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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 ...
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Serine Protease Inhibitor
Serpins are a superfamily of proteins with similar structures that were first identified for their protease inhibition activity and are found in all kingdoms of life. The acronym serpin was originally coined because the first serpins to be identified act on chymotrypsin-like serine proteases (serine protease inhibitors). They are notable for their unusual mechanism of action, in which they irreversibly inhibit their target protease by undergoing a large conformational change to disrupt the target's active site. This contrasts with the more common competitive mechanism for protease inhibitors that bind to and block access to the protease active site. Protease inhibition by serpins controls an array of biological processes, including coagulation and inflammation, and consequently these proteins are the target of medical research. Their unique conformational change also makes them of interest to the structural biology and protein folding research communities. The conformationa ...
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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 ...
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Anticoagulant
An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which help keep the bite area unclotted long enough for the animal to obtain blood. As a class of medications, anticoagulants are used in therapy for thrombotic disorders. Oral anticoagulants (OACs) are taken by many people in pill or tablet form, and various intravenous anticoagulant dosage forms are used in hospitals. Some anticoagulants are used in medical equipment, such as sample tubes, blood transfusion bags, heart–lung machines, and dialysis equipment. One of the first anticoagulants, warfarin, was initially approved as a rodenticide. Anticoagulants are closely related to antiplatelet drugs and thrombolytic drugs by manipulating the various pathways of blood coagulation. Specifically, antiplatelet drugs inhibit platelet agg ...
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Heparin Cofactor II
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 protease 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 III 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. A purification experiment of heparin cofactor II was performed in 1981, in which it was discovered that the purified version of the protein consists of a single polypeptide chain. Further experimentation demonstrated that whether β-Mercaptoethanol is present does not affect HCII's activity in gel electrophoresis. β-Mercapto ...
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Coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation involves Platelet-activating factor, activation, Cell adhesion, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin. Coagulation begins almost instantly after an injury to the endothelium that lines a blood vessel. Exposure of blood to the subendothelial space initiates two processes: changes in platelets, and the exposure of subendothelial Tissue factor, platelet tissue factor to coagulation 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 factors beyond factor VII (#Coagulation factors, listed below) respond in a c ...
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Blood Coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process 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 that lines a blood vessel. Exposure of blood to the subendothelial space initiates two processes: changes in platelets, and the exposure of subendothelial platelet tissue factor to coagulation 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 factors beyond factor VII ( listed below) respond in a cascade to form fibrin strands, which strengthen the platelet plug. Coagulation is ...
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Liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of various proteins and various other Biochemistry, biochemicals necessary for digestion and growth. In humans, it is located in the quadrants and regions of abdomen, right upper quadrant of the abdomen, below the thoracic diaphragm, diaphragm and mostly shielded by the lower right rib cage. Its other metabolic roles include carbohydrate metabolism, the production of a number of hormones, conversion and storage of nutrients such as glucose and glycogen, and the decomposition of red blood cells. Anatomical and medical terminology often use the prefix List of medical roots, suffixes and prefixes#H, ''hepat-'' from ἡπατο-, from the Greek language, Greek word for liver, such as hepatology, and hepatitis The liver is also an accessory digestive ...
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Thrombin
Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin (Factor IIa) (, fibrose, thrombase, thrombofort, topical, thrombin-C, tropostasin, activated blood-coagulation factor II, E thrombin, beta-thrombin, gamma-thrombin) is a serine protease, that converts fibrinogen into strands of insoluble 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 enhanced by binding to activated Factor V (Va), termed the prothrombinase complex. Prothrombin is prod ...
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Factor X
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 Tenase, intrinsic pathway; and factor VII with its cofactor, tissue factor in a complex known as Tenase, 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 arginine, Arg-threonine, Thr and then an arginine, Arg-isoleucine, Ile bond), which yields the active thrombin. This process is optimized when factor Xa is complexed with activated factor V, co-factor V in the prothrombinase complex. Factor Xa is inactivated by protein Z-dependent protease inhibitor (ZPI), a serine protease inhibitor (serpin). ...
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