• antithrombin deficiency;
  • protein C deficiency;
  • protein S deficiency;
  • pregnancy;
  • venous thromboembolism


Pregnancy is associated with an increased risk of venous thromboembolism, which probably varies according to the presence of single or multiple thrombophilic defects. This retrospective family cohort study assessed the risk of venous thromboembolism during pregnancy and puerperium, and the contribution of concomitant thrombophilic defects in families with hereditary antithrombin, protein C or protein S deficiencies. Probands were excluded. Of 222 female relatives, 101 were deficient and 121 non-deficient. Annual incidences of venous thromboembolism were 1·76% in deficient women versus 0·19% in non-deficient women [adjusted relative risk (RR) 11·9; 95% confidence interval (CI), 3·9–36·2]. Other single and multiple thrombophilic defects increased the risk in deficient women from 1·55% to 2·14% and 2·92%, and in non-deficient women from 0·16% to 0·09% and 0·54% respectively. Deficient women were at lower risk (1·37%; 0·80–2·19) than deficient women that had never been pregnant (2·96%; 1·53–5·18); RR 0·5 (0·2–0·99). This difference was due to the predominance of events related to oral contraceptives in deficient women that had never been pregnant (75%), while 71% of events in deficient women that had had at least one pregnancy were pregnancy-related. In conclusion, women with hereditary deficiencies of antithrombin, protein C or protein S are at high risk of pregnancy-related venous thromboembolism. This risk is increased by multiple additional thrombophilic defects.