Prothrombin activation to thrombin. Prothrombin is first activated as part of the prothrombinase complex to meizothrombin by cleavage at R320. The Gla and kringle (K1 and K2) domains are cleaved at R271, allowing thrombin to diffuse away. Thrombin has 3 regions that are functionally inaccessible in prothrombin and become exposed on activation: the active site, exosite I, and exosite II.