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Prothrombinase
The prothrombinase enzyme complex consists of factor Xa (a serine protease) and factor Va (a protein cofactor). The complex assembles on negatively charged phospholipid membranes in the presence of calcium ions. The prothrombinase complex catalyzes the conversion of prothrombin (factor II), an inactive zymogen, to thrombin (factor IIa), an active serine protease. The activation of thrombin is a critical reaction in the coagulation cascade, which functions to regulate hemostasis in the body. To produce thrombin, the prothrombinase complex cleaves two peptide bonds in prothrombin, one after Arg271 and the other after Arg320. Although it has been shown that factor Xa can activate prothrombin when unassociated with the prothrombinase complex, the rate of thrombin formation is severely decreased under such circumstances. The prothrombinase complex can catalyze the activation of prothrombin at a rate 3 x 105-fold faster than can factor Xa alone. Thus, the prothrombinase comple ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Factor Xa
Coagulation factor X (), or Stuart factor, is an enzyme of the coagulation cascade, encoded in humans by ''F10'' gene. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for its synthesis. Factor X is activated, by hydrolysis, into factor Xa by both factor IX with its cofactor, factor VIII in a complex known as intrinsic pathway; and factor VII with its cofactor, tissue factor in a complex known as extrinsic pathway. It is therefore the first member of the ''final common pathway'' or ''thrombin pathway''. It acts by cleaving prothrombin in two places (an Arg- Thr and then an Arg- Ile bond), which yields the active thrombin. This process is optimized when factor Xa is complexed with activated co-factor V in the prothrombinase complex. Factor Xa is inactivated by protein Z-dependent protease inhibitor (ZPI), a serine protease inhibitor (serpin). The affinity of this protein for factor Xa is increa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Edoxaban
Edoxaban, sold under the brand name Lixiana among others, is an anticoagulant medication and a direct factor Xa inhibitor. It is taken by mouth. Compared with warfarin, it has fewer drug interactions, and does not require regular assessment of blood samples for prothrombin time to assure safe anticoagulant therapy. It was developed by Daiichi Sankyo and approved in July 2011, in Japan for prevention of venous thromboembolisms following lower-limb orthopedic surgery. It was also approved in the United States by the Food and Drug Administration (FDA) in January 2015, for the prevention of stroke and non–central-nervous-system systemic embolism. It was approved for use in the European Union in June 2015. It is on the World Health Organization's List of Essential Medicines. Medical uses In the United States, edoxaban is indicated to treat deep vein thrombosis and pulmonary embolism following five to ten days of initial therapy with a parenteral anticoagulant. It is also ind ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Factor IX
Factor IX (), also known as Christmas factor, is one of the serine proteases involved in coagulation; it belongs to peptidase family S1. Deficiency of this protein causes haemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to haemophilia. Coagulation factor IX is on the WHO Model List of Essential Medicines, World Health Organization's List of Essential Medicines. Physiology Factor IX is produced as a zymogen, an inactive precursor. It is processed to remove the signal peptide, Glycosylation, glycosylated and then cleaved by factor XIa (of the contact pathway) or factor VIIa (of the tissue factor pathway) to produce a two-chain form, where the chains are linked by a disulfide bridge. When activated into factor IXa, in the presence of Ca2+, membrane phospholipids, and a Factor VIII cofactor, it hydrolyses one arginine-isoleucine bond in factor X to form factor Xa. Factor IX is inhibited by ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Apixaban
Apixaban, sold under the brand name Eliquis, is an anticoagulant medication used to treat and prevent blood clots and to prevent stroke in people with nonvalvular atrial fibrillation through directly inhibiting factor Xa. It is used as an alternative to warfarin to prevent blood clots following hip or knee replacement and in those with a history of prior clots and does not require monitoring by blood tests or dietary restrictions. It is taken by mouth. Common side effects include bleeding and nausea. Other side effects may include bleeding around the spine and allergic reactions. Use is not recommended during pregnancy or breastfeeding. Use appears to be relatively safe in those with mild kidney problems. Compared to warfarin it has fewer interactions with other medications. It is a direct factor Xa inhibitor. In 2007, Pfizer and Bristol-Myers Squibb began the development of apixaban as an anticoagulant. Apixaban was approved for medical use in the European Union in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rivaroxaban
Rivaroxaban, sold under the brand name Xarelto among others, is an anticoagulant medication (blood thinner) used to treat and reduce the risk of blood clots. Specifically it is used to treat deep vein thrombosis and pulmonary emboli and prevent blood clots in atrial fibrillation and following hip or knee surgery. It is taken by mouth. Common side effects include bleeding. Other serious side effects may include spinal hematoma and anaphylaxis. It is unclear if use in pregnancy and breastfeeding is safe. Compared to warfarin it has fewer interactions with other medications. It works by blocking the activity of the clotting protein factor Xa. Rivaroxaban was patented in 2007 and approved for medical use in the United States in 2011. It is available as a generic medication. It is on the World Health Organization's List of Essential Medicines. In 2022, it was the 90th most commonly prescribed medication in the United States, with more than 7million prescriptions. Medical use ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Idraparinux
Idraparinux sodium is an anticoagulant medication in development by Sanofi-Aventis. It has a similar chemical structure and the same method of action as fondaparinux, but with an elimination half-life about five to six times longer (an increase from fondaparinux's 17 hours to approximately 80 hours), which means that the drug should only need to be injected once a week. Supriya Dey et al recently reported shortest chemical synthesis of Idraparinux for the large-scale production. Sanofi discontinued the development of idraparinux sodium. Negative clinical trial A phase III trial of idraparinux sodium for stroke prevention in patients with AF (AMADEUS) was halted prematurely due to excessive clinically relevant and intracranial bleeding. Bleedings were particularly increased in elderly patients and those with renal impairment. Sanofi discontinued the development of idraparinux sodium in favour of a biotinylated formulation of the drug called idrabiotaparinux sodium. Method of a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fondaparinux
Fondaparinux (trade name Arixtra) is an anticoagulant medication chemically related to low molecular weight heparins. It is marketed by Viatris. A generic version developed by Alchemia is marketed within the US by Dr. Reddy's Laboratories. Medical uses Clinically, it is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism. Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long-term mortality and morbidity. It has been investigated for use in conjunction with streptokinase. Comparison to other agents One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for heparin-induced thrombocytopenia (HIT) is substantially lower. Furthermore, there have been case reports of fondaparinux being used to anti-coagulate patients with establi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Factor V Leiden
Factor V Leiden (rs6025 or ''F5'' p.R506Q) is a variant (mutated form) of human factor V (one of several substances that helps blood clot), which causes an increase in blood clotting (hypercoagulability). Due to this mutation, protein C, an anticoagulant protein that normally inhibits the pro-clotting activity of factor V, is not able to bind normally to factor V, leading to a hypercoagulable state, i.e., an increased tendency for the patient to form abnormal and potentially harmful blood clots. Factor V Leiden is the most common hereditary hypercoagulability (prone to clotting) disorder amongst ethnic Europeans. It is named after the Dutch city of Leiden, where it was first identified in 1994 by Rogier Maria Bertina under the direction of (and in the laboratory of) Pieter Hendrik Reitsma. Despite the increased risk of venous thromboembolisms, people with one copy of this gene have not been found to have shorter lives than the general population. It is an autosomal dominant genetic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, heart attacks and unstable angina. It can be given intravenously or by subcutaneous injection, injection under the skin. Its anticoagulant properties make it useful to prevent blood clotting in blood specimen test tubes and kidney dialysis machines. Common side effects include bleeding, pain at the injection site, and thrombocytopenia, low blood platelets. Serious side effects include heparin-induced thrombocytopenia. Greater care is needed in those with poor kidney function. Heparin is contraindicated for suspected cases of Post-vaccination embolic and thrombotic events, vaccine-induced pro-thrombotic immune thrombocytopenia (VIPIT) secondary to SARS-CoV-2 vaccination, as heparin may further increase the risk of bleeding in an anti-PF4 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antithrombin
Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. It is a 464-amino-acid protein produced by the liver. It contains three disulfide bonds and a total of four possible glycosylation sites. α-Antithrombin is the dominant form of antithrombin found in blood plasma and has an oligosaccharide occupying each of its four glycosylation sites. A single glycosylation site remains consistently un-occupied in the minor form of antithrombin, β-antithrombin. Its activity is increased manyfold by the anticoagulant drug heparin, which enhances the binding of antithrombin to thrombin, factor IIa (thrombin) and factor Xa. Structure Antithrombin is also termed antithrombin III (AT III). 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 binding of thrombin to fibrin, after thrombin has activated fibrinogen, at a non-ca ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and cell death and maintaining the permeability of blood vessel walls in humans and other animals. Activated protein C (APC) performs these operations primarily by proteolytically inactivating proteins Factor Va and Factor VIIIa. APC is classified as a serine protease since it contains a residue of serine in its active site. In humans, protein C is encoded by the ''PROC'' gene, which is found on chromosome 2. The zymogenic form of protein C is a vitamin K-dependent glycoprotein that circulates in blood plasma. Its structure is that of a two-chain polypeptide consisting of a light chain and a heavy chain connected by a disulfide bond. The protein C zymogen is activated when it binds to thrombin, another protein heavily involved in coagulation, and protein C' ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Factor VIII
Coagulation factor VIII (Factor VIII, FVIII, also known as anti-hemophilic factor (AHF)) is an essential blood clotting protein. In humans, it is encoded by ''F8'' gene. Defects in this gene result in hemophilia A, an X-linked bleeding disorder. Factor VIII is produced in the liver's liver sinusoid, sinusoidal cells and endothelial cells outside the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to another molecule called von Willebrand factor, until an injury that damages blood vessels occurs. In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein (sometimes written as coagulation factor VIIIa) interacts with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot. Factor VIII participates in blood coagulation; it is a cofactor for factor IXa, which, in the presence of Ca2+ and phosph ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
