Management and Outcome of 11 Pregnancies in Women with Polycythemia Vera

Background: Unlike to Essential Thrombocythemia, Polycythemia Vera (PV) is rare in women of childbearing age, with only few previous pregnancies reported in literature; a positive outcome of pregnancy has been described in about 2/3 of cases and maternal complications in about 1/4 of delivery.

Aims and Methods: We retrospectively analyzed outcome and complications in a series of 11 pregnancies in 7 females with PV. These patients were diagnosed and managed between 2000 and 2017 in 3 Italian Centers. PV diagnosis was perfomed or revised according to WHO 2016 criteria. Different therapeutic approaches have been assessed prior and during each pregnancy.

Results: Median age at diagnosis and at conception were 24.3 and 30.1 years, respectively. According to molecular status, all patients presented JAK2V617F mutations. Four patients (57.1%) had two pregnancies. All patients received phlebotomies as required, with a median hematocrit (Ht) level at the time of conception of 45.2% (range: 41.4-46.8). Median values of WBC and PLT at conception were 9.9 x 10⁹/l (range: 6.7-18.3) and 510 x 10⁹/l (250-917). Only one patient presented a history of thrombosis (2 TIA) occurred before first pregnancy. Three (42.8%) females presented cardiovascular risk factors at the time of conception, while a thrombophilic predisposition was documented in 3 patients (42.8%).

Among the 11 pregnancies, 8 (72.7%) ended with a full term delivery, while 2 (18.2%) were complicated by a fetal loss in the first trimester and by an Intrauterine growth retardation with preterm delivery. It is worth of note that the fetal loss was reported in the patient with prior arterial thrombosis and concomitant signs of myeloproliferation (mild leukocytosis, Ht level > 45% and PLT level > 900 x 10⁹/l), while the intrauterine growth retardation was reported in a patient with Ht level > 45%, despite the typical hemodiluition of pregnancy. The remaining pregnancy was characterized by maternal complications, consisting of an extra-tubal pregnancy with consequent laparoscopic surgery approach and fetal death. The global live birth rate was 81.8 %.

Anti-thrombotic treatment was administered in all but one pregnancy, consisting of low-dose acetil salicylic acid (ASA) already started since PV diagnosis and continued during pregnancy in 6 pregnancies (54.5%), or a combination of ASA and Low Molecular Weight Heparin (LMWH) during the second and last trimester of pregnancy and post-partum in the remaining 4 pregnancies (36.3%). Two patients were also treated with interferon-alfa during their pregnancy. One patient was receiving hydroxyurea at the time of conception, which was immediately stopped.

Conclusions: Our data indicate that PV patients may develop pregnancy complications in about 1/4 of cases (27.2%), but the risk of fetal loss (18.2%) is lower than recently reported in similar series of PV females. The vast majority of our patients received ASA +/- LMWH during pregnancy and post-partum, suggesting an important role of anti-thrombotic treatment in reducing incidence of fetal complications. The history of prior thrombosis and the signs of myeloproliferation at conception and at delivery seem to be associated to development of fetal complications. Considering the current guidelines for the management of PV, in particular the more aggressive control of Ht (with Ht target < 45%), it is possible that the large application of this approach also in PV pregnancies could further improve the rate of fetal complications. Larger collaborative multicenter studies, in order to better clarify the optimal management of pregnancy in PV, are warranted.