Antithrombins: Endogenous factors and drugs that directly inhibit the action of THROMBIN, usually by blocking its enzymatic activity. They are distinguished from INDIRECT THROMBIN INHIBITORS, such as HEPARIN, which act by enhancing the inhibitory effects of antithrombins.Antithrombin Proteins: An endogenous family of proteins belonging to the serpin superfamily that neutralizes the action of thrombin. Six naturally occurring antithrombins have been identified and are designated by Roman numerals I to VI. Of these, Antithrombin I (see FIBRIN) and ANTITHROMBIN III appear to be of major importance.Heparin: 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.Laboratories: Facilities equipped to carry out investigative procedures.Antithrombin III: 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.Diagnostic Techniques and Procedures: Methods, procedures, and tests performed to diagnose disease, disordered function, or disability.Menu PlanningPlasticizers: Materials incorporated mechanically in plastics (usually PVC) to increase flexibility, workability or distensibility; due to the non-chemical inclusion, plasticizers leach out from the plastic and are found in body fluids and the general environment.Laboratory Animal Science: The science and technology dealing with the procurement, breeding, care, health, and selection of animals used in biomedical research and testing.Abbreviations as Topic: Shortened forms of written words or phrases used for brevity.Antithrombin III Deficiency: An absence or reduced level of Antithrombin III leading to an increased risk for thrombosis.Blood Coagulation Tests: Laboratory tests for evaluating the individual's clotting mechanism.Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Protein S Deficiency: An autosomal dominant disorder showing decreased levels of plasma protein S antigen or activity, associated with venous thrombosis and pulmonary embolism. PROTEIN S is a vitamin K-dependent plasma protein that inhibits blood clotting by serving as a cofactor for activated PROTEIN C (also a vitamin K-dependent protein), and the clinical manifestations of its deficiency are virtually identical to those of protein C deficiency. Treatment with heparin for acute thrombotic processes is usually followed by maintenance administration of coumarin drugs for the prevention of recurrent thrombosis. (From Harrison's Principles of Internal Medicine, 12th ed, p1511; Wintrobe's Clinical Hematology, 9th ed, p1523)Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Thrombosis: Formation and development of a thrombus or blood clot in the blood vessel.Aptamers, Nucleotide: Nucleotide sequences, generated by iterative rounds of SELEX APTAMER TECHNIQUE, that bind to a target molecule specifically and with high affinity.SELEX Aptamer Technique: A method of generating a large library of randomized nucleotides and selecting NUCLEOTIDE APTAMERS by iterative rounds of in vitro selection. A modified procedure substitutes AMINO ACIDS in place of NUCLEOTIDES to make PEPTIDE APTAMERS.Aptamers, Peptide: Peptide sequences, generated by iterative rounds of SELEX APTAMER TECHNIQUE, that bind to a target molecule specifically and with high affinity.Fibrinogen: 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.Eosine I Bluish: A red fluorescein dye used as a histologic stain. It may be cytotoxic, mutagenic, and inhibit certain mitochondrial functions.Fluoresceins: A family of spiro(isobenzofuran-1(3H),9'-(9H)xanthen)-3-one derivatives. These are used as dyes, as indicators for various metals, and as fluorescent labels in immunoassays.Fluorescein: A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium such as the aqueous humor.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Receptors, Thrombin: A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity.Antibodies: 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).Goats: Any of numerous agile, hollow-horned RUMINANTS of the genus Capra, in the family Bovidae, closely related to the SHEEP.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Factor Xa: 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.Dental Caries Activity Tests: Diagnostic tests conducted in order to measure the increment of active DENTAL CARIES over a period of time.Dithioerythritol: A compound that, along with its isomer, Cleland's reagent (DITHIOTHREITOL), is used for the protection of sulfhydryl groups against oxidation to disulfides and for the reduction of disulfides to sulfhydryl groups.Cerebrospinal Fluid: A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Blood Coagulation: The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.Fibrinolysis: The natural enzymatic dissolution of FIBRIN.Hemostasis: 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.Fibrin Fibrinogen Degradation Products: Soluble protein fragments formed by the proteolytic action of plasmin on fibrin or fibrinogen. FDP and their complexes profoundly impair the hemostatic process and are a major cause of hemorrhage in intravascular coagulation and fibrinolysis.Venous Thrombosis: The formation or presence of a blood clot (THROMBUS) within a vein.CitratesUltrasonography, Doppler: Ultrasonography applying the Doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. (Stedman, 25th ed)Ultrasonography, Doppler, Color: Ultrasonography applying the Doppler effect, with the superposition of flow information as colors on a gray scale in a real-time image. This type of ultrasonography is well-suited to identifying the location of high-velocity flow (such as in a stenosis) or of mapping the extent of flow in a certain region.Coronary Thrombosis: Coagulation of blood in any of the CORONARY VESSELS. The presence of a blood clot (THROMBUS) often leads to MYOCARDIAL INFARCTION.Ultrasonography: The visualization of deep structures of the body by recording the reflections or echoes of ultrasonic pulses directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz.Ultrasonography, Doppler, Pulsed: Ultrasonography applying the Doppler effect, with velocity detection combined with range discrimination. Short bursts of ultrasound are transmitted at regular intervals and the echoes are demodulated as they return.Universal Precautions: Prudent standard preventive measures to be taken by professional and other health personnel in contact with persons afflicted with a communicable disease, to avoid contracting the disease by contagion or infection. Precautions are especially applicable in the diagnosis and care of AIDS patients.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Molecular Sequence Data: 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.DNA, Recombinant: Biologically active DNA which has been formed by the in vitro joining of segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected.Amino Acid Sequence: 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.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

Anticoagulant heparan sulfate precursor structures in F9 embryonal carcinoma cells. (1/701)

To understand the mechanisms that control anticoagulant heparan sulfate (HSact) biosynthesis, we previously showed that HSact production in the F9 system is determined by the abundance of 3-O-sulfotransferase-1 as well as the size of the HSact precursor pool. In this study, HSact precursor structures have been studied by characterizing [6-3H]GlcN metabolically labeled F9 HS tagged with 3-O-sulfates in vitro by 3'-phosphoadenosine 5'-phospho-35S and purified 3-O-sulfotransferase-1. This later in vitro labeling allows the regions of HS destined to become the antithrombin (AT)-binding sites to be tagged for subsequent structural studies. It was shown that six 3-O-sulfation sites exist per HSact precursor chain. At least five out of six 3-O-sulfate-tagged oligosaccharides in HSact precursors bind AT, whereas none of 3-O-sulfate-tagged oligosaccharides from HSinact precursors bind AT. When treated with low pH nitrous or heparitinase, 3-O-sulfate-tagged HSact and HSinact precursors exhibit clearly different structural features. 3-O-Sulfate-tagged HSact hexasaccharides were AT affinity purified and sequenced by chemical and enzymatic degradations. The 3-O-sulfate-tagged HSact hexasaccharides exhibited the following structures, DeltaUA-[6-3H]GlcNAc6S-GlcUA-[6-3H]GlcNS3(35)S+/-6S-++ +IdceA2S-[6-3H]Glc NS6S. The underlined 6- and 3-O-sulfates constitute the most critical groups for AT binding in view of the fact that the precursor hexasaccharides possess all the elements for AT binding except for the 3-O-sulfate moiety. The presence of five potential AT-binding precursor hexasaccharides in all HSact precursor chains demonstrates for the first time the processive assembly of specific sequence in HS. The difference in structures around potential 3-O-sulfate acceptor sites in HSact and HSinact precursors suggests that these precursors might be generated by different concerted assembly mechanisms in the same cell. This study permits us to understand better the nature of the HS biosynthetic pathway that leads to the generation of specific saccharide sequences.  (+info)

Exosites 1 and 2 are essential for protection of fibrin-bound thrombin from heparin-catalyzed inhibition by antithrombin and heparin cofactor II. (2/701)

Assembly of ternary thrombin-heparin-fibrin complexes, formed when fibrin binds to exosite 1 on thrombin and fibrin-bound heparin binds to exosite 2, produces a 58- and 247-fold reduction in the heparin-catalyzed rate of thrombin inhibition by antithrombin and heparin cofactor II, respectively. The greater reduction for heparin cofactor II reflects its requirement for access to exosite 1 during the inhibitory process. Protection from inhibition by antithrombin and heparin cofactor II requires ligation of both exosites 1 and 2 because minimal protection is seen when exosite 1 variants (gamma-thrombin and thrombin Quick 1) or an exosite 2 variant (Arg93 --> Ala, Arg97 --> Ala, and Arg101 --> Ala thrombin) is substituted for thrombin. Likewise, the rate of thrombin inhibition by the heparin-independent inhibitor, alpha1-antitrypsin Met358 --> Arg, is decreased less than 2-fold in the presence of soluble fibrin and heparin. In contrast, thrombin is protected from inhibition by a covalent antithrombin-heparin complex, suggesting that access of heparin to exosite 2 of thrombin is hampered when ternary complex formation occurs. These results reveal the importance of exosites 1 and 2 of thrombin in assembly of the ternary complex and the subsequent protection of thrombin from inhibition by heparin-catalyzed inhibitors.  (+info)

Thrombophilia as a multigenic disease. (3/701)

BACKGROUND AND OBJECTIVE: Venous thrombosis is a common disease annually affecting 1 in 1000 individuals. The multifactorial nature of the disease is illustrated by the frequent identification of one or more predisposing genetic and/or environmental risk factors in thrombosis patients. Most of the genetic defects known today affect the function of the natural anticoagulant pathways and in particular the protein C system. This presentation focuses on the importance of the genetic factors in the pathogenesis of inherited thrombophilia with particular emphasis on those defects which affect the protein C system. INFORMATION SOURCES: Published results in articles covered by the Medline database have been integrated with our original studies in the field of thrombophilia. STATE OF THE ART AND PERSPECTIVES: The risk of venous thrombosis is increased when the hemostatic balance between pro- and anti-coagulant forces is shifted in favor of coagulation. When this is caused by an inherited defect, the resulting hypercoagulable state is a lifelong risk factor for thrombosis. Resistance to activated protein C (APC resistance) is the most common inherited hypercoagulable state found to be associated with venous thrombosis. It is caused by a single point mutation in the factor V (FV) gene, which predicts the substitution of Arg506 with a Gln. Arg506 is one of three APC-cleavage sites and the mutation results in the loss of this APC-cleavage site. The mutation is only found in Caucasians but the prevalence of the mutant FV allele (FV:Q506) varies between countries. It is found to be highly prevalent (up to 15%) in Scandinavian populations, in areas with high incidence of thrombosis. FV:Q506 is associated with a 5-10-fold increased risk of thrombosis and is found in 20-60% of Caucasian patients with thrombosis. The second most common inherited risk factor for thrombosis is a point mutation (G20210A) in the 3' untranslated region of the prothrombin gene. This mutation is present in approximately 2% of healthy individuals and in 6-7% of thrombosis patients, suggesting it to be a mild risk factor of thrombosis. Other less common genetic risk factors for thrombosis are the deficiencies of natural anticoagulant proteins such as antithrombin, protein C or protein S. Such defects are present in less than 1% of healthy individuals and together they account for 5-10% of genetic defects found in patients with venous thrombosis. Owing to the high prevalence of inherited APC resistance (FV:Q506) and of the G20210A mutation in the prothrombin gene, combinations of genetic defects are relatively common in the general population. As each genetic defect is an independent risk factor for thrombosis, individuals with multiple defects have a highly increased risk of thrombosis. As a consequence, multiple defects are often found in patients with thrombosis.  (+info)

Acceleration of Ca2+ ionophore-induced arachidonic acid liberation by thrombin without the proteolytic action toward the receptor in human platelets. (4/701)

We investigated the regulation of arachidonic acid liberation catalyzed by group-IV cytosolic phospholipase A2 (cPLA2) in human platelets upon stimulation with thrombin through interaction with protease-activated receptor-1 (PAR-1) or glycoprotein Ib. Leupeptin, a protease inhibitor, completely inhibited thrombin-induced arachidonic acid liberation and Ca2+ mobilization, with inhibition of its protease activity. However, preincubation with thrombin in the presence of leupeptin potentiated Ca2+ ionophore-induced arachidonic acid liberation. The preincubation did not affect the intracellular Ca2+ level or cPLA2 activity in response to ionomycin. Human leukocyte elastase, which cleaves glycoprotein Ib, did not inhibit the enhancement of arachidonic acid liberation by thrombin in the presence of leupeptin. However, the effect of thrombin with leupeptin was abolished by a peptide corresponding to residues 54-65 of hirudin (hirudin peptide), which impairs the binding of thrombin to PAR-1. Furthermore, Phe-Pro-Arg chloromethyl ketone (PPACK)-thrombin, which binds to platelets but has no protease activity, also enhanced Ca2+ ionophore-induced arachidonic acid liberation. In contrast, trypsin with leupeptin did not mimic the effect of thrombin with leupeptin, and furthermore trypsin-induced arachidonic acid liberation was insensitive to hirudin peptide. On the basis of the present results, we suggest that thrombin may accelerate cPLA2-catalyzed arachidonic acid liberation through non-proteolytic action toward PAR-1 but not toward glycoprotein Ib in co-operation with the proteolytic action leading to Ca2+ mobilization.  (+info)

Antithrombin activity during the period of percutaneous coronary revascularization: relation to heparin use, thrombotic complications and restenosis. (5/701)

OBJECTIVES: This study evaluated changes in antithrombin (AT) activity around the time of percutaneous transluminal coronary revascularization (PTCR) with unfractionated heparin anticoagulation and the effects these changes had on major thrombotic complications of PTCR. BACKGROUND: Heparin is used during PTCR to prevent thrombosis. However, heparin, a cofactor for AT, causes AT activity to fall. AT activity <70% is associated with thrombosis. There is a prothrombotic state after heparin discontinuation that has not been well explained. METHODS: Antithrombin activity was sampled at the start and end of PTCR and the next two mornings in 250 consecutive patients. We recorded occurrence of major thrombotic events, defined as 1) major thrombotic complications of PTCR; 2) major in-lab thrombus formation; or 3) subacute occlusion. Discriminant analysis was employed to evaluate the relationship of AT activity to these events. Change in AT activity and its relationship to heparin was evaluated. Evidence of restenosis at six months was obtained. RESULTS: There were 14 major thrombotic events. Antithrombin activity <70% was strongly (p = 0.006) associated with these events. The AT activity fell significantly through the morning after PTCR when 21% of patients had AT activity <70%; AT activity did not normalize until >20 h after heparin discontinuation. Pre-PTCR use of heparin led to lower AT activity in proportion to duration of heparin use. There was no relationship between AT activity and restenosis. CONCLUSIONS: Low AT activity may contribute to major thrombotic complications of PTCR. The way heparin is used before and after PTCR is important to development of low AT activity.  (+info)

Risk of venous thromboembolism and clinical manifestations in carriers of antithrombin, protein C, protein S deficiency, or activated protein C resistance: a multicenter collaborative family study. (6/701)

Deficiencies of antithrombin (AT), protein C (PC) or protein S (PS), and activated protein C resistance (APCR) are very well-established coagulation defects predisposing to venous thromboembolism (VTE). We performed a retrospective cohort family study to assess the risk for VTE in individuals with AT, PC, or PS deficiency, or APCR. Five hundred thirteen relatives from 9 Italian centers were selected from 233 families in which the proband had had at least 1 episode of VTE. We calculated the incidence of VTE in the whole cohort and in the subgroups after stratification by age, sex, and defect. The overall incidence of VTE (per 100 patient-years) in the group of relatives was 0.52. It was 1.07 for AT, 0.54 for PC, 0.50 for PS, 0.30 for APCR, and 0.67 in the group with a double defect. The incidence was associated with age, but not with sex. The mean age at onset was between 30 and 40 years for all the coagulation defects. Women had the peak of incidence in the age range of 21 to 40 years, earlier than men. The lifetime risk for VTE was 4.4 for AT versus APCR, 2.6 for AT versus PS, 2.2 for AT versus PC, 1.9 for PC versus APCR, and 1.6 for PS versus APCR. AT deficiency seems to have a higher risk for VTE than the other genetic defects. There is a relation between age and occurrence of thrombosis for both men and women. The latter had the peak of incidence earlier than the former.  (+info)

Structure of heparin-derived tetrasaccharide complexed to the plasma protein antithrombin derived from NOEs, J-couplings and chemical shifts. (7/701)

A complex of the synthetic tetrasaccharide AGA*IM [GlcN, 6-SO3-alpha(1-4)-GlcA-beta(1-4)-GlcN,3, 6-SO3-alpha(1-4)-IdoA-alphaOMe] and the plasma protein antithrombin has been studied by NMR spectroscopy. 1H and 13C chemical shifts, three-bond proton-proton (3JH-H) and one-bond proton-carbon coupling constants (1JC-H) as well as transferred NOEs and rotating frame Overhauser effects (ROEs) were monitored as a function of the protein : ligand molar ratio and temperature. Considerable changes were observed at both 20 : 1 and 10 : 1 ratios (AGA*IM : antithrombin) in 1H as well as 13C chemical shifts. The largest changes in 1H chemical shifts, and the linewidths, were found for proton resonances (A1, A2, A6, A6', A1*, A2*, A3*, A4*) in GlcN, 6-SO3 and GlcN,3,6-SO3 units, indicating that both glucosamine residues are strongly involved in the binding process. The changes in the linewidths in the IdoA residue were considerably smaller than those in other residues, suggesting that the IdoA unit experienced different internal dynamics during the binding process. This observation was supported by measurements of 3JH-H and 1JC-H. The magnitude of the three-bond proton-proton couplings (3JH1-H2 = 2.51 Hz and 3JH4-H5 = 2.23 Hz) indicate that in the free state an equilibrium exists between 1C4 and 2S0 conformers in the ratio of approximately 75 : 25. The chair form appears the more favourable in the presence of antithrombin, as inferred from the magnitude of the coupling constants. In addition, two-dimensional NOESY and ROESY experiments in the free ligand, as well as transferred NOESY and ROESY spectra of the complex, were measured and interpreted using full relaxation and conformational exchange matrix analysis. The theoretical NOEs were computed using the geometry of the tetrasaccharide found in a Monte Carlo conformational search, and the three-dimensional structures of AGA*IM in both free and bound forms were derived. All monitored NMR variables, 1H and 13C chemical shifts, 1JC-H couplings and transferred NOEs, indicated that the changes in conformation at the glycosidic linkage GlcN, 6-SO3-alpha(1-4)-GlcA were induced by the presence of antithrombin and suggested that the receptor selected a conformer different from that in the free state. Such changes are compatible with the two-step model [Desai, U.R., Petitou, M., Bjork, I. & Olson, S. (1998) J. Biol. Chem. 273, 7478-7487] for the interaction of heparin-derived oligosaccharides with antithrombin, but with a minor extension: in the first step a low-affinity recognition complex between ligand and receptor is formed, accompanied by a conformational change in the tetrasaccharide, possibly creating a complementary three-dimensional structure to fit the protein-binding site. During the second step, as observed in a structurally similar pentasaccharide [Skinner, R., Abrahams, J.-P., Whisstock, J.C., Lesk, A.M., Carrell, R.W. & Wardell, M.R. (1997) J. Mol. Biol. 266, 601-609; Jin, L., Abrahams, J.-P., Skinner, R., Petitou, M., Pike, R. N. & Carrell, R.W. (1997) Proc. Natl Acad. Sci. USA 94, 14683-14688], conformational changes in the binding site of the protein result in a latent conformation.  (+info)

Effect of thrombin inhibition in vascular dementia and silent cerebrovascular disease. An MR spectroscopy study. (8/701)

BACKGROUND AND PURPOSE: Silent cerebrovascular disease (CVD) has been proposed as a predisposing condition for clinically overt stroke and vascular dementia. Recently, we found increased thrombin generation in silent CVD patients. Here, we report the effect of thrombin inhibition using a potent selective thrombin inhibitor on the cerebral metabolism and function in peripheral arterial occlusive disease (PAOD) patients with or without silent CVD. METHODS: We examined 17 mild chronic PAOD patients, including 2 cases of vascular dementia. We divided the patients into 2 groups: 1 was the advanced CVD group with multiple lacunar infarction and/or advanced periventricular hyperintensity detected by brain MRI (n=12), and the other was the no CVD group that had none of these abnormalities (n=5). We assessed the cerebral biochemical compounds in the deep white matter area and cerebellar hemisphere (8 cm3) by proton MR spectroscopy before and after infusion of argatroban (10 mg/d IV) over 2 hours for 7 days. RESULTS: The ratio of N-acetylasparate (NAA) to total creatine (Cre) in the deep white matter area was significantly lower in the advanced CVD group than in the no CVD group, whereas there were no significant differences in this ratio in the cerebellar hemisphere between the 2 groups. In the former group, this decreased NAA/Cre ratio significantly increased after argatroban therapy, whereas there was no change in the latter group. The 2 patients with vascular dementia showed clinical improvement with marked increases in the NAA/Cre ratio and mini-mental score. CONCLUSIONS: These results suggest that increased thrombin generation may have some pathophysiological roles in developing vascular dementia and its chronic predisposing conditions. Thrombin inhibition may break this vicious cycle and lead to clinical improvement.  (+info)

A method for the differential determination of plasma antithrombins, antithrombin III and alpha2 macroglobulin, is described. The method is based on the selective inactivation of plasma alpha2 macroglobulin by treatment with 0-1 M methylamine for 10 minutes at 37 degrees C and on the observation that antithrombin III and alpha2 macroglobulin inhibited in defibrinated plasma low concentrations of thrombin without mutual interference and according to pseudo-first order reaction. In healthy subjects antithrombin III was shown to account for about 70% of the total antithrombin activity. But in patients with liver cirrhosis, where low levels of total antithrombin activity were observed, the relative contribution of antithrombin III was found to be noticeably lower.. ...
TY - JOUR. T1 - Issues in antithrombin therapy for UA/NSTEMI. AU - Alpert, Joseph S.. AU - Budaj, A. J.. AU - Gurfinkel, E. P.. AU - Henry, T. D.. PY - 2001/8/27. Y1 - 2001/8/27. N2 - In September 2000, participants at the 4th Annual Experts Meeting of the International Cardiology Forum convened to discuss guidelines for the management of unstable angina/non-ST-elevation MI, recently published by North American and European task forces. Discussion of new recommendations for antithrombin therapy focused on the role of low-molecular-weight heparin (LMWH). Although most participants found the new guidelines largely consistent with existing data, and sufficiently adaptable to most clinical settings, there was concern that neither task force specified LMWH as the antithrombin of choice for the medical management of these patients. The new guidelines continue to endorse the use of unfractionated heparin, particularly for high-risk patients, despite the evidence for the efficacy of LMWH in this ...
Heparin was first studied in ACS in 1988 and has been a mainstay for acute ischemic heart disease therapy since then. Heparins represent a heterogeneous group of negatively charged, heavily sulfated glycosaminoglycans. Heparins have a heterogeneous effect on the coagulation cascade, although most of the effect is mediated through binding with antithrombin, causing a conformational change leading to inactivation of multiple enzymes in the coagulation cascade. While factors IXa, XIa, and XIIa are targets as well, thrombin (factor IIa) and factor Xa are the most clinically relevant. As mentioned, thrombin inhibition leads to inhibition of fibrin formation and factors needed for its cross-linking and stabilization. Heparins also have an impact on arterial and venous thrombosis by increasing vessel wall permeability and binding to von Willebrand factor, leading to some inhibition in platelet activation. Unfractionated heparin (UFH) represents a heterogeneous compound with some important limitations: ...
Antithrombin, a plasma serpin, is relatively inactive as an inhibitor of the coagulation proteases until it binds to the heparan side chains that line the microvasculature. The binding specifically occurs to a core pentasaccharide present both in the heparans and in their therapeutic derivative heparin. The accompanying conformational change of antithrombin is revealed in a 2.9-A structure of a dimer of latent and active antithrombins, each in complex with the high-affinity pentasaccharide. Inhibitory activation results from a shift in the main sheet of the molecule from a partially six-stranded to a five-stranded form, with extrusion of the reactive center loop to give a more exposed orientation. There is a tilting and elongation of helix D with the formation of a 2-turn helix P between the C and D helices. Concomitant conformational changes at the heparin binding site explain both the initial tight binding of antithrombin to the heparans and the subsequent release of the antithrombin-protease ...
Base dose on pretreatment functional antithrombin activity and body weight. Initiate before delivery (peri-partum use) or about 24 hrs before surgery (surgical patients). If pregnant and undergoing surgery other than C-section, use peri-partum dose regimen. Give loading dose as 15 mins IV infusion, then maintenance dose by continuous IV infusion. Monitor antithrombin activity once or twice daily and adjust to maintain antithrombin activity between 80% and 120% of normal. May give another bolus dose if antithrombin activity is ,80% immediately post-procedure (use most recent antithrombin activity data to calculate dose). Thereafter, restart maintenance dose at the same rate of infusion as before the bolus. See literature.. ...
Live from AHA 2017 Dr. Datta from VERSEON Pharmaceuticals discusses a new Direct Thrombin Inhibitor in Phase 1 Clinical Development., TV Network
Conformational diseases are a newly recognized group of heterogeneous disorders resulting from the conformational instability of individual proteins. Such instability allows the formation of intermolecular linkages between b-sheets, to give protein aggregation and inclusion body formation. The serpin family of serine protease inhibitors provides the best-studied examples of the structural changes involved. Notably, mutations of a-1-antitrypsin result in its intracellular polymerization and accumulation in the liver leading eventually to cirrhosis. Here we consider how other conformational changes in another serpin, antithrombin, can cause its inactivation with consequent thrombosis. Thirteen different missense mutations in antithrombin are associated with either oligomer formation or with conversion of the active molecule into an inactive latent form. Each of these variant antithrombins is associated with an increased risk of thrombosis that typically occurs in an unexpectedly severe and sudden ...
An endogenous family of proteins belonging to the serpin superfamily that neutralizes the action of thrombin. Six naturally occurring antithrombins have been identified and are designated by Roman numerals I to VI. Of these, Antithrombin I (see FIBRIN) and ANTITHROMBIN III appear to be of major importance. . ...
In this Cochrane meta-analysis, researchers analyzed the overall efficacy and safety of direct thrombin inhibitors, compared to warfarin or LMWH, in preventing VTE after orthopedic surgeries (hip and knee arthroplasty). In14 studies involving over 20,000 participants, they found no difference in efficacy between direct thrombin inhibitors, warfarin, or LMWH, but did find higher mortality and bleeding in the thrombin group compared to LMWH (but no difference between the thrombin group and warfarin) (abstract). The timing of the thrombin inhibitors also matters, as pre-operative dosing results in fewer VTEs but likely higher bleeding. Dabigatran is the oral direct thrombin inhibitor that is currently approved in Canada and throughout Europe, but US FDA approval is pending.. ...
Direct thrombin inhibitors (DTIs) represented by dabigatran were expected to be available for therapeutic use without the need for routine monitoring, in contrast to warfarin. However, clinical concerns regarding impacts of plasma dabigatran concentrations on the rate of major bleeding have been raised.1 Clinical and basic aspects of DTIs aid in studying how best to address concerns regarding bleeding risk in therapeutic use. Based on enzymatic examinations with a synthetic substrate, S-2238, it has been well recognised that dabigatran and another DTI argatroban reversibly and competitively inhibit thrombin reaction.2 ,3 However, it still remains unclear whether the type of inhibition by DTIs of thrombin reaction with S-2238 can be applied to the anticoagulant effects.. The Clauss assay is classical but most popular even now for quantification of plasma fibrinogen concentrations.4 This is based on the quantitative relationship between fibrinogen concentrations and time for fibrin clot formation ...
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DIRECT THROMBIN INHIBITORS : USES: Direct thrombin inhibitors (DTIs) are used as anticoagulants. Argatroban, bivalirudin, desirudin, and lepirudin are used parenterally and are indicated for adjuvant anticoagulation for percutaneous cardiac interventions or as a substitution for heparin/low-molecular-weight heparins in cases of heparin-induced thrombocytopenia. Dabigatran etexilate is an oral medication approved for treatment of venous thromboembolism and stroke prophylaxis in atrial fibrillation. PHARMACOLOGY: These agents directly inhibit thrombin, leading to inhibition of clot formation and stabilization. TOXICOLOGY: The toxic effects are extensions of the pharmacologic effects and primarily include bleeding complications. EPIDEMIOLOGY: Outpatient overdose has not yet been reported. Inpatient medication errors may occur in 1% to 2% of patients receiving DTIs. The incidence of overdose is likely to increase as new DTIs are approved for in-hospital parenteral use and oral anticoagulation ...
Effect of Nonspecific Binding to Plasma Proteins on the Antithrombin Activities of Unfractionated Heparin, Low-Molecular-Weight Heparin, and Dermatan Sulfate Academic Article ...
Argatroban is a direct, selective thrombin inhibitor. The American College of Cardiologists (ACC) recommend using bivalirudin or argatroban in patients who have had, or at risk for, heparin induced thrombocytopenia (HIT) and are undergoing percutaneous coronary intervention. Argatroban is a non-heparin anticoagulant shown to both normalize platelet count in patients with HIT and prevent the formation of thrombi. Parental anticoagulants must be stopped and a baseline activated partial thromboplastin time must be obtained prior to administering argatroban.
Abstract. Inhibition of two key serine proteases in the coagulation cascade, thrombin (IIa) and factor Xa, are currently being exploited for direct, oral antit
ATryn® (also known as ATIII) is a recombinant form of human antithrombin. This product demonstrates the high potential for the use of transgenic technology in the production of biotherapeutics. Antithrombin is a plasma protein with anti-coagulative and anti-inflammatory properties that, like many other proteins currently derived from human blood supply, has been difficult to manufacture using conventional recombinant protein production methods.. ...
Two drugs that are direct inhibitors of thrombin but that do not involve antithrombin III or vitamin K in their mechanism of action have been approved to
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Abstract Thrombolysis is the current standard of care for ischemic stroke. In order to better understand its underlying mechanisms, a closer look at the basic... ...
Differentiated osteoclasts were generated and then cultured for 48 h in serum-free medium supplemented with 20 ng/ml M-CSF and 2 ng/ml RANKL. Conditioned medium was harvested, centrifuged. to remove cells and debris, and 600 μl/well was added to 24-well plates. Serum-free medium and medium containing 10% FBS, were supplemented with M-CSF and RANKL, and used as negative and positive controls, respectively. Wortmannin order Prior to the chemotaxis assay, γδ T cells were activated for 12 h with 100 U/ml rhIL-2. γδ T cells were then re-suspended in serum-free medium at 106 cells/ml and 80 μl of cell suspension was added into Transwell inserts (8 μm pore size). γδ T cells were incubated for 4 h at 37 °C to allow migration through the http://www.selleckchem.com/products/Staurosporine.html Transwell membrane. Cells that had migrated into the bottom chamber were harvested and quantified using flow cytometric analysis on an LSRII flow cytometer (BD Biosciences) by counting an equivalent volume ...
The highest DNA binding by 3-NBA in ES cells was observed at 10 μM after 24 h with 863 ± 74 adducts per 108 nucleotides (Fig. 3C). Interestingly, and in contrast to BaP, adduct levels for 3-NBA in MEFs were only 1.5-fold higher. (1266 ± 188 adduct per 108 nucleotides) under the same experimental conditions (Fig. 3D). DNA binding LDK378 in vivo was highest in MEFs at 10 μM after 48 h with 2478 ± 455 adducts per 108 nucleotides. Previously, in primary HUFs previously treated with 10 μM 3-NBA for 48 h, adduct levels were 680 ± 147 adducts per 108 nucleotides (Kucab et al., 2012). As 3-NBA is predominantly activated by NQO1 (Arlt et al., 2005), the expression of Nqo1 was studied in ES cells and MEFs by RT-PCR and revealed that Nqo1 mRNA expression increased in both cell types up to ∼60-fold; the induction was higher in MEFs than in ES cells ( Fig. 6C and D). This is in line with a previous study showing that Nqo1 protein levels were inducible in primary and immortal HUFs upon treatment with ...
The generic name of Pradaxa is Dabigatran which is an anticoagulant medication orally administered to the patient, it belongs to the class of direct thrombin inhibitor.
Chromogenic anti-IIa method for measuring homogeneously heparin in purified systems, using a kinetics/competitive method. Offers a wide measurement range from 0 to 6 IU/mL and is appropriatefor testing heparins for their antithrombin activity.
Opens the Highlight Feature Bar and highlights feature annotations from the FEATURES table of the record. The Highlight Feature Bar can be used to navigate to and highlight other features and provides links to display the highlighted region separately. Links in the FEATURES table will also highlight the corresponding region of the sequence. More... ...
The FDA requires all potential medication risks for ARGATROBAN (injection) be disclosed to consumers, no matter how rare. Here are the warnings and precautions for Argatroban.
Iam not able to watch the video.Its not buffering at all. Any one has any ideas about this? Thanks. Posted on 2009-10-21 19:13:28 by Dr. Santhosh Reddy Mannem.. ...
Background and Purpose-Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage.. ...
Background: Dabigatran etexilate is one of the few direct thrombin inhibitors with anti-coagulant activities and the following distinctive features: taken orally, no need to closely monitor for complications, and no need for regular dose adjustments. Relying on the above mentioned valuable advantages, dabigatran etexilate can be considered as a premier choice ...
Test results may vary depending on your age, gender, health history, the method used for the test, and other things. Your test results may not mean you have a problem. Ask your healthcare provider what your test results mean for you. The results for both activity and antigen tests are given as percentages. Different labs use slightly different normal ranges, but in general, 80% to 120% is considered normal for adults. Newborns usually have about half as much antithrombin as adults. Thrombin levels in infants rise to adult levels by about 6 months of age.. People with genetically inherited antithrombin deficiency typically have test results between 40% and 60%.. In both type 1 and type 2 AT deficiency, the antithrombin activity test shows a low result because you dont have as much working antithrombin as you should have. When the AT activity test shows that levels are low, the antithrombin antigen test can then be used to find out whether the deficiency is type 1 or type 2.. If the follow-up ...
Direct thrombin inhibitors (DTIs) are a class of anticoagulant drugs that can be used to prevent and treat embolisms and blood clots caused by various diseases. They inhibit thrombin, a serine protease which affects the coagulation cascade in many ways. DTIs have undergone rapid development since the 90s. With technological advances in genetic engineering the production of recombinant hirudin was made possible which opened the door to this new group of drugs. Before the use of DTIs the therapy and prophylaxis for anticoagulation had stayed the same for over 50 years with the use of heparin derivatives and warfarin which have some well known disadvantages. DTIs are still under development, but the research focus has shifted towards factor Xa inhibitors, or even dual thrombin and fXa inhibitors that have a broader mechanism of action by both inhibiting factor IIa (thrombin) and Xa. A recent review of patents and literature on thrombin inhibitors has demonstrated that the development of allosteric ...
Heparin cofactor II (HCII), a protein encoded by the SERPIND1 gene, is a coagulation factor that inhibits IIa, and is a cofactor for heparin and dermatan sulfate ("minor antithrombin"). The product encoded by this gene is a serine proteinase inhibitor which rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. The gene contains five exons and four introns. This protein shares homology with antithrombin and other members of the alpha 1-antitrypsin superfamily. Mutations in this gene are associated with heparin cofactor II deficiency. Heparin Cofactor II deficiency can lead to increased thrombin generation and a hypercoagulable state. GRCh38: Ensembl release 89: ENSG00000099937 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000022766 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: SERPIND1 serpin peptidase inhibitor, clade D (heparin cofactor), member 1". Griffith MJ, Carraway T, White GC, Dombrose FA (1983). "Serpin receptor 1: ...
We have studied the interaction of 125I-antithrombin (125I-AT) with microvascular endothelial cells (RFPEC) to localize the cellular site of anticoagulantly active heparan sulfate proteoglycans (HSPG). The radiolabeled protease inhibitor bound specifically to the above HSPG with a Kd of approximately 50 nM. Confluent monolayer RFPEC cultures exhibited a linear increase in the amount of AT bound per cell for up to 16 d, whereas suspension RFPEC cultures possessed a constant number of protease inhibitor binding sites per cell for up to 5 d. These results suggest that monolayer RFPEC cultures secrete anticoagulantly active HSPG, which then accumulate in the extracellular matrix. This hypothesis was confirmed by quantitative light and EM level autoradiography which demonstrated that the AT binding sites are predominantly located in the extracellular matrix with only small quantities of protease inhibitor complexed to the cell surface. We have also pinpointed the in vivo position of anticoagulantly ...
Test results may vary depending on your age, gender, health history, the method used for the test, and other things. Your test results may not mean you have a problem. Ask your healthcare provider what your test results mean for you. The results for both activity and antigen tests are given as percentages. Different labs use slightly different normal ranges, but in general, 80% to 120% is considered normal for adults. Newborns usually have about half as much antithrombin as adults. Thrombin levels in infants rise to adult levels by about 6 months of age. People with genetically inherited antithrombin deficiency typically have test results between 40% and 60%. In both type 1 and type 2 AT deficiency, the antithrombin activity test shows a low result because you dont have as much working antithrombin as you should have. When the AT activity test shows that levels are low, the antithrombin antigen test can then be used to find out whether the deficiency is type 1 or type 2. If the follow-up ...
Fibrin split product D-dimer (DD) is most probably involved in the development of vascular disorders. At 1.5 μM concentration DD inhibited the incorporation of D-[1-3H]glucosamine hydrochloride and [2-14C]acetate · Na into pericellular heparan sulphate (HS) of rabbit coronary endothelial cells without affecting other groups of glycosaminoglycans (GAGs). At the same time, DD reduced HS ability to bind antithrombin (AT) and suppressed NO production. The effect of DD on pericellular GAGs was similar to that of Nw-methyl-L-arginine, the competitive inhibitor of endothelial NO synthase (eNOS). L-Ascorbic acid, eNOS activator, increased the level of endogenous NO in the DD-treated cells, and restored HS accumulation and antithrombin binding. It is suggested that DD influence on endothelial HS may be mediated by NO production. Another effect of DD, namely, stimulation of plasminogen activator inhibitor-1 (PAI-1) secretion did not depend on the NO level. The decreased HS content, reduced anticoagulant ...
NPC313Hu01, AT3; ATIII; SERPINC1; Anti-Thrombin Antibodies; Serpin Peptidase Inhibitor Clade C Member 1; Coding Sequence Signal Peptide Antithrombin Part 1 | Products for research use only!
Antithrombin-III exerts antiinflammatory effects via ligation of heparan sulfate proteoglycans. Here we show in vitro that recombinant human antithrombin-III attenuates CD11b/CD18 expression of activated neutrophils and monocytes in whole blood ex vivo. As leukocyte integrin expression is triggered by extracorporeal circulation, this observation may be of relevance for pharmacological treatment during cardiopulmonary bypass ...
0038] Pharmacological agents suitable for inclusion in prosthesis materials and/or coatings, according to embodiments of the present invention include, but are not limited to, drugs and other biologically active materials, and may be intended to perform a variety of functions, including, but not limited to: anti-cancer treatment (e.g., Resan), anti-clotting or anti-platelet formation, the prevention of smooth muscle cell growth and migration on a vessel wall, and cell cycle inhibitors. Pharmacological agentsmay include antineoplastics, antimitotics, antiinflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antiproliferatives, antibiotics, antioxidants, immunosuppressives, and antiallergic substances as well as combinations thereof. Examples of such antineoplastics and/or antimitotics include paclitaxel (e.g., TAXOL® by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g., TAXOTERE® from Aventis S. A., Frankfurt, Germany) methotrexate, azathioprine, vincristine, ...
... is a protein in the blood that helps regulate blood clot formation. Antithrombin testing is used to investigate the cause of recurrent blood clot formation (such as DVT) and to identify an antithrombin deficiency.
How can this seemingly disparate evidence be integrated with what was known before? Older data, upon which the guidelines were based, had established that thrombophilia testing was predictive of the relative risk for initial VTE. The situation is completely different for patients who have already had a spontaneous VTE. Why? It has long been known that patients with spontaneous VTE are hypercoagulable, (untreated recurrence rates of 2% to 5% per year) no matter the result of thrombophilia testing. In part this is because comprehensive laboratory testing of clinically thrombophilic patients will yield negative results---no "laboratory lesion"--- in about 30%-40% of cases. The thinking is that those patients have a thrombophilic state that hasnt been discovered yet. To keep it in perspective, remember that the concept of hereditary thrombophilia has been around since the discovery, in 1963, of antithrombin deficiency (Egeberg O: Inherited antithrombin deficiency causing thrombophilia. Thrombosis ...
Heparin cofactor II (HCII) is a serine proteinase inhibitor in human plasma that rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. To understand the molecular mechanism for HCII deficiency in a patient with reduced circulating HCII antigen, we studied a Japanese .... ...
Thrombin is a serine protease that in humans is encoded by the F2 gene. Thrombin is an intriguing coagulation protease demonstrating an array of effects on endothelial cells, vascular smooth muscle cells (VSMC), monocytes, and platelets, all of which are involved in the pathophysiology of atherosclerosis. There is mounting evidence that thrombin acts as a powerful modulator of many processes like regulation of vascular tone, permeability, migration and proliferation of VSMC, recruitment of monocytes into the atherosclerotic lesions, induction of diverse pro-inflammatory markers, and all of these are related to the progression of cardiovascular disease. Recent studies in transgenic mice models indicate that the deletion of the natural thrombin inhibitor heparin cofactor II promotes an accelerated atherogenic state. The combined evidence points to thrombin as a pivotal contributor to vascular pathophysiology. Considering the clinical development of selective anticoagulants including direct ...
Abstract. We have investigated the basis of antithrombin deficiency in an asymptomatic individual (and family) with borderline levels (≈70% antigen and activit
Current recommendations and labeling regarding the use of dabigatran will not change, based on the results of a large observational cohort study comparing the risks of the direct thrombin inhibitor...
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Sodium atom in PDB 3qx5: Thrombin Inhibition By Pyridin Derivatives
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Sodium atom in PDB 3qtv: Thrombin Inhibition By Pyridin Derivatives
The plasma antithrombin stages, determined as anti-FXa action, experienced a typical distribution in the GAIT study, with a medium worth of 109.05% of the
Heparin functions as an anticoagulant primarily through activation of AT-mediated inhibition of blood coagulation factors such as thrombin and factor Xa. Several steps are involved in the interaction of heparin with AT and serine proteases. First, a low-affinity interaction between GAG and AT takes place, mediated by a well-defined unique pentasaccharide sequence within heparin (Figure 1B). This binding generates a conformational change in the structure of AT, which enables additional interactions between AT and heparin, resulting in stronger binding. The conformational change also expels a protease reactive loop in AT.54,55 A ternary complex is formed, after which the AT interaction reverts to low-affinity binding, resulting in the release of heparin from the covalent AT-protease complex.. The structure of the heparin-binding site in AT was mapped initially through the chemical modification of specific residues, resulting in decreased heparin affinity and by studying natural recombinant ...
Binds to endothelial cell surfaces and plasma proteins and its activity depends on antithrombin. Heparin binds to antithrombin, causes a conformational change in the inhibitor, exposing its active site for more rapid interaction with proteases. Heparin acts as a co factor for the antithrombin-proteases reaction Antithrombin inhibits proteases espec thrombin 2a, 9a, 10a by forming stable complexes with them and the presence of heparin accelerates this reaction 1000x. The binding of AT Ill and unfractionated heparin t degradation of both factor Xa and thrombin. Pass: Binds to AT III. ...
The first decade of the 21st century had seen the proliferation of a whole host of new anti-coagulants, which were touted as an alternative to the famous rat poison, warfarin. These new groups, some of whose names I have difficulty pronouncing, I often call the -xatans, and the - gatrans. They include dabigatran, apixaban, rivaroxaban, etc., etc. They are all either factor Xa inhibitors or direct thrombin inhibitors. They are expensive ( obviously more expensive than warfarin, which is dirt cheap ). After all these years of trials, what is their role. I suppose, their role in preventing DVT is established. Dabigatrans role in stroke prevention is also FDA approved, but I must say that my own reading tells me that the 110mg dose does carry with it an increase risk of bleebing, which is of great concern for us ...
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Anticoagulants, Risk, Bioavailability, Direct Thrombin Inhibitors, Enzymes, Factor Xa, Glycosaminoglycans, Half-life, Heparin, Hirudin, Inhibition, Injection, Lmwh, Osteoporosis, Patients, Pharmacology, Plasma, Plasma Proteins, Proteins, Subcutaneous Injection
Buy our Antithrombin III 293T transfected lysate (positive control). ab94043 has been validated in western blot. Abcam now offers a 12-month guarantee.
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This study is investigating the efficacy of bivalirudin in children and adolescents with deep vein thrombosis. The primary endpoint is thrombosis event rate
This patent search tool allows you not only to search the PCT database of about 2 million International Applications but also the worldwide patent collections. This search facility features: flexible search syntax; automatic word stemming and relevance ranking; as well as graphical results.
... is a blood thinner used to prevent blood clots and strokes. This eMedTV article offers an in-depth look at this prescription drug, including details on possible side effects, how it works, dosing tips, and what to discuss with your doctor.
1015167-40-4 - CSZFDMHIDSUHPI-KWONYSJQSA-N - Dabigatran 1-acylglucuronide - Similar structures search, synonyms, formulas, resource links, and other chemical information.
1MU6: Metabolism-directed optimization of 3-aminopyrazinone acetamide thrombin inhibitors. Development of an orally bioavailable series containing P1 and P3 pyridines.
INTENDED USE: BIOPHEN H-CoII kit is a chromogenic assay for measuring Heparin Cofactor II activity in human plasma or in purified systems, using a chromogenic method, manual or automated, based on the inhibition of a constant but in excess amount of thrombin. TEST PRINCIPLE: Heparin Cofactor II is an anticoagulant protein which inhibits specifically thrombin. This inhibition is highly enhanced by glycoaminoglycans such as Dermatan Sulfate (1). By contrast with Heparin, Dermatan Sulfate activates specifically Heparin Cofactor II (7). The BIOPHEN H-CoII assay is a chromogenic method based on the inhibition of a constant and in excess amount of thrombin, by the tested Heparin Cofactor II in presence of dermatan sulfate, and measurement of residual thrombin by its amidolytic activity on a thrombin specific chromogenic substrate (SIIa-01). pNA is then released from the substrate. The amount of pNA released is directly related to the residual thrombin activity. There is an inverse relationship
PRODUCT MONOGRAPH Pr PRADAXA Dabigatran Etexilate Capsules Capsules 75 mg, 110 mg and 150 mg Dabigatran Etexilate, (as Dabigatran Etexilate Mesilate) Anticoagulant Boehringer Ingelheim Canada Ltd. 5180
Background. This study assessed the feasibility of replacing intravenous (i.v.) dalteparin with the direct thrombin inhibitor (DTI) melagatran administered via dialysis fluid in patients undergoing haemodialysis, and also examined the pharmacokinetics of melagatran with and without dialysis.. Methods. During two 4 h haemodialysis sessions, 10 adult patients were administered i.v. dalteparin. During two subsequent sessions, melagatran was administered as an i.v. bolus before dialysis, and in the dialysis fluid. The pharmacokinetics of melagatran administered as a bolus before dialysis, and of i.v. melagatran during a dialysis-free day, were studied. Dialysis performances were evaluated from clinical criteria including clot formation in the dialyzer and bloodlines, pre-post dialyzer pressures and iohexol clearance. Anticoagulant efficacy was evaluated from dialysis success.. Results. All dialysis sessions were successful, with no apparent difference in clot formation between the two treatments. ...
Dabigatran etexilate, a prodrug of dabigatran, which reversibly inhibits the active site of thrombin, has an oral bioavailability of ≈6%.39 After oral administration, dabigatran etexilate is rapidly and completely converted to dabigatran by esterases. Plasma levels of dabigatran peak ≈2 hours after drug administration. Dabigatran has a half-life of 14 to 17 hours, which permits once- or twice-daily administration, and ≈80% of the drug is excreted unchanged by the kidneys. Dabigatran etexilate is a substrate of the P-glycoprotein (P-gp) transporter. This efflux transporter is highly expressed in the intestine and kidneys, and coadministration of potent P-gp inhibitors, such as quinidine, can increase plasma levels of dabigatran by reducing its clearance.37 Consequently, quinidine is contraindicated in patients taking dabigatran etexilate. Coadministration of dabigatran etexilate and amiodarone, a weak P-gp inhibitor, increases dabigatran levels by ≈50% without significantly affecting ...
This study investigated the pharmacikinetics and pharmacodynamics of dabigatran etexilate after switching from enoxaparin sodium to dabigatran etexilate as
Comparisons between dabigatran trough plasma levels as predicted by simulations to those observed in the study are performed to validate the dosing algorithm for Dabigatran Etexilate (DE).. (As the trial was stopped prematurely, EOT may not be 12 weeks after randomisation for most of the patients). Despite the primary endpoint only being assessed in patients who received dabigatran etexilate, Warfarin was included as a comparator treatment in this study in order to facilitate informal comparisons of outcome events, and to look for efficacy signals in this previously unexplored population. ...
Comparisons between dabigatran trough plasma levels as predicted by simulations to those observed in the study are performed to validate the dosing algorithm for Dabigatran Etexilate (DE).. (As the trial was stopped prematurely, EOT may not be 12 weeks after randomisation for most of the patients). Despite the primary endpoint only being assessed in patients who received dabigatran etexilate, Warfarin was included as a comparator treatment in this study in order to facilitate informal comparisons of outcome events, and to look for efficacy signals in this previously unexplored population. ...
[128 Pages Report] Check for Discount on Global Dabigatran Etexilate Sales Market Report 2016 report by QYResearch Group. Notes: Sales, means the sales volume of Dabigatran Etexilate Revenue,...
One of the downsides of Dabigatran are lack of a specific inhibitor. This means that if Dabigatran causes bleeding it cannot be directly reversed. A pooled analysis comparing outcomes of patients who were treated with dabigatran and bled to those of patients treated with warfarin was published in Circulation in 2013. Although patients treated with dabigatran tended to be older and to be treated with more anti-platelet agents, they trended to have better outcomes. There are ways, however, to deal with a patient bleeding from Dabigatran. These include time, plasma complex concentrates and tranexamic acid. Neutralizing antibodies are also in development. Read about reversal of direct thrombin inhibitors to learn more.. Surgery can be performed in patient who have received Dabigatran, but time should pass. After dabigatran you should wait 24-72 hours, depending on bleeding risk (low, moderate and high risk). Urgent surgery should never be delayed, even without preparation.. If tPA is needed (such as ...
A biomaterial with both antithrombin and antiplatelet properties is the ideal surface for use in extracorporeal circulation (ECC) as it targets both fibrin generation and platelet adhesion. A hemocompatible surface coating avoids the need for systemic anticoagulation by providing a local anticoagulant effect
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[03-29-2011] The U.S. Food and Drug Administration (FDA) is alerting the public to important storage and handling requirements for Pradaxa (dabigatran etexilate mesylate) capsules.
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Piperazinyl-amide derivatives of N-alpha-(3-trifluoromethyl-benzenesulfonyl)-L-arginine (1) were synthesized as graftable thrombin inhibitors. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position was evaluated in vitro, against human alpha-thrombin, and in blood coagulation assay. Molecular modelling (in silico analysis) and X-ray diffraction studies of thrombin-inhibitor complexes were also performed. The fixation of bioactive molecules on poly(butylene terephthalate) (PBT) and poly(ethylene terephthalate) (PET) membranes was performed by wet chemistry treatment and evaluated by XPS analysis. Surface grafting of inhibitor 1d improved the membrane hemocompatibility by reducing blood clot formation on the modified surface. ...
antithrombin III Glasgow: abnormal antithrombin with increased heparin affinity & reduced ability to inactivate thrombin; associated with familial thrombosis; tryptic peptides Ala(371)-Arg(393) & Ser(394)-Arg(399) present in reduced amounts; Asp(187) replaced by Lys
warfarin, Buy dream Priligy online pharmaceutical heparin, either unfractio- nated heparin (UFH) or low-molecular-weight heparin (LMWH); danaparoid (heparinoid); fondaparinux (in- direct factor Xa-inhibiting pentasaccharide); drotreco- gin О (recombinant human activated protein C APC); direct thrombin inhibitors (DTIs), including hirudin derivatives (e. Gaze-evoked nystagmus also occurs with brainstem lesions. 42в44 Both complete absorption of subretinal fluid and improvement of visual acuity have been reported after TTT. D.
TY - JOUR. T1 - Insight into the mode of action of coumarins as thrombin inhibitors. AU - Frédérick, Raphaël. AU - Charlier, Caroline. AU - De Ruyck, Jerome. AU - Dieu, Marc. AU - Robert, Séverine. AU - Masereel, Bernard. AU - Pochet, Lionel. PY - 2004. Y1 - 2004. M3 - Literature review. VL - 18. SP - 595. JO - Fundamental and Clinical Pharmacology. JF - Fundamental and Clinical Pharmacology. SN - 0767-3981. ER - ...
The Food and Drug Administration approved Pradaxa use in October 2010. Shortly after, the agency received a number of reports that the drug causes adverse side effects which are both serious and often fatal.. Pradaxa (dabigatran) is a medication designed to treat patients diagnosed with non-valvular atrial fibrillation. It is included in a class of drugs referred to as direct thrombin inhibitors that work by preventing an enzyme which causes blood to clot. When not treated, blood clots have the tendency to travel through the body to the brain and cause stroke which can in most cases lead to death. Increased concerns associated with Pradaxa use caused the FDA to issue a safety communication in December 2011, warning the public and medical community about the risk of injury and other complications associated with Pradaxa.. Reported side effects of Pradaxa include internal bleeding, caused by the drug hindering kidney function leading to an excess of the drug spreading through the system, brain ...
WASHINGTON -- The FDA said it will begin a safety review of reports of excess bleeding associated with dabigatran (Pradaxa), an oral direct thrombin inhibitor that is approved for prevention of stroke
Dabigatran - Get up-to-date information on Dabigatran side effects, uses, dosage, overdose, pregnancy, alcohol and more. Learn more about Dabigatran
Health, ...21 May 2013 Paris France: Results from a large observational study r...European and US NSTE-ACS guidelines currently recommend bivalirudin al...Researchers compared 30-day mortality with heparin alone to that with ...Oskar Angers Consultant Cardiology at Sahlgrenska University Hospital...,Registry,questions,superiority,of,bivalirudin,over,heparin,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Antithrombin III for critically ill patients Edited (no change to conclusions) answers are found in the Cochrane Abstracts powered by Unbound Medicine. Available for iPhone, iPad, Android, and Web.
Coagulation proteases, in addition to their role in the regulation of blood coagulation, can modulate intracellular signaling events by activating a subfamily o...
The Global and Chinese Argatroban Market, 2012-2022 Industry Research Report is an exhaustive study on the present market scenario of the global Argatroban
1CA8: Highly selective mechanism-based thrombin inhibitors: structures of thrombin and trypsin inhibited with rigid peptidyl aldehydes
Navarro-Fernandez, J.; Perez-Sanchez, H.; Martinez-Martinez, I.; Meliciani, I.; Guerrero, J.A.; Vicente, V.; Corral, J.; Wenzel, W ...
ORG 31706: synthetic derivative of natural pentasaccharide of heparin which contains 1 additional 3-O-sulfate moiety at the first and last glucose moiety of the natural pentasaccharide; has longer duration of action than the natural pentasaccharide; structure given in first source
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The primary role of platelets in arterial thrombotic occlusion has been documented in patients with coronary artery disease1 as well as in animal models.2 3 Besides its central role in the coagulation cascade,4 thrombin is a potent platelet agonist and thus constitutes an interesting target for drugs that would prevent the formation of fibrin- and platelet-rich thrombi induced by thrombin.. Recently, new specific thrombin inhibitors such as hirudin and hirulog, which are derived from Hirudo medicinalis,5 were shown to be promising new antithrombotics in various animal models and tested in clinical situations associated with coronary thrombosis.6 7 8 9 Their superiority over heparin has been predicated on the fact that for a similar prolongation of the activated partial thromboplastin time (aPTT), the specific thrombin inhibitors were more antithrombotic than heparin.10 11 12 13 14 15 16 Today, the aPTT has wide acceptance in clinical use and is used to monitor heparin therapy for the prevention ...
TY - JOUR. T1 - Antithrombin during extracorporeal membrane oxygenation in adults. T2 - National survey and retrospective analysis. AU - Iapichino, Giacomo E.. AU - Protti, Alessandro. AU - Andreis, Davide T.. AU - Panigada, Mauro. AU - Artoni, Andrea. AU - Novembrino, Cristina. AU - Pesenti, Antonio. AU - Gattinoni, Luciano. PY - 2019/3/1. Y1 - 2019/3/1. N2 - The impact of antithrombin replacement during extracorporeal membrane oxygenation (ECMO) in adults remains unclear. This work comprises a survey, showing that antithrombin is routinely supplemented in many Italian ECMO-Centers, and a retrospective analysis on 66 adults treated with veno-venous ECMO and unfractionated heparin at our Institution. Twenty-four to 72 h after the beginning of ECMO, antithrombin activity was ≤70% in 47/66 subjects and activated partial thromboplastin time (aPTT) ratio was ,1.5 in 20/66 subjects. Activated partial thromboplastin time ratio ,1.5 was associated not with lower antithrombin activity (61 ± 17 vs. 63 ...
The interior of the tube wall is coated with lithium heparin, ammonium heparin or sodium heparin. The anticoagulant heparin activates antithrombins, thus blocking the coagulation cascade and producing a whole blood / plasma sample instead of clotted blood plus serum. Plasma separator tubes (PST) are tubes with lithium heparin and gel contain a barrier gel in the tube. The specific gravity of this material lies between that of the blood cells and plasma. During centrifugation the gel barrier moves upwards providing a stable barrier separating the plasma from cells. Plasma may be aspirated directly from the collection tube, eliminating the need for manual transfer to another container. This barrier allows for the stability of certain parameters in the primary tube under the recommended storage conditions for up to 48 hours. Check the heparin additive before use. Do not use heparin plasma tubes for TDM measurements, lithium heparin for lithium determinations, sodium heparin for sodium ...
Novel conjugates of glycosaminoglycans, particularly heparin and dermatan sulfate, and amine containing species and therapeutic uses thereof are described. In particular, mild methods of conjugating heparins to proteins, such as antithrombin III and heparin cofactor II, which provide covalent conjugates which retain maximal biological activity are described. Uses of these conjugates to prevent thrombogenesis, in particular in lung airways, such as found in infant and adult respiratory distress syndrome are also described.
Coronary artery often reoccludes after therapy of acute myocardial infarction with recombinant tissue plasminogen activator rt-PA, most likely due to in situ thrombin generation during thrombolysis. Previous studies with high molecular weight thrombin inhibitors, such as hirudin, have shown variable improvement in the frequency of sustained thrombolysis. This study was conducted to examine the modulation of thrombolysis, indices of thrombin generation and activated partial thromboplastin time (APTT) by a novel low molecular weight direct thrombin inhibitor, inogatran. A stable occlusive intracoronary thrombus was created in 19 dogs. Nine dogs were given an intravenous bolus of saline (group A), and 5 dogs were given inogatran (group B) followed by rapid infusion of rt-PA (1 mg/kg over 20 min), whereas saline or inogatran was continuously infused for 2 hr. Five other dogs were given inogatran (bolus and continuous infusion) only after thrombolysis by rt-PA was obtained (group C). Time to reflow ...
Study information from Be Involved at CepEsperu Baptist Medical Center for: Study of the Safety and Efficacy of oral Dabigatran Etexilate for the prevention of recurring Venous Thromboembolism
Boehringer Ingelheim Pharmaceuticals, Inc. Release: Pradaxa(R) (dabigatran etexilate mesylate) U.S. Label Now Affirms Superior Reduction in Ischemic and Hemorrhagic Stroke Versus Warfarin in Patients with Non-Valvular Atrial Fibrillation - read this article along with other careers information, tips and advice on BioSpace
The optimal antithrombotic therapy for preventing ischemic complications while limiting bleeding risk in patients with acute coronary syndrome (ACS) who are undergoing primary percutaneous coronary intervention (pPCI) remains an area of great controversy (1). The quest for an ideal parenteral anticoagulant agent able to replace unfractionated heparin (UFH) has remained an ongoing topic for investigation since the 1990s. Bivalirudin was compared with UFH first in experimental models and then in patients with coronary artery disease (CAD). During this long-lasting journey, contrasting evidence has been accumulated on bivalirudin efficacy and safety profile compared with UFH. After initial promising findings in the early 1990s, HAS/BAS (Hirulog/Bivalirudin Angioplasty Study) published in 1995 (conducted in 1993 to 1994) showed that bivalirudin (bolus of 1.0 mg/kg followed by infusion of 2.5 mg/kg/h for 4 h, then 0.2 mg/kg/h for 14 to 20 h) had similar efficacy but lower bleeding risk than high and ...
A superiority for the anti-clotting drug bivalirudin for treating patients with acute coronary syndromes was detected when this was used as monotherapy, but not when this direct thrombin inhibitor was combined with glycoprotein IIb/IIIa inhibition. Thus found the ACUITY trial reported to the ACCs Atlanta meeting by Gregg Stone of Columbia University. He told Audio Medica the bottom line finding from the study ...
This study demonstrates that UA/NSTEMI patients who would have been excluded from the randomized enoxaparin trials can be safely treated with a weight-adjusted regimen of subcutaneous enoxaparin, as long as particular attention is paid to age and renal function to further adjust the dosing regimen. The EP population represents a high-risk group of patients who had a fourfold increase in death or MI at 30 days. Hypertension and the use of GP IIb/IIIa inhibitors were the only predictors of bleeding found in our study population.. There is strong evidence that antithrombin therapy is beneficial in UA/NSTEMI patients and that subcutaneous enoxaparin is superior to UH in this setting (1-3). However, this demonstration has been obtained in selected populations, and it is not known whether these results can be applied to all comers who present with UA/NSTEMI, including those who would have been excluded from these randomized trials. Furthermore, the safety of enoxaparin in a population at a high risk ...
Anticoagulants are mainly categorized as herapins, warfarin, low molecular weight heparins (LMWHs), factor Xa inhibitors, and direct thrombin inhibitors (D
Antithrombin-III. *Lipoprotein lipase. *Apolipoproteins. *Growth factors. *Chemokines. The enzymes and proteins listed above ...
primary: Antithrombin III deficiency. *Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden ... Levels of protein C, free and total protein S, factor VIII, antithrombin, plasminogen, tissue plasminogen activator (TPA) and ... in these situations is generally best performed using a chromogenic assay based on the inhibition of factor Xa by antithrombin ...
prothrombin (kringle domain-2), antithrombin III fragment. inhibit cell proliferation of endothelial cells. ...
primary: Antithrombin III deficiency. *Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden ...
Antithrombin III deficiency. altered coagulation. [14] Falls and hip fracture. related to immobility. [17] ...
... it has been found to significantly decrease levels of the anticoagulatory antithrombin III, which may indicate a potential risk ...
primary: Antithrombin III deficiency. *Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden ...
Decrease antithrombin III. *Increase platelet adhesiveness. *Lipid *Increase HDL, triglyceride. *Decrease LDL, fat deposition ...
primary: Antithrombin III deficiency. *Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden ...
primary: Antithrombin III deficiency. *Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden ...
"The anticoagulant activation of antithrombin by heparin". Proceedings of the National Academy of Sciences of the United States ...
Thromboembolic disorders: particularly those caused by a decrease in blood antithrombin III levels due to leakage. Antithrombin ... Treatment is with oral anticoagulants (not heparin as heparin acts via anti-thrombin 3 which is lost in the proteinuria so it ... is a greater predisposition for the formation of blood clots that is caused by a decrease in the levels of antithrombin III in ... antithrombin or the immunoglobulins to pass through the cell membrane and appear in urine.[16] ...
Antithrombin protein therapeuticsEdit. The antithrombin protein itself is used as a protein therapeutic that can be purified ... It works by activating antithrombin III, which blocks thrombin from clotting blood. Heparin can be used in vivo (by injection ... Antithrombin is approved by the FDA as an anticoagulant for the prevention of clots before, during, or after surgery or ... "Antithrombin (Recombinant) US Package Insert ATryn for Injection February 3, 2009" (PDF).. ...
Some in the late stage also showed increased antithrombin.[24] This form of smallpox occurred in anywhere from 3 to 25 percent ... and an increase in circulating antithrombin. Patients in the late stage had significant thrombocytopenia, and deficiency of ...
"European Regulators Curdle Plans for Goat Milk Human Antithrombin". Retrieved 2006-06-23.. ...
... antithrombin (AT) to inactivate several coagulation factors IIa, Xa, XIa and XIIa. The affinity of unfractionated heparin and ...
In human adults, the normal blood level of antithrombin activity has been measured to be around 1.1 units/mL. Newborn levels of ... Heparin increases the affinity of antithrombin to thrombin (as well as factor Xa). The direct thrombin inhibitors, a newer ... Thrombin is also inactivated by antithrombin, a serine protease inhibitor. The molecular weight of prothrombin is approximately ...
antithrombin III. Inhibits IIa, Xa, and other proteases. Antithrombin III deficiency. heparin cofactor II. Inhibits IIa, ... AntithrombinEdit. Antithrombin is a serine protease inhibitor (serpin) that degrades the serine proteases: thrombin, FIXa, FXa ... whereas heparin and related compounds increase the action of antithrombin on thrombin and factor Xa. A newer class of drugs, ... Quantitative or qualitative deficiency of antithrombin (inborn or acquired, e.g., in proteinuria) leads to thrombophilia. ...
"The nontoxic mushroom Auricularia auricula contains a polysaccharide with anticoagulant activity mediated by antithrombin". ...
REG1(英语:REG1) · 去纤苷(英语:Defibrotide) · 雷马曲班(英语:Ramatroban) · 抗凝血酶(英语:Antithrombin) · 蛋白质C(英语:Protein C)(Drotrecogin alfa(英语: ... bind 抗凝血酶(英语:Antithrombin)). 低分子量肝素(贝米肝素(英语:Bemiparin sodium)、舍托肝素(英语:Certoparin sodium)、达肝素(英语:Dalteparin sodium)、依诺肝素、那屈肝素(英语 ... 肝素經由它的硫化五糖序列與酵素抑制劑抗凝血酶(英语
PITX3 Antithrombin III deficiency; 613118; AT3 Antley-Bixler syndrome; 207410; FGFR2 Antley-Bixler syndrome-like with ... antithrombin\' Pittsburgh; 613490; SERPINA1 Hemosiderosis, systemic, due to aceruloplasminemia; 604290; CP Hennekam ...
"Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism of antithrombin activation". The EMBO Journal. ... In the dimer (of antithrombin), the RCL and part of the A-sheet incorporates into the A-sheet of another serpin molecule. The ... Similarly, antithrombin can also spontaneously convert to the latent state, as an additional modulation mechanism to its ... For example, after injury to the blood vessel wall, heparin is exposed, and antithrombin is activated to control the clotting ...
... is inhibited by antithrombin. Factor IX expression increases with age in humans and mice. In mouse models mutations ...
... antithrombin-III, alpha-antitrypsin, and ovalbumin; epidermal growth factor and the light chain of coagulation factor X; and ...
primary: Antithrombin III deficiency. *Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden ...
U. Hedner, I.M. Nilsson, Antithrombin III in clinical material. Thrombos. Res. 3:631-641 (1973).CrossRefGoogle Scholar ... J.R. OBrien, Antithrombin III and heparin clotting times in thrombosis and atherosclerosis. Thromb. Piathes. Haemorrh. 32:116- ... O.R. Odegard, M.K. Fagerhol, M. Lie, Heparin cofactor activity and antithrombin III concentration in plasma related to age and ... R.H. Yue, M.M. Gertler, T. Staar, R. Koutrouby, Alteration of plasma antithrombin III levels in ischemic heart disease. ...
The results indicate that antithrombin III-heparin cofactor activity is significantly lower... ... The antithrombin III-heparin cofactor activity of 65 baboons and 130 healthy human subjects was measured. ... Antithrombin III deficiency in a Dutch family.J. Clin. Path., 26: 532-538.PubMedGoogle Scholar ... Assay of progressive antithrombin in plasma.Thromb. Diath. Haemorrh., 24: 224-229.PubMedGoogle Scholar ...
... ,ARUP Laboratories is a national reference laboratory and a worldwide leader in innovative laboratory ... Antithrombin, Antigen. 2. Antithrombin, Enzymatic (Activity). 3. Farnsworth Panel D15 test evaluation. 4. B-VAT® Flat Panel ...
Congenital antithrombin III deficiency is a genetic disorder that causes the blood to clot more than normal. ... The abnormal gene leads to a low level of the antithrombin III protein. This low level of antithrombin III can cause abnormal ... Antithrombin III is a protein in the blood that blocks abnormal blood clots from forming. It helps the body keep a healthy ... Congenital antithrombin III deficiency is an inherited disease. It occurs when a person receives one abnormal copy of the ...
LSBio Antithrombin-III Elisa Kits [LifeSpan BioSciences, Inc.] LSBio Antithrombin-III Elisa Kits. LifeSpan BioSciences, Inc. ... LSBio Antithrombin-III Proteins [LifeSpan BioSciences, Inc.] LSBio Antithrombin-III Proteins. LifeSpan BioSciences, Inc. ... LSBio Antithrombin-III Antibodies [LifeSpan BioSciences, Inc.] LSBio Antithrombin-III Antibodies. LifeSpan BioSciences, Inc. ... antithrombin-III precursor [Bos taurus] antithrombin-III precursor [Bos taurus]. gi,77736341,ref,NP_001029870.1, ...
Antithrombin III (AT III) is a protein that helps control blood clotting. A blood test can determine the amount of AT III ... Antithrombin; AT III; AT 3; Functional antithrombin III; Clotting disorder - AT III; DVT - AT III; Deep vein thrombosis - AT ... Antithrombin III (AT III) is a protein that helps control blood clotting. A blood test can determine the amount of AT III ... Antithrombin III (AT-III) test - diagnostic. In: Chernecky CC, Berger BJ, eds. Laboratory Tests and Diagnostic Procedures. 6th ...
Species: Antithrombin-III (IPR015555). Key Species. Key species. Number of proteins. FASTA. Protein IDs. ...
Antithrombin is also termed Antithrombin III (AT III). The designations Antithrombin I through to Antithrombin IV originate in ... Native antithrombin can be converted to latent antithrombin (L-antithrombin) by heating alone or heating in the presence of ... Type I antithrombin deficiency is characterised by a decrease in both antithrombin activity and antithrombin concentration in ... Type II antithrombin deficiency is characterised by normal antithrombin levels but reduced antithrombin activity in the blood ...
antithrombin synonyms, antithrombin pronunciation, antithrombin translation, English dictionary definition of antithrombin. n ... Related to antithrombin: heparin, Antithrombin deficiency. antithrombin. (ˌæntɪˈθrɒmbɪn) n. biochem a substance that ... Antithrombin - definition of antithrombin by The Free Dictionary https://www.thefreedictionary.com/antithrombin ... They express antithrombin resistance conferring a major susceptibility to thrombosis ([4,5]).. The c.1787G>T and c.1787G>A ...
Advice and warnings for the use of Antithrombin (recombinant) (ATryn) during pregnancy. FDA Pregnancy Category C - Risk cannot ... Antithrombin (recombinant) Breastfeeding Warnings. There are no data on the excretion of antithrombin recombinant into human ... Antithrombin (recombinant) Pregnancy and Breastfeeding Warnings. Antithrombin (recombinant) is also known as: ATryn ... Antithrombin recombinant has been assigned to pregnancy category C by the FDA. Animal studies have failed to reveal evidence of ...
Thrombate III (Antithrombin III [Human]) is a form of protein found in the blood used to treat patients with hereditary ... Our Thrombate III (Antithrombin III [Human]) Side Effects Drug Center provides a comprehensive view of available drug ... Dosage should be determined on an individual basis based on the pre-therapy plasma antithrombin III (AT-III) level, in order to ... antithrombin III deficiency in connection with surgical or obstetrical procedures or when they suffer from thromboembolism. ...
Antithrombin III activity is markedly potentiated by heparin, the principle mechanism by which both heparin and low molecular ... Antithrombin III (ATIII) is a nonvitamin K-dependent protease that inhibits coagulation by lysing thrombin and factor Xa. ... encoded search term (Antithrombin III Deficiency) and Antithrombin III Deficiency What to Read Next on Medscape. Related ... Laboratory studies that can be performed in the workup for antithrombin III deficiency include the following:. * Antithrombin ...
Antithrombin III deficiency (abbreviated ATIII deficiency) is a deficiency of antithrombin III. It is a rare hereditary ... Information on antithrombin from UIUC Non-profit advocacy group for patients and families with antithrombin deficiency. ... ATIII binds to thrombin and then forms the thrombin-anti thrombin complex or TAT complex. This is a major natural pathway of ... Antithrombin Editor: Robert J Kurman, Blausteins Pathology of the Female Genital Tract, Fifth Edition, 2002, Ch. 23, Diseases ...
... antithrombin III), which can be distinguished from autoimmune anti-thrombin. Anti-thrombin antibodies can react with both types ... Autoimmune anti-thrombin was also found to inhibit the binding of antithrombin III to thrombin. Such activities are more often ... Inhibitory anti-thrombin antibodies can be divided into 2 groups, those that inhibit coagulation activity and those the inhibit ... Anti-thrombin antibodies are autoantibodies directed against thrombin that may constitute a fraction of lupus anticoagulant and ...
Thrombin-antithrombin complex (TAT) is a protein complex of thrombin and antithrombin. Lippi G, Cervellin G, Franchini M, ...
Anti-thrombin aptamers are G-quadruplex-bearing oligonucleotides, which recognizes the exosites of human thrombin. The first ... anti-thrombin aptamer, TBA, was generated through via SELEX (Systematic Evolution of Ligands by Exponential Enrichment) ...
No sex-related difference is noted in terms of the prevalence of congenital antithrombin III deficiency. Women of childbearing ... Antithrombin-a for the prophylaxis of venous thrombosis in congenital antithrombin deficiency. Expert Rev Hematol. 2009 Oct. 2( ... Role of antithrombin concentrate in treatment of hereditary antithrombin deficiency. An update. Thromb Haemost. 2009 May. 101(5 ... Deficiency Of Antithrombin III (AT III) - Case Report and Review of the Literature. Curr Health Sci J. 2014 Apr-Jun. 40 (2):141 ...
... antithrombin I pronunciation, antithrombin I translation, English dictionary definition of antithrombin I. n biochem a ... Related to antithrombin I: antithrombin test, Antithrombin deficiency. antithrombin. (ˌæntɪˈθrɒmbɪn) n. biochem a substance ... Antithrombin is an important protein in the regulation of hemostasis.. Antithrombin Levels Are Unaffected by Warfarin Use ... antithrombin. (redirected from antithrombin I). Also found in: Medical, Encyclopedia. ...
... antithrombin), member 1 Antithrombin dimer drawn from PDB 1E03. Available structures: 1ant, 1ath, 1azx, 1br8, ... Antithrombin is officially termed antithrombin III (AT III) and it is a member of a larger family of antithrombins, numbered ... For more details on this topic, see Antithrombin III deficiency.. Evidence for the important role antithrombin plays in ... Antithrombin has a half life in blood plasma of around 3 days.[2] The normal antithrombin concentration in human blood plasma ...
... when antithrombin tests are requested, and what the results of an antithrombin (III) test might mean ... Antithrombin testing measures the function and quantity of antithrombin. Antithrombin is a protein produced by the liver to ... If the antithrombin activity is low, then the antithrombin antigen test is performed to determine the quantity of antithrombin ... Antithrombin antigen, which measures the quantity of antithrombin present. 2. Acquired antithrombin deficiencies may occur at ...
Antithrombin III. Definition. Antithrombin III (AT III) is a protein that helps control blood clotting. A blood test can ... Antithrombin; AT III; AT 3; Functional antithrombin III; Clotting disorder - AT III; DVT - AT III; Deep vein thrombosis - AT ... Antithrombin III (AT-III) test - diagnostic. In: Chernecky CC, Berger BJ, eds. Laboratory Tests and Diagnostic Procedures. 6th ...
The Conformational Activation of Antithrombin. A 2. 85-A Structure of a Fluorescein Derivative Reveals an Electrostatic Link ... Antithrombin; Chain I, domain 2 Antithrombin, subunit I, domain 2 L1. 1dzgL01. Mainly Beta Roll Alpha-1-antitrypsin; domain 1 ... Antithrombin Human (Homo sapiens) [TaxId: 9606] L. d1dzgl_. Multi-domain proteins (alpha and beta) Serpins Serpins Serpins ...
Anti-Thrombin antibody (ab83981). *Datasheet. *SDS. Abreviews (3). Q&A (4)Specific References (1) ...
Anti-Thrombin Receptor antibody (ab111976) at 0.5 µg/ml + HeLa lysate (in RIPA buffer) at 35 µg. Developed using the ECL ...
Immunocytochemistry/ Immunofluorescence - Anti-Thrombin antibody [BDI905] (ab20877). ICC/IF image of ab20877 stained MCF7 cells ...
  • Hypersensitivity to any ingredient in antithrombin (recombinant), or to goat or goat milk proteins. (medindia.net)
  • Antithrombin is a plasma protein with anti-coagulative and anti-inflammatory properties that, like many other proteins currently derived from human blood supply, has been difficult to manufacture using conventional recombinant protein production methods. (xvivo.net)
  • Antithrombin replaces proteins to stop and treat blood clots. (loveysmarket.com)
  • Hypercoagulability states as a pre-existing condition in pregnancy include both acquired ones, such as antiphospholipid antibodies, and congenital ones, including factor V Leiden, prothrombin mutation, proteins C and S deficiencies, and antithrombin III deficiency. (wikipedia.org)
  • Genetic factors that increase the risk of VTE include deficiencies of three proteins that normally prevent blood from clotting-protein C, protein S, and antithrombin-in addition to non-O blood type and mutations in the factor V and prothrombin genes. (wikipedia.org)
  • During sepsis, signalling by the inflammatory cytokines, interleukin-1 and tumour necrosis factor, mediate altered protein transcription in the systemic inflammatory response, resulting in decreased synthesis of the regulatory proteins antithrombin, protein C and protein S, with increased synthesis of prothrombotic proteins Factor VIII, von Willebrand factor, and fibrinogen. (wikipedia.org)
  • Between 1913 and 1915, he worked in the William Henry Howell's lab at the Johns Hopkins Medical School in Baltimore, MD., studying blood thinning proteins, such as antithrombin. (wikipedia.org)
  • These enzymes and proteins include: Endothelial nitric oxide synthase (Endothelial NOS) Extracellular superoxide dismutase (SOD3) Angiotensin converting enzyme Antithrombin-III Lipoprotein lipase Apolipoproteins Growth factors Chemokines The enzymes and proteins listed above serve to reinforce the glycocalyx barrier against vascular and other diseases. (wikipedia.org)
  • These core proteins carry three to five heparan sulfate and chondroitin sulfate chains, which allow for interaction with a large variety of ligands including fibroblast growth factors, vascular endothelial growth factor, transforming growth factor-beta, fibronectin and antithrombin-1. (wikipedia.org)
  • Our Thrombate III (Antithrombin III [Human]) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication. (rxlist.com)
  • The density of yellow coloration is directly proportional to the amount of antithrombin III captured in plate. (abcam.com)
  • GTC states that one genetically modified goat can produce the same amount of antithrombin in a year as 90,000 blood donations. (wikipedia.org)
  • Protease inactivation results as a consequence of trapping the protease in an equimolar complex with antithrombin in which the active site of the protease enzyme is inaccessible to its usual substrate. (wikipedia.org)
  • The formation of an antithrombin-protease complex involves an interaction between the protease and a specific reactive peptide bond within antithrombin. (wikipedia.org)
  • In particular, the observed hydrogen bonding of these residues to the body of the molecule in the latent form explains the mechanism for the release of newly formed antithrombin-protease complexes into the circulation for catabolic removal. (rcsb.org)
  • The endothelium normally provides a non-thrombogenic surface because it contains, for example, heparan sulfate which acts as a cofactor for activating antithrombin, a protease that inactivates several factors in the coagulation cascade. (wikipedia.org)