protrombin

Prothrombin, also known as factor II, is a vitamin K–dependent plasma glycoprotein produced by the liver. It is the zymogen form of thrombin, a serine protease that plays a central role in blood coagulation. Prothrombin contains a gamma-carboxylated glutamate (Gla)–containing region that enables binding to calcium and phospholipid surfaces, which localizes it to the site of injury where activation occurs.

Activation and function: In response to vascular injury, prothrombin is converted to thrombin by the prothrombinase complex, which includes factor Xa, factor Va, calcium ions, and a phospholipid surface. Thrombin then converts soluble fibrinogen into insoluble fibrin, forming the clot. It also activates platelets and several other coagulation factors (V, VIII, XI, XIII), amplifying the coagulation cascade.

Genetics and variants: The F2 gene on chromosome 11 encodes prothrombin. Genetic variants can affect prothrombin levels or function. The G20210A mutation is associated with elevated prothrombin levels and an increased risk of venous thrombosis in some individuals.

Clinical relevance: Vitamin K is required for the gamma-carboxylation of prothrombin, a post-translational modification that enables calcium binding and activity. Antagonists of vitamin K, such as warfarin, reduce the gamma-carboxylation of prothrombin and other vitamin K–dependent factors, producing anticoagulant effects. Prothrombin time (PT) testing, often reported as the international normalized ratio (INR), assesses the extrinsic pathway of coagulation and is used to monitor warfarin therapy.

Overall, prothrombin is a key coagulation factor whose activation to thrombin initiates clot formation and regulates hemostasis.