Prothrombin is activated on the surface of a phospholipid membrane that binds the amino end of prothrombin and factors Va and Xa in Ca-dependent interactions. Factor Xa removes the activation peptide and cleaves the remaining part into light and heavy chains. The activation process starts slowly because factor V itself has to be activated by the initial, small amounts of thrombin. Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Thrombin functions in blood homeostasis, inflammation and wound healing. Defects in thrombin are the cause of factor II deficiency (FA2D), a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. Genetic variations in thrombin are linked to ischemic stroke and to thrombosis (THR), a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation.