Schematic of prothrombin activation. Human prothrombin consists of fragment 1 (F1), fragment 2 (F2), and the A and B chains of α-thrombin. Prothrombin is activated to α-thrombin by cleavage at Arg271 (R271) and Arg320 (R320). Initial cleavage at Arg271 (left pathway) generates fragment 1.2 and the inactive intermediate prethrombin-2. Subsequent cleavage at Arg320 generates α-thrombin. Alternatively, the active intermediate meizothrombin is produced when initial cleavage occurs at Arg320 (right pathway). Subsequent cleavage at Arg271 produces both α-thrombin and fragment 1.2.