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ACTIVATED protein C (APC) is a serine protease with potent anti-coagulant properties, which is formed in blood on the endothelium from an inactive precursor¹. During normal haemostasis, APC limits clot formation by proteolytic inactivation of factors Va and Villa (ref. 2). To do this efficiently the enzyme needs a non-enzymatic cofactor, protein S (ref. 3). Recently it was found that the anticoagulant response to APC (APC resistance) ⁴ was very weak in the plasma of 21% of unselected consecutive patients with thrombosis⁵ and about 50% of selected patients with a personal or family history of thrombosis^6,7; moreover, 5% of healthy indi-viduals show APC resistance, which is associated with a sevenfold increase in the risk for deep vein thrombosis⁵. Here we demonstrate that the phenotype of APC resistance is associated with hetero-zygosity or homozygosity for a single point mutation in the factor V gene (at …