protrombiinin

Prothrombin, also known as coagulation factor II, is a vitamin K–dependent glycoprotein produced by the liver and circulating in plasma as a zymogen that becomes thrombin. The mature molecule contains a gamma-carboxyglutamic acid–rich Gla domain, two kringle domains, and a serine protease domain. Gamma-carboxylation of the Gla domain, which requires vitamin K, enables calcium binding and interaction with phospholipid surfaces during coagulation.

Activation of prothrombin occurs via the prothrombinase complex, formed on phospholipid surfaces in the presence of tissue factor and factor VIIa, with factors Xa and Va and calcium. This complex cleaves prothrombin to thrombin, the central enzyme of coagulation. Thrombin then converts fibrinogen to fibrin, polymerizes fibrin, and activates multiple coagulation factors and platelets, amplifying the cascade and stabilizing a hemostatic plug.

Genetics and clinical relevance: The F2 gene encodes prothrombin and is located on chromosome 11. A common variant, G20210A in F2, is associated with elevated prothrombin levels and increased risk of venous thrombosis. Rare inherited prothrombin deficiencies cause bleeding diatheses. Acquired reductions or dysfunctions can occur with vitamin K deficiency or antagonism (for example, warfarin therapy).

Clinical measurements and management: Prothrombin time (PT) assesses the extrinsic pathway and is prolonged when prothrombin function is reduced. Warfarin therapy aims to lower functional prothrombin via vitamin K antagonism; reversal may use prothrombin complex concentrates containing coagulation factors II, VII, IX, and X. Biomarkers such as prothrombin fragments (F1+2) reflect thrombin generation in various states of coagulation.