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Mutations in the factor V gene (factor V Leiden [FVL]) and the prothrombin gene (prothrombin G20210A [PTm]) are associated with pregnancy complications, including recurrent early pregnancy loss and late pregnancy loss, both of which might be caused by thrombosis of placental vessels. Thrombotic tendencies and altered pregnancy outcomes also have been observed in patients with essential thrombocythemia (ET); many women with ET have mutations in the Janus kinase 2 gene (JAK2). In two new studies, investigators examined outcomes of subsequent pregnancies after first pregnancy losses in women with FVL or PTm and pregnancy complications in women with ET and JAK2 mutations.
In the first study, investigators retrospectively evaluated 498 pregnant Dutch women who carried either FVL or PTm and 495 pregnant controls without either mutation. First pregnancies were successful in 825 women, and pregnancy losses occurred in 67 carriers (13%) and 43 controls (9%; relative risk, 1.5; 95% confidence interval, 1.1–2.2). Among women with first pregnancy losses, second pregnancies were successful in 74% of carriers and in 77% of controls (RR, 1.0). Among women who had late pregnancy losses (>12 weeks’ gestation), subsequent live birth rates were lower for carriers than for controls (68% vs. 80%), but this difference was not statistically significant.
In the second study, a group of Italian university investigators evaluated 96 pregnancies that occurred in 58 patients with ET. During pregnancy, median blood values were measured: platelet count, 601/µL (range, 266–1660/μL); white blood–cell count, 7.1/µL (range, 4.2–15.3/μL); and hemoglobin level, 13.1 g/dL (range, 11.5–15.4 g/dL). Twenty-four of 49 genotyped women carried JAK2 mutations. First-pregnancy complications (8 spontaneous abortions, 3 cases of intrauterine growth retardation, 2 stillbirths, 2 women with preeclampsia, and 2 women with hypertension) occurred in 17 JAK2 mutation carriers (71%). JAK2 mutation was an independent risk factor for pregnancy complications (P=0.01) and fetal loss (P=0.05). Many patients (62%) received daily aspirin (100 mg) during their pregnancies, but this therapy conveyed no benefit for pregnancy outcomes.
Coppens M et al. Outcome of the subsequent pregnancy after a first loss in women with the factor V Leiden or prothrombin 20210A mutations. J Thromb Haemost 2007 Jul; 5:1444-8.
Passamonti F et al. Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation. Blood 2007 Jul 15; 110:485-9.
Comment
Findings from these two studies confirm that thrombophilia is a risk factor for impaired pregnancy outcome. Whereas FVL and PTm seem to be relatively weak risk factors, ET, and especially ET with the JAK2 mutation, is particularly strong. In the Dutch study, second pregnancies were equally likely to be successful in carriers (none of whom received anticoagulants) and controls, so use of anticoagulants during pregnancy in women with FVL or PTm and one pregnancy loss was not supported. The Italian study indicated that aspirin does not prevent adverse fetal outcomes in women with ET.