Abstract: The present application generally relates to methods to prevent or treat bleeding and/or hypocoagulation in an individual in need thereof, and compositions for use in such methods. The methods comprise administration of FVa, preferably an APC resistant FVa (such as superFVa), alone or in combination with FVIIa, preferably rhFVIIa (such as NovoSeven® or another FVIIa having enhanced activity or half-life). When administered in combination, FVa and FVIIa elicit a synergistic benefit when used to treat or prevent bleeding or hypocoagulation in subjects in need thereof, e.g.

Abstract: The present application generally relates to methods to prevent or treat bleeding and/or hypocoagulation in an individual in need thereof, and compositions for use in such methods. The methods comprise administration of FVa, preferably an APC resistant FVa (such as superFVa), alone or in combination with FVIIa, preferably rhFVIIa (such as NovoSeven® or another FVIIa having enhanced activity or half-life). When administered in combination, FVa and FVIIa elicit a synergistic benefit when used to treat or prevent bleeding or hypocoagulation in subjects in need thereof, e.g.

Abstract: Variants (mutants) of recombinant activated protein C (APC) or recombinant protein C (prodrug, capable of being converted to APC) that have substantial reductions in anticoagulant activity but that retain normal levels of anti-apoptotic activity are provided. Three examples of such recombinant APC mutants are KKK191-193AAA-APC, RR229/230AA-APC, and RR229/230AA plus KKK191-193AAA-APC. APC variants and prodrugs of the invention have the desirable property of being cytoprotective (anti-apoptotic effects), while having significantly reduced risk of bleeding. The invention also provides a method of using the APC variants or prodrugs of the invention to treat subjects who will benefit from APC's cytoprotective activities that are independent of APC's anticoagulant activity. These subjects include patients at risk of damage to blood vessels or tissue in various organs caused, at least in part, by apoptosis.

Abstract: Variants (mutants) of recombinant activated protein C (APC) or recombinant protein C (prodrug, capable of being converted to APC) that have substantial reductions in anticoagulant activity but that retain normal levels of anti-apoptotic activity are provided. Two examples of such recombinant APC mutants are KKK191-193AAA-APC and RR229/230M-APC. APC variants and prodrugs of the invention have the desirable property of being cytoprotective (anti-apoptotic effects), while having significantly reduced risk of bleeding. The invention also provides a method of using the APC variants or prodrugs of the invention to treat subjects who will benefit from APC's cytoprotective activities that are independent of APC's anticoagulant activity. These subjects include patients at risk of damage to blood vessels or tissue in various organs caused, at least in part, by apoptosis.