Prothrombinase

Prothrombinase is the calcium-dependent enzyme complex that converts prothrombin (factor II) to thrombin (factor IIa) on a phospholipid surface. In its active form it consists of factor Xa bound to factor Va, with calcium ions and a suitable anionic phospholipid surface—typically provided by activated platelets or other cell membranes.

As part of the common pathway of coagulation, prothrombinase catalyzes the proteolytic conversion of prothrombin to thrombin. Thrombin then cleaves fibrinogen to fibrin, promotes platelet activation, and accelerates the cascade by activating factors V, VIII, and XIII, creating a positive feedback loop that amplifies thrombin generation.

Factor Xa is generated by extrinsic tenase (tissue factor–VIIa–Ca2+) and intrinsic tenase (IXa–VIIIa–Ca2+). Once Xa is anchored on the phospholipid surface, Va binds to Xa to form prothrombinase, positioning thrombin’s active site to efficiently cleave prothrombin.

Regulation of prothrombinase activity occurs through localization on platelet membranes and the action of anticoagulants that limit thrombin formation. Genetic variants can shift the balance toward thrombosis or bleeding; for example, Factor V Leiden renders Va less susceptible to inactivation by activated protein C, increasing clot risk, while the prothrombin G20210A mutation increases prothrombin levels. Anticoagulant therapies and direct inhibitors of factor Xa or thrombin disrupt prothrombinase-mediated thrombin generation to prevent pathological clotting.