Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation

Abstract

Essential thrombocythemia (ET) may occur in women of childbearing age. To investigate the risk of pregnancy complications, we studied 103 pregnancies that occurred in 62 women with ET. The 2-tailed Fisher exact test showed that pregnancy outcome was independent from that of a previous pregnancy. The rate of live birth was 64%, and 51% of pregnancies were uneventful. Maternal complications occurred in 9%, while fetal complications occurred in 40% of pregnancies. The Mantel-Haenszel method showed that fetal loss in women with ET was 3.4-fold higher (95% confidence interval [CI]: 3-3.9; P < .001) than in the general population. Half of the women studied carried the JAK2 (617V>F) mutation, and a multivariate logistic regression model identified this mutation as an independent predictor of pregnancy complications (P ‫؍‬ .01). Neither the platelet count nor the leukocyte count was a risk factor. JAK2 ( IntroductionEssential thrombocythemia (ET) is a chronic myeloproliferative disorder with an increased risk of vascular complications. Despite these events, life expectancy of patients with ET is not significantly affected by the disease in any age category. 1 Patients with ET are predominantly women, and some of them are diagnosed at childbearing age. 2 Decision-making on pregnancy is therefore a common issue in the clinical management of young women with ET.There is limited information regarding the outcome of pregnancy in patients with ET, mainly from case reports. Papers reviewing published studies on pregnancies in patients with ET 3-5 report live birth rates of 50% to 70% and spontaneous abortion rates of 25% to 50%. Concerning risk factors, the study of Wright and Tefferi 6 on 43 pregnancies indicates that preconception platelet count and aspirin therapy do not predict the risk of abortion.The JAK2 (617VϾF) mutation has been recently identified in approximately half of patients with ET. 7-10 It has been suggested that the presence of the mutation in patients with ET characterizes a disease with a higher risk of vascular events. 9 To date, the relationship between JAK2 mutational status and the outcome of pregnancy in women with ET is unknown.We studied 103 pregnancies occurring in 62 patients with ET to investigate the risk of complications and to find predictors of pregnancy outcome. Patients, materials, and methods PatientsThis study includes 103 consecutive pregnancies that occurred in 62 patients with ET who were followed between 1980 and 2006 at the Division of Hematology of the Fondazione Policlinico San Matteo, University of Pavia; the Division of Internal Medicine of the University of Padova; and the Division of Hematology of the Niguarda Ca' Granda Hospital of Milan, Italy. The study was approved by the institutional ethics committee of Pavia, and the procedures followed were in accordance with the Helsinki Declaration of 1975, as revised in 2000. Samples for molecular analysis were obtained after patients provided written informed consent.Diagnostic criteria of ET were those in use at the time of the fi...

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

“…First-trimester spontaneous miscarriage rate in ET or PV (>30%) [79][80][81] is significantly higher than the 15% rate expected in the control population and does not appear to be influenced by specific treatment [79]. Late obstetric complications as well as maternal thrombohemorrhagic events are relatively infrequent and platelet count usually decreases substantially during the second and third trimesters [82].…”

A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications

“…18 PCR was performed on a RotorGene 6000TM real-time analyzer on a 100-well Gene Disk (Corbett Life Sciences, Mortlake, NSW, Australia) in two separate tubes for normal and mutated alleles. In all, 40 nanograms of genomic DNA were amplified in a 40-cycle PCR at an annealing temperature of 55 1C.…”

Evidence and expertise in the management of polycythemia vera and essential thrombocythemia

“…61 Interestingly, a recent study showed that JAK2 V617F is an independent predictor of pregnancy complications and that aspirin did not prevent complications in mutated patients and appear to worsen outcome in patients without the mutation. 62 Our management of pregnancy in MPNs is summarized in Table 5.…”