There is provided FV derivatives that reduce blood clotting activity, by reducing thrombin generation, when compared to wild-type FV. In particular, the FV of the present invention comprises single-point and multi-point mutations, encompassed by aspartic acid 79 to glutamic acid 119 of the wild type sequence (SEQ ID NO:2). The derivatives can be used to treat patient with conditions necessitating reduced clotting activity.