A CXC chemokine that is found in the alpha granules of PLATELETS. The protein has a molecular size of 7800 kDa and can occur as a monomer, a dimer or a tetramer depending upon its concentration in solution. Platelet factor 4 has a high affinity for HEPARIN and is often found complexed with GLYCOPROTEINS such as PROTEIN C.
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
A phospholipid from the platelet membrane that contributes to the blood clotting cascade by forming a phospholipid-protein complex (THROMBOPLASTIN) which serves as a cofactor with FACTOR VIIA to activate FACTOR X in the extrinsic pathway of BLOOD COAGULATION.
A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, pre-eclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders.
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.
The number of PLATELETS per unit volume in a sample of venous BLOOD.
Endogenous substances, usually proteins, that are involved in the blood coagulation process.
The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.
Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.
Serum proteins with an electrophoretic mobility that falls between ALPHA-GLOBULINS and GAMMA-GLOBULINS.
Coagulant substances inhibiting the anticoagulant action of heparin.
Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.
A subnormal level of BLOOD PLATELETS.
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.
An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.
The transfer of blood platelets from a donor to a recipient or reinfusion to the donor.
A fibrin-stabilizing plasma enzyme (TRANSGLUTAMINASES) that is activated by THROMBIN and CALCIUM to form FACTOR XIIIA. It is important for stabilizing the formation of the fibrin polymer (clot) which culminates the coagulation cascade.
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.
The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.
A deficiency of blood coagulation factor V (known as proaccelerin or accelerator globulin or labile factor) leading to a rare hemorrhagic tendency known as Owren's disease or parahemophilia. It varies greatly in severity. Factor V deficiency is an autosomal recessive trait. (Dorland, 27th ed)
A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.
Laboratory examination used to monitor and evaluate platelet function in a patient's blood.
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.
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.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
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.
Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function.
Formation and development of a thrombus or blood clot in the blood vessel.
Cell adhesion molecule and CD antigen that mediates the adhesion of neutrophils and monocytes to activated platelets and endothelial cells.
Two small peptide chains removed from the N-terminal segment of the alpha chains of fibrinogen by the action of thrombin during the blood coagulation process. Each peptide chain contains 18 amino acid residues. In vivo, fibrinopeptide A is used as a marker to determine the rate of conversion of fibrinogen to fibrin by thrombin.
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.
Laboratory tests for evaluating the individual's clotting mechanism.
Condensed areas of cellular material that may be bounded by a membrane.
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.
Disorders caused by abnormalities in platelet count or function.
Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease.
Human alloantigens expressed only on platelets, specifically on platelet membrane glycoproteins. These platelet-specific antigens are immunogenic and can result in pathological reactions to transfusion therapy.
Agents that cause clotting.
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).
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).
Activated form of factor V. It is an essential cofactor for the activation of prothrombin catalyzed by factor Xa.
The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.
An autosomal recessive characteristic or a coagulation disorder acquired in association with VITAMIN K DEFICIENCY. FACTOR VII is a Vitamin K dependent glycoprotein essential to the extrinsic pathway of coagulation.
A group of simple proteins that yield basic amino acids on hydrolysis and that occur combined with nucleic acid in the sperm of fish. Protamines contain very few kinds of amino acids. Protamine sulfate combines with heparin to form a stable inactive complex; it is used to neutralize the anticoagulant action of heparin in the treatment of heparin overdose. (From Merck Index, 11th ed; Martindale, The Extra Pharmacopoeia, 30th ed, p692)
Agents that prevent clotting.
A defense mechanism operating unconsciously, in which the individual attempts to justify or make consciously tolerable, by plausible means, feelings, behavior, and motives that would otherwise be intolerable.
A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.
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.
A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.
Platelet membrane glycoprotein IIb is an integrin alpha subunit that heterodimerizes with INTEGRIN BETA3 to form PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX. It is synthesized as a single polypeptide chain which is then postranslationally cleaved and processed into two disulfide-linked subunits of approximately 18 and 110 kDa in size.
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.
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.
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.
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.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
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.
A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and BASOPHILS.
A hereditary deficiency of blood coagulation factor XI (also known as plasma thromboplastin antecedent or PTA or antihemophilic factor C) resulting in a systemic blood-clotting defect called hemophilia C or Rosenthal's syndrome, that may resemble classical hemophilia.
Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors.
An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).
Stable blood coagulation factor involved in the intrinsic pathway. The activated form XIa activates factor IX to IXa. Deficiency of factor XI is often called hemophilia C.

Characterization of a neutrophil cell surface glycosaminoglycan that mediates binding of platelet factor 4. (1/470)

Platelet factor 4 (PF-4) is a platelet-derived alpha-chemokine that binds to and activates human neutrophils to undergo specific functions like exocytosis or adhesion. PF-4 binding has been shown to be independent of interleukin-8 receptors and could be inhibited by soluble chondroitin sulfate type glycosaminoglycans or by pretreatment of cells with chondroitinase ABC. Here we present evidence that surface-expressed neutrophil glycosaminoglycans are of chondroitin sulfate type and that this species binds to the tetrameric form of PF-4. The glycosaminoglycans consist of a single type of chain with an average molecular mass of approximately 23 kDa and are composed of approximately 85-90% chondroitin 4-sulfate disaccharide units type CSA (-->4GlcAbeta1-->3GalNAc(4-O-sulfate)beta1-->) and of approximately 10-15% di-O-sulfated disaccharide units. A major part of these di-O-sulfated disaccharide units are CSE units (-->4GlcAbeta1-->3GalNAc(4,6-O-sulfate)beta1-->). Binding studies revealed that the interaction of chondroitin sulfate with PF-4 required at least 20 monosaccharide units for significant binding. The di-O-sulfated disaccharide units in neutrophil glycosaminoglycans clearly promoted the affinity to PF-4, which showed a Kd approximately 0.8 microM, as the affinities of bovine cartilage chondroitin sulfate A, porcine skin dermatan sulfate, or bovine cartilage chondroitin sulfate C, all consisting exclusively of monosulfated disaccharide units, were found to be 3-5-fold lower. Taken together, our data indicate that chondroitin sulfate chains function as physiologically relevant binding sites for PF-4 on neutrophils and that the affinity of these chains for PF-4 is controlled by their degree of sulfation.  (+info)

Mast cell migratory response to interleukin-8 is mediated through interaction with chemokine receptor CXCR2/Interleukin-8RB. (2/470)

To explore the role of chemokines in mast cell chemotaxis and accumulation at sites of inflammation, we first investigated the response of human mast cells to 18 different chemokines by induction of intracellular calcium mobilization in the human mast cell line, HMC-1. Only a subgroup of CXC chemokines defined by the conserved sequence motif glutamic acid-leucine-arginine (ELR) tripeptide motif, which included interleukin-8 (IL-8), growth-regulated oncogene alpha (GROalpha), neutrophil-activating peptide-2 (NAP-2), and epithelial cell-derived neutrophil activating peptide-78 (ENA-78), induced calcium flux in the cells. These observations suggested that the receptor CXCR2 (IL-8RB) should be expressed on the surface of these cells. Using the RNAse protection assay, CXCR2 mRNA, but not CXCR1 (IL-8RA) mRNA expression was detected in HMC-1 cells. Flow cytometry analysis documented the surface expression of CXCR2. A binding analysis performed with 125I-IL-8 determined that there were approximately 3,600 high affinity IL-8 binding sites per HMC-1 cell, with a calculated kd of 1.2 to 2 nmol/L. The activity of this receptor was further explored using IL-8, which was found to induce dose-dependent chemotactic and haptotactic responses in both HMC-1 cells and in vitro cultured human cord blood-derived mast cells. These results show the expression of functional CXCR2 receptors on the surface of human mast cells, which may play an important role in mast cell recruitment during the genesis of an inflammatory response.  (+info)

Consequences of GATA-1 deficiency in megakaryocytes and platelets. (3/470)

In the absence of the hematopoietic transcription factor GATA-1, mice develop thrombocytopenia and an increased number of megakaryocytes characterized by marked ultrastructural abnormalities. These observations establish a critical role for GATA-1 in megakaryopoiesis and raise the question as to how GATA-1 influences megakaryocyte maturation and platelet production. To begin to address this, we have performed a more detailed examination of the megakaryocytes and platelets produced in mice that lack GATA-1 in this lineage. Our analysis demonstrates that compared with their normal counterparts, GATA-1-deficient primary megakaryocytes exhibit significant hyperproliferation in liquid culture, suggesting that the megakaryocytosis seen in animals is nonreactive. Morphologically, these mutant megakaryocytes are small and show evidence of retarded nuclear and cytoplasmic development. A significant proportion of these cells do not undergo endomitosis and express markedly lower levels of mRNA of all megakaryocyte-associated genes tested, including GPIbalpha, GPIbbeta, platelet factor 4 (PF4), c-mpl, and p45 NF-E2. These results are consistent with regulation of a program of megakaryocytic differentiation by GATA-1. Bleeding times are significantly prolonged in mutant animals. GATA-1-deficient platelets show abnormal ultrastructure, reminiscent of the megakaryocytes from which they are derived, and exhibit modest but selective defects in platelet activation in response to thrombin or to the combination of adenosine diphosphate (ADP) and epinephrine. Our findings indicate that GATA-1 serves multiple functions in megakaryocyte development, influencing both cellular growth and maturation.  (+info)

Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin : clinical implications for heparin-induced thrombocytopenia. (4/470)

BACKGROUND: Cardiopulmonary bypass (CPB) induces platelet activation with release of platelet factor 4 (PF4), and patients are exposed to high doses of heparin (H). We investigated whether this contributes to the development of antibodies to H-PF4 and heparin-induced thrombocytopenia (HIT). METHODS AND RESULTS: CPB was performed with unfractionated heparin (UFH) in 328 patients. After surgery, patients received UFH (calcium heparin, 200 IU. kg-1. d-1) (group 1, n=157) or low-molecular-weight heparin (LMWH, Dalteparin, 5000 IU once daily) (group 2, n=171). Eight days after surgery, antibodies to H-PF4 were present in 83 patients (25.3%), 46 in group 1 and 37 in group 2 (P=0.12). Most patients (61%) had IgG1 to H-PF4, but only 8 samples with antibodies induced platelet activation with positive results on serotonin release assay. HIT occurred in 6 patients in group 1, but no thrombocytopenia was observed in subjects receiving LMWH, although 2 had high levels of antibodies with positive serotonin release assay results. When antibodies to H-PF4 were present, mean platelet counts were lower only in patients with FcgammaRIIA R/R131 platelets. CONCLUSIONS: These results provide evidence that the development of antibodies to H-PF4 after CPB performed with UFH is not influenced by the postoperative heparin treatment. The antibodies associated with high risk of HIT are mainly IgG1, which is present at high titers in the plasma of patients continuously treated with UFH.  (+info)

Complexes of heparin and platelet factor 4 specifically stimulate T cells from patients with heparin-induced thrombocytopenia/thrombosis. (5/470)

Heparin-induced thrombocytopenia with thrombosis (HITT) is associated with antibodies specific for complexes consisting of heparin and platelet factor 4 (PF4). Studies in individual patients with HITT have demonstrated immunoglobulin (Ig) class switching from IgM to the IgG or IgA isotypes. This transition is thought to require helper T cells, but no studies of the cellular or molecular basis of this process have yet been reported. To characterize T-cell involvement in HITT, peripheral blood mononuclear cells (PBMC) from two patients with classical HITT obtained shortly after the acute episode were restimulated with heparin:PF4 complexes, PF4 alone, heparin alone, and medium alone in the presence of autologous antigen-presenting cells (APC). Responding T cells were then examined using the technique of "spectratyping," in which sequences encoding CDR3 domains of individual V beta (BV) families are amplified and separated by gel electrophoresis. After 14 days in culture with antigen (heparin:PF4 complexes), but not after culture with PF4, heparin, or medium alone, patient cells, but not cells from normal subjects, preferentially expressed T-cell receptor (TCR)-containing beta chains of the BV 5.1 family. Nucleotide sequencing of BV 5.1 TCR CDR3 showed that each patient had a personal repertoire, but also shared a tetrapeptide motif (PGTG). These findings provide evidence that the humoral immune response associated with HITT is driven by helper T cells that presumably recognize peptides derived from PF4. Identification of a common beta-chain CDR3 motif in responding T cells from each of two patients suggests that a limited number of helper TCRs may be used to mount an antibody response to heparin:PF4 complexes. TCR spectratyping appears to offer a new way to examine the molecular basis of pathologic immune responses and may be useful in further studies of HITT and other immune-mediated hematologic disorders.  (+info)

Increased formation of thromboxane in vivo in humans with mastocytosis. (6/470)

Clinical manifestations of mastocytosis are mediated, at least in part, by release of the mast cell mediators histamine and prostaglandin D2. It has been previously reported that in addition to prostaglandin D2, mast cells produce other eicosanoids, including thromboxane. Nonetheless, little information exists regarding the formation of other prostanoids in vivo. The most accurate method to examine the systemic production of eicosanoids in vivo is the quantitation of urinary metabolites. We previously developed a highly accurate assay employing mass spectrometry to measure a major urinary metabolite of thromboxane, 11-dehydro-thromboxane B2, in humans. We utilized this assay to quantitate thromboxane production in 17 patients with histologically proven mastocytosis. We report that thromboxane formation was significantly increased (>2 SD above the mean) in at least one urine sample from 65% of patients studied. Of these, 91% of patients with documented systemic involvement had elevated thromboxane generation. In addition, endogenous formation of thromboxane was highly correlated with the urinary excretion of the major urinary metabolite of prostaglandin D2 (r = 0.98) and Ntau-methylhistamine (r = 0.91), suggesting that the cellular source of increased thromboxane in vivo could be the mastocyte. Enhanced thromboxane formation in patients with this disorder is unlikely to be of platelet origin as other markers of platelet activation, platelet factor 4 and beta-thromboglobulin, were not increased in three patients with marked overproduction of thromboxane. Furthermore, the recovery of 11-dehydro-thromboxane B2 excretion in two patients after the administration of aspirin occurred significantly more rapidly than the recovery of platelet thromboxane generation. These studies, therefore, report that thromboxane production is significantly increased in the majority of patients with mastocytosis that we examined and provide the basis to elucidate the role of this eicosanoid in disorders of mast cell activation.  (+info)

Inhibition of in vitro angiogenesis by platelet factor-4-derived peptides and mechanism of action. (7/470)

In this study, we examined in detail the interaction of platelet factor-4 (PF-4) with fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) and the effect of PF-4-derived synthetic peptides. We show that a peptide between amino acids 47 and 70 that contains the heparin-binding lysine-rich site inhibits FGF-2 or VEGF function. This is based on the following observations: PF-4 peptide 47-70 inhibited FGF-2 or VEGF binding to endothelial cells; it inhibited FGF-2 or VEGF binding to FGFRs or VEGFRs in heparan sulfate-deficient CHO cells transfected with FGFR1 (CHOFGFR1) or VEGFR2 (CHOmVEGFR2) cDNA; it blocked proliferation or tube formation in three-dimensional angiogenesis assays; and, finally, it competed with the direct association of (125)I-PF-4 with FGF-2 or VEGF, respectively, and inhibited heparin-induced FGF-2 dimerization. A shorter C-terminal peptide (peptide 58-70), which still contained the heparin-binding lysin-rich site, had no effect. Peptide 17-58, which is located in the central part of the molecule, although it does not inhibit FGF-2 or VEGF binding or biologic activity in endothelial cells, inhibited heparin-dependent binding of (125)I-FGF-2 or (125)I-VEGF to CHOmFGFR1 or CHOmVEGFR2 cells, respectively. Shorter peptides (peptides 34-58 and 47-58) did not show any of these effects.  (+info)

Inhibition of murine neutrophil recruitment in vivo by CXC chemokine receptor antagonists. (8/470)

In this study, we have examined the ability of chemokine receptor antagonists to prevent neutrophil extravasation in the mouse. Two murine CXC chemokines, macrophage-inflammatory protein (MIP)-2 and KC, stimulated the accumulation of leukocytes into s.c. air pouches, although MIP-2 was considerably more potent. The leukocyte infiltrate was almost exclusively neutrophilic in nature. A human CXC chemokine antagonist, growth-related oncogene (GRO)-alpha(8-73), inhibited calcium mobilization induced by MIP-2, but not by platelet-activating factor in leukocytes isolated from the bone marrow, indicating that this antagonist inhibits MIP-2 activity toward murine leukocytes. Pretreatment of mice with GROalpha(8-73) inhibited, in a dose-dependent manner, the MIP-2-induced influx of neutrophils to levels that were not significantly different from control values. Moreover, this antagonist was also effective in inhibiting the leukocyte recruitment induced by TNF-alpha, LPS, and IL-1beta. Leukocyte infiltration into the peritoneal cavity in response to MIP-2 was also inhibited by prior treatment of mice with GROalpha(8-73) or the analogue of platelet factor 4, PF4(9-70). The results of this study indicate 1) that the murine receptor for MIP-2 and KC, muCXCR2, plays a major role in neutrophil recruitment to s.c. tissue and the peritoneal cavity in response to proinflammatory agents and 2) that CXCR2 receptor antagonists prevent acute inflammation in vivo.  (+info)

Platelet Factor 4 (PF4), also known as CXCL4, is a chemokine that is primarily secreted by activated platelets and involved in hemostasis and inflammation. It is a small protein with a molecular weight of approximately 8 kDa and is stored in the alpha granules of resting platelets. Upon activation, platelets release PF4 into the bloodstream, where it plays a role in attracting immune cells to sites of injury or infection.

PF4 can bind to various negatively charged molecules, including heparin, DNA, and RNA, which can lead to the formation of immune complexes. In some cases, these immune complexes can trigger an abnormal immune response, resulting in conditions such as heparin-induced thrombocytopenia (HIT) or vaccine-induced immune thrombotic thrombocytopenia (VITT).

In summary, Platelet Factor 4 is a chemokine released by activated platelets that plays a role in hemostasis and inflammation but can also contribute to the development of certain immune-related disorders.

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 Factor 3 (PF3) is not a separate protein entity but rather refers to the complex formed when platelets are activated and expose their inner membrane, specifically a phospholipid-rich granule called the granule membrane particle, to the outside. This complex of platelet membrane with coagulation factors then serves as a catalytic surface for the acceleration of thrombin formation in the coagulation cascade.

In other words, PF3 is a part of the activated platelet's surface that plays an important role in blood clotting by promoting the conversion of prothrombin to thrombin and the subsequent fibrin formation, which helps to strengthen the clot.

Beta-thromboglobulin is a type of protein that is released from platelets (a component of blood) when they are activated. It is often used as a marker for platelet activation, which can occur in various physiological and pathological conditions such as hemostasis, thrombosis, inflammation, and atherosclerosis.

Beta-thromboglobulin is a member of the thromboglobulin family, which also includes platelet factor 4 (PF4) and other proteins that are involved in hemostasis and thrombosis. These proteins play important roles in the regulation of blood clotting and wound healing, but their excessive release or activation can contribute to the development of various cardiovascular diseases, such as myocardial infarction (heart attack) and stroke.

Elevated levels of beta-thromboglobulin have been found in patients with thromboembolic disorders, inflammatory bowel disease, cancer, and other conditions associated with platelet activation. Therefore, the measurement of beta-thromboglobulin can be useful in the diagnosis and monitoring of these diseases.

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.

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.

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.

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.

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.

Beta-globulins are a group of proteins found in the beta region of a serum protein electrophoresis, which is a laboratory test used to separate and identify different types of proteins in the blood. This group includes several important proteins such as:

1. Beta-lipoproteins: These are responsible for transporting fat molecules, including cholesterol, throughout the body.
2. Transferrin: A protein that binds and transports iron in the blood.
3. Complement components: These proteins play a crucial role in the immune system's response to infection and inflammation.
4. Beta-2 microglobulin: A protein involved in the functioning of the immune system, elevated levels of which can be found in various conditions such as kidney disease and autoimmune disorders.
5. Hemopexin: A protein that binds and transports heme (a component of hemoglobin) in the blood.

It is important to note that any significant increase or decrease in beta-globulins can indicate an underlying medical condition, such as liver disease, kidney disease, or an autoimmune disorder. Therefore, abnormal results should be further evaluated by a healthcare professional for proper diagnosis and treatment.

Heparin antagonists, also known as heparin neutralizers or reversal agents, are medications used to reverse the anticoagulant effects of heparin, a type of blood thinner. Heparin works by activating antithrombin III, which inactivates clotting factors IIa and Xa. Heparin antagonists, such as protamine sulfate, work by binding to heparin, forming a stable complex that is unable to bind to and activate antithrombin III, thereby neutralizing its anticoagulant effect.

Protamine sulfate is the most commonly used heparin antagonist. It is a highly basic protein derived from fish sperm that can neutralize the anticoagulant effects of heparin by forming a stable complex with it. The dose of protamine required to reverse the effects of heparin depends on the amount and type of heparin administered, as well as the timing of administration.

It is important to note that while heparin antagonists can reverse the anticoagulant effects of heparin, they do not reverse the underlying coagulation disorder or prevent further clot formation. Therefore, additional treatments may be necessary to manage the underlying condition and prevent recurrent thrombosis.

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.

Thrombocytopenia is a medical condition characterized by an abnormally low platelet count (thrombocytes) in the blood. Platelets are small cell fragments that play a crucial role in blood clotting, helping to stop bleeding when a blood vessel is damaged. A healthy adult typically has a platelet count between 150,000 and 450,000 platelets per microliter of blood. Thrombocytopenia is usually diagnosed when the platelet count falls below 150,000 platelets/µL.

Thrombocytopenia can be classified into three main categories based on its underlying cause:

1. Immune thrombocytopenia (ITP): An autoimmune disorder where the immune system mistakenly attacks and destroys its own platelets, leading to a decreased platelet count. ITP can be further divided into primary or secondary forms, depending on whether it occurs alone or as a result of another medical condition or medication.
2. Decreased production: Thrombocytopenia can occur when there is insufficient production of platelets in the bone marrow due to various causes, such as viral infections, chemotherapy, radiation therapy, leukemia, aplastic anemia, or vitamin B12 or folate deficiency.
3. Increased destruction or consumption: Thrombocytopenia can also result from increased platelet destruction or consumption due to conditions like disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or severe bacterial infections.

Symptoms of thrombocytopenia may include easy bruising, prolonged bleeding from cuts, spontaneous nosebleeds, bleeding gums, blood in urine or stools, and skin rashes like petechiae (small red or purple spots) or purpura (larger patches). The severity of symptoms can vary depending on the degree of thrombocytopenia and the presence of any underlying conditions. Treatment for thrombocytopenia depends on the cause and may include medications, transfusions, or addressing the underlying condition.

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.

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).

A platelet transfusion is the process of medically administering platelets, which are small blood cells that help your body form clots to stop bleeding. Platelet transfusions are often given to patients with low platelet counts or dysfunctional platelets due to various reasons such as chemotherapy, bone marrow transplantation, disseminated intravascular coagulation (DIC), and other medical conditions leading to increased consumption or destruction of platelets. This procedure helps to prevent or treat bleeding complications in these patients. It's important to note that platelet transfusions should be given under the supervision of a healthcare professional, taking into account the patient's clinical condition, platelet count, and potential risks associated with transfusion reactions.

Factor XIII, also known as fibrin stabilizing factor, is a protein involved in the clotting process of blood. It is a transglutaminase enzyme that cross-links fibrin molecules to form a stable clot. Factor XIII becomes activated during the coagulation cascade, and its activity helps strengthen the clot and protect it from premature degradation by proteolytic enzymes. A deficiency in Factor XIII can lead to a bleeding disorder characterized by prolonged bleeding after injury or surgery.

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.

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.

Factor V deficiency is a rare bleeding disorder that is caused by a mutation in the gene that produces coagulation factor V, a protein involved in the clotting process. This condition can lead to excessive bleeding following injury or surgery, and may also cause menorrhagia (heavy menstrual periods) in women.

Factor V deficiency is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) in order to develop the condition. People who inherit only one copy of the mutated gene are carriers and may have a milder form of the disorder or no symptoms at all.

Treatment for factor V deficiency typically involves replacement therapy with fresh frozen plasma or clotting factor concentrates, which can help to reduce bleeding episodes and prevent complications. In some cases, medications such as desmopressin or antifibrinolytics may also be used to manage the condition.

Platelet-activating factor (PAF) is a potent phospholipid mediator that plays a significant role in various inflammatory and immune responses. It is a powerful lipid signaling molecule released mainly by activated platelets, neutrophils, monocytes, endothelial cells, and other cell types during inflammation or injury.

PAF has a molecular structure consisting of an alkyl chain linked to a glycerol moiety, a phosphate group, and an sn-2 acetyl group. This unique structure allows PAF to bind to its specific G protein-coupled receptor (PAF-R) on the surface of target cells, triggering various intracellular signaling cascades that result in cell activation, degranulation, and aggregation.

The primary functions of PAF include:

1. Platelet activation and aggregation: PAF stimulates platelets to aggregate, release their granules, and activate the coagulation cascade, which can lead to thrombus formation.
2. Neutrophil and monocyte activation: PAF activates these immune cells, leading to increased adhesion, degranulation, and production of reactive oxygen species (ROS) and pro-inflammatory cytokines.
3. Vasodilation and increased vascular permeability: PAF can cause vasodilation by acting on endothelial cells, leading to an increase in blood flow and facilitating the extravasation of immune cells into inflamed tissues.
4. Bronchoconstriction: In the respiratory system, PAF can induce bronchoconstriction and recruitment of inflammatory cells, contributing to asthma symptoms.
5. Neurotransmission modulation: PAF has been implicated in neuroinflammation and may play a role in neuronal excitability, synaptic plasticity, and cognitive functions.

Dysregulated PAF signaling has been associated with several pathological conditions, including atherosclerosis, sepsis, acute respiratory distress syndrome (ARDS), ischemia-reperfusion injury, and neuroinflammatory disorders. Therefore, targeting the PAF pathway may provide therapeutic benefits in these diseases.

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.

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.

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.

Adenosine diphosphate (ADP) is a chemical compound that plays a crucial role in energy transfer within cells. It is a nucleotide, which consists of a adenosine molecule (a sugar molecule called ribose attached to a nitrogenous base called adenine) and two phosphate groups.

In the cell, ADP functions as an intermediate in the conversion of energy from one form to another. When a high-energy phosphate bond in ADP is broken, energy is released and ADP is converted to adenosine triphosphate (ATP), which serves as the main energy currency of the cell. Conversely, when ATP donates a phosphate group to another molecule, it is converted back to ADP, releasing energy for the cell to use.

ADP also plays a role in blood clotting and other physiological processes. In the coagulation cascade, ADP released from damaged red blood cells can help activate platelets and initiate the formation of a blood clot.

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.

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.

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.

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).

Fibrinopeptide A is a small protein molecule that is cleaved and released from the larger fibrinogen protein during the blood clotting process. Specifically, it is removed by the enzyme thrombin as part of the conversion of fibrinogen to fibrin, which is the main structural component of a blood clot. The measurement of Fibrinopeptide A in the blood can be used as a marker for ongoing thrombin activation and fibrin formation, which are key events in coagulation and hemostasis. Increased levels of Fibrinopeptide A may indicate abnormal or excessive blood clotting, such as in disseminated intravascular coagulation (DIC) or deep vein thrombosis (DVT).

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.

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.

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.

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.

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.

Factor V, also known as proaccelerin or labile factor, is a protein involved in the coagulation cascade, which is a series of chemical reactions that leads to the formation of a blood clot. Factor V acts as a cofactor for the activation of Factor X to Factor Xa, which is a critical step in the coagulation cascade.

When blood vessels are damaged, the coagulation cascade is initiated to prevent excessive bleeding. During this process, Factor V is activated by thrombin, another protein involved in coagulation, and then forms a complex with activated Factor X and calcium ions on the surface of platelets or other cells. This complex converts prothrombin to thrombin, which then converts fibrinogen to fibrin to form a stable clot.

Deficiency or dysfunction of Factor V can lead to bleeding disorders such as hemophilia B or factor V deficiency, while mutations in the gene encoding Factor V can increase the risk of thrombosis, as seen in the Factor V Leiden mutation.

Human platelet antigens (HPAs) are a group of cell surface proteins found on platelets and megakaryocytes, which are the precursor cells that produce platelets. These antigens can stimulate an immune response when they are recognized as foreign by the body's immune system, leading to the production of antibodies against them.

HPAs are classified into several different systems based on their genetic inheritance and immunological properties. The most well-known HPA systems are HPA-1, HPA-2, HPA-3, HPA-4, and HPA-5. Each system consists of a pair of alleles, one inherited from each parent, that code for different variants of the antigen.

HPAs can play a role in the development of certain bleeding disorders, such as neonatal alloimmune thrombocytopenia (NAIT) and post-transfusion purpura (PTP). NAIT occurs when a pregnant woman develops antibodies against her fetus's HPAs, leading to low platelet counts and bleeding in the newborn. PTP can occur after a transfusion of blood products containing HPAs that are not compatible with the recipient's HPAs, leading to an immune response and destruction of the transfused platelets.

It is important for healthcare providers to consider HPA compatibility when performing platelet transfusions or managing pregnant women at risk of developing antibodies against HPAs.

Coagulants are substances that promote the process of coagulation or clotting. They are often used in medical settings to help control bleeding and promote healing. Coagulants work by encouraging the formation of a clot, which helps to stop the flow of blood from a wound or cut.

There are several different types of coagulants that may be used in medical treatments. Some coagulants are naturally occurring substances, such as vitamin K, which is essential for the production of certain clotting factors in the body. Other coagulants may be synthetic or semi-synthetic compounds, such as recombinant activated factor VII (rFVIIa), which is used to treat bleeding disorders and prevent excessive bleeding during surgery.

Coagulants are often administered through injection or infusion, but they can also be applied topically to wounds or cuts. In some cases, coagulants may be used in combination with other treatments, such as compression or cauterization, to help control bleeding and promote healing.

It is important to note that while coagulants can be helpful in controlling bleeding and promoting healing, they can also increase the risk of blood clots and other complications. As a result, they should only be used under the guidance and supervision of a qualified healthcare professional.

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.

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.

Factor V, also known as proaccelerin or labile factor, is a protein involved in the coagulation cascade, which is a series of chemical reactions that leads to the formation of a blood clot. Factor V acts as a cofactor for the conversion of prothrombin to thrombin, which is a critical step in the coagulation process.

Inherited deficiencies or abnormalities in Factor V can lead to bleeding disorders. For example, Factor V Leiden is a genetic mutation that causes an increased risk of blood clots, while Factor V deficiency can cause a bleeding disorder.

It's worth noting that "Factor Va" is not a standard medical term. Factor V becomes activated and turns into Factor Va during the coagulation cascade. Therefore, it is possible that you are looking for the definition of "Factor Va" in the context of its role as an activated form of Factor V in the coagulation process.

Aspirin is the common name for acetylsalicylic acid, which is a medication used to relieve pain, reduce inflammation, and lower fever. It works by inhibiting the activity of an enzyme called cyclooxygenase (COX), which is involved in the production of prostaglandins, hormone-like substances that cause inflammation and pain. Aspirin also has an antiplatelet effect, which means it can help prevent blood clots from forming. This makes it useful for preventing heart attacks and strokes.

Aspirin is available over-the-counter in various forms, including tablets, capsules, and chewable tablets. It is also available in prescription strengths for certain medical conditions. As with any medication, aspirin should be taken as directed by a healthcare provider, and its use should be avoided in children and teenagers with viral infections due to the risk of Reye's syndrome, a rare but serious condition that can affect the liver and brain.

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter that is found primarily in the gastrointestinal (GI) tract, blood platelets, and the central nervous system (CNS) of humans and other animals. It is produced by the conversion of the amino acid tryptophan to 5-hydroxytryptophan (5-HTP), and then to serotonin.

In the CNS, serotonin plays a role in regulating mood, appetite, sleep, memory, learning, and behavior, among other functions. It also acts as a vasoconstrictor, helping to regulate blood flow and blood pressure. In the GI tract, it is involved in peristalsis, the contraction and relaxation of muscles that moves food through the digestive system.

Serotonin is synthesized and stored in serotonergic neurons, which are nerve cells that use serotonin as their primary neurotransmitter. These neurons are found throughout the brain and spinal cord, and they communicate with other neurons by releasing serotonin into the synapse, the small gap between two neurons.

Abnormal levels of serotonin have been linked to a variety of disorders, including depression, anxiety, schizophrenia, and migraines. Medications that affect serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs), are commonly used to treat these conditions.

Factor VII deficiency is a bleeding disorder that is caused by a deficiency or dysfunction of coagulation factor VII, which is a protein involved in the coagulation cascade and is necessary for the initiation of blood clotting. This condition can lead to prolonged bleeding after injury or surgery, easy bruising, and spontaneous bleeding. The severity of the disorder varies widely, depending on the level of factor VII activity. In severe cases, factor VII activity may be less than 1% of normal, leading to a high risk of bleeding. In milder cases, factor VII activity may be between 5-40% of normal, leading to a lower risk of bleeding. Treatment typically involves replacement therapy with fresh frozen plasma or recombinant factor VIIa to control bleeding episodes and prevent complications.

Protamines are small, arginine-rich proteins that are found in the sperm cells of many organisms. They play a crucial role in the process of sperm maturation, also known as spermiogenesis. During this process, the DNA in the sperm cell is tightly packed and compacted by the protamines, which helps to protect the genetic material during its journey to fertilize an egg.

Protamines are typically composed of around 50-100 amino acids and have a high proportion of positively charged arginine residues, which allow them to interact strongly with the negatively charged DNA molecule. This interaction results in the formation of highly condensed chromatin structures that are resistant to enzymatic digestion and other forms of damage.

In addition to their role in sperm maturation, protamines have also been studied for their potential use in drug delivery and gene therapy applications. Their ability to bind strongly to DNA makes them attractive candidates for delivering drugs or genetic material directly to the nucleus of a cell. However, more research is needed to fully understand the potential benefits and risks associated with these applications.

Anticoagulants are a class of medications that work to prevent the formation of blood clots in the body. They do this by inhibiting the coagulation cascade, which is a series of chemical reactions that lead to the formation of a clot. Anticoagulants can be given orally, intravenously, or subcutaneously, depending on the specific drug and the individual patient's needs.

There are several different types of anticoagulants, including:

1. Heparin: This is a naturally occurring anticoagulant that is often used in hospitalized patients who require immediate anticoagulation. It works by activating an enzyme called antithrombin III, which inhibits the formation of clots.
2. Low molecular weight heparin (LMWH): LMWH is a form of heparin that has been broken down into smaller molecules. It has a longer half-life than standard heparin and can be given once or twice daily by subcutaneous injection.
3. Direct oral anticoagulants (DOACs): These are newer oral anticoagulants that work by directly inhibiting specific clotting factors in the coagulation cascade. Examples include apixaban, rivaroxaban, and dabigatran.
4. Vitamin K antagonists: These are older oral anticoagulants that work by inhibiting the action of vitamin K, which is necessary for the formation of clotting factors. Warfarin is an example of a vitamin K antagonist.

Anticoagulants are used to prevent and treat a variety of conditions, including deep vein thrombosis (DVT), pulmonary embolism (PE), atrial fibrillation, and prosthetic heart valve thrombosis. It is important to note that anticoagulants can increase the risk of bleeding, so they must be used with caution and regular monitoring of blood clotting times may be required.

In the context of psychology and psychiatry, "rationalization" is not a term that has a specific medical definition. However, it is a psychological concept that is often used in medical settings. Rationalization refers to the process of creating logical explanations or justifications for behaviors, emotions, or beliefs that may actually be driven by unconscious desires or motives.

Rationalization can serve as a defense mechanism that allows individuals to avoid acknowledging unpleasant or uncomfortable feelings, thoughts, or impulses. By providing a rational explanation for their behavior, individuals can maintain a positive self-image and avoid feeling anxious, guilty, or threatened.

For example, a person who engages in excessive spending may rationalize their behavior by telling themselves that they deserve to treat themselves or that they need the items they are purchasing. In reality, their overspending may be driven by deeper emotional issues such as low self-esteem or a fear of missing out.

While rationalization is not a medical term per se, it is an important concept in understanding human behavior and motivation, and it can have implications for mental health treatment. Therapists may help individuals identify instances of rationalization and explore the underlying emotions and motivations that are driving their behavior. By gaining insight into these unconscious processes, individuals can develop more adaptive coping mechanisms and make more informed choices about their actions and decisions.

Antithrombin III is a protein that inhibits the formation of blood clots (thrombi) in the body. It does this by inactivating several enzymes involved in coagulation, including thrombin and factor Xa. Antithrombin III is produced naturally by the liver and is also available as a medication for the prevention and treatment of thromboembolic disorders, such as deep vein thrombosis and pulmonary embolism. It works by binding to and neutralizing excess clotting factors in the bloodstream, thereby reducing the risk of clot formation.

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.

Protein C is a vitamin K-dependent protease that functions as an important regulator of coagulation and inflammation. It is a plasma protein produced in the liver that, when activated, degrades clotting factors Va and VIIIa to limit thrombus formation and prevent excessive blood clotting. Protein C also has anti-inflammatory properties by inhibiting the release of pro-inflammatory cytokines and reducing endothelial cell activation. Inherited or acquired deficiencies in Protein C can lead to an increased risk of thrombosis, a condition characterized by abnormal blood clot formation within blood vessels.

Glycoprotein IIb (also known as integrin αIIbβ3 or CD41/CD61) is a type of protein found on the surface of platelets, which are small cell fragments involved in blood clotting. This glycoprotein plays a crucial role in the final pathway of platelet activation and aggregation, which ultimately leads to the formation of a clot to stop bleeding.

More specifically, Glycoprotein IIb is responsible for binding fibrinogen, von Willebrand factor, and other adhesive proteins in the blood, allowing platelets to bind together and form a clot. Mutations or defects in this glycoprotein can lead to bleeding disorders such as Glanzmann thrombasthenia, which is characterized by abnormal platelet function and excessive bleeding.

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.

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.

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.

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.

Antibodies are proteins produced by the immune system in response to the presence of a foreign substance, such as a bacterium or virus. They are capable of identifying and binding to specific antigens (foreign substances) on the surface of these invaders, marking them for destruction by other immune cells. Antibodies are also known as immunoglobulins and come in several different types, including IgA, IgD, IgE, IgG, and IgM, each with a unique function in the immune response. They are composed of four polypeptide chains, two heavy chains and two light chains, that are held together by disulfide bonds. The variable regions of the heavy and light chains form the antigen-binding site, which is specific to a particular antigen.

"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.

Affinity chromatography is a type of chromatography technique used in biochemistry and molecular biology to separate and purify proteins based on their biological characteristics, such as their ability to bind specifically to certain ligands or molecules. This method utilizes a stationary phase that is coated with a specific ligand (e.g., an antibody, antigen, receptor, or enzyme) that selectively interacts with the target protein in a sample.

The process typically involves the following steps:

1. Preparation of the affinity chromatography column: The stationary phase, usually a solid matrix such as agarose beads or magnetic beads, is modified by covalently attaching the ligand to its surface.
2. Application of the sample: The protein mixture is applied to the top of the affinity chromatography column, allowing it to flow through the stationary phase under gravity or pressure.
3. Binding and washing: As the sample flows through the column, the target protein selectively binds to the ligand on the stationary phase, while other proteins and impurities pass through. The column is then washed with a suitable buffer to remove any unbound proteins and contaminants.
4. Elution of the bound protein: The target protein can be eluted from the column using various methods, such as changing the pH, ionic strength, or polarity of the buffer, or by introducing a competitive ligand that displaces the bound protein.
5. Collection and analysis: The eluted protein fraction is collected and analyzed for purity and identity, often through techniques like SDS-PAGE or mass spectrometry.

Affinity chromatography is a powerful tool in biochemistry and molecular biology due to its high selectivity and specificity, enabling the efficient isolation of target proteins from complex mixtures. However, it requires careful consideration of the binding affinity between the ligand and the protein, as well as optimization of the elution conditions to minimize potential damage or denaturation of the purified protein.

Interleukin-8 (IL-8) receptors are a type of cell surface receptor that bind to and are activated by the cytokine IL-8. There are two main types of IL-8 receptors, known as CXCR1 and CXCR2. Both of these receptors belong to the G protein-coupled receptor (GPCR) family and play important roles in the immune response, particularly in the recruitment and activation of neutrophils, a type of white blood cell that helps to fight infection.

IL-8A, also known as CXCR1, is a specific subtype of IL-8 receptor. It is a 354-amino acid protein that is expressed on the surface of many different types of cells, including neutrophils, monocytes, and certain tumor cells. When IL-8 binds to CXCR1, it activates a variety of signaling pathways within the cell that lead to changes in gene expression, cell activation, and chemotaxis (directed movement) towards the source of IL-8.

CXCR1 plays an important role in the immune response to bacterial and fungal infections, as well as in the development and progression of certain inflammatory diseases and cancers. It is also a target for drug development, particularly in the areas of cancer therapy and inflammatory disease.

Factor XI deficiency, also known as Hemophilia C or Rosenthal syndrome, is a rare bleeding disorder caused by a deficiency or dysfunction of coagulation factor XI. This protease plays an important role in the intrinsic pathway of blood coagulation. Factor XI deficiency can lead to prolonged bleeding after surgery, trauma, or menstruation, but it typically does not cause spontaneous bleeding like Hemophilia A and B. The severity of the condition varies widely among affected individuals. Inheritance is autosomal recessive, meaning that two defective copies of the gene (one from each parent) are necessary to have the disease.

Factor Xa is a serine protease that plays a crucial role in the coagulation cascade, which is a series of reactions that lead to the formation of a blood clot. It is one of the activated forms of Factor X, a pro-protein that is converted to Factor Xa through the action of other enzymes in the coagulation cascade.

Factor Xa functions as a key component of the prothrombinase complex, which also includes calcium ions, phospholipids, and activated Factor V (also known as Activated Protein C or APC). This complex is responsible for converting prothrombin to thrombin, which then converts fibrinogen to fibrin, forming a stable clot.

Inhibitors of Factor Xa are used as anticoagulants in the prevention and treatment of thromboembolic disorders such as deep vein thrombosis and pulmonary embolism. These drugs work by selectively inhibiting Factor Xa, thereby preventing the formation of the prothrombinase complex and reducing the risk of clot formation.

Thromboxane A2 (TXA2) is a potent prostanoid, a type of lipid compound derived from arachidonic acid. It is primarily produced and released by platelets upon activation during the process of hemostasis (the body's response to stop bleeding). TXA2 acts as a powerful vasoconstrictor, causing blood vessels to narrow, which helps limit blood loss at the site of injury. Additionally, it promotes platelet aggregation, contributing to the formation of a stable clot and preventing further bleeding. However, uncontrolled or excessive production of TXA2 can lead to thrombotic events such as heart attacks and strokes. Its effects are balanced by prostacyclin (PGI2), which is produced by endothelial cells and has opposing actions, acting as a vasodilator and inhibiting platelet aggregation. The balance between TXA2 and PGI2 helps maintain vascular homeostasis.

Factor XI, also known as plasma thromboplastin antecedent (PTA) or antihemophilic factor C, is a protein involved in blood coagulation. It is one of the factors in the intrinsic pathway of coagulation, which is activated when blood comes into contact with negatively charged surfaces, such as damaged blood vessels.

When Factor XI is activated (usually by thrombin or activated Factor XII), it activates more Factor XI and also activates Factor IX, leading to the formation of a complex that converts Factor X to its active form, Factor Xa. This ultimately leads to the formation of a fibrin clot and helps to stop bleeding.

Deficiencies in Factor XI can lead to an increased risk of bleeding, although the severity of the bleeding disorder can vary widely among individuals with Factor XI deficiency. Treatment for Factor XI deficiency typically involves replacement therapy with fresh frozen plasma or recombinant Factor XI concentrate.

Platelet-activating factor Platelet-derived growth factor GRCh38: Ensembl release 89: ENSG00000163737 - Ensembl, May 2017 ... Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif ... "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)". Lasagni L, Francalanci M, Annunziato F, Lazzeri E, ... Platelet+factor+4 at the U.S. National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ...
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... may be up-regulated by platelet factor 4. This cytokine is conjectured to improve activation of protein C by forming ... Factor VIIIa augments Factor X activation by a factor of around 200,000. Because of its importance in clotting, Factor VIII is ... It acts as a serine protease zymogen: APC proteolyses peptide bonds in activated Factor V and Factor VIII (Factor Va and Factor ... Factor VII, Factor IX and Factor X.: 1215 Protein C synthesis occurs in the liver and begins with a single-chain precursor ...
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It is a type of chemokine (C-X-C motif) ligand 7. Along with platelet factor 4 (PF4), β-TG is one of the best-characterized ... Kaplan KL, Owen J (February 1981). "Plasma levels of beta-thromboglobulin and platelet factor 4 as indices of platelet ... Cella G, Scattolo N, Girolami A, Sasahara AA (1984). "Are platelet factor 4 and beta-thromboglobulin markers of cardiovascular ... β-TG and PF4 are stored in platelet alpha granules and are released during platelet activation. As a result, they are useful ...
"Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged ... In 2023 platelet factor 4 (FF4) has been proposed as an exerkine. Sibley and Etnier (2003) performed a meta-analysis that ... and brain-derived neurotrophic factor (BDNF). These factors play crucial roles in promoting cellular survival, neuroprotection ... July 2020). "Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain". Science. ...
VEGFD Platelet-activating factor Platelet-derived growth factor receptor atheroma platelet involvement in smooth muscle ... Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In ... "Vascular endothelial growth factor: A new member of the platelet-derived growth factor gene family". Biochemical and ... Platelet-derived growth factor is a dimeric glycoprotein that can be composed of two A subunits (PDGF-AA), two B subunits (PDGF ...
The binding of platelet factor 4 (CXCL4) appears to be critical for the platelet induced killing of P. falciparum. The Duffy ... CXCL1 Platelet factor 4 - CXCL4 ENA-78 - CXCL5 Neutrophil activating peptide-2 (NAP-2) - CXCL7 Interleukin-8 (IL-8) - CXCL8 ... "Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum". Science. 338 (6112): 1348-51. ... "Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum". Science. 338 (6112): 1348-51. ...
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... receptor Platelet-derived growth factor Zimmerman GA, McIntyre TM, Prescott SM, Stafforini DM (May ... Platelet Activating Factor) Platelet+Activating+Factor at the U.S. National Library of Medicine Medical Subject Headings (MeSH ... cytoplasmic platelet-activating factor acetylhydrolase 2, and platelet-activating factor acetylhydrolase 1b. Cations are one ... an enzyme that catabolizes platelet-activating factor. It is an important mediator of bronchoconstriction. It causes platelets ...
The platelet-activating factor receptor (PAF-R) is a G-protein coupled receptor which binds platelet-activating factor. It is ... "Entrez Gene: PTAFR platelet-activating factor receptor". Correa-Costa M (Apr 2014). "Activation of platelet-activating factor ... Valone FH (1984). "Isolation of a platelet membrane protein which binds the platelet-activating factor 1-0-hexadecyl-2-acetyl- ... platelet+activating+factor+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH) This article ...
Platelets also secrete platelet-derived growth factor (PDGF). Platelets modulate neutrophils by forming platelet-leukocyte ... platelet-derived epidermal growth factor, and vascular endothelial growth factor. Local application of these factors in ... "Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in ... The platelets from rats were conclusively shown to express tissue factor protein and also it was proved that the rat platelets ...
"Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex". ... Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet- ... Platelet-Derived+Growth+Factor+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Portal: ... Heldin CH, Ostman A, Eriksson A, Siegbahn A, Claesson-Welsh L, Westermark B (March 1992). "Platelet-derived growth factor: ...
"Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene". Blood. 101 (12 ... Wang Y, Yin L, Hillgartner FB (Jun 2001). "The homeodomain proteins PBX and MEIS1 are accessory factors that enhance thyroid ... "A conserved motif N-terminal to the DNA-binding domains of myogenic bHLH transcription factors mediates cooperative DNA binding ... Transcription factors, All stub articles, Human chromosome 2 gene stubs). ...
"Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene". Blood. 101 (12 ... Pre-B-cell leukemia transcription factor 2 is a protein that in humans is encoded by the PBX2 gene. This gene encodes a ... 19 (4): 3051-61. doi:10.1128/mcb.19.4.3051. PMC 84099. PMID 10082572. Monica K, Galili N, Nourse J, Saltman D, Cleary ML (Dec ... 19 (4): 3051-61. doi:10.1128/MCB.19.4.3051. PMC 84099. PMID 10082572. Fujino T, Yamazaki Y, Largaespada DA, Jenkins NA, ...
Markers of platelet activation (primary hemostasis) include platelet factor 4 (PF4), β-thromboglobulin (β-TG), and P-selectin. ... Gurney D, Lip GY, Blann AD (June 2002). "A reliable plasma marker of platelet activation: does it exist?". Am J Hematol. 70 (2 ... 33 (4): 333-42. doi:10.1111/j.1751-553X.2011.01345.x. PMID 21692994. S2CID 30451755. Kyrle PA, Rosendaal FR, Eichinger S ( ... 30 (4): 459-71. doi:10.1007/s11239-010-0460-x. PMID 20213258. S2CID 23806848. Merlini PA, Ardissino D (1995). "Laboratory ...
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Brown KJ, Parish CR (1994). "Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by ... Barillari G, Gendelman R, Gallo RC, Ensoli B (1993). "The Tat protein of human immunodeficiency virus type 1, a growth factor ... Lyon M, Deakin JA, Mizuno K, Nakamura T, Gallagher JT (1994). "Interaction of hepatocyte growth factor with heparan sulfate. ... "HIV-tat protein is a heparin-binding angiogenic growth factor". Oncogene. 12 (2): 289-97. PMID 8570206. Soussi-Yanicostas N, ...
Administration of aspirin in patients with MA has been shown to be effective in reducing platelet factor 4 (PF4) concentration ... Zeller, J. A.; Frahm, K.; Baron, R.; Stingele, R.; Deuschl, G. (2004-07-01). "Platelet-leukocyte interaction and platelet ... Additionally, platelet activation is enhanced in patients with MA, even during aura-free and headache-free periods. Moreover, ... Enhanced platelet activation during MA has been observed which directly increases the risk of developing thrombosis. ...
1997). "An alternative form of nucleolysin binds to a T-cluster DNA in the silencer element of platelet factor 4 gene". Biochem ... Involvement of divergent RNA-binding factors HuR, KSRP and TIAR". Int. J. Cancer. 113 (6): 911-9. doi:10.1002/ijc.20675. PMID ...
Hawkins, P.T.; Jackson, T.R.; Stephens, L.R. (1992). "Platelet-derived growth factor stimulates synthesis of Ptdlns(3,4,5)P3 by ... Later, they showed that PtdIns(3,4,5)P3 was responsible for the recruitment of both PKB and PDK1 to the membrane, and therefore ... Together with his long-time collaborator Phillip Thomas Hawkins, he established that PtdIns(4,5)P2 is the main substrate of ... They - in parallel with Dario Alessi - identified phosphoinositide-dependent kinase-1 as the PtdIns(3,4,5)P3-activated link ...
... A is also linked to autoimmunity; for example, the production of antibodies against platelet factor 4 (PF4) bound to CD32A ... CD32A is an activating subtype of CD32 that can be found on a variety of immune cells - notably, CD32A is found on platelets, ... CD32A also plays an important role in platelet activation, adhesion, and aggregation in response to injured blood vessels. When ... Hamzeh-Cognasse H, Damien P, Chabert A, Pozzetto B, Cognasse F, Garraud O (2015-02-26). "Platelets and infections - complex ...
... platelet-rich fibrin gels are ideal since they have a high concentration of platelet releasing growth factors and bioactive ... transforming growth factor beta 1, transforming growth factor beta 2, nerve growth factor, brain derived neurotrophic factor ... Another study to assess if fibrin glue enriched with platelet is better than just platelet rich plasma (PRP) on bone formation ... neural cell adhesion molecule and platelet factor 4, respectively. Heparin-binding growth factors can be attached to heparin ...
... platelet factor 4 [PF4] and fibrinogen). Proteomic studies have identified more than 300 soluble proteins that are involved in ... Other platelet granules have been described. Platelets contain about 1-3 lysosomes per platelet and peroxisomes, the platelet- ... α-Granules are unique to platelets and are the most abundant of the platelet granules, numbering 50-80 per platelet 2. These ... Dense granules (also known as δ-granules) are the second most abundant platelet granules, with 3-8 per platelet. They measure ...
... resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily". Hum. Genet. 84 (2): 185- ... "Nuclear factor-kappaB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an ... IL-8 has also been implied to have a role in colorectal cancer by acting as an autocrine growth factor for colon carcinoma cell ... IL-8 and other inflammatory cytokines form a vicious cycle with the transcription factor NF-κB in cystic fibrosis. NF-κB ...
... resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily". Hum. Genet. 84 (2): 185- ... T-cell replacing factor III, B-cell activating factor, B-cell differentiation factor, and "Heidikine") and interleukin 2 (TSF, ... These include granulocyte colony-stimulating factor (GCSF) and myelomonocytic growth factor (MGF). GCSF acts in hematopoiesis ... Schindler R, Dinarello CA (1990). "Interleukin 1". In Habenicht A (ed.). Growth Factors, Differentiation Factors, and Cytokines ...
Thrombin also activates factor XIII that stabilizes the fibrin complex and therefore the clot and it stimulates platelets, ... which results from a platelet-activating immune response triggered by the interaction of heparin with platelet factor 4 (PF4). ... factor VII comes into contact with tissue factors which starts a process called the blood coagulation cascade. Its purpose is ... Most of those drugs are in the class of direct factor Xa inhibitors, but there is one DTI called AZD0837, which is a follow-up ...
Platelet-activating factor Platelet-derived growth factor GRCh38: Ensembl release 89: ENSG00000163737 - Ensembl, May 2017 ... Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif ... "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)". Lasagni L, Francalanci M, Annunziato F, Lazzeri E, ... Platelet+factor+4 at the U.S. National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ...
Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif ... Platelet-derived growth factor. References. *↑ 1.0 1.1 Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M (July 1990). " ... 1987). "Human platelet factor 4 gene is mapped to 4q12----q21". Cytogenet. Cell Genet. 45 (2): 67-69. doi:10.1159/000132431. ... Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with ...
ELISA Based Anti-Platelet Factor 4 Polyspecific and IgG-Specific Antibody Detection Assays Compared to the Unfractionated ... Heparin-Induced Thrombocytopenia Testing: ELISA Based Anti-Platelet Factor 4 Polyspecific and IgG-Specific Antibody Detection ... Heparin-Induced Thrombocytopenia Testing: ELISA Based Anti-Platelet Factor 4 Polyspecific and IgG-Specific Antibody Detection ... Heparin-Induced Thrombocytopenia Testing: ELISA Based Anti-Platelet Factor 4 Polyspecific and IgG-Specific Antibody Detection ...
Binding of anti-platelet factor 4/heparin antibodies depends on the thermodynamics of conformational changes in platelet factor ... Binding of anti-platelet factor 4/heparin antibodies depends on the thermodynamics of conformational changes in platelet factor ... Binding of anti-platelet factor 4/heparin antibodies depends on the thermodynamics of conformational changes in platelet factor ... The chemokine platelet factor 4 (PF4) undergoes conformational changes when complexing with polyanions. This can induce the ...
B chain and the plasma platelet factor 4 (PF4) levels were measured in 17 healthy controls and 55 brain tumour patients. In the ... The plasma concentration of the platelet-derived growth factor (PDGF)- ... The plasma concentration of the platelet-derived growth factor (PDGF)-B chain and the plasma platelet factor 4 (PF4) levels ... Plasma platelet-derived growth factor-B chain is elevated in patients with extensively large brain tumour Acta Neurochir (Wien) ...
Platelet factor 4 has a high affinity for HEPARIN and is often found complexed with GLYCOPROTEINS such as PROTEIN C. ... "Platelet Factor 4" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... This graph shows the total number of publications written about "Platelet Factor 4" by people in this website by year, and ... Park KS, Rifat S, Eck H, Adachi K, Surrey S, Poncz M. Biologic and biochemic properties of recombinant platelet factor 4 ...
... fibroblast growth factors basic (FGF basic), hepatocyte growth factor (HGF), interleukin-8, platelet-derived growth factor, ... ELISA for angiogenic factors, chemokine platelet factor 4 (PF4) and serotonin. The concentrations of angiogenic factors were ... 12 Platelets are also the main physiological transporters of proangiogenic and antiangiogenic factors.13 Proangiogenic factors ... hepatocyte growth factor; IL-8, interleukin 8; PDGFR, platelet-derived growth factor; TIMP-1, metalloproteinase inhibitor 1; ...
... coagulation factors, and the endothelial cells lining the blood vessels. The platelets arise from the fragmentation of the ... The platelet GP IIb/IIIa complex mediates platelet-to-platelet interactions (platelet aggregation). On resting platelets, GP ... Overview of Platelet Disorders Overview of Platelet Disorders. The hemostatic system consists of platelets, coagulation factors ... Platelet adhesion to vWF via platelet GP Ib platelet activation. *Platelet aggregation mediated by the interaction of GP IIb/ ...
... and platelet counts started to recover on the fifth day after ECC. With the extension of ECC time, the drop in platelet counts ... We concluded that thrombocytopenia was common after ECC, maximum drop of the platelet counts after ECC was usually seen on the ... with different time on platelet count in patients undergoing cardiac surgery. A total of 427 patients who underwent elective ... and the recovery level and speed of platelet counts is lower. ... Platelets derived growth factor and fibroblast growth factor-2 ...
... coagulation factors, and the endothelial cells lining the blood vessels. The platelets arise from the fragmentation of the ... The platelet GP IIb/IIIa complex mediates platelet-to-platelet interactions (platelet aggregation). On resting platelets, GP ... Overview of Platelet Disorders Overview of Platelet Disorders. The hemostatic system consists of platelets, coagulation factors ... Platelet adhesion to vWF via platelet GP Ib platelet activation. *Platelet aggregation mediated by the interaction of GP IIb/ ...
Pro-inflammatory platelet factor 4 (CXCL4/PF4) signaling in rheumatoid arthritis To, Jeffrey Abstract. Background: Rheumatoid ... Of particular interest is platelet factor 4 (PF4), a major constituent of platelet alpha-granules. Methods: Cultured SW982 ... Of particular interest is platelet factor 4 (PF4), a major constituent of platelet alpha-granules. Methods: Cultured SW982 ... Platelets also function as immune cells that contain and secrete pro-inflammatory molecules but their role in RA is not ...
The high mortality associated with VITT was highest among patients with a low platelet count and intracranial hemorrhage. ... by a factor of 1.7 (95% CI, 1.3 to 2.3) for every 50% decrease in the baseline platelet count, by a factor of 1.2 (95% CI, 1.0 ... Overall mortality was 22%. The odds of death increased by a factor of 2.7 (95% confidence interval [CI], 1.4 to 5.2) among ... Conclusions: The high mortality associated with VITT was highest among patients with a low platelet count and intracranial ...
Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior ... An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying ... To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4 ... and platelet factor 4/heparin IgG antibodies (optical density ,0.4, in a subset of patients with previously collected plasma ...
Platelet factor 4 binds to vascular proteoglycans and controls both growth factor activities and platelet activation. ... Dive into the research topics of Platelet factor 4 binds to vascular proteoglycans and controls both growth factor activities ...
Scully et al.: Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination; 22 patients presented with acute ... Scully et al.: Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination; 22 patients presented with acute ... Scully et al.: Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination; 22 patients presented with acute ... Scully et al.: Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination; 22 patients presented with acute ...
H. M. McGowan, R. Vandongen, L. D. Kelly, K. J. Hill; Increased levels of platelet-activating factor (1-O-alkyl-2- ... Increased levels of platelet-activating factor (1-O-alkyl-2-acetylglycerophosphocholine) in blood after reversal of renal clip ... hypertensive rats for the presence of platelet-activating factor (PAF), a potent vasodilator and a putative mediator of the ... The extract was analysed for PAF by a bioassay using 5-hydroxy-[14C]tryptamine-labelled platelets. ...
Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination.external icon Scully et al. NEJM (April 16, 2021). ... Triggering and predisposing factors are unknown. The formation of antibodies against PF4 may cause platelet consumption with ... Antibodies to platelet factor 4 (PF4) were positive in 22 patients and negative in 1 patient. ... Possible contributing factors include disruptions to opioid use disorder treatment services, social patterns in drug usage, and ...
The protein is called platelet factor 4 (PF4). We know that in the course of infection, many people make antibodies that stick ... Billions of platelets get used up in these clots, leading to low numbers of platelets in the blood. In some patients, this led ... In our lab, we work on how platelets get activated in VITT. In 2021, our team showed the main mechanism for platelet activation ... These complexes bind to and activate small cells called platelets that are vital for blood clotting. Normally, platelets float ...
PF4V1; platelet factor 4 variant 1 [KO:K05407]. 9547 CXCL14; C-X-C motif chemokine ligand 14 [KO:K10033]. ... GRB2; growth factor receptor bound protein 2 [KO:K04364]. 6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO: ... CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell ... CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10]. ...
platelet factor 4. ISO. protein:increased expression:plasma. RGD. PMID:26283469. RGD:401794584. NCBI chr14:17,298,304... ... complement factor B. ISO. RGD. PMID:6900632. RGD:7411737. NCBI chr20:3,970,643...3,976,510 Ensembl chr20:3,951,474...3,976,505 ... transforming growth factor, beta 1. ISO. DNA:polymorphism:promoter:exon (human). RGD. PMID:21640045. RGD:5147902. NCBI chr 1: ... coagulation factor V. no_association. ISO. DNA:mutation: :1691G>A (human). RGD. PMID:15077257. RGD:7394769. NCBI chr13: ...
platelet factor 4. involved_in. ISS. ISO. GO_REF:0000024. (PMID:2140694). UniProt. RGD. PMID:2140694. GO_REF:0000024. NCBI ... MAF bZIP transcription factor B. involved_in. ISO. (PMID:8620536). RGD. PMID:8620536. NCBI chr 3:148,998,111...149,000,031 ... KLF transcription factor 13. involved_in. ISO. (MGI:3796470,PMID:18285334). RGD. PMID:18285334. MGI:3796470. NCBI chr 1: ... RUNX family transcription factor 1. involved_in. ISO. (PMID:9199349). RGD. PMID:9199349. NCBI chr11:31,839,880...32,074,427 ...
Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. 10.1056/NEJMoa2105385. ... CBC with platelet count and peripheral smear. Median initial platelet count in largest series was 47 x 109/L with a wide range ... The platelet count at presentation is often 10 x 109/L, somewhat lower than in VITT (median, 20 x 109/L), and thromboses have ... A patient who presents with thrombosis and a normal platelet count post-vaccination might be in an early stage of VITT. ...
Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination. N. Engl. J. Med. 2021, 384, 2202-2211. [Google ... may result in very rare events of producing autoantibodies against platelet-factor 4, potentially causing catastrophic ... SARS-CoV-2 infection is associated with a pro-thrombotic platelet phenotype. Cell Death Dis. 2021, 12, 50. [Google Scholar] [ ... Gallie, D.R. Cap-independent translation conferred by the 5′ leader of tobacco etch virus is eukaryotic initiation factor 4G ...
Migration of THP-1 monocytes in response to complete or fractionated platelet releasate was assessed and located to just one of ... The presence of PEDF and involucrin, two proteins not previously reported in platelet releasate, was confirmed by western ... Here, we describe an experimental approach that fractionates proteins released from human platelets, linking bioassay activity ... in particular platelet activation, adhesion, and wound healing. ... platelet factor 4, platelet basic protein, and actin binding ...
Aqueous Gel Formation of a Synthetic Peptide Derived from the β-Sheet Domain of Platelet Factor-4. Biomacromolecules 2002, 3 (6 ... Cite this: Nano Letters 2002, 2, 4, 295-299. Publication Date (Web):February 21, 2002. Publication History. *Received10 ... Download Hi-Res ImageDownload to MS-PowerPointCite This:Nano Lett. 2002, 2, 4, 295-299 ... The Journal of Physical Chemistry B 2023, 127 (4) , 912-920. https://doi.org/10.1021/acs.jpcb.2c06404. ...
Laghrissi-Thode, F., et al., Elevated platelet factor 4 and beta-thromboglobulin plasma levels in depressed patients with ... Ford, D.E., et al., Depression is a risk factor for coronary artery disease in men: the precursors study. Arch Intern Med, 1998 ... Williams, R.B. and A.B. Littman, Psychosocial factors: role in cardiac risk and treatment strategies. Cardiol Clin, 1996. 14(1 ... Kop, W.J., et al., Inflammation and coagulation factors in persons , 65 years of age with symptoms of depression but without ...
... we observed no evidence of platelet recombination, using platelet factor 4 (Pf4)-Cre; Rosa26Ai14 mice (well known to recombine ... 2015) Broader expression of the mouse platelet factor 4-cre transgene beyond the megakaryocyte lineage Journal of Thrombosis ... Although we saw robust labeling of platelets in PF4-Cre; Ai14 mice, we saw no recombination of platelets in P2ry12-CreER mice ( ... 1977) Amino acid sequence of human platelet factor 4 PNAS 74:2256-2258. ...
Increased platelet factor 4 and aberrant permeability of follicular fluid in PCOS Authors: CC Huang, CH Chou, SU Chen, HN Ho, ... Neuroprotective Effects of Human Mesenchymal Stem Cells and Platelet-Derived Growth Factor on Human Retinal Ganglion Cells ... Angiogenesis stimulated by human kallikrein-related peptidase 12 acting via a platelet-derived growth factor B-dependent ... B-Cell Activating Factor Enhances Hepatocyte-Driven Angiogenesis via B-Cell CLL/Lymphoma 10/Nuclear Factor-KappaB Signaling ...
Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux ... Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement ... A dose-finding study with TAK-442, an oral factor Xa inhibitor, in patients undergoing elective total knee replacement surgery ... Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study ...
4-Methoxytrityl chloride; p-Anisylchlorodiphenylmethane; p-Monomethoxytrityl chloride; MMT; Linear Formula: CH3OC6H4C(C6H5)2Cl ... Analogues of platelet activating factor. 6. Mono- and bis-aryl phosphate antagonists of platelet activating factor. ... A series of aryl phosphoglyceride (3, 19-61) and bis-aryl phosphate (67-135) antagonists of platelet activating factor (PAF) ... CH3OC6H4C(C6H5)2Cl ...
  • Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic. (scilifelab.se)
  • An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. (scilifelab.se)
  • In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. (scilifelab.se)
  • Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies. (scilifelab.se)
  • Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. (cdc.gov)
  • Antibodies to platelet factor 4 (PF4) were positive in 22 patients and negative in 1 patient. (cdc.gov)
  • We also see a lot of variation in how platelets from healthy people respond to PF4 and VITT antibodies. (allafrica.com)
  • Remarkably, more and more patients with clots, low platelets, and VITT-like antibodies are being found . (allafrica.com)
  • Antibodies that bind to a protein called platelet factor 4 may be behind rare, but dangerous, blood clots (one illustrated) that develop in some people vaccinated with AstraZeneca's or Johnson & Johnson's COVID-19 vaccines. (sciencenews.org)
  • Of 23 patients who received AstraZeneca's jab and had symptoms of clots or low platelets, 21 tested positive for antibodies to PF4 , researchers report April 16 in the New England Journal of Medicine . (sciencenews.org)
  • 1 In face of the clinical picture, i.e., thrombocytopenia and thrombosis, with the presence of anti-PF4 antibodies and positive platelet activation tests within 30 days after vaccination with ChadOx1 nCov-19, VITT was diagnosed. (haematologica.org)
  • 2,4 Some patients may develop circulating antibodies against the heparin-platelet factor 4 (PF4) complex, leading to a hypercoagulable state. (clinicaladvisor.com)
  • Based on studies conducted among the patients diagnosed with immune thrombotic thrombocytopenia after the AstraZeneca COVID-19 vaccine in Europe, the pathogenesis of these rare and unusual adverse events after vaccination may be associated with platelet-activating antibodies against platelet factor-4 (PF4), a type of protein. (cdc.gov)
  • In classical HIT, antibodies form against platelet factor 4 (PF4), a tetramer that has an heparin-binding site but also heparin-independent binding sites for other antigens 7 . (eso-stroke.org)
  • VITT develops in relation to heparin-independent antibodies, although also with formation of PF4/IgG complexes leading to platelet consumption, clearance and pancellular activation 7 . (eso-stroke.org)
  • 9 /L), elevated plasma D-dimer levels (>0.5 mg/L), and positive test for anti-PF4 (platelet factor 4) antibodies 8,10 . (eso-stroke.org)
  • METHODS: In this secondary analysis, we tested patients in the Matisse VTE studies at study entry for heparin-dependent antibodies and further tested patients with enzyme-linked immunosorbent assay (ELISA)-positive results for platelet-activating antibodies. (mcmaster.ca)
  • 50% fall in platelet count, heparin-dependent antibodies, no contradicting features) between patients treated with heparin (either unfractionated or low molecular weight [enoxaparin]) vs those who received fondaparinux. (mcmaster.ca)
  • 95% CI, 0.2%-0.6%) had platelet-activating antibodies. (mcmaster.ca)
  • CONCLUSIONS: Of patients with VTE, 0.4% had pathologic platelet-activating heparin-dependent antibodies rather than the 3.2% detected by the recommended cutoff of the commercial ELISA. (mcmaster.ca)
  • Among study patients with acute VTE who had platelet-activating antibodies, treatment with fondaparinux reduced the risk of precipitating rapid-onset HIT. (mcmaster.ca)
  • Transfusion with PLA-1-positive platelets stimulates formation of anti-PLA-1 antibodies, which (by an unknown mechanism) can react with the patient's PLA-1-negative platelets. (msdmanuals.com)
  • Recombinant coagulation factor VIIa is approved for bleeding episodes and perioperative management in patients with GT refractory to platelet transfusions, with or without antibodies to platelets. (medscape.com)
  • We concluded that thrombocytopenia was common after ECC, maximum drop of the platelet counts after ECC was usually seen on the second day after ECC, and platelet counts started to recover on the fifth day after ECC. (nature.com)
  • The study suggested that ECC was a major risk factor leading to thrombocytopenia after operation 1 . (nature.com)
  • Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. (scilifelab.se)
  • Clinicians should avoid platelet transfusions in suspected vaccine-induced thrombosis and thrombocytopenia and should consider administering a non-heparin anticoagulant and intravenous immune globulin. (cdc.gov)
  • The initial laboratory investigations on the day of admission revealed that the patient was suffering from marked thrombocytopenia (i.e., platelet count of 10,000 per mm 3 ), dramatically increased D-dimers plasma levels (i.e. (haematologica.org)
  • In patients with heparin-induced thrombocytopenia (HIT), this antibody-antigen complex leads to platelet activation, removal of platelets from the circulation, and ultimately, thrombocytopenia. (clinicaladvisor.com)
  • In these cases, a type of blood clot called cerebral venous sinus thrombosis (CVST) was seen in combination with low levels of blood platelets (thrombocytopenia). (cdc.gov)
  • 150,000 platelets per microliter of blood), consistent with a condition known as thrombotic thrombocytopenia, with platelet nadir counts ranging from 10,000 to 127,000 during their hospitalizations. (cdc.gov)
  • Examples of this type of situation can be when CVT develops as part of an autoimmune-mediated thrombocytopenia, as for heparin-induced thrombocytopenia (HIT) 4 or as part of a vaccine-induced thrombocytopenia (VITT), with thrombosis happening also at other uncommon sites 3,5 . (eso-stroke.org)
  • After heparin exposure, heparin-induced thrombocytopenia (HIT) can develop, with a concrete risk of developing thrombosis at both arterial and venous sites 4,6 . (eso-stroke.org)
  • Such mechanism differs from other drug-induced thrombocytopenia (e.g., vancomycin), which usually have a steep decrease in platelet count, due to direct platelet clearance (disruption). (eso-stroke.org)
  • may develop nonimmunologic thrombocytopenia, possibly secondary to deposition of platelets in the pulmonary capillary bed. (msdmanuals.com)
  • Except for heparin , drug-induced thrombocytopenia occurs typically when a drug bound to the platelet or a carrier protein creates a new and "foreign" antigen, causing an immune reaction. (msdmanuals.com)
  • This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. (wikipedia.org)
  • Serglycin proteoglycan deletion induces defects in platelet aggregation and thrombus formation in mice. (jefferson.edu)
  • The platelet GP IIb/IIIa complex mediates platelet-to-platelet interactions (platelet aggregation). (medscape.com)
  • A number of bleeding disorders arise as a result of mutations in the genes for proteins involved in platelet aggregation. (hindawi.com)
  • viscosity, reduced red cell deformability, The main objectives of this study were abnormal red cell adhesive properties, en- to assess platelet aggregation patterns and dothelial intimal proliferation, bone marrow levels of PC, PS and AT III in SCA patients or fat embolism and a chronic hypercoagula- in the steady state and in vaso-occlusive ble state [6]. (who.int)
  • Adjacent platelets are cross-linked through the αIIβ3, resulting in platelet aggregation and hemostasis. (medscape.com)
  • [ 5 ] Acquired Glanzmann thrombasthenia is characterized by anti-αIIbβ3 autoantibodies or paraproteins that block platelet aggregation. (medscape.com)
  • We propose an alternative strategy of cfDNA and NET stabilization with chemokine platelet factor 4 (PF4, CXCL4). (jci.org)
  • We discovered that the exerkine CXCL4/Platelet factor 4 or PF4, which is released from platelets after exercise, results in regenerative and cognitive improvements when injected into aged mice," Dr. Leiter said. (scitechdaily.com)
  • The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole. (wikipedia.org)
  • 245 bp of 5'-flanking region from the human platelet factor 4 gene is sufficient to drive megakaryocyte-specific expression in vivo. (jefferson.edu)
  • Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M. Structural and functional comparison of the genes for human platelet factor 4 and PF4alt. (jefferson.edu)
  • Results Our findings indicate that the platelets in HD are dysfunctional with respect to the release of angiogenic factors and functions including thrombosis, angiogenesis and vascular haemostasis. (bmj.com)
  • Under physiological circumstances, the resistance of the endothelial cell lining to interactions with platelets and coagulation factors prevents thrombosis. (medscape.com)
  • If VITT is suspected , perform immediate CBC with platelet count and imaging for thrombosis based on symptoms. (hematology.org)
  • Platelets are anucleate cells that are important for haemostasis, thrombosis, and atherosclerotic disease. (hindawi.com)
  • The goals of the studies proposed in this Project are to extend past analyses of platelet thrombus formation and structure from the microvasculature to the macrovasculature, from mice to humans, and from hemostasis to thrombosis. (hhs.gov)
  • Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. (wikipedia.org)
  • A CXC chemokine that is found in the alpha granules of PLATELETS. (jefferson.edu)
  • Platelets contain two unique types of granules: alpha granules and dense granules. (medscape.com)
  • The alpha granules contain hemostatic proteins such as fibrinogen, vWf, and growth factors (eg, platelet-derived growth factor and transforming growth factors). (medscape.com)
  • Of particular interest is platelet factor 4 (PF4), a major constituent of platelet alpha-granules. (ubc.ca)
  • This initial interaction (platelet adhesion) sets the stage for other adhesive reactions that allow the platelets to interact with other agonists in the vicinity of vessel injury, such as adenosine 5'-diphosphate (ADP), subendothelial collagen, and thrombin. (medscape.com)
  • Following activation by agonists such as thrombin, platelets release storage granules and membrane vesicles that contain prothrombotic (e.g., fibrinogen), mitogenic (e.g., platelet derived growth factor), immunomodulatory (e.g., neutrophil-activating peptide 2), and adhesive (e.g., platelet endothelial cell adhesion molecule) proteins. (hindawi.com)
  • A previous study from our laboratory using a MuDPIT (multidimensional protein identification technology) approach identified over 300 proteins secreted by platelets upon thrombin activation [ 1 ]. (hindawi.com)
  • After binding to its ligand thrombin, CD141 activates protein C, which degrades clotting factors Va and VIIIa, and as a consequence the amount of thrombin is reduced. (biolegend.com)
  • After thrombin binding, CD141 activates protein C, which degrades clotting factors Va and VIIIa and reduces the amount of thrombin generated. (biolegend.com)
  • This leads to moderate platelet consumption and thrombin formation, with a prothrombotic state. (eso-stroke.org)
  • Platelet destruction can develop because of immunologic causes (viral infection, drugs, connective tissue or lymphoproliferative disorders, blood transfusions) or nonimmunologic causes (sepsis, acute respiratory distress syndrome). (msdmanuals.com)
  • Patients with Glanzmann thrombasthenia can have severe bleeding problems, but their prognosis remains good with appropriate supportive care and platelet transfusions if necessary. (medscape.com)
  • Platelets play a primary role in this process, interacting with subendothelium-bound von Willebrand factor (vWf) via the membrane glycoprotein (GP) Ib complex. (medscape.com)
  • In vitro, hPF4 also inhibits cfDNA-induced endothelial tissue factor surface expression and von Willebrand factor release. (jci.org)
  • The GPIb-IX-V complex can attach (bind) to a protein called von Willebrand factor, fitting together like a lock and its key. (medlineplus.gov)
  • Von Willebrand factor is found on the inside surface of blood vessels, particularly when there is an injury. (medlineplus.gov)
  • Binding of the GPIb-IX-V complex to von Willebrand factor allows platelets to stick to the blood vessel wall at the site of the injury. (medlineplus.gov)
  • Other mutations impair the complex's interaction with von Willebrand factor. (medlineplus.gov)
  • Cauwenberghs N, Vanhoorelbeke K, Vauterin S, Deckmyn H. Structural determinants within platelet glycoprotein Ibalpha involved in its binding to von Willebrand factor. (medlineplus.gov)
  • [ 4 ] With platelet activation, the αIIbβ3 complex shifts into its active configuration, which allows the binding of fibrinogen and/or von Willebrand factor (vWF). (medscape.com)
  • Typically tumor cells secrete a complex milieu of growth factors, cytokines and chemokines, some of which are pro-tumorogenic [ 7 , 8 , 9 ]. (iospress.com)
  • In addition to forming hemostatic plugs at sites of vascular injury, platelets make important contributions to processes such as inflammation, tissue regeneration, host defense, angiogenesis, lymphatic development, and tumor metastasis. (hhs.gov)
  • The chemokine platelet factor 4 (PF4) undergoes conformational changes when complexing with polyanions. (fu-berlin.de)
  • Studies suggest that some inoculated people develop an immune response that attacks a protein called platelet factor 4 or PF4, which makes platelets form clots. (sciencenews.org)
  • These platelets form clots, plugging holes in the blood vessels to help stop bleeding. (medlineplus.gov)
  • PROGRAM INTRODUCTION SUMMARY: This is the re-submission of a new Program Project (HL146373-01) that we have re-named "Studies of Physiologic and Pathologic Platelet Plug Formation" to more accurately reflect the topics the Program Project addresses. (hhs.gov)
  • Pathologic platelet thrombi are also responsible for much of the morbidity and mortality of arterial vascular disease. (hhs.gov)
  • There remain large gaps in our understanding of physiologic and pathologic platelet function. (hhs.gov)
  • The platelet integrin αIIbβ3, also known as the glycoprotein GPIIb/IIIa (CD41/CD61) complex, is essential for normal platelet function. (medscape.com)
  • Most patients have a normal platelet size and count. (medscape.com)
  • Lenvatinib inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3, fibroblast growth factor (FGF) receptors FGFR1-4, platelet-derived growth factor receptor alpha (PDGFR⍺), stem cell factor receptor (KIT) and rearranged during transfection (RET). (pharmacytimes.com)
  • Glanzmann thrombasthenia (GT) is a rare platelet disorder in which the platelets have qualitative or quantitative deficiencies of the fibrinogen receptor αIIbβ3. (medscape.com)
  • The hemostatic system consists of platelets, coagulation factors, and the endothelial cells lining the blood vessels. (medscape.com)
  • Platelet disorders lead to defects in primary hemostasis and produce signs and symptoms different from coagulation factor deficiencies (disorders of secondary hemostasis). (medscape.com)
  • Antithrombin's anticoagulant effect results from its inactivation of certain coagulation factors, for the most part IIa and Xa, by enzymatic cleavage (serine protease). (medscape.com)
  • Therefore, LMWH more specifically inhibits coagulation by inactivating factor Xa more than UH. (medscape.com)
  • The high mortality associated with VITT was highest among patients with a low platelet count and intracranial hemorrhage. (nih.gov)
  • In VITT, platelets are strongly activated and this causes blood clots. (allafrica.com)
  • In our lab, we work on how platelets get activated in VITT. (allafrica.com)
  • CVT is critically more frequent in VITT compared to HIT, a further point suggesting that main or secondary pathophysiological mechanisms differ 4 . (eso-stroke.org)
  • Despite the rarity of this syndrome, CVT is critically more frequent in VITT compared to HIT 4 . (eso-stroke.org)
  • Because infused platelet factor 4, as well as the monoclonal antibody KKO that binds to the complex of platelet factor 4 and heparin, block DNA digestion, both will be protective in sepsis. (hhs.gov)
  • the observed mortality was 73% among patients with platelet counts below 30,000 per cubic millimeter and intracranial hemorrhage. (nih.gov)
  • A second platelet concentrate (roughly 4.5x10 11 platelets) was administered to allow initiation of anticoagulation as the platelet count was still below 30,000 per mm 3 . (haematologica.org)
  • On resting platelets, GP IIb/IIIa is unable to bind fibrinogen or vWf. (medscape.com)
  • Platelet activation allows binding of these proteins, which bridges adjacent platelets. (medscape.com)
  • Here, we describe an experimental approach that fractionates proteins released from human platelets, linking bioassay activity to identity. (hindawi.com)
  • Over 300 proteins were identified in the releasate, with a wide range of annotated biophysical and biochemical properties, in particular platelet activation, adhesion, and wound healing. (hindawi.com)
  • The presence of PEDF and involucrin, two proteins not previously reported in platelet releasate, was confirmed by western blotting. (hindawi.com)
  • Thus, altered or deregulated platelet function underpins many diseases, and platelet proteins are potential targets for novel therapeutic agents. (hindawi.com)
  • Previous proteomic studies of intact platelets have collectively identified hundreds of proteins using a variety of fractionation strategies including 2-dimensional electrophoresis (2DE), multidimensional chromatographic separations, membrane prefractionation techniques, and adsorption to combinatorial hexapeptide ligand libraries [ 1 - 6 ]. (hindawi.com)
  • These proteins may modulate the interaction of platelets with their local cellular environment. (hindawi.com)
  • The proteins produced from these genes are pieces (subunits) of a protein complex called glycoprotein (GP)Ib-IX-V. This complex is found on the surface of platelets and plays an important role in blood clotting . (medlineplus.gov)
  • However, since the corresponding PF4 levels suggested the platelet activation, the increased plasma PDGF-B may have originated from platelets. (nih.gov)
  • Platelet activation pathways. (medscape.com)
  • In 2021, our team showed the main mechanism for platelet activation and have recently discovered another mechanism . (allafrica.com)
  • Senescent cells exhibit chronic activation of the transcription factor nuclear factor (NF)-κB, a known mediator of the pro-inflammatory senescence-associated secretory phenotype (SASP) and skeletal muscle atrophy. (jci.org)
  • Billions of platelets get used up in these clots, leading to low numbers of platelets in the blood. (allafrica.com)
  • So these patients wind up with both the rare clots and low levels of blood platelets. (sciencenews.org)
  • The initial hemostatic plug, composed primarily of platelets, is stabilized further by a fibrin mesh generated in secondary hemostasis. (medscape.com)
  • With the extension of ECC time, the drop in platelet counts is more pronounced, the volume of perioperative blood loss and blood products transfusion are more, and the recovery level and speed of platelet counts is lower. (nature.com)
  • The major structural and functional changes related to the airway circulation include the proliferation of blood vessels (angiogenesis) 2 - 4 , increased blood flow 5 , 6 , increased microvascular permeability 7 , 8 , and oedema formation in the airway wall 9 . (ersjournals.com)
  • The plasma concentration of the platelet-derived growth factor (PDGF)-B chain and the plasma platelet factor 4 (PF4) levels were measured in 17 healthy controls and 55 brain tumour patients. (nih.gov)
  • The plasma PDGF-B and PF4 levels from the 17 normal controls and those observed in the platelet releasing experiments correlated with a regression line of Y = 240 + 4.86X (Y:PDGF, X:PF4). (nih.gov)
  • The study evaluates the ability of osteoprogenitors treated with platelet-derived growth factor BB (PDGF-BB) delivered on vinyl styrene microbeads (VSM) to regenerate rat calvarial critical-size defects (CSDs). (allenpress.com)
  • Platelet-derived growth factor BB (PDGF-BB) is the most potent mitogenic and chemotactic member of PDGFs. (allenpress.com)
  • The pretreatment of osteoblastic cells with PDGF-BB before transplantation into osseous defects is investigated in the present study to further investigate the role of this growth factor in bone regeneration. (allenpress.com)
  • Objectives Seeking to elucidate the origin of these vascular and BBB abnormalities, we studied platelets that are known to play a role in maintaining the integrity of the vasculature and thrombotic pathways linked to this, given they surprisingly contain the highest concentration of mHtt of all blood cells. (bmj.com)
  • Baseline characteristics and clinicopathological features of the patients, risk factors, treatment, and markers of poor prognosis were determined. (nih.gov)
  • Of 952 patients, 865 with available baseline platelet count were included. (scilifelab.se)
  • Furthermore, the anti-Xa assay is the most accurate methodology for monitoring UH, especially in the presence of a circulating inhibitor or when the baseline PTT is already prolonged (as in factor XII deficiency). (medscape.com)
  • We can now target platelets to promote neurogenesis, enhance cognition, and counteract age-related cognitive decline. (scitechdaily.com)
  • Methods We assessed the functional status of platelets by performing ELISA, western blot and RNA sequencing in a cohort of 71 patients and 68 age- and sex-matched healthy control subjects. (bmj.com)
  • Use of a non-heparin anticoagulant may be indicated if patient is 4 to 42 days post-vaccine with all other facets of the syndrome pending PF4 ELISA testing and additional CBCs. (hematology.org)
  • A pregnant black woman, aged 37 years, who had a history of pre-eclampsia and pulmonary embolism and was on subcutaneous heparin, presented to labor and delivery with a tender, 4-cm dusk, and erythematous patch on the lower abdomen. (clinicaladvisor.com)
  • Our objective was to observe the effects of extracorporeal circulation (ECC) with different time on platelet count in patients undergoing cardiac surgery. (nature.com)
  • However, there are few studies on the effects of ECC time on platelet count in patients after cardiac surgery, especially the effects of different ECC time on postoperative platelet count has not been reported. (nature.com)
  • The purpose of this study was to conduct a retrospective study to observe the effects of ECC with different time on platelet count in patients undergoing cardiac surgery, so as to provide reference for improving the prognosis of patients undergoing cardiac surgery. (nature.com)
  • Elevated platelet factor 4 and beta-thromboglobulin plasma levels in depressed patients with ischemic heart disease. (medhelp.org)
  • Occasional patients have had a chromosomal rearrangement with a 4q12 breakpoint, such as t(1;4)(q44;q12), which ultimately led to the identification of the fusion gene or t(4;10)(q12;p11) (Cools et al. (atlasgeneticsoncology.org)
  • Approximately 15%-20% of COVID-19 patients develop severe symptoms and exhibit systemic hyperinflammation with elevated cytokine levels and lung immune cell infiltration, which may result in acute damage to capillaries and lung epithelia/alveoli [4]. (researchsquare.com)
  • We profiled the cellular constituents and concentrations of 40 cytokines, chemokines and cellular factors (collectively "soluble factors") involved in inflammatory and immune signalling pathways in pleural effusion samples from 50 mesothelioma patients. (iospress.com)
  • Survival analysis revealed that IL8, IL2Ra (CD25) and PF4 were independent determinants of a more negative prognosis in mesothelioma patients, independent of other known prognostic factors. (iospress.com)
  • These patients have a poor prognosis, with unselected large series revealing median survivals between 7 and 11 months [ 3 , 4 ]. (iospress.com)
  • Patients with GT who are bleeding require platelet transfusion. (medscape.com)
  • The body's reaction to vessel wall injury is rapid adhesion of platelets to the subendothelium. (medscape.com)
  • The inflammatory process in asthma involves the increased expression of various pro-inflammatory chemokines, cytokines, growth factors, lipid mediators, adhesion molecules, enzymes, and receptors for the same inflammatory mediators 21 . (ersjournals.com)
  • Li R, Emsley J. The organizing principle of the platelet glycoprotein Ib-IX-V complex. (medlineplus.gov)
  • Platelet factor 4 has a high affinity for HEPARIN and is often found complexed with GLYCOPROTEINS such as PROTEIN C. (jefferson.edu)
  • Analytes include soluble growth and differentiation factors, extracellular matrix components, proteases, membrane-bound receptors, and intracellular signaling molecules. (rndsystems.com)
  • The platelets arise from the fragmentation of the cytoplasm of megakaryocytes in the bone marrow and circulate in blood as disc-shaped anucleate particles for 7-10 days. (medscape.com)
  • Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes. (msdmanuals.com)
  • Indeed, platelet releasate has previously been shown to induce endothelial cell permeability, endothelial cell chemotaxis, and corneal epithelial cell proliferation in cellular assays [ 7 - 9 ]. (hindawi.com)
  • The extract was analysed for PAF by a bioassay using 5-hydroxy-[ 14 C]tryptamine-labelled platelets. (portlandpress.com)
  • The gene for human PF4 is located on human chromosome 4. (wikipedia.org)
  • An interstitial deletion del(4)(q12q12) generating a FIP1L1-PDGFRA fusion gene is observed in diverse eosinophilia-associated hematologic disorders like hyperseosinophilic syndrome (HES), systemic mastocytosis (SM) and chronic eosinophilic leukemia (CEL). (atlasgeneticsoncology.org)
  • Although most people with only one copy of the mutated gene do not show signs and symptoms of the condition, some have platelets that are slightly larger than normal or very mild bleeding abnormalities. (medlineplus.gov)
  • 6 It has been shown that these microbeads are capable of delivering transforming growth factor-β (TGF-β) to rat calvarial critical-size defects. (allenpress.com)
  • [ 4 ] and are provided in concentration of anti-factor Xa (units/mL). (medscape.com)
  • Ensembl chr 4:148,423,194. (mcw.edu)
  • Ensembl chr 4:30,646,460. (mcw.edu)
  • Ensembl chr 4:81,323,382. (mcw.edu)
  • Platelets also function as immune cells that contain and secrete pro-inflammatory molecules but their role in RA is not understood. (ubc.ca)
  • To address this, platelet releasing experiments were performed on citrated blood samples from 5 normal individuals. (nih.gov)
  • 1. This study analyses whole blood in acutely unclipped one-kidney, one-clip (1K,1C) hypertensive rats for the presence of platelet-activating factor (PAF), a potent vasodilator and a putative mediator of the rapid blood pressure (BP) fall seen after unclipping. (portlandpress.com)
  • These complexes bind to and activate small cells called platelets that are vital for blood clotting. (allafrica.com)
  • Normally, platelets float around in the blood in an inactive state, but once activated they spread out, get very sticky, and spew out hundreds of different chemicals. (allafrica.com)
  • That advisory group to the U.S. Centers for Disease Control and Prevention is assessing what needs to be done to lift a temporary pause on administering the Johnson & Johnson jab that was prompted by blood clot concerns ( SN: 4/13/21 ). (sciencenews.org)
  • On September 8, 2009, a 22-year-old male US soldier who worked in field operations outside Kandahar City, Afghanistan, sought care at a military medical clinic for a 4-d history of nonbloody diarrhea, abdominal pain, bloody emesis, and fever (39.2°C). The patient reported frequent outdoor activities, tick bites, and exposure to undercooked goat meat and blood the week before the onset of illness. (cdc.gov)
  • Researchers have discovered that injecting a specific blood factor can mimic the brain benefits of exercise. (scitechdaily.com)
  • An injection of a specific blood factor can replicate exercise's brain benefits, offering potential treatments for age-related cognitive decline. (scitechdaily.com)
  • Pre-clinical trials by University of Queensland scientists have found that an injection of a specific blood factor can replicate the benefits of exercise in the brain. (scitechdaily.com)
  • Dr. Odette Leiter and Dr. Tara Walker from UQ's Queensland Brain Institute led a team that discovered platelets, the tiny blood cells critical for blood clotting, secrete a protein that rejuvenates neurons in aged mice in a similar way to physical exercise. (scitechdaily.com)
  • Timing of monitoring LMWH: Blood must be drawn 4 hours after subcutaneous injection unless trough level needs to be assessed. (medscape.com)
  • Bernard-Soulier syndrome is a bleeding disorder associated with abnormal platelets, which are blood cells involved in blood clotting. (medlineplus.gov)
  • The dense granules contain proaggregatory factors such as ADP, calcium, and 5-hydroxytryptamine (serotonin). (medscape.com)
  • Project 4, entitled "Platelet Factor 4 and Heparin in NETosis and Sepsis", will test the hypothesis that NETs, neutrophil extracellular traps composed of chromatin released by neutrophils, require partial digestion and release of DNA and histones to be toxic during sepsis. (hhs.gov)
  • Plasma must be separated from cellular components within 1 hour (platelet factor 4, released by platelets, neutralizes the effect of heparin). (medscape.com)
  • Primary outcome was the platelet count before operation (T 1 ), at the end of operation (T 2 ), on the first day (T 3 ), the second day (T 4 ) and the fifth day after operation (T 5 ). (nature.com)
  • The platelet count rapidly improved, i.e., 53,000 per mm 3 , and anticoagulation was started with fondaparinux 5 mg once a day (od) subcutaneously from day 1 to day 3 (taking into account renal failure, i.e. (haematologica.org)
  • When the drug is stopped, the platelet count typically begins to increase within 1 to 2 days and recovers to normal within 7 days. (msdmanuals.com)
  • Once activated, platelets have two major mechanisms to recruit additional platelets to the growing hemostatic plug. (medscape.com)
  • Thus, the release reaction and prostaglandin synthesis act to consolidate the initial hemostatic plug by promoting the participation of other platelets in the growing hemostatic plug. (medscape.com)
  • 2 , 3 Bone engineering involves the delivery of cells or biologic molecules such as growth factors to a defect site for tissue regeneration. (allenpress.com)