The C-terminal acidic region in the A1 domain of factor VIII facilitates thrombin-catalyzed activation and cleavage at Arg372.

Residues 346-349 with sulfated Tyr provided a thrombin-interactive site responsible for activation and cleavage at Arg372 . A hirugen-hybrid A1 mutant showed more efficient thrombin-catalyzed cleavage at Arg372 .