Molecular and Clinical Risk Factors Associated with Thrombosis and Bleeding in Myelofibrosis Patients.

Abstract

Background:  The risk of thrombosis and bleeding in myelofibrosis (MF) has been historically underappreciated. We sought to investigate potential molecular and clinical risk factors for venous (VTE) and arterial (ATE) thrombotic events as well as bleeding episodes.

Methods:  Data from 246 consecutive MF patients were analyzed. Driver mutations were tested in 191 patients.

Results:  In total, 181 mutations were found in 177 MF patients: 118 (61.8%) patients showed JAK2-V617F, 50 patients (26.2%) showed CALR, and 6 patients (3.1%) showed MPL mutations. Two patients were JAK2-V617F and MPL positive and one patient was positive for all three genes. Fourteen (7.3%) patients were triple negative. The JAK2-V617F allele burden was assessed in 63 JAK2-V617F-mutated patients, revealing a median of 35.6% (range: 5.0-96.0). At the time of MF diagnosis and during follow-up, 84 thrombotic events (52 VTEs and 32 ATEs) were observed, corresponding to 6.6% of patients per year. A significant association was found between JAK2-V617F mutation (OR: 2.5, 95% CI: 1.1-5.6) and prior VTE (OR: 7.6, 95% CI: 2.1-27.1) with an increased risk of VTE. Patients with prefibrotic MF had a higher rate of ATE than patients with overt MF. Hemorrhagic events occurred in 34 (13.8%) patients, corresponding to 3.8% of patients per year. Fibrosis grade 3 was associated with bleeding risk (OR: 3.4, 95% CI: 1.2-9.2, p = 0.02).

Conclusions:  The presence of the JAK2-V617F mutation, regardless of allele burden, and prior thrombosis were strongly associated with an increased risk of VTE. Patients with prefibrotic MF might be considered at high risk for developing ATE.