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ASXL1 Mutation Identified as High-Risk Bleeding Factor in MPN
Researchers performed a retrospective analysis of bleeding risk factors in patients with myeloproliferative neoplasms (MPNs); this data was presented at the 2021 Annual American Society of Hematology (ASH) Meeting.
“Bleeding and thrombosis are prevalent across all MPN subtypes and have a significant impact on morbidity and mortality. Identifying patients at high risk for bleeding can guide the duration of anticoagulation and predict complications during surgery,” explained Amro Elshoury, MBBChir, Roswell Park Comprehensive Cancer Center, New York, and co-investigators.
In the analysis, bleeding events were identified as minor or major events as defined by the International Society of Thrombosis and Hemostasis (ISTH). Cox regression models were used to evaluate associations between candidate risk factors with identified bleeding events in univariate and multivariable analyses.
Records of 170 patients with MPN between 2005 and 2021 were analyzed with a median follow-up time of 43.5 months. The rate of major and minor bleeding events was 4.9/100 patient-years, and the rate of thrombosis was 5.1/100 patient-years. Additional rates were 5.4/100 patient-years for arterial thrombosis and 2.9/100 patient-years for venous thrombosis.
Findings in the univariable analysis showed predictors of bleeding includes patients over 60 years old of age (hazard ratio [HR] 2.8; 95% CI, 1.47-5.34; P=0.001), diagnoses of primary myelofibrosis (MF; HR 2.98; 95% CI, 1.29-6.9; P=0.01) and myelodysplastic syndrome (MDS)/MPN overlap syndrome (HR 4.56, 95% CI, 1.91-10.88; P=0.0004).
Further predictors include prior history of thrombosis (HR 3.3, 95% CI, 1.27-8.8; P=0.01) and presences of ASXL1 (HR 4.13, 95% CI, 2.13-8.04; P=0.0001), JAK2 V617F (HR 0.58; 95% CI, 0.31-1.08; P=0.08), and TET2 mutations (HR 3.46; 95% CI, 1.5-7.9; P=0.003).
Under multivariable analysis, the expression of JAK2 V617F (HR 4.8; 95% CI, 1-21.5; P=0.03) and ASXL1 (HR 12.7, 95% CI, 1.7-93; P=0.01) mutations were associated with increased risk of bleeding. Patients with polycythemia vera were at a lower risk of bleeding (HR -3.5, 95% CI, 0-0.8; P=0.03).
The association between the ASXL1 mutation and a higher risk of bleeding led researchers to observe other clinical variables.
Patients with ASXL1 mutations were more likely to have a diagnosis of PMF and MDS-MPN overlap syndrome, risk for thrombosis, lower hematocrit, and platelets, but higher white blood cell count. This mutation was not associated with a statistically significant lower VIII/Von Willebrand complex (VWF).
“ASXL1 mutations are associated with a significantly higher risk of bleeding in adult patients with MPN. The risk of bleeding with ASXL1 mutations was independent of prior thrombosis and was not associated with abnormalities in VMF or factor V. Confirmation of these findings in additional patients are ongoing,” concluded Dr Elshoury, et al.—Alexa Stoia
