Inactivation of factor Va (FVa) by activated protein C (APC) is a predominant mechanism in the down-regulation of thrombin generation. In normal FVa, APC-mediated inactivation occurs after cleavage at Arg306 (with corres-pondingrate constantk¢306) or after cleavage at Arg506 (k506 ) and subsequent cleavage at Arg306 (k306). We have studied the influence of heparin on APC-catalyzed FVa inactivation by kinetic analysis of the time courses of inac-tivation. Peptide bond cleavage was identified by Western blottingusingFV-specific antibodies. .