THROMBOTIC RISK OF WOMEN WITH HEREDITARY ANTITHROMBIN-III-DEFICIENCY,PROTEIN C-DEFICIENCY AND PROTEIN S-DEFICIENCY TAKING ORAL-CONTRACEPTIVE MEDICATION

The thrombotic risk of women with a heterozygous natural clotting inhi bitor deficiency taking oral contraceptives (OC) has not been evaluate d. Therefore, a retrospective collaborative controlled cohort-study wa s carried out in 8 coagulation laboratories and thrombosis units in Au stria, Germany and Switzerland. The incidence of thromboembolism in 48 females heterozygous for hereditary type I deficiency of antithrombin III (n = 15), protein C (n = 16) or protein S (n = 17), who had taken OC al least once in their life were compared with that of 48 deficien t women, who had never taken OC (controls). Diagnosis of the deficienc y state was made in the participating centers. Data on the onset and d uration of OC intake and the date and site of thrombotic events were o btained from a questionnaire filled in by the patient or a physician d uring a visit at a participating center. The observation period in the OC patients was started with onset of OC intake and was terminated wh en a thromboembolic event had occurred or when OC medication were disc ontinued. In the patients without OC, the observation period began at an age matched to that of the OC patient and ended when a thromboembol ic event had occurred or was continued as long as the corresponding OC patient was on treatment. In AT III-deficient females the probability for thrombosis was significantly higher for patients taking OC compar ed to the non-OC-patients (Wilcoxon test p = 0.004, Log Rank test p = 0.005). In patients with protein C- (beta-error 0.8) and protein S-def iciency (beta-error 0.05) there was no significant difference between the OC- and non-OC-group. The incidence of thrombosis/patient year in AT III-, PC- and PS-deficient females on OC was 27.5%, 12% and 6.5%, r espectively and 3.4%, 6.9% and 8.6%, respectively, in the control pati ents. We conclude that females with hereditary antithrombin III-defici ency are at high risk for venous thromboembolism when taking OC. There fore, OC should be strictly avoided in these females and AT III measur ement is mandatory in female relatives of AT III-deficient patients at young age before starting OC. There is no evidence for an excess thro mbotic risk by OC intake in PS-deficient females. In protein C-deficie nt women OC medication was not associated with a significant increase of thrombosis, but an increased risk cannot be excluded.