Activation and degradation of normal FV and FV Leiden. FV circulates as a single-chain high-molecular-weight protein. Thrombin (or FXa) cleaves a number of peptide bonds, which results in the liberation of the B domain and generation of FVa. Three peptide bonds in FVa are cleaved by APC (Arg306, Arg506, and Arg679) resulting in inhibition of FVa activity. The FV Leiden mutation eliminates one of the APC cleavage sites, which impairs the degradation of FVa. Illustration by Marie Dauenheimer.