APC resistance is often associated with the occurrence of a single point mutation in factor V (factor V".,u",) at a predominant cleavage site for the natural anticoagulant, activated protein C (APC). In this article we will discuss the effects of this mutation (Argso0-6rn) on the down-regulation of factor Va cofactor activity and on thrombin formation by APC in model systems and in plasma. Our studies on the effects of APC on thrombin formation in plasma resulted in the development of a new

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... od for the screening of APC resistance that is based on measurement of the effect of APC on the endogenous thrombin potential (the time integral of thrombin generated in clotting plasma). It appeared that sensitivities for APC determined via this method were considerably affected by the use of oral contraceptives (OC) and that women who use OC become acquired APC resistant. The fact that acquired APC resistance in women who use third-generation OC was more pronounced than in users of second-generation OC may explain the further increased risk for yenous thrombosis associated with the use of third-generation OC. Some 20 yeirrs ago it was recognizedthat the activated form of the plasma protein protein C, called APC, is a serine protease that down-regulates thrombin forma-