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The coagulation of human blood is a fairly complex process by which blood becomes solid clots. It is an important part of hemostasis where a damaged blood vessel is ultimately covered by a fibrin clot to stop hemorrhage. Disorders in coagulation can lead to increased hemorrhage on the one side and thrombosis and embolism on the other.
Ordinarily coagulation is initiated within seconds after an injury occurs when platelets form a plug at the site of injury. This is called primary hemostasis. Following this, various plasma components, called clotting factors respond (in a complex cascade) to form fibrin strands which strengthen the platelet plug.
The use of adsorbent chemicals, such as zeolite, and other hemostatic agent s is also being explored for use in sealing severe injuries quickly.
Primary hemostasis is initiated when platelets adhere, using a specific platelet collagen receptor glycoprotein Ia/IIa, to collagen fibers in the vascular endothelium. This adhesion is mediated by von Willebrand factor (vWF), which forms links between the platelet glycoprotein Ib/IX/X and collagen fibrils.
The platelets are then activated and release the contents of their granules in to the plasma, this inturn activates other platelets and white blood cells. They undergo a change in their shape which exposes a phospholipid surface for those coagulation factors that require it. Fibrinogen, which links adjacent platelets by forming links via the glycoprotein IIb/IIIa.In addition, thrombin activates platelets.
The coagulation cascade of secondary hemostasis has two pathways, the Contact Activation pathway (formally known as the Intrinsic Pathway) and the Tissue Factor pathway (formally known as the Extrinsic pathway) that lead to fibrin formation. It was previously thought that the coagulation cascade consisted of two pathways of equal importance joined to a common pathway. It is now known that the primary pathway for the initiation of blood coagulation is the Tissue Factor pathway. The pathways are a series of reactions, in which a zymogen of a serine proteaseIn biochemistry, a serine proteases or serine endopeptidases (newer name) are a class of peptidases which are characterised by the presence of a serine residue in the active domain of the enzyme. Serine proteases participate in a wide range of functions i and its glycoprotein co-factor are activated to become active components that then catalyze the next reaction in the cascade. Coagulation factors are generally indicated by Roman numerals, with a lowercase a appended to indicate an active form, ultimately resulting in cross-linked fibrin.
The coagulation factors are serine proteaseIn biochemistry, a serine proteases or serine endopeptidases (newer name) are a class of peptidases which are characterised by the presence of a serine residue in the active domain of the enzyme. Serine proteases participate in a wide range of functions is except FVIII and FV which are glycoproteins., which act by cleaving other proteins. Factor XIII is a transglutaminaseTransglutaminases are a family of enzymes that catalyze the formation of a covalent bond between a free amine group (e. protein- or peptide-bound lysine) and the gamma-carboxamid group of protein- or peptide bound glutamine. Transglutaminase is now produc. Protein C is a serine protease.
The coagulation cascade can be summarised as follows:
Following activation by the contact factor or tissue factor pathways the coagulation cascade is maintained in a prothrombotic state by the continued activation of FVIII and FIX to form the tenase complex, until it is down regulated by the anticoagulant pathways.