due to their small size, easy care, and friendly nature. In a medical context, understanding the biology and behavior of Cricetinae species can be important for individuals who keep them as pets or for researchers studying their physiology.

CHO cells, or Chinese Hamster Ovary cells, are a type of immortalized cell line that are commonly used in scientific research and biotechnology. They were originally derived from the ovaries of a female Chinese hamster (Cricetulus griseus) in the 1950s.

CHO cells have several characteristics that make them useful for laboratory experiments. They can grow and divide indefinitely under appropriate conditions, which allows researchers to culture large quantities of them for study. Additionally, CHO cells are capable of expressing high levels of recombinant proteins, making them a popular choice for the production of therapeutic drugs, vaccines, and other biologics.

In particular, CHO cells have become a workhorse in the field of biotherapeutics, with many approved monoclonal antibody-based therapies being produced using these cells. The ability to genetically modify CHO cells through various methods has further expanded their utility in research and industrial applications.

It is important to note that while CHO cells are widely used in scientific research, they may not always accurately represent human cell behavior or respond to drugs and other compounds in the same way as human cells do. Therefore, results obtained using CHO cells should be validated in more relevant systems when possible.

Protein conformation refers to the specific three-dimensional shape that a protein molecule assumes due to the spatial arrangement of its constituent amino acid residues and their associated chemical groups. This complex structure is determined by several factors, including covalent bonds (disulfide bridges), hydrogen bonds, van der Waals forces, and ionic bonds, which help stabilize the protein's unique conformation.

Protein conformations can be broadly classified into two categories: primary, secondary, tertiary, and quaternary structures. The primary structure represents the linear sequence of amino acids in a polypeptide chain. The secondary structure arises from local interactions between adjacent amino acid residues, leading to the formation of recurring motifs such as α-helices and β-sheets. Tertiary structure refers to the overall three-dimensional folding pattern of a single polypeptide chain, while quaternary structure describes the spatial arrangement of multiple folded polypeptide chains (subunits) that interact to form a functional protein complex.

Understanding protein conformation is crucial for elucidating protein function, as the specific three-dimensional shape of a protein directly influences its ability to interact with other molecules, such as ligands, nucleic acids, or other proteins. Any alterations in protein conformation due to genetic mutations, environmental factors, or chemical modifications can lead to loss of function, misfolding, aggregation, and disease states like neurodegenerative disorders and cancer.

Thrombophilia is a medical condition characterized by an increased tendency to form blood clots (thrombi) due to various genetic or acquired abnormalities in the coagulation system. These abnormalities can lead to a hypercoagulable state, which can cause thrombosis in both veins and arteries. Commonly identified thrombophilias include factor V Leiden mutation, prothrombin G20210A mutation, antithrombin deficiency, protein C deficiency, and protein S deficiency.

Acquired thrombophilias can be caused by various factors such as antiphospholipid antibody syndrome (APS), malignancies, pregnancy, oral contraceptive use, hormone replacement therapy, and certain medical conditions like inflammatory bowel disease or nephrotic syndrome.

It is essential to diagnose thrombophilia accurately, as it may influence the management of venous thromboembolism (VTE) events and guide decisions regarding prophylactic anticoagulation in high-risk situations.

Hematologic pregnancy complications refer to disorders related to the blood and blood-forming tissues that occur during pregnancy. These complications can have serious consequences for both the mother and the fetus if not properly managed. Some common hematologic pregnancy complications include:

1. Anemia: A condition characterized by a decrease in the number of red blood cells or hemoglobin in the blood, which can lead to fatigue, weakness, and shortness of breath. Iron-deficiency anemia is the most common type of anemia during pregnancy.
2. Thrombocytopenia: A condition characterized by a decrease in the number of platelets (cells that help blood clot) in the blood. Mild thrombocytopenia is relatively common during pregnancy, but severe thrombocytopenia can increase the risk of bleeding during delivery.
3. Gestational thrombotic thrombocytopenic purpura (GTTP): A rare but serious disorder that can cause blood clots to form in small blood vessels throughout the body, leading to a decrease in the number of platelets and red blood cells. GTTP can cause serious complications such as stroke, kidney failure, and even death if not promptly diagnosed and treated.
4. Disseminated intravascular coagulation (DIC): A condition characterized by abnormal clotting and bleeding throughout the body. DIC can be triggered by various conditions such as severe infections, pregnancy complications, or cancer.
5. Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome: A serious complication of pregnancy that can cause damage to the liver and lead to bleeding. HELLP syndrome is often associated with preeclampsia, a condition characterized by high blood pressure and damage to organs such as the liver and kidneys.

It's important for pregnant women to receive regular prenatal care to monitor for these and other potential complications, and to seek prompt medical attention if any concerning symptoms arise.

Rheology is not a term that is specific to medicine, but rather it is a term used in the field of physics to describe the flow and deformation of matter. It specifically refers to the study of how materials flow or deform under various stresses or strains. This concept can be applied to various medical fields such as studying the flow properties of blood (hematology), understanding the movement of tissues and organs during surgical procedures, or analyzing the mechanical behavior of biological materials like bones and cartilages.

I must clarify that the term "pedigree" is not typically used in medical definitions. Instead, it is often employed in genetics and breeding, where it refers to the recorded ancestry of an individual or a family, tracing the inheritance of specific traits or diseases. In human genetics, a pedigree can help illustrate the pattern of genetic inheritance in families over multiple generations. However, it is not a medical term with a specific clinical definition.

Heparin is defined as a highly sulfated glycosaminoglycan (a type of polysaccharide) that is widely present in many tissues, but is most commonly derived from the mucosal tissues of mammalian lungs or intestinal mucosa. It is an anticoagulant that acts as an inhibitor of several enzymes involved in the blood coagulation cascade, primarily by activating antithrombin III which then neutralizes thrombin and other clotting factors.

Heparin is used medically to prevent and treat thromboembolic disorders such as deep vein thrombosis, pulmonary embolism, and certain types of heart attacks. It can also be used during hemodialysis, cardiac bypass surgery, and other medical procedures to prevent the formation of blood clots.

It's important to note that while heparin is a powerful anticoagulant, it does not have any fibrinolytic activity, meaning it cannot dissolve existing blood clots. Instead, it prevents new clots from forming and stops existing clots from growing larger.

Fibronectin is a high molecular weight glycoprotein that is found in many tissues and body fluids, including plasma, connective tissue, and the extracellular matrix. It is composed of two similar subunits that are held together by disulfide bonds. Fibronectin plays an important role in cell adhesion, migration, and differentiation by binding to various cell surface receptors, such as integrins, and other extracellular matrix components, such as collagen and heparan sulfate proteoglycans.

Fibronectin has several isoforms that are produced by alternative splicing of a single gene transcript. These isoforms differ in their biological activities and can be found in different tissues and developmental stages. Fibronectin is involved in various physiological processes, such as wound healing, tissue repair, and embryonic development, and has been implicated in several pathological conditions, including fibrosis, tumor metastasis, and thrombosis.

Shear strength is a property of a material that describes its ability to withstand forces that cause internal friction and sliding of one portion of the material relative to another. In the context of human tissues, shear strength is an important factor in understanding how tissues respond to various stresses and strains, such as those experienced during physical activities or injuries.

For example, in the case of bones, shear strength is a critical factor in determining their ability to resist fractures under different types of loading conditions. Similarly, in soft tissues like ligaments and tendons, shear strength plays a crucial role in maintaining the integrity of these structures during movement and preventing excessive deformation or injury.

It's worth noting that measuring the shear strength of human tissues can be challenging due to their complex structure and anisotropic properties. As such, researchers often use specialized techniques and equipment to quantify these properties under controlled conditions in the lab.

Includes: Type 1 von Willebrand Disease, Type 2A von Willebrand Disease, Type 2B von Willebrand Disease, Type 2M von Willebrand ... Von Willebrand Factor's primary function is binding to other proteins, in particular factor VIII, and it is important in ... June 2011). "Plasma von Willebrand factor levels are an independent risk factor for adverse events including mortality and ... Although von Willebrand did not identify the definite cause, he distinguished von Willebrand disease (vWD) from hemophilia and ...
Von Willebrand factor C and EGF domain-containing protein (VWCE) Von Willebrand factor (VWF) Chordin (CHRD) Chordin-like 1 ( ... Von Willebrand factor, type C (VWFC or VWC)is a protein domain is found in various blood plasma proteins: complement factors B ... "The secondary structure of the von Willebrand factor type A domain in factor B of human complement by Fourier transform ... For the von Willebrand factor the duplicated VWFC domain is thought to participate in oligomerization, but not in the initial ...
The von Willebrand factor type A (vWA) domain is a protein domain named after its occurrence in von Willebrand factor (vWF), a ... "The secondary structure of the von Willebrand factor type A domain in factor B of human complement by Fourier transform ... Perkins SJ, Edwards YJ (1995). "The protein fold of the von Willebrand factor type A domain is predicted to be similar to the ... Ruggeri ZM, Ware J (1993). "von Willebrand factor". FASEB J. 7 (2): 308-316. doi:10.1096/fasebj.7.2.8440408. PMID 8440408. ...
... (vWD) is an evolutionarily-conserved protein domain found in, among others, the von ... The vWD domain D'/D3 of the von Willebrand factor (vWF) serves as a carrier of clotting factor VIII (FVIII). The native ... domain of von Willebrand factor induced by CYS 25 and CYS 95 mutations lead to factor VIII binding defect and multimeric ... "The von Willebrand factor D'D3 assembly and structural principles for factor VIII binding and concatemer biogenesis". Blood. ...
See articles on Von Willebrand factor and on Von Willebrand factor type A domain. ENSG00000223757, ENSG00000227144, ... Von Willebrand factor A domain containing 7 is a protein that in humans is encoded by the VWA7 gene. ... "Entrez Gene: Von Willebrand factor A domain containing 7". Retrieved 2016-07-25. Valdes AM, Thomson G (2009). "Several loci in ...
Since this time, the factor causing the long bleeding time was called the "von Willebrand factor" in honor of Erik Adolf von ... Sadler JE (April 1994). "A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of ... The von Willebrand factor is undetectable in the VWF antigen assay. Since the VWF protects coagulation factor VIII from ... "Canine von Willebrand Disease - Breed Summaries". ahdc.vet.cornell.edu. 2019-02-08. "Canine von Willebrand Disease". vetgen.com ...
... and is known as von Willebrand factor. Von Willebrand factor has two functions. Firstly, it is the carrier molecule for factor ... Von Willebrand disease and von Willebrand factor are named after him. He also researched metabolism, obesity and gout, and was ... now known as von Willebrand factor, that enables hemostasis. Von Willebrand was born on 1 February 1870 in Vaasa, then part of ... Von Willebrand, E. A. (1938). "Rasfrågor i modern belysning". Östnylandsk Ungdom (in Swedish): 5. Von Willebrand, E. A. (1939 ...
"Vonvendi (von willebrand factor- recombinant kit". DailyMed. 13 February 2019. Retrieved 27 March 2020. "Veyvondi-epar product ... against von Willebrand factor, causing the medicine to stop working and resulting in a loss of bleeding control. The most ... It is a recombinant von Willebrand factor. The most common adverse reactions are generalized itching, vomiting, nausea, ... Tran T, Arnall J, Moore DC, Ward L, Palkimas S, Man L (April 2020). "Vonicog alfa for the management of von Willebrand disease ...
1994 found CelVav and a von Willebrand factor A domain and with Wilson et al. 1998 provides the first credible evidence for an ... Sadler, J. Evan (1998). "Biochemistry and genetics of von Willebrand factor". Annual Review of Biochemistry. Annual Reviews. 67 ... C. elegans has been a model organism for research into ageing; for example, the inhibition of an insulin-like growth factor ... The tra-1 is a gene within the TRA-1 transcription factor sex determination pathway that is regulated post-transcriptionally ...
... such as Von Willebrand factor and vascular endothelial growth factor (VEGF). These substances could also have a role in PDP ... 1992). "Von Willebrand factor antigen in hypertrophic osteoarthropathy". J Rheumatol. 19 (5): 765-767. PMID 1613707. Silveria ... Von Willebrand factor is a marker of platelet and endothelial activation. This suggests that the activation of endothelial ... platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). It has not been described yet what role these ...
... also known as von Willebrand factor-cleaving protease (VWFCP)-is a zinc-containing metalloprotease enzyme that cleaves von ... Fujimura Y, Matsumoto M, Yagi H, Yoshioka A, Matsui T, Titani K (January 2002). "Von Willebrand factor-cleaving protease and ... Kremer Hovinga JA, Studt JD, Lämmle B (2005). "The von Willebrand factor-cleaving protease (ADAMTS-13) and the diagnosis of ... Sonneveld MA, de Maat MP, Leebeek FW (July 2014). "Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic ...
Moake JL (2004). "von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura". Seminars in Hematology. 41 (1): 4 ... "Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic ... 173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis". Arthritis ...
"Entrez Gene: von Willebrand factor A domain containing 2". Sengle G, Kobbe B, Morgelin M, Paulsson M, Wagener R (December 2003 ... von Willebrand factor A domain-containing protein 2, also known as A domain-containing protein similar to matrilin and collagen ... AMACO is a member of the von Willebrand factor A-like (VWA) domain containing protein superfamily and consists of three VWA- ... a new member of the von Willebrand factor A-like domain protein superfamily with a regulated expression in the kidney". The ...
This gene encodes a member of the von Willebrand factor A domain containing protein family. This family of proteins is thought ... This protein contains five von Willebrand factor A domains. The specific function of this gene has not yet been determined. Two ... the closest relative of cartilage matrix protein within the von Willebrand factor type A-like module superfamily". J Biol Chem ...
Moake, JL (2004). "von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura". Semin Hematol. 41 (1): 4-14. doi ... factor H, factor HR1 or HR3, membrane cofactor protein, factor I, factor B, complement C3, and thrombomodulin). This results in ... an enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting, into smaller pieces. (TTP also ... The complement system activation may be due to mutations in the complement regulatory proteins (factor H, factor I, or membrane ...
It is an anti-von Willebrand factor humanized immunoglobulin. It acts by blocking platelet aggregation to reduce organ injury ...
This results in decreased break down of large multimers of von Willebrand factor (vWF) into smaller units. Less commonly TTP is ... In 1982, the disease had been linked with abnormally large von Willebrand factor multimers. The identification of a deficient ... ADAMTS13 is a metalloproteinase responsible for the breakdown of von Willebrand factor (vWF), a protein that links platelets, ... Moake JL (January 2004). "Von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura". Seminars in Hematology. ...
"Entrez Gene: Von Willebrand factor A domain containing 5A". Retrieved 2017-06-06. Zhou YQ, Chen SL, Ju JY, Shen L, Liu Y, Zhen ... Von Willebrand factor A domain containing 5A is a protein that in humans is encoded by the VWA5A gene. GRCh38: Ensembl release ...
It cleaves fibrin, fibronectin, thrombospondin, laminin, and von Willebrand factor. Plasmin, like trypsin, belongs to the ... and factor XII (Hageman factor). Fibrin is a cofactor for plasminogen activation by tissue plasminogen activator. Urokinase ... "Hepatic to pancreatic switch defines a role for hemostatic factors in cellular plasticity in mice". Proceedings of the National ... "Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3". The American Journal of ...
The von Willebrand factor (VWF) serves as an essential accessory molecule. In general terms, platelet activation initiated by ... FGF (Fibroblast Growth Factor) ligands bind to receptors tyrosine kinase, FGFR (Fibroblast Growth Factor Receptors), and form a ... "Nuclear factor erythroid 2-related factor 2 facilitates neuronal glutathione synthesis by upregulating neuronal excitatory ... They are involved in regulation of kinases and phosphatases, G protein associated factors and transcriptional factors. Gaseous ...
More recently, he has described an allosteric disulfide that controls platelet capture via von Willebrand factor at sites of ... "Autoregulation of von Willebrand factor function by a disulfide bond switch". Science Advances. 4 (2): eaaq1477. Bibcode: ... Specifically, he found that an allosteric disulfide bond in tissue factor plays a crucial role in the coagulation process. ... His early research explored the molecular process that transitions tissue factor from a cryptic to active form. ...
An example a protein with calcium coordination is von Willebrand factor (vWF) which has an essential role in blood clot ... Calcium modulates force sensing by the von Willebrand factor A2 domain. Nature Communications 2011 Jul 12;2:385. [1] Dougherty ... Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also ...
Healthy volunteers displayed an increase in von-Willebrand-factor (vWf) activity. Isolated molecules formed under Oprelvekin ... IL-11 is a member of a family of human growth factors and is being produced in the bone marrow of healthy adults. Synonyms are ... These increases in coagulation factors may contribute to the development of stroke (see under side-effects), but a precise ... Oprelvekin is recombinant interleukin eleven (IL-11), a thrombopoietic growth factor that directly stimulates the proliferation ...
One is von Willebrand factor (vWF), a multimeric protein that plays a major role in blood coagulation. Storage of long polymers ... They manufacture, store and release two principal molecules, von Willebrand factor and P-selectin, and thus play a dual role in ... Lenting PJ, Christophe OD, Denis CV (26 March 2015). "von Willebrand factor biosynthesis, secretion, and clearance: connecting ... Type III von Willebrand Disease is a severe bleeding disorder, like severe hemophilia type A or B. VWF acts in primary ...
Handa, M; Titani, K; Holland, L Z; Roberts, J R; Ruggeri, Z M (1986). "The von Willebrand factor-binding domain of platelet ... Von Willebrand factor. She went on to examine reproduction in sea urchins, salps, and amphioxus, known as lancelet. Holland ...
Titani K, Takio K, Handa M, Ruggeri ZM (August 1987). "Amino acid sequence of the von Willebrand factor-binding domain of ... The Gp Ib functions as a receptor for von Willebrand factor (VWF). The complete receptor complex includes noncovalent ... Analysis of the botrocetin-mediated interaction between von Willebrand factor and the human platelet membrane glycoprotein Ib- ... June 2002). "Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein ...
... s also reduce factor VIII-Ag Von Willebrand factor, thereby decreasing platelet function. Clots formed after ... and in certain intravenous fluids to solubilize other factors, such as iron (in a solution known as Iron Dextran). Intravenous ...
March 2005). "The prevalence of the cysteine1584 variant of von Willebrand factor is increased in type 1 von Willebrand disease ... von Willebrand factor is modified by ABO blood group genotype and is a major determinant of plasma von Willebrand factor ... O'Donnell J, Laffan MA (August 2001). "The relationship between ABO histo-blood group, factor VIII and von Willebrand factor". ... November 2006). "High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, ...
Marchant, R. E.; Lea, A. S.; Andrade, J. D.; Bockenstedt, P. (1992). "Interactions of von Willebrand factor on mica studied by ...
Alternatively, cryoprecipitate contains other coagulation factors, factors VIII, XIII, and von Willebrand factor. There are no ... The only risk factor is if both parents of a child carry the recessive allele linked to the disorder.[citation needed] ... Factor I Deficiency Neerman-Arbez, Marguerite; De Moerloose, Philippe (2007). "Mutations in the fibrinogen gene cluster ... doi:10.2147/vhrm.s5305 "Factor I deficiency (Fibrinogen deficiency) - Canadian Hemophilia Society". www.hemophilia.ca. ...
Includes: Type 1 von Willebrand Disease, Type 2A von Willebrand Disease, Type 2B von Willebrand Disease, Type 2M von Willebrand ... Von Willebrand Factors primary function is binding to other proteins, in particular factor VIII, and it is important in ... June 2011). "Plasma von Willebrand factor levels are an independent risk factor for adverse events including mortality and ... Although von Willebrand did not identify the definite cause, he distinguished von Willebrand disease (vWD) from hemophilia and ...
encoded search term (von Willebrand Factor Antigen (Factor VIII:R Antigen)) and von Willebrand Factor Antigen (Factor VIII:R ... When is a von Willebrand factor antigen (vWF:Ag) assay indicated?. Which factors affect the accuracy of a von Willebrand factor ... Changes in von Willebrand factor level and von Willebrand activity with age in type 1 von Willebrand disease. Haemophilia. 2015 ... Increase of von Willebrand factor with aging in type 1 von Willebrand disease: fact or fiction?. Haematologica. 2017 Nov. 102 ( ...
Von Willebrand disease is a bleeding disorder that slows the blood clotting process, causing prolonged bleeding after an injury ... Variants that severely reduce or eliminate von Willebrand factor cause type 3 von Willebrand disease. People with type 3 von ... von Willebrand factor forms clots too easily. The clots are removed from the body, so there is not enough von Willebrand factor ... Variants in the VWF gene that reduce the amount of von Willebrand factor cause type 1 von Willebrand disease. In type 1C, the ...
... multimer analysis is primarily a qualitative tests to identify variants of type II von Willebrand disease (vWD); therefore, ... encoded search term (von Willebrand Factor Multimers) and von Willebrand Factor Multimers What to Read Next on Medscape ... The von Willebrand factor (vWF) multimer analysis is primarily a qualitative tests to identify variants of type II von ... von Willebrand Factor Multimers Updated: May 02, 2014 * Author: Carlos Solano Loran, MD; Chief Editor: Eric B Staros, MD more ...
... multimer analysis is primarily a qualitative tests to identify variants of type II von Willebrand disease (vWD); therefore, ... encoded search term (von Willebrand Factor Multimers) and von Willebrand Factor Multimers What to Read Next on Medscape ... The von Willebrand factor (vWF) multimer analysis is primarily a qualitative tests to identify variants of type II von ... von Willebrand Factor Multimers Updated: May 02, 2014 * Author: Carlos Solano Loran, MD; Chief Editor: Eric B Staros, MD more ...
Von Willebrand factor. * Cell adhesion molecules (ie, P-selectin, vascular endothelial adhesion molecule-1 [VCAM-1] ... What are the factors associated with endothelial dysfunction in eclampsia?. What is the role of antiangiogenic factors in the ... von Dadelszen P, Payne B, Li J, et al. Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of ... Etiologic and Risk Factors for Preeclampsia/Eclampsia. The mechanism(s) responsible for the development eclampsia remain(s) ...
... von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand Factor (VWF). Patients ... Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations ... Title : Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 ... 2015). Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 ...
The ability of von Willebrand factor (VWF) to initiate platelet adhesion depends on the number of monomers in individual VWF ... High-density lipoprotein modulates thrombosis by preventing von Willebrand factor self-association and subsequent platelet ... Factor de von Willebrand/metabolismo Animales Apolipoproteína A-I/uso terapéutico Plaquetas/citología Plaquetas/metabolismo ... Factor de von Willebrand/química ...
The von Willebrand factor (vWf) is a complex protein whose release is a marker for endothelial damage; serum levels of its ... Spinal cord disorders; Biomarkers; Back pain; Vibration effects; Author Keywords: Low back pain; von Willebrand factor antigen ... The effect of vibration on back discomfort and serum levels of von Willebrand factor antigen: a preliminary communication. ...
Specific medical condition(s) (i.e. Factor VIII, von Willebrand disease, etc.); ... Bleeding disorders, such as hemophilia and von Willebrand disease (VWD), are conditions in which the blood does not clot ... Teach family and friends how to give the factor by mixing the clotting factor into a syringe and putting the needle into the ... Injections of treatment products, called clotting factor concentrates (or factor), into a vein - a process known as infusion - ...
... recessive disorder caused by deficiency of functional plasma clotting factor VIII (FVIII). In a significant number of cases, ... The factor VIII/von Willebrand factor complex: basic and clinical issues. Haematologica. 2003 Jun. 88(6):EREP02. [QxMD MEDLINE ... TF also adsorbs factor X to enhance the reaction between factor VIIa, factor X, and calcium ions. Factor IXa and factor XII ... In the extrinsic system, the conversion of factor X to factor Xa involves tissue factor (TF), or thromboplastin; factor VII; ...
Monitoring of Von Willebrand Factor Inhibitors in Patients with Type 3 Von Willebrand Disease Using a Quantitative Assay. 2021; ... other than hemophilia and von Willebrand disease, receiving care at Hemophilia Treatment Centers in the United States. ... The Clinical Genetics of Hemophilia B (Factor IX Deficiency). Appl Clin Genet. 2021;14:445-454. ...
Plasma von Willebrand factor concentrations were significantly increased (+14%) by WPS. Erythrocyte numbers (+15%) and ... Tumor necrosis factor alpha and interleukin 6 concentrations were significantly increased in BAL fluid. Lipid peroxidation in ... JID: 8502536; 0 (Antioxidants); 0 (Interleukin-6); 0 (Tumor Necrosis Factor-alpha); EC 1.15.1.1 (Superoxide Dismutase); EC 2.5. ... multivariate analyses adjusted for other risk factors. We also collected the water from Chinese water pipes to assess the ...
... we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. Excess mortality was observed in ... we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. Excess mortality was observed in ... we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. Excess mortality was observed in ...
Von Willebrand Disease - Etiology, pathophysiology, symptoms, signs, diagnosis & prognosis from the MSD Manuals - Medical ... Diagnosis is based on low levels of von Willebrand factor antigen and von Willebrand factor activity (ristocetin cofactor ... Diagnosis of Von Willebrand Disease *. Total plasma von Willebrand factor (VWF) antigen concentration ... Von Willebrand disease (VWD) is a hereditary quantitative deficiency or functional abnormality of von Willebrand factor (VWF), ...
Hepatitis A Among Persons with Hemophilia Who Received Clotting Factor Concentrate -- United States, September-December 199 ... a 28-year-old woman with type 2 von Willebrand disease was found to have elevated liver enzymes and was IgM anti-HAV positive. ... Hepatitis A in Factor VIII Recipients Case 1. On September 5, 1995, a 13-year-old boy with mild hemophilia A (factor VIII ... Other plasma-derived factor VIII and factor IX concentrates manufactured using similar or different viral-reducing steps also ...
Forty-seven percent were treated with plasma-derived von Willebrand factor VIII concentrates. The results of this study ... Data on infants and toddlers (ITs) with von Willebrand disease (VWD) are lacking. We used data collected in the US Hemophilia ... A thematic map capturing the concepts matching the key contributing factors to the public health burden of infodemics was used ... In March 2021, we conducted a survey to examine the perceptions toward COVID-19 vaccines and identify the factors associated ...
The substance contained what would later be known as the von Willebrand factor. The drug used in the treatment was produced in ...
Factor VII deficiency. Factor XI deficiency. Severe von Willebrand disease. Amyloidosis with factor X deficiency. Postsurgical ... Tissue factor-dependent action of recombinant factor VIIa. The tissue factor-dependent pathway is shown by gray shading. Dashed ... Tissue factor-dependent action of recombinant factor VIIa. The tissue factor-dependent pathway is shown by gray shading. Dashed ... At the site of injury, tissue factor (TF) and factor VIIa activate factors X and IX. Thrombin is generated, and fibrin is ...
... study of the long-term safety and efficacy of intravenous recombinant coagulation factor VIII Fc-von Willebrand factor-XTEN ... study of the long-term safety and efficacy of intravenous recombinant coagulation factor VIII Fc-von Willebrand factor-XTEN ...
Congenital factor XI deficiency 128630=Congenital deficiency of other clotting factors 128640=von Willebrand`s disease ... Endocrine malfunction arising from mental factors 130670=Organs of special sense malfunction arising from mental factors ... Congenital factor VIII disorder 128610=Congenital factor IX disorder 128620= ... Musculoskeletal malfunction arising from mental factors 130610=Respiratory malfunction arising from mental factors 130620= ...
von Recklinghausen Disease use Neurofibromatosis 1 von Willebrand Disease von Willebrand Factor ... Vascular Endothelial Growth Factor, Endocrine-Gland-Derived Vascular Endothelial Growth Factor-A use Vascular Endothelial ...
von Recklinghausen Disease use Neurofibromatosis 1. von Willebrand Disease. von Willebrand Factor ...
von Recklinghausen Disease use Neurofibromatosis 1 von Willebrand Disease von Willebrand Factor ... Vascular Endothelial Growth Factor, Endocrine-Gland-Derived Vascular Endothelial Growth Factor-A use Vascular Endothelial ...
von Recklinghausen Disease use Neurofibromatosis 1. von Willebrand Disease. von Willebrand Factor ...
von Recklinghausen Disease use Neurofibromatosis 1 von Willebrand Disease von Willebrand Factor ... Vascular Endothelial Growth Factor, Endocrine-Gland-Derived Vascular Endothelial Growth Factor-A use Vascular Endothelial ...
von Recklinghausen Disease use Neurofibromatosis 1. von Willebrand Disease. von Willebrand Factor ...
  • Therefore, VWF deficiency or dysfunction (von Willebrand disease) leads to a bleeding tendency, which is most apparent in tissues having high blood flow shear in narrow vessels. (wikipedia.org)
  • Title : Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations Personal Author(s) : Boylan, Brian;Rice, Anne S.;De Staercke, Christine;Eyster, M. Elaine;Yaish, Hassan M.;Knoll, Christine M.;Bean, Christopher J.;Miller, Connie H. (cdc.gov)
  • Bleeding disorders, such as hemophilia and von Willebrand disease (VWD) , are conditions in which the blood does not clot properly due to a lack of specific clotting factor proteins in the blood. (cdc.gov)
  • A reconstitution device (a device used to "reconstitute" or mix factor with a liquid [usually water], called a diluent, before it can be infused or given to a person with hemophilia). (cdc.gov)
  • Hemophilia A is an X-linked, recessive disorder caused by deficiency of functional plasma clotting factor VIII (FVIII), which may be inherited or arise from spontaneous mutation. (medscape.com)
  • Published findings from a Community Counts study that estimates the number of people with rare bleeding disorders, other than hemophilia and von Willebrand disease, receiving care at Hemophilia Treatment Centers in the United States. (cdc.gov)
  • In type 2 N, there is impaired binding of VWF to factor VIII and significant reduction in factor VIII levels (ie, to 1 to 5%) similar to that seen in hemophilia A. (msdmanuals.com)
  • Hemophilia Hemophilias are common hereditary bleeding disorders caused by deficiencies of either clotting factor VIII or IX. (msdmanuals.com)
  • On September 5, 1995, a 13-year-old boy with mild hemophilia A (factor VIII deficiency) became acutely ill with nausea and vomiting after a 2-week period of fatigue, poor appetite, and low-grade fever. (cdc.gov)
  • In response to this bulletin, two brothers with hemophilia A (aged 6 and 7 years) who had received this clotting factor concentrate were identified and tested for anti-HAV on November 17. (cdc.gov)
  • Recombinant factor VIIa (rFVIIa) has become available for treating people with hemophilia with inhibitors who experience bleeding or require surgery. (medscape.com)
  • Originally, rFVIIa was developed for the treatment of bleeding complications in patients with hemophilia with alloantibodies (inhibitors) against exogenous factor VIII or IX. (medscape.com)
  • We describe the uses of rFVIIa in conditions unrelated to hemophilia and the treatment of acquired inhibitors of factors VIII and IX. (medscape.com)
  • Von Willebrand factor (VWF) (German: [fɔn ˈvɪləbʁant]) is a blood glycoprotein involved in hemostasis, specifically, platelet adhesion. (wikipedia.org)
  • the A3 domain, which binds to collagen (von Willebrand factor type A domain) the C4 domain, in which the RGD motif binds to platelet integrin αIIbβ3 when this is activated (von Willebrand factor type C domain) the other C domains, which may interact in ER dimers: the larger protein show six beads of (C and C-like) domains under cryo-EM. (wikipedia.org)
  • the "cystine knot" domain (at the C-terminal end of the protein), which VWF shares with platelet-derived growth factor (PDGF), transforming growth factor-β (TGFβ) and β-human chorionic gonadotropin (βHCG, of pregnancy test fame). (wikipedia.org)
  • Von Willebrand Factor's primary function is binding to other proteins, in particular factor VIII, and it is important in platelet adhesion to wound sites. (wikipedia.org)
  • Every monomer contains particular binding domains that provide them the capacity to interact and bind other proteins specifically, factor VIII, collagen, and some platelet receptors. (medscape.com)
  • High-density lipoprotein modulates thrombosis by preventing von Willebrand factor self-association and subsequent platelet adhesion. (bvsalud.org)
  • The ability of von Willebrand factor (VWF) to initiate platelet adhesion depends on the number of monomers in individual VWF multimers and on the self - association of individual VWF multimers into larger structures. (bvsalud.org)
  • Von Willebrand disease (VWD) is a hereditary quantitative deficiency or functional abnormality of von Willebrand factor (VWF), which causes platelet dysfunction. (msdmanuals.com)
  • vWF antigen, vWF activity, and factor VIII activity are required before performing this test. (medscape.com)
  • The effect of vibration on back discomfort and serum levels of von Willebrand factor antigen: a preliminary communication. (cdc.gov)
  • Diagnosis is based on low levels of von Willebrand factor antigen and von Willebrand factor activity (ristocetin cofactor activity). (msdmanuals.com)
  • elements of note are: the D'/D3 domain, which binds to factor VIII (von Willebrand factor type D domain). (wikipedia.org)
  • factor VIII degrades rapidly when not bound to VWF. (wikipedia.org)
  • Factor VIII is released from VWF by the action of thrombin. (wikipedia.org)
  • when carried by intact VWF, factor VIII has a half-life of 8-12 hours. (wikipedia.org)
  • In addition, vWF is a carrier protein for factor VIII and prevents its proteolytic degradation in plasma. (medscape.com)
  • vWF also binds circulating factor VIII and prevents it peripheral degradation. (medscape.com)
  • VWF is also required to maintain normal plasma factor VIII levels. (msdmanuals.com)
  • During September-November 1995, three cases of hepatitis A in recipients of Alphanate (TM) * factor VIII concentrate (Alpha Therapeutic Corporation, Los Angeles, California) from lot number AP5014A were reported to CDC. (cdc.gov)
  • During the 6 weeks preceding illness, the patient had used 68 vials (approximately 34,000 units) from the implicated lot (i.e., lot number AP5014A) of Alphanate (TM) and nine vials from four lots of another brand of factor VIII concentrate. (cdc.gov)
  • clotting, von Willebrand factor and fac- hypercholesterolaemia and hyperten- tor VIII [9]. (who.int)
  • This increase in the thrombin burst occurs after direct rFVIIa activation of factors IX and X on the surface of activated platelets (even in the absence of factor VIII or IX). (medscape.com)
  • Recent research also suggests that von Willebrand Factor is involved in the formation of blood vessels themselves, which would explain why some people with von Willebrand disease develop vascular malformations (predominantly in the digestive tract) that can bleed excessively. (wikipedia.org)
  • Von Willebrand factor is synthesized and secreted by vascular endothelium to form part of the perivascular matrix. (msdmanuals.com)
  • Overview of Hemostasis Hemostasis, the arrest of bleeding from an injured blood vessel, requires the combined activity of Vascular factors Platelets Plasma coagulation factors Regulatory mechanisms counterbalance. (msdmanuals.com)
  • The extent of factor deficiency determines the probability and severity of bleeding. (msdmanuals.com)
  • Draw specimen before coagulation factor replacement therapy. (medscape.com)
  • It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome. (wikipedia.org)
  • A study by Ladikou et al indicated that patients with coronavirus disease 2019 (COVID-19) commonly have high levels of vWF and factor VIIIc, which may play a role in the hypercoagulable state and increased venous thromboembolism (VTE) rate encountered in COVID-19. (medscape.com)
  • Mild forms of von Willebrand disease may become apparent only when abnormal bleeding occurs following surgery or a serious injury. (medlineplus.gov)
  • In severe cases of von Willebrand disease, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). (medlineplus.gov)
  • Symptoms of von Willebrand disease may change over time. (medlineplus.gov)
  • Von Willebrand disease is divided into three types. (medlineplus.gov)
  • Von Willebrand disease is estimated to affect 1 in 100 to 10,000 individuals. (medlineplus.gov)
  • Most researchers agree that von Willebrand disease is the most common genetic bleeding disorder. (medlineplus.gov)
  • Variants in the VWF gene cause von Willebrand disease. (medlineplus.gov)
  • Abnormally slow blood clotting causes the prolonged bleeding episodes seen in people with von Willebrand disease. (medlineplus.gov)
  • The three types of von Willebrand disease are classified based on the amount of von Willebrand factor that is produced or its ability to function. (medlineplus.gov)
  • Variants in the VWF gene that reduce the amount of von Willebrand factor cause type 1 von Willebrand disease. (medlineplus.gov)
  • People with type 1 von Willebrand disease have varying amounts of von Willebrand factor in their bloodstream. (medlineplus.gov)
  • Variants that impair the function of von Willebrand factor cause the four subtypes of type 2 von Willebrand disease. (medlineplus.gov)
  • People with type 2 von Willebrand disease can have bleeding episodes of varying severity depending on the extent of the von Willebrand factor abnormalities, but the bleeding episodes are typically similar to those seen in type 1. (medlineplus.gov)
  • This test allows identifying qualitatively abnormal variants of the vWF, also known as type II von Willebrand disease (vWD). (medscape.com)
  • Acquired von Willebrand disease is rare and is characterized by low levels of VWF due to decreased production or increased clearance of VWF from the circulation but is not inherited. (msdmanuals.com)
  • Bleeding manifestations in the most common type I von Willebrand disease (VWD) include bruising, mucosal bleeding, bleeding from small skin cuts that may stop and start over hours, increased menstrual bleeding, and sometimes bleeding after surgical procedures (eg, tooth extraction, tonsillectomy). (msdmanuals.com)
  • On October 20, during a hospital visit to evaluate vaginal bleeding 1 month postpartum, a 28-year-old woman with type 2 von Willebrand disease was found to have elevated liver enzymes and was IgM anti-HAV positive. (cdc.gov)
  • Injections of treatment products, called clotting factor concentrates (or factor), into a vein - a process known as infusion - can help manage and treat bleeding disorders . (cdc.gov)
  • von Willebrand factor type C domain) Monomers are subsequently N-glycosylated, arranged into dimers in the endoplasmic reticulum and into multimers in the Golgi apparatus by crosslinking of cysteine residues via disulfide bonds. (wikipedia.org)
  • Another form of the disorder, acquired von Willebrand syndrome, is not caused by inherited gene variants (also called mutations). (medlineplus.gov)
  • von Willebrand factor (vWF) is a large multimeric glycoprotein synthesized as a 2050 amino acid monomer in endothelium, megakaryocytes, and the subendothelial connective tissue. (medscape.com)
  • Von Willebrand factor acts as a glue that holds blood clots together and prevents the breakdown of other blood clotting proteins. (medlineplus.gov)
  • In types 2M and 2N, von Willebrand factor is unable to interact with other structures or proteins needed to form blood clots. (medlineplus.gov)
  • This has become the case for treatment of hemorrhage with recombinant factor VIIa (rFVIIa). (medscape.com)
  • No other factor products had been used during this interval, and no other sources of infection were identified. (cdc.gov)
  • The rFVIIa seems to work in a TF-independent manner directly on factors IX and X on the phospholipid surface of activated platelets. (medscape.com)
  • rFVIIa is able to activate factor X on phospholipid vesicles, activated platelets, or monocytes independent of TF, although the TF-independent generation of thrombin is much less efficient than the TF-dependent thrombin generation by rFVIIa. (medscape.com)
  • Testing for inhibitors is indicated when bleeding is not controlled after infusion of adequate amounts of factor concentrate during a bleeding episode. (medscape.com)
  • Cloudy plasma may result in underestimation of vWF:Ag levels, while the presence of rheumatoid factor in the plasma can produce overestimation. (medscape.com)
  • In COVID-19+ patients, we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. (lu.se)
  • Hepatitis A outbreaks associated with receipt of clotting factor concentrate previously have been recognized in Europe but not in the United States (1-5). (cdc.gov)
  • In addition, one case of hepatitis A in a recipient of AlphaNine S-D (TM) factor IX concentrate (Alpha Therapeutic Corporation) has been reported and is under investigation. (cdc.gov)
  • During 1995, her only exposure to factor concentrate was use of 48 vials (approximately 24,000 units) of Alphanate (TM) from the implicated lot on September 19. (cdc.gov)
  • The VWF gene provides instructions for making a blood clotting protein called von Willebrand factor, which is essential for the formation of blood clots . (medlineplus.gov)
  • If von Willebrand factor does not function normally or too little of the protein is available, blood clots cannot form properly. (medlineplus.gov)
  • Affected individuals produce a normal amount of von Willebrand factor, but the protein cannot function properly. (medlineplus.gov)
  • The decrease in fibrinolysis might be due to an increase in thrombin-activatable fibrinolysis inhibitor and an increase in factor XIIIa. (medscape.com)
  • Ces résultats semblent indiquer que l'utilisation de l'alun en tant qu'antiplaquettaire oral pourrait faire l'objet d'études complémentaires, en tenant compte des effets secondaires éventuels notamment chez les patients dont la fonction rénale est altérée. (who.int)
  • Les données ont été recueillies à partir des dossiers de 920 patients atteints de diabète, d'hypertension et d'hypercholestérolémie en consultation dans des hôpitaux, des cliniques et des laboratoires d'analyses de Bagdad, et de 200 témoins en bonne santé. (who.int)
  • The plasma von Willebrand factor (vWF) multimer analysis provides a qualitative visual assessment of the size spectrum and the banding pattern of VWF multimers present in plasma compared with a normal control. (medscape.com)
  • Factor is stored in powdered form because it rapidly loses its power once mixed into a solution. (cdc.gov)
  • multivariate analyses adjusted for other risk factors. (who.int)
  • At the site of injury, tissue factor (TF) and factor VIIa activate factors X and IX. (medscape.com)