Mechanism of thrombin-catalyzed FV activation. Schematic representation of the human factor V activation pathway. Cleavage of the a2-B domain linker after Arg⁷⁰⁹ is followed by processing at the Arg¹⁰¹⁸-Thr¹⁰¹⁹ site, liberating the so-called fragment E (Ser⁷¹⁰-Arg¹⁰¹⁸). Finally, slower proteolysis of the Arg¹⁵⁴⁵-Ser¹⁵⁴⁶ peptide bond releases fragment C1 (Thr¹⁰¹⁹-Arg¹⁵⁴⁵), and generates a fully functional cofactor.^48,49  Activated protein C (APC) cleavages at Arg³⁰⁶-Asn³⁰⁷, Arg⁵⁰⁶-Gly⁵⁰⁷, and Arg⁶⁷⁹-Lys⁶⁸⁰ that inactivate FVa are also indicated with arrowheads.