No abstract

Summary Hereditary thrombophilia is associated with an increased risk of fetal loss. Assuming that fetal loss is due to placental thrombosis, anticoagulant treatment might improve pregnancy outcome. In an observational family cohort study, we prospectively assessed the effects of anticoagulant drugs on fetal loss rates in women with hereditary deficiencies of antithrombin, protein C or protein S. The cohort contained 376 women (50 probands and 326 deficient or non‐deficient relatives). Probands were consecutive deficient patients with venous tromboembolism. Thromboprophylaxis during pregnancy was recommended in deficient women, irrespective of prior venous thromboembolism, and in non‐deficient women with prior venous thromboembolism. Outcome of first pregnancy was analysed in 55 eligible women. Of 37 deficient women, 26 (70%) received thromboprophylaxis during pregnancy, compared with three of 18 (17%) non‐deficient women. Fetal loss rates were 0% in deficient women with thromboprophylaxis versus 45% in deficient women without (P = 0·001) and 7% in non‐deficient women without thromboprophylaxis (P = 0·37). The adjusted relative risk of fetal loss in women who received thromboprophylaxis versus women who did not was 0·07 (95% confidence interval 0·001–0·7; P = 0·02). Our data suggest that anticoagulant treatment during pregnancy reduces the high fetal loss rate in women with hereditary deficiencies of antithrombin, protein C or protein S.

SummaryPregnancy 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 nondeficient. Annual incidences of venous thromboembolism were 1AE76% in deficient women versus 0AE19% in non-deficient women [adjusted relative risk (RR) 11AE9; 95% confidence interval (CI), 3AE9-36AE2]. Other single and multiple thrombophilic defects increased the risk in deficient women from 1AE55% to 2AE14% and 2AE92%, and in non-deficient women from 0AE16% to 0AE09% and 0AE54% respectively. Deficient women were at lower risk (1AE37%; 0AE80-2AE19) than deficient women that had never been pregnant (2AE96%; 1AE53-5AE18); RR 0AE5 (0AE2-0AE99). 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.

Summary. Background: The factor V Leiden (FVL) and prothrombin 20210A (PTm) mutations are associated with single late pregnancy loss and recurrent early pregnancy loss. The prognosis after an initial loss in women with thrombophilia is uncertain. Objective: To assess the pregnancy outcome of the second pregnancy after a first loss in women with and without either FVL or PTm mutations. Methods: We selected women with a first pregnancy loss out of two family cohorts of first degree relatives of probands with FVL or PTm mutations and a history of documented venous thromboembolism or premature atherosclerosis. Results: Ninety-three women had had a first pregnancy loss and became pregnant a second time. Their risk of loss of the subsequent pregnancy was higher than in 825 women with a successful first pregnancy [25 vs. 12%, relative risk (RR) 2.0, 95% CI 1.4-3.0]. The live birth rate of the second pregnancy after an early first loss (£ 12 weeks of gestation) was 77% (95% CI 62-87) for carriers and 76% (95% CI 57-89) for non-carriers (RR 1.0, 95% CI 0.8-1.3). After a late first loss (> 12 weeks), the live birth rates were 68% (95% CI 46-85) and 80% (95% CI 49-94) for carriers and non-carriers, respectively (RR 0.9, 95% CI 0.5-1.3). Conclusions: Women with a first pregnancy loss have a 2-fold increased risk of loss of the subsequent pregnancy, regardless of their carrier status. More importantly, the outcome of the second pregnancy is rather favorable in absolute terms, even for those with thrombophilia and a late loss, which raises concern regarding the risks and presumed benefits of anticoagulant therapy in these women.

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