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.
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.
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.

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)

Antithrombins are substances that prevent the formation or promote the dissolution of blood clots (thrombi). They include:

1. Anticoagulants: These are medications that reduce the ability of the blood to clot. Examples include heparin, warfarin, and direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, and dabigatran.
2. Thrombolytic agents: These are medications that break down existing blood clots. Examples include alteplase, reteplase, and tenecteplase.
3. Fibrinolytics: These are a type of thrombolytic agent that specifically target fibrin, a protein involved in the formation of blood clots.
4. Natural anticoagulants: These are substances produced by the body to regulate blood clotting. Examples include antithrombin III, protein C, and protein S.

Antithrombins are used in the prevention and treatment of various thromboembolic disorders, such as deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, and myocardial infarction (heart attack). It is important to note that while antithrombins can help prevent or dissolve blood clots, they also increase the risk of bleeding, so their use must be carefully monitored.

Antithrombin proteins are a type of protein found in the blood that inhibit the formation of blood clots. They work by binding to and neutralizing thrombin and other coagulation factors, such as factor Xa, that are involved in the coagulation cascade. Antithrombin proteins are an important part of the body's natural anticoagulant system, which helps to prevent excessive clotting and maintain proper blood flow.

Antithrombin proteins can be increased through the use of medications such as heparin, which binds to and enhances the activity of antithrombin. This is why heparin is often used as a treatment for conditions associated with abnormal blood clotting, such as deep vein thrombosis or pulmonary embolism.

It's worth noting that while antithrombin proteins are important for preventing excessive clotting, having too few of these proteins can also be a problem, as it can increase the risk of abnormal bleeding.

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

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

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

... 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 characterized by a decrease in both antithrombin activity and antithrombin concentration in ... Type II antithrombin deficiency is characterized by normal antithrombin levels but reduced antithrombin activity in the blood ...
Antithrombin Găman AM, Găman GD (2014). "Deficiency Of Antithrombin III (AT III) - Case Report and Review of the Literature". ... Antithrombin III deficiency (abbreviated ATIII deficiency) is a deficiency of antithrombin III. This deficiency may be ... The prevalence of antithrombin deficiency is estimated at ~0.02 to 0.2% of the general population, and 1-5% of patients with ... Testing for antithrombin activity can confirm deficiency if the levels are less than 70%. Deficiency can result from genetic ...
... 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 ...
... (TAT) is a protein complex of thrombin and antithrombin. It is a marker of net activation of ... Since thrombin is rapidly bound by antithrombin, TAT is a useful measure for thrombin level in the blood. Thrombin can pass the ... "Analysis of thrombin-antithrombin complex contents in plasma and hematoma fluid of hypertensive intracerebral hemorrhage ...
... 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) ...
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 ...
An extremely rare form of Pi, termed PiPittsburgh, functions as an antithrombin (a related serpin), due to a mutation ( ... Owen MC, Brennan SO, Lewis JH, Carrell RW (September 1983). "Mutation of antitrypsin to antithrombin. alpha 1-antitrypsin ...
Antithrombin deficiency is present in 0.2% of the general population and 0.5-7.5% of people with venous thrombosis. Protein C ... Even small perturbances of proteins, such as the reduction of antithrombin to only 70-80% of the normal level, can increase the ... The process is inhibited by TFPI (which inactivates the first step catalyzed by factor VIIa/tissue factor), antithrombin (which ... The first major form of thrombophilia to be identified by medical science, antithrombin deficiency, was identified in 1965, ...
Austin RC, Rachubinski RA, Ofosu FA, Blajchman MA (May 1991). "Antithrombin-III-Hamilton, Ala 382 to Thr: an antithrombin-III ... "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 ...
... 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 ...
O-sulfation of the antithrombin-binding region". J. Biol. Chem. 263 (30): 15474-84. PMID 3139669. Shworak NW, Fritze LM, Liu J ...
Jin L, Abrahams JP, Skinner R, Petitou M, Pike RN, Carrell RW (1997). "The anticoagulant activation of antithrombin by heparin ...
... particularly those caused by a decrease in blood antithrombin III levels due to leakage. Antithrombin III counteracts the ... Treatment is with oral anticoagulants (not heparin as heparin acts via anti-thrombin 3 which is lost in the proteinuria so it ... antithrombin or the immunoglobulins to pass through the cell membrane and appear in urine. Albumin is the main protein in the ... is a greater predisposition for the formation of blood clots that are caused by a decrease in the levels of antithrombin III in ...
Some examples of heparin binding proteins include antithrombin III. It is thought that much protein interaction with heparin is ...
GTC states that one genetically modified goat can produce the same amount of antithrombin in a year as 90,000 blood donations. ... Microinjection was used to insert human antithrombin genes into the cell nucleus of their embryos. ATryn is the first medicine ... ATryn is the brand name of the anticoagulant antithrombin manufactured by the Massachusetts-based U.S. company rEVO Biologics ( ... Jones, Phillip B. C. (April 2006). "European Regulators Curdle Plans for Goat Milk Human Antithrombin". Archived from the ...
"European Regulators Curdle Plans for Goat Milk Human Antithrombin" (PDF). Retrieved 2006-06-23. "Go-ahead for 'pharmed' goat ...
Unlike thrombin, reptilase is resistant to inhibition by antithrombin III. Thus, the reptilase time is not prolonged in blood ...
Examples include albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, transcortin. The decrease of such ...
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 ...
... binds antithrombin and accelerates its inhibition of factor Xa. Apart from the O-methyl group at the reducing end ... Unlike direct factor Xa inhibitors, it mediates its effects indirectly through antithrombin III, but unlike heparin, it is ... Binding of heparin or HS to AT has been shown to increase the anti-coagulant activity of antithrombin 1000 fold. In contrast to ... sulfate this monomeric sequence is thought to form the high-affinity binding site for the anti-coagulant factor antithrombin ( ...
This activity, sometimes referred to as antithrombin I, limits clotting. Fibrin also mediates blood platelet and endothelial ...
The principal inhibitor of thrombin in normal blood circulation is antithrombin. Similar to antithrombin, the anticoagulant ... Unlike antithrombin, hirudin binds to and inhibits only the activated thrombin, with a specific activity on fibrinogen. ...
In contrast, batroxobin isn't inhibited by antithrombin and heparin cofactor II. Batroxobin also has a high Kd value for ... There are also clotting inhibitors like antithrombin and heparin cofactor II, which prevent clotting when it isn't necessary. ...
Antithrombin: the levels of antithrombin increase with age. Antithrombin levels in newborns are less than 50% of the levels in ... Antithrombin is an anticoagulant protein and is important in preventing blood clotting. In animal studies, Antithrombin in ... There is an increase in the concentration of a specific isoform of Antithrombin, Latent Antithrombin with age. This form of ... There is also an increased activity of another form of Antithrombin, Beta Antithrombin in newborns compared to older children ...
Chuang YJ, Swanson R, Raja SM, Olson ST (May 2001). "Heparin enhances the specificity of antithrombin for thrombin and factor ... Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the ... Heparin binds to the enzyme inhibitor antithrombin III (AT), causing a conformational change that results in its activation ... It also rapidly binds to endothelial cells, which precludes the binding to antithrombin that results in anticoagulant action. ...
The antithrombin protein itself is used as a protein therapeutic that can be purified from human plasma or produced ... Fondaparinux is a synthetic sugar composed of the five sugars (pentasaccharide) in heparin that bind to antithrombin. It is a ... "Antithrombin (Recombinant) US Package Insert ATryn for Injection February 3, 2009" (PDF). Food and Drug Administration. ... UFH binds to the enzyme inhibitor antithrombin III (AT), causing a conformational change that results in its activation. The ...
However, the other major anticoagulants, protein C and antithrombin III, remain constant. Fibrinolysis is impaired by an ... and antithrombin III deficiency. Hypercoagulability in pregnancy, particularly due to inheritable thrombophilia, can lead to ...
Castro MA, Goodwin TM, Shaw KJ, Ouzounian JG, McGehee WG (1996). "Disseminated intravascular coagulation and antithrombin III ...
After the antithrombin III binds to Factor Xa, the Fondaparinux is released and can activate another antithrombin. Another drug ... "Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of ... Fondaparinux binds to antithrombin III and activates the molecule for Factor Xa inhibition. In fact, Fondaparinux imparts an ... Idraparinux also binds antithrombin III, however with a 30-fold increase in affinity as compared to Fondaparinux. Idraparinux ...
  • Hereditary antithrombin deficiency is a disorder of blood clotting. (medlineplus.gov)
  • In hereditary antithrombin deficiency, abnormal blood clots usually form only in veins, although they may rarely occur in arteries. (medlineplus.gov)
  • About half of people with hereditary antithrombin deficiency will develop at least one abnormal blood clot during their lifetime. (medlineplus.gov)
  • Other factors can increase the risk of abnormal blood clots in people with hereditary antithrombin deficiency. (medlineplus.gov)
  • The combination of hereditary antithrombin deficiency and other inherited disorders of blood clotting can also influence risk. (medlineplus.gov)
  • Women with hereditary antithrombin deficiency are at increased risk of developing an abnormal blood clot during pregnancy or soon after delivery. (medlineplus.gov)
  • Hereditary antithrombin deficiency is estimated to occur in about 1 in 2,000 to 3,000 individuals. (medlineplus.gov)
  • Of people who have experienced an abnormal blood clot, about 1 in 20 to 200 have hereditary antithrombin deficiency. (medlineplus.gov)
  • Hereditary antithrombin deficiency is caused by mutations in the SERPINC1 gene. (medlineplus.gov)
  • Most of the mutations that cause hereditary antithrombin deficiency change single protein building blocks (amino acids) in antithrombin, which disrupts its ability to control blood clotting. (medlineplus.gov)
  • Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis and treatment options. (medlineplus.gov)
  • Patnaik MM, Moll S. Inherited antithrombin deficiency: a review. (medlineplus.gov)
  • Congenital antithrombin III deficiency is a genetic disorder that causes the blood to clot more than normal. (medlineplus.gov)
  • Congenital antithrombin III deficiency is an inherited disease. (medlineplus.gov)
  • Once a person is diagnosed with antithrombin III deficiency, all close family members should be screened for this disorder. (medlineplus.gov)
  • In 1965, Olav Egeberg described the first family with thrombotic disease due to inherited antithrombin deficiency, providing convincing evidence of the clinical importance of antithrombin. (medscape.com)
  • The molecule, a recombinant Antithrombin, has been manufactured by rEVO Biologics and has been useful in treating patients suffering from hereditary antithrombin (AT) deficiency undergoing surgery or giving birth. (openpr.com)
  • Moreover, patients undergoing heparin therapy and chemotherapy may also suffer from antithrombin deficiency. (openpr.com)
  • Transient inherited antithrombin deficiency: a real phenomenon? (whiterose.ac.uk)
  • Using DNA probes in a structural study of the antithrombin III gene locus we found no evidence of gene deletion in two British kindreds with inherited antithrombin III deficiency. (bmj.com)
  • However, linkage analysis between a common DNA polymorphism and the antithrombin III deficiency trait showed that the defect lies at or close to the antithrombin III structural gene. (bmj.com)
  • These results are consistent with previously published data suggesting that mutation of the antithrombin III structural gene is the cause of inherited antithrombin III deficiency in some families. (bmj.com)
  • Antithrombin deficiency is associated with a high risk of thromboembolic disorders. (diapharma.com)
  • This medicine is used to prevent and treat antithrombin deficiency. (foundhealth.com)
  • The measurement of antithrombin activity (functional antithrombin level) is a widely used laboratory test in clinical practice, while the antithrombin antigen (immunological antithrombin level) assay, which is used to confirm inherited antithrombin deficiency only, is rarely used. (medscape.com)
  • Inherited antithrombin deficiency is less common than acquired deficiency. (medscape.com)
  • [ 3 ] The diagnosis of hereditary deficiency requires testing of both antithrombin activity and antithrombin antigen, and repeated testing and family studies may be needed. (medscape.com)
  • Antithrombin deficiency can increase the risk of recurrent miscarriage. (medscape.com)
  • Laboratory tests for antithrombin deficiency. (medscape.com)
  • Because antithrombin inhibits thrombin and factors Xa, IXa, and XIa, deficiency of antithrombin predisposes to venous thrombosis. (msdmanuals.com)
  • 1. Pabinger I, Thaler J . How I treat patients with hereditary antithrombin deficiency. (msdmanuals.com)
  • In patients with antithrombin deficiency, inactivation of thrombin is reduced. (msdmanuals.com)
  • Since rare patients with antithrombin deficiency express dysfunctional antithrombin proteins, activity assays are favored over antigen assays for the diagnosis of antithrombin deficiency. (msdmanuals.com)
  • Antithrombin Deficiency is inherited as an autosomal dominant trait. (ilbcdi.org)
  • THROMBATE III ® (antithrombin III [human]) is indicated in patients with hereditary antithrombin deficiency for treatment and prevention of thromboembolism and for prevention of perioperative and peripartum thromboembolism. (thrombate.com)
  • Prevention and treatment of venous thromboembolism in pregnancy and patients with hereditary antithrombin deficiency. (thrombate.com)
  • 7. Kottke-Marchant K, Duncan A. Antithrombin deficiency: issues in laboratory diagnosis. (thrombate.com)
  • 8. Mitton BA, Steineck A. Antithrombin deficiency. (thrombate.com)
  • 10. Pabinger I, Schneider B. Thrombotic risk in hereditary antithrombin III protein C, or protein S deficiency. (thrombate.com)
  • Clinical applications include management of patients with hereditary antithrombin III (AT-III) deficiency. (hemonc.org)
  • Thus, although the antithrombin III deficiency in fulminant hepatic failure can be corrected by supplementation with antithrombin III concentrate, its use in the prevention of intravascular coagulation and to avoid microvessel plugging needs to be studied at an earlier stage in the disease. (uea.ac.uk)
  • The authors report a case of intrahepatic portal vein thrombosis in a sixty-four-year-old Japanese man with antithrombin III deficiency who successfully underwent cholecystec tomy and common bile duct exploration. (elsevierpure.com)
  • To their knowledge, this is the first report of portal vein thrombosis due to primary antithrombin III deficiency. (elsevierpure.com)
  • Type I, which is quantitative, results from heterozygous point mutations or major gene deletions leading to low antithrombin antigen and activity levels. (medscape.com)
  • Blood was sampled for thrombin-antithrombin complex (TAT), prothrombin activation fragments 1 + 2 (F(1 + 2)), von Willebrand factor antigen (VWF:Ag), D-dimer, and interleukin-6 (IL-6) at baseline and after 2 h. (nih.gov)
  • Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. (wikipedia.org)
  • Antithrombin IV (AT IV) refers to an antithrombin that becomes activated during and shortly after blood coagulation. (wikipedia.org)
  • Managing the right level of the coagulation protein antithrombin in human body is essential. (openpr.com)
  • Antithrombin (AT) or Heparin Cofactor I is the major inhibitor of blood coagulation and is essential for effective heparin therapy. (diapharma.com)
  • Antithrombin is a natural anticoagulant that inhibits the activated coagulation factors thrombin (factor IIa), factor Xa, and, to a lesser extent, factor XIa and factor IXa. (medscape.com)
  • The antithrombin level does not influence the results of screening coagulation tests such as partial thromboplastin time (PTT), prothrombin time (PT), and thrombin time. (medscape.com)
  • Heparin normally inhibits coagulation by accelerating inactivation of thrombin by antithrombin. (msdmanuals.com)
  • Antithrombin III is a serum protease inhibitor that inhibits the blood coagulation protease, thrombin, and is an important regulator of hemostasis. (scrippslabs.com)
  • The purpose of this retrospective case-control study is to determine the effect of continuous antithrombin III (ATIII) infusion on extracorporeal membrane oxygenation (ECMO) coagulation. (umn.edu)
  • Since antithrombin III supplementation has been shown to be beneficial in animal models of septic shock with disseminated intravascular coagulation, a controlled study was performed to investigate the effect of antithrombin III supplementation in fulminant hepatic failure. (uea.ac.uk)
  • Brouwer JL, Lijfering WM, Ten Kate MK, Kluin-Nelemans HC, Veeger NJ, van der Meer J. High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin. (medlineplus.gov)
  • However, the treatment is not yet approved for indications in patients suffering from hereditary antithrombin deficient. (openpr.com)
  • The normal antithrombin concentration in human blood plasma is high at approximately 0.12 mg/ml, which is equivalent to a molar concentration of 2.3 μM. (wikipedia.org)
  • A falsely normal antithrombin concentration might be determined in antithrombin-deficient patients treated with thrombin inhibitors, but not with anti-Xa inhibitors. (medscape.com)
  • A procedure is described for performing a functional assay of serum antithrombin activity. (bmj.com)
  • The INNOVANCE® Antithrombin Assay is a state-of-the-art reagent for the detection of congenital or acquired antithrombin deficiencies. (siemens-healthineers.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Rat Antithrombin (AT) in samples from plasma with no significant corss-reactivity with analogues from other species. (antibody-tech.com)
  • Description: A sandwich quantitative ELISA assay kit for detection of Human Antithrombin (AT) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids. (antibody-tech.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Antithrombin (AT) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids. (antibody-tech.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Antithrombin (AT) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids with no significant corss-reactivity with analogues from other species. (antibody-tech.com)
  • Thus, even short periods of abnormal liver function may reduce antithrombin production, leading to potential thrombosis. (medscape.com)
  • Evidence linking familial thrombosis with a defective antithrombin III gene in two British kindreds. (bmj.com)
  • Antithrombin is a plasma protein that inhibits thrombin and factors Xa, IXa, and XIa, thereby inhibiting thrombosis. (msdmanuals.com)
  • Clinical outcomes of antithrombin III-based therapy for patients with portal vein thrombosis: A retrospective, multicenter study. (bvsalud.org)
  • Its activity is increased manyfold by the anticoagulant drug heparin, which enhances the binding of antithrombin to factor IIa (thrombin) and factor Xa. (wikipedia.org)
  • Its anticoagulant activity was due to catalysis of thrombin inhibition by antithrombin but not by heparin cofactor II. (nih.gov)
  • Heparin exerts its anticoagulant effect by activating antithrombin. (msdmanuals.com)
  • Antithrombin is a naturally occurring anticoagulant that inactivates serine proteases such as thrombin, and clotting factors IXa, Xa, XIa, and XIIa. (ilbcdi.org)
  • Correcting AT levels using antithrombin concentrate products is recommended for planned major surgery. (medscape.com)
  • Numerous studies have shown that fibrin-bound thrombin (IIa) is protected from inhibition by antithrombin (AT) + heparin (H) due to the formation of a ternary fibrin.IIa.H complex. (mcmaster.ca)
  • Recombinant antithrombins with properties similar to those of normal human antithrombin have been produced using baculovirus-infected insect cells and mammalian cell lines grown in cell culture. (wikipedia.org)
  • These recombinant antithrombins generally have different glycosylation patterns to normal antithrombin and are typically used in antithrombin structural studies. (wikipedia.org)
  • The recent FDA approval of recombinant antithrombins in major region has increasingly boosted the market. (openpr.com)
  • Nevertheless, recent advances in clinical studies in evaluating the potential of recombinant antithrombins in prolonging gestation so as to improve maternal and neonatal outcomes have opened up exciting opportunities for market players. (openpr.com)
  • The substantial growth in these regional markets is attributed to the early adoption of recombinant antithrombins in preventing various clinical conditions caused by the prevention of blood clots. (openpr.com)
  • However, Asia Pacific is projected to witness a robust demand for recombinant antithrombins. (openpr.com)
  • In addition, the growing incidence of various cardiovascular diseases is expected to propel the demand for recombinant antithrombins in various countries of Asia Pacific. (openpr.com)
  • previously referred to as antithrombin III) is a 58-kDa molecule belonging to the serine protease inhibitor (serpin) superfamily that plays a central role in anticoagulation and regulating appropriate wound healing in mammalian circulation systems. (medscape.com)
  • Furthermore, ATryn, the recently approved recombinant antithrombin by U.S. FDA, is found to have contraindications in patients who have hypersensitivity to goat milk proteins. (openpr.com)
  • Antithrombin - neutralization set for ATIII (AT-NU10) is a Neutralization Paired Antibody Set for Neutralizing ATIII - 10 determinations. (quadratech.co.uk)
  • Antithrombin blocks the activity of proteins that promote blood clotting, especially a protein called thrombin. (medlineplus.gov)
  • Individuals with this condition do not have enough functional antithrombin to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots. (medlineplus.gov)
  • Antithrombin III is a protein in the blood that blocks abnormal blood clots from forming. (medlineplus.gov)
  • This low level of antithrombin III can cause abnormal blood clots (thrombi) that can block blood flow and damage organs. (medlineplus.gov)
  • Compared patterns of antithrombin III, protein C, and protein S deficiencies. (qxmd.com)
  • Molecular defects in the antithrombin gene may result in deficiencies or abnormal activity of antithrombin. (ilbcdi.org)
  • The residual thrombin in the test mixture is inversely proportional to the functional antithrombin concentration in the patient's plasma. (msdmanuals.com)
  • As deduced from protein and cDNA sequencing, cow, sheep, rabbit and mouse antithrombins are all 433 amino acids in length, which is one amino acid longer than human antithrombin. (wikipedia.org)
  • Plasma antithrombin is comprised of 432 amino acids, 6 of which are cysteine residues that form 3 intramolecular disulfide bonds. (medscape.com)
  • α-Antithrombin is the dominant form of antithrombin found in blood plasma and has an oligosaccharide occupying each of its four glycosylation sites. (wikipedia.org)
  • Antithrombin II (AT II) refers to a cofactor in plasma, which together with heparin interferes with the interaction of thrombin and fibrinogen. (wikipedia.org)
  • Antithrombin III (AT III) refers to a substance in plasma that inactivates thrombin. (wikipedia.org)
  • Antithrombin has a half-life in blood plasma of around 3 days. (wikipedia.org)
  • Antithrombin has been isolated from the plasma of a large number of species additional to humans. (wikipedia.org)
  • Antithrombin is a serpin (serine protease inhibitor) and is thus similar in structure to most other plasma protease inhibitors, such as alpha 1-antichymotrypsin, alpha 2-antiplasmin and Heparin cofactor II. (wikipedia.org)
  • Treatment with thrombin inhibitors may lead to overestimation of the antithrombin level in plasma. (medscape.com)
  • 3. Heparin treatment may lower plasma antithrombin. (mghlab.com)
  • Description: A sandwich ELISA kit for detection of Antithrombin from Rat in samples from blood, serum, plasma, cell culture fluid and other biological fluids. (antibody-tech.com)
  • Antithrombin plasma levels decrease is associated with preeclampsia worsening. (unimore.it)
  • Antithrombin plasma levels (AT) have been found decreased in women with preeclampsia (PE), but little is known about the trend of AT during the course of this disease. (unimore.it)
  • 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)
  • This gene provides instructions for producing a protein called antithrombin (previously known as antithrombin III). (medlineplus.gov)
  • It occurs when a person receives one abnormal copy of the antithrombin III gene from a parent with the disease. (medlineplus.gov)
  • The abnormal gene leads to a low level of the antithrombin III protein. (medlineplus.gov)
  • A high concentration of hemoglobin, bilirubin, and triglycerides might affect antithrombin measurement. (medscape.com)
  • Fass environmental information for Atenativ (antithrombin III, human) from Octapharma (downloaded 2019-09-03). (janusinfo.se)
  • 2017. https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Lab-and-Diagnostic-Tests/425209/all/Antithrombin. (unboundmedicine.com)
  • Antithrombin I (AT I) refers to the binding of thrombin to fibrin, after thrombin has activated fibrinogen, at a non-catalytic binding site of thrombin. (wikipedia.org)
  • The designations Antithrombin I through to Antithrombin IV originate in early studies carried out in the 1950s by Seegers, Johnson and Fell.Antithrombin I (AT I) refers to the absorption of thrombin onto fibrin after thrombin has activated fibrinogen. (abebio.cn)
  • Already the discovery of the first families presenting a defect in antithrombin (AT) led to the description of the genetic causes of this defect. (intechopen.com)
  • Paul Morawitz at the University of Tubingen first coined the term antithrombin in 1905 to describe plasma's ability to neutralize thrombin activity. (medscape.com)
  • Standardisation of a simple method for the determination of antithrombin activity. (bmj.com)
  • The ready-to-use reagent offers improved onboard stability and, due to its Xa-based activity, shows excellent sensitivity to detect antithrombin mutations. (siemens-healthineers.com)
  • Antithrombin activity is measured by synthetic chromogenic activity in the presence of excess heparin levels. (medscape.com)
  • Antithrombin III activity increased from 0.26 +/- 0.04 SE U/ml to 0.82 +/- 0.07 U/ml at 3 h post infusion (normal range 0.80-1.20 U/ml) and remained greater than 0.80 U/ml throughout the study without any apparent increase in the frequency of bleeding. (uea.ac.uk)
  • Antithrombin is glycoprotein (molecular weight, 58 kDa) that is synthesized in the liver. (medscape.com)
  • The physiological target proteases of antithrombin are those of the contact activation pathway (formerly known as the intrinsic pathway), namely the activated forms of Factor X (Xa), Factor IX (IXa), Factor XI (XIa), Factor XII (XIIa) and, to a greater extent, Factor II (thrombin) (IIa), and also the activated form of Factor VII (VIIa) from the tissue factor pathway (formerly known as the extrinsic pathway). (wikipedia.org)
  • Antithrombin levels are dependent on the patient's age and other associated conditions. (ilbcdi.org)
  • All these sites are occupied by covalently attached oligosaccharide side-chains in the predominant form of human antithrombin, α-antithrombin, resulting in a molecular weight for this form of antithrombin of 58,200. (wikipedia.org)
  • Vallerand AHA, Sanoski CAC, Quiring CC. Antithrombin (human). (unboundmedicine.com)
  • Scripps Laboratories is a world-leading producer and supplier of purified human Antithrombin III. (scrippslabs.com)
  • For monitoring of recombinant human antithrombin III during cell culture processes and subsequent purification steps a rapid method for quantitative determination was developed. (uni-bielefeld.de)
  • Büntemeyer H, Tebbe H, Lütkemeyer D, Lehmann J. Rapid high-performance liquid chromatographic quantification of recombinant human antithrombin III during production and purification. (uni-bielefeld.de)
  • Rapid high-performance liquid chromatographic quantification of recombinant human antithrombin III during production and purification", Journal of Chromatography, B: Biomedical Sciences and Applications , vol. 662, 1994, pp. 209-216. (uni-bielefeld.de)
  • Efficient single step chromatographic purification of recombinant human antithrombin (rhAT) from Saccharomyces cerevisiae. (uni-bielefeld.de)
  • The protein molecules have also gained importance to boost the levels of Antithrombin in patients. (openpr.com)
  • This study aimed to evaluate the outcome in patients with PVT who received antithrombin III-based therapy . (bvsalud.org)
  • viscosity, reduced red cell deformability, The main objectives of this study were abnormal red cell adhesive properties, en- to assess platelet aggregation patterns and dothelial intimal proliferation, bone marrow levels of PC, PS and AT III in SCA patients or fat embolism and a chronic hypercoagula- in the steady state and in vaso-occlusive ble state [6]. (who.int)
  • The health care provider can also order a blood test to check if you have a low level of antithrombin III. (medlineplus.gov)
  • Antithrombin III (AT III) is a protein that helps control blood clotting. (medlineplus.gov)
  • Engineered recombinant antithrombin has gained clinical significant in recent years for the prevention of various peri-partum and peri-operative thromboembolic events or blood clots. (openpr.com)
  • The growing prevalence of this disease, both among men and women, is a key factor propelling the demand for antithrombin drugs and therapies. (openpr.com)
  • Inhibition of Factor Xa by antithrombin was not catalyzed by the polysaccharide. (nih.gov)
  • 11. Ranucci M. Antithrombin III: key factor in extracorporeal circulation. (thrombate.com)
  • Antithrombotic drugs help in the prevention or inhibition of thrombus by mimicking the role of antithrombin, a protein molecule produced in our body which helps in clotting. (openpr.com)
  • As its name implies, antithrombin was first characterized as an inhibitor of thrombin. (medscape.com)
  • However, the limited efficacy of antithrombin to improve neonatal outcomes is likely to impede the market to an extent. (openpr.com)