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Prothrombinase
The prothrombinase complex consists of the serine protease, Factor Xa, and the protein cofactor, Factor Va. 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 complex is required ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Factor Xa
Factor X, also known by the eponym Stuart–Prower factor, is an enzyme () of the coagulation cascade. 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 tenase'') and factor VII with its cofactor, tissue factor (a complex known as ''extrinsic tenase''). 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 increased 1000-fold by the pres ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Coagulation Cascade
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin. Coagulation begins almost instantly after an injury to the endothelium lining a blood vessel. Exposure of blood to the subendothelial space initiates two processes: changes in platelets, and the exposure of subendothelial tissue factor to plasma factor VII, which ultimately leads to cross-linked fibrin formation. Platelets immediately form a plug at the site of injury; this is called ''primary hemostasis. Secondary hemostasis'' occurs simultaneously: additional coagulation (clotting) factors beyond factor VII ( listed below) respond in a cascade to form fibrin strands, which strengthen the platelet plug. Disorders of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and apoptosis, cell death and maintaining the vascular permeability, permeability of blood vessel walls in humans and other animals. Activated protein C (APC) performs these operations primarily by proteolysis, proteolytically inactivating proteins Factor V, Factor Va and Factor VIII, Factor VIIIa. APC is classified as a serine protease since it contains a residue (chemistry), residue of serine in its active site. In humans, protein C is encoded by the ''PROC'' gene, which is found on chromosome 2 (human), 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 zymog ... [...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 prevent 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. In the United States, it will not be available as a generic medication until 2024. It is on the World Health Organization's List of Essential Medicines. In 2020, it was the 86th most commonly prescribed medication in the United States, with more than 8mill ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Factor V
Factor V (pronounced factor five) is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor. Deficiency leads to predisposition for hemorrhage, while some mutations (most notably factor V Leiden) predispose for thrombosis. Genetics The gene for factor V is located on the first chromosome (1q24). It is genomically related to the family of multicopper oxidases, and is homologous to coagulation factor VIII. The gene spans 70 kb, consists of 25 exons, and the resulting protein has a relative molecular mass of approximately 330kDa. Structure Factor V protein consists of six domains: A1-A2-B-A3-C1-C2. The A domains are homologous to the A domains of the copper-binding protein ceruloplasmin, and form a triangular as in that protein. A copper ion is bound in the A1-A3 interface, and A3 interacts with the plasma. The C domains belong to the p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thrombin
Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma-thrombin'') is a serine protease, an enzyme that, in humans, is encoded by the ''F2'' gene. Prothrombin (coagulation factor II) is proteolytically cleaved to form thrombin in the clotting process. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions. History After the description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converts fibrinogen into fibrin in 1872. Prothrombin was discovered by Pekelharing in 1894. Physiology Synthesis Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). The activity of factor Xa is greatly ... [...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. Specifically it is used to prevent blood clots following hip or knee replacement and in those with a history of prior clots. It is used as an alternative to warfarin 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 development of apixaban as an anticoagulant. Apixaban was approved for medical use in the Eu ... [...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 act ... [...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 GlaxoSmithKline. 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 establ ... [...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 Hendrick 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. Signs and symptoms The symptoms of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatment of heart attacks and unstable angina. It is given intravenously or by injection under the skin. Other uses for its anticoagulant properties include inside blood specimen test tubes and kidney dialysis machines. Common side effects include bleeding, pain at the injection site, and 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 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/heparin complex autoimmune manner, in favor of alternative anticoagulant medications (such as arg ... [...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 432-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 factor IIa (prothrombin) and factor Xa. Nomenclature 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 absorption of thrombin onto fibrin after thrombin has activated fibrinogen. Antithro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
