Activated protein C resistance and deficiencies of antithrombin III, protein C or protein S and the risk of thromboembolic disease in users of oral contraceptives.

The objective of this paper was to assess the risk of thrombosis in users of oral contraceptives. Furthermore, the sensitivity, specificity and predictive values of potential screening tests for the prediction of thromboembolic complications in users of oral contraceptives were calculated for the approximately six million German pill users. Despite high specificity, the predictive values of a positive family history, or evidence of either antithrombin III, protein C or protein S deficiency or resistance to activated protein C, are low due to the very low absolute risk of thrombosis among pill users. More than half of the 840 annual cases would pass the screening protocol undetected. A two-step screening protocol is suggested using family history as a selection criterion (thus reducing the need for laboratory screening by 85%) for laboratory investigation of activated protein C sensitivity and deficiencies of antithrombin III, protein C or protein S. Genotyping for factor V Leiden mutation is useful in cases with equivocal activated protein C sensitivities or to confirm a homozygous genotype.