Distinctive features of patients with MPN during pregnancy: Thrombotic risk, molecular drivers, and differential outcomes by subtype

Abstract Introduction: Ph-negative myeloproliferative neoplasms (MPNs), particularly essential thrombocythemia (ET) and polycythemia vera (PV), account for up to 20% of cases in women of reproductive age. For these patients, pregnancy planning and achieving successful birth outcomes present significant challenges due to disease-related risks, including thrombotic complications, placental insufficiency, and adverse pregnancy outcomes. Material and methods: This study analyzed pregnancy outcomes in women with Ph-negative MPNs treated at the National Medical Research Center of Hematology (2014-2024), focusing on risk-adapted management strategies, and maternal-fetal complications. Results: This study analyzed 150 pregnancies in 110 patients with Ph-negative MPNs, including ET, PV, and primary myelofibrosis (PMF). The cohort consisted of 60(54.5%) ET patients with 76(50.67%) pregnancies, 35 (31.8%) PV patients with 50(33.4%) pregnancies, and 15(13.6%) PMF patients-24(40%) pregnancies. Thrombotic risk assessment by R-IPSET in ET before pregnancy showed that 24 (40%) patients had very low risk, 33 (55%)- low risk, and 3 (5%) had high risk, including one arterial and two venous thromboses. Among PV patients assessed by Marchioli thrombosis risk score revealed low risk in 23 (65.7%) patients, 5 (14.3%) patients with intermediate risk and 7 (20%) high risk, with six venous thromboses. Most PMF patients had low-risk DIPSS scores, except one intermediate-1 case. Genetic analysis revealed JAK2 V617F mutations in 35 (58.3%) of ET and 6 (40%) of PMF patients, while CALR mutations were present in 17 (28.3%) of ET and 6 (40%) of PMF cases. Additionally, 15 patients had hereditary thrombophilia (ET-4, PMF-1 and PV 10 patients), and eight were diagnosed with antiphospholipid syndrome (ET-1, PMF-1 and PV 6 patients). Among 19 women with an adverse obstetric history, 7(11,7%) were diagnosed with ET, 7(20%) with PV, and 5(33,4%) with PMF. Pregnancy outcomes showed an overall loss rate of 26% (39/150), with ET having the lowest rate 15.7% (12/76) compared to PV 36% (18/50) and PMF 37.5% (9/24). Live births occurred in 80.2% of ET, 51% of PV, and 54.1% of PMF pregnancies. Common complications included first-trimester miscarriage threat 16% (24/150), preterm birth 14% (21/150), and bleeding 11.3% (17/150). Perinatal deaths occurred in four cases, three of which were in PV patients, along with fetal malformations (four cases) and intrauterine growth restriction (three cases). Treatment strategies predominantly involved interferon-alpha (INF-α)- 57.3% of pregnancies, often combined with low-molecular-weight heparin (LMWH) and aspirin. Most often, patients received INF-α, LMWH and ASA together (32.6%), INF-α and ASA (34.7%), LMWH and ASA (13.3%), and only ASA (15.3%). High thrombotic risk during pregnancy was observed in 42.1% (32/76) of ET, 74% (37/50) of PV, and 50% (12/24) of PMF cases. Despite therapy, 20% of pregnancies proceeded without complications, with ET showing the most favorable outcomes -23.7% (18/76) compared to PV-16% (8/50) and PMF-16.7% (4/24). Conclusion: Pregnancies carrying multiple risk factors including, adverse obstetric history, hereditary thrombophilia, antiphospholipid syndrome, are considered higher risk. However, our data show that pregnancies in ET patients generally fare better with fewer complications, with approximately 20% proceeding without adverse events. These findings highlight the increased risks in PV and PMF pregnancies, underscoring the need for individualized management in MPN patients.