Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects: a retrospective family study.

OBJECTIVE: To assess the absolute risk of fetal loss associated with hereditary deficiencies of antithrombin (AT), protein C (PC) and protein S (PS), and the contribution of additional thrombophilic defects to this risk. DESIGN: A retrospective family cohort study. SETTING: A tertiary referral teaching hospital. POPULATION: Women from families with hereditary deficiencies of AT, PC and PS, and their non-deficient relatives. METHODS: We assessed the absolute risk of fetal loss, comparing deficient women with non-deficient female relatives. MAIN OUTCOME MEASURES: Early, late and total fetal loss rates; odds ratios of fetal loss. RESULTS: We evaluated 289 women, who had 860 pregnancies. The total fetal loss rates were 23% (AT deficient), 26% (PC deficient), 11% (type-I PS deficient) and 15% (type-III PS deficient), compared with 11, 18, 12 and 13% in non-deficient women, respectively. Odds ratios were 2.3 (95% CI 0.9-6.1), 2.1 (95% CI 0.9-4.7), 0.7 (95% CI 0.2-1.8) and 1.1 (95% CI 0.6-2.0), none of which reached statistical significance. Differences were mainly the result of higher late fetal loss rates in women deficient in AT (OR 11.3, 95% CI 3.0-42.0) and PC (OR 4.7, 95% CI 1.3-17.4). The concomitance of factor-V Leiden and prothrombin G20210A was observed in 19% of women, and did not increase the risk of fetal loss. CONCLUSIONS: Although absolute risks of fetal loss were high, odds ratios of total fetal loss were not statistically significant in deficient versus non-deficient women. However the higher absolute risks appeared to reflect higher late fetal loss rates as opposed to early fetal loss rates. An additional effect of concomitance of factor-V Leiden and prothrombin G20210A was not demonstrated, which may result from the exclusion of women at highest risk of venous thromboembolism, or from the small numbers sampled in the study.

Outcome of the subsequent pregnancy after a first loss in women with the factor V Leiden or prothrombin 20210A mutations.

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), 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.