Prothrombin activation pathways. The proteolytic conversion of the zymogen prothrombin to the enzyme thrombin is the result of proteolytic cleavage at Arg271 and Arg320. In the presence of factor Xa alone, initial cleavage at Arg271 produces F1.2 and pre2 (left pathway), followed by cleavage at Arg320 generating active thrombin. In the presence of factor Va and phospholipids, factor Xa cleaves Arg320 producing the active intermediate meizothrombin, which is further processed at Arg271 to release thrombin from F1.2 (right pathway). The Gla domain (GLA), kringle 1 (K1), kringle 2 (K2), and protease domains (Pro) are shown as ovals showing linkers between each as lines.