protrombiini

Prothrombin, also known as coagulation factor II, is a vitamin K–dependent glycoprotein produced primarily by the liver and circulating in blood plasma as an inactive zymogen. It is part of the coagulation cascade’s common pathway and is converted into thrombin (factor IIa) by the prothrombinase complex, which consists of activated factor X (Xa), factor Va, calcium ions, and phospholipid surfaces.

Activation and function: The activation of prothrombin to thrombin is a key amplification step in hemostasis. Thrombin then cleaves fibrinogen to form fibrin, activates additional coagulation factors (V, VIII, XI, XIII), and promotes platelet aggregation, leading to the formation of a stable clot. The prothrombin molecule contains a gamma-carboxyglutamate (Gla)–rich domain that enables calcium-dependent binding to phospholipid surfaces, facilitating its activation.

Regulation and clinical relevance: The gamma-carboxylation of prothrombin requires vitamin K. Anticoagulants such as warfarin inhibit vitamin K–dependent carboxylation, reducing prothrombin activity and prolonging clotting times. Deficiency or impairment of prothrombin production or function can lead to excessive bleeding, while increased prothrombin activity can contribute to thrombotic risk.

Genetics and testing: The F2 gene encodes prothrombin. A common inherited mutation, G20210A in the 3' noncoding region, is associated with higher plasma prothrombin levels and an elevated risk of venous thrombosis. Prothrombin time (PT) and the international normalized ratio (INR) are clinical tests used to assess the extrinsic pathway of coagulation and monitor anticoagulant therapy.