Assessing Best Practices in Managing Pregnancy, Myeloproliferative Neoplasms

In women with myeloproliferative neoplasms (MPN), pregnancy events have been reported most frequently in those with essential thrombocythemia (ET), followed by polycythemia vera (PV) and primary myelofibrosis (PMF).

As researchers noted in a critical review published in the American Journal of Hematology, MPNs pose unique fetal and maternal challenges, particularly risk of fetal loss. For ET, live birth rate is estimated at 70% with first trimester loss serving as the major complication in these populations, affecting 30%.

“Both pregnancy and MPN impart a hypercoagulable milieu, conferring a heightened risk for thrombosis,” said the authors. “In addition, bleeding diathesis may escalate at the time of delivery and in the postpartum phase, especially in the context of treatment with aspirin and/or low molecular weight heparin.”

With hematological and obstetrical challenges becoming increasingly prevalent for patients with MPNs during pregnancy, researchers sought to review these issues, as well as provide their systematic approach to management.

As they highlighted, it is now well established that patients with PV or ET experience a higher rate of both arterial and venous thrombotic events. However, current thrombotic risk stratification models in MPN have limited applicability in determining pregnancy complications, with risk suggested to be relatively low in those without prior thrombotic events and high if otherwise.

“In regards to thrombotic events, risk of venous thromboembolism is increased 4-fold to 6-fold during pregnancy, with the greatest risk in the post-partum phase,” they wrote.

Discussing pregnancy outcomes in MPN overall, researchers noted that existing knowledge suffers from immense variability that stems from the heterogeneity in published literature. The best evidence to date involves 2 recent systematic reviews and meta-analyses: (1) a review published in Expert Review Hematology that includes 793 patients with ET, 158 with PV, and 15 with PMF, and (2) a study published in JAMA Network Open including 1210 ET and PV pregnancies.

In findings from the latter report, the live birth rate was found to be inferior to the general population at 71% and 67% for ET and PV, respectively, with 59% of fetal losses occurring in the first trimester. Conversely, maternal thrombosis and postpartum hemorrhage were infrequent, occurring in 1.5% each with a 3% incidence of preeclampsia, added the study authors.

Efficacy of potential therapies, such as aspirin, cytoreductive therapy, and systemic anticoagulation, was also noted to suffer from a lack of controlled evidence. Based on their practice experience and that of the evidence available, they say that aspirin alone may be sufficient in ameliorating fetal and maternal complications in low risk patients.

In high risk patients, they recommended that cytoreductive therapy in the form of interferon-alpha (INF-α) might be needed, particularly for those with ET or PV, in addition to aspirin therapy. They say that INF-α can also be considered for select low-risk patients with ET or PV with a history of recurrent fetal loss, prominent splenomegaly, or suboptimal hematocrit control with phlebotomy.

“In addition, all women with PV should maintain strict hematocrit control less than 45% with the aid of phlebotomy,” they wrote.

For patients with a history of venous thrombosis, systemic anticoagulation in the form of low molecular weight heparin was advised.

“Moving forward, formulation and implementation of prospective risk-adapted therapeutic interventions geared towards securing favorable fetal and maternal outcomes are a priority,” concluded the study authors.

Reference

Gangat N, Tefferi A. Myeloproliferative neoplasms and pregnancy: Overview and practice recommendations. Am J Hematol. Published online December 9, 2020. doi:10.1002/ajh.26067