Myocardial Ischemia in Patients Living with Myeloproliferative Neoplasms: Epidemiology and Outcomes
Authors: Singhal Sachi , Thomas Rachel , Rizwan Farsha , Kashinath Sanjana 
Published: December 2024

Introduction: BCR-ABL negative Myeloproliferative neoplasms (MPNs) originate from hematopoietic multipotent stem cell after acquiring a clonal proliferative advantage in the marrow. There exists a dearth of information for post-myocardial infarction (MI) outcomes of patients with MPNs. We performed a retrospective study to evaluate outcomes in patients with MPNs who developed a cardiac event.

Methods: The admissions database for Temple University Health System was scanned for hospitalizations with diagnosis codes of MPNs and Coronary artery disease (CAD) between 2014-2024. 191 patient charts were reviewed. After excluding duplicate charts and coding errors, 39 patients were included. Immediate, 30,90-day thrombosis/bleeding, comorbidities, socio-demographic and MPN-associated variables were collected.

Results: The median age was 76(55-92) yrs, and male predominance (25 males, 14 females) was noted. Racial distribution included 14 Caucasians, 16 African Americans, 5 Hispanics, and 4 (other). An equal number of PV and ET (n=14 each) were seen, followed by MF(n=10) and pre-MF (n=1). The primary mutation was predominantly JAK2 V617F (n=25), followed by CALR (n=9), triple negative (n=3) and JAK2 Exon 12(n=1). Of the 13 patients with an available molecular profile, ASXL1 was noted (n=3) followed by ZRSR2,DNMT3A (n=2 each),TP53, IDH and ATRX (n=1 each). Counts on presentation - WBC ranged from 2-35, Hb from 6-20, HCT 21-62.6, plts 44-1156; with a mean of 10, 12, 36.5 and 488 respectively. Most patients (n=30) on MPN-therapy; Hydroxyurea (HU) was the most common (n=24), followed by Ruxolitinib (n=4) and supportive care (n=2). 21 patients were on treatment for &gt;1 year (1-26 years)

16 patients suffered from stable angina, 14 patients NSTEMI, 9 STEMI, and an equal proportion underwent coronary artery bypass grafting, percutaneous intervention, and medical management (n=13 each). All patients were on Aspirin (ASA) after, and 3 were on ASA from before. Overall, 10 patients experienced significant bleeding, and this occurred more frequently around 90 days from the index event (n=6).The average length of hospital stay for patients developing major bleeding was 20.42 (6-37) days, compared to others at 8.8 (1-32) days. 5 patients developed arterial thrombosis, where one was on DAPT, one was on triple therapy, and 4 of the 5 patients were on anticoagulation. Most (4 out of 5) were on HU for their underlying MPN. 2 developed a venous thrombotic event and were on warfarin and ASA at the time.

A subset of interest is the group (n=14) that was initiated on dual antiplatelet therapy (DAPT) after developing MI; a majority (n=13) were on ASA/Plavix. The most common mutation was JAK2 V617F (n=11); 3 patients developed major bleeding while being on DAPT, and 2 patients developed arterial thrombosis (between days 30 - 90).

Discussion:

Patients with MPNs that developed MI have both major bleeding and thrombotic complications even while being on guideline-directed therapy. Despite managing the MPN (most commonly with HU), its effect on the prevention of recurrent thrombosis is uncertain, especially with near normal counts. JAK2 V617 has been associated previously with a risk of thrombosis, and remained the predominant primary mutation in our cohort regardless of underlying MPN, specifically so in the DAPT subset. The role of secondary mutations is coming to light in recent years. DNMT3A and ASXL1 were previously seen to increase risk of thrombosis, and knowing the molecular profile may play a key role in predicting recurrent thrombotic events. ATRX mutation, noted in one patient in our cohort, has been associated with a lower risk of thrombosis in CNS tumors, but its effect in MPN thrombosis is unclear. The rates of major bleeding were noted to be high with an observed longer hospital stay. The continued development of arterial and venous thrombosis despite being on anticoagulation/antiplatelet agents raises several questions on the effectiveness of therapies and whether a change in MPN therapy is warranted after an MI.

Conclusion: Thrombosis and hemorrhage continue to pose a significant burden in patients with MPN after a cardiac event. It is imperative to tailor the management of myocardial ischemia in this population based on their underlying primary mutation and molecular profile. Along with more intensive therapies for both MPN and anticoagulation, close attention must be paid to aggressive cardiovascular risk reduction.