Leukocytosis Linked With Subsequent Thrombotic Events in Polycythemia Vera

Polycythemia vera (PV) is a myeloproliferative neoplasm that is characterized by clonal erythrocytosis. Thrombotic complications are a major cause of morbidity and mortality for patients with PV, and previous research has identified prior arterial events and hypertension as risk factors for arterial thrombosis, as well as prior venous events and an age of 65 years or older as risk factors for venous thrombosis in patients with PV. A recent single-center study at the Mayo Clinic sought to validate these findings and identify additional risk factors for arterial versus venous thrombosis.

The investigators followed a cohort of 587 patients with PV for a median of 109 months. The patients had a median age of 60 years (range, 17-94), among whom 64% were classified as high risk (ie, having an age of 65 years or older and/or a history of thrombosis). The cardiovascular risk factors among the cohort were hypertension (42%), diabetes (9%), hyperlipidemia (21%), and history of smoking (29%). Most patients had JAK2 mutations, and 18% and 11%, respectively, had TET2 and ASXL1 mutations.

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In total, 235 patients (40%) had experienced a thrombotic event, including 153 (26%) arterial events and 104 (18%) venous events. Pre-diagnosis, 146 patients (25%) had a thrombotic event, and 40 (27%) had a recurrent event after diagnosis. Post-diagnosis, 128 thrombotic events occurred, with 11 (5%) patients having both venous and arterial events.

The investigators found that prior thrombotic events and leukocytosis were linked to subsequent thrombotic events in general, and prior arterial events and hyperlipidemia were linked with subsequent arterial events. The presence of major hemorrhage at diagnosis, leukocytosis, and prior venous events were all linked with future venous events. TET2 and ASXL1 mutations, however, did not appear to exert an influence on future arterial or venous events.

In examining thrombotic events that happened at any time—before or after diagnosis with PV—salient associations were noted between arterial thrombosis and an age over 60 years, hypertension, diabetes, hyperlipidemia, and normal cytogenetics. By contrast, younger patients, women, patients with palpable splenomegaly, and patients with a history of major hemorrhage were more likely to experience venous thrombotic events. Those with venous events were less likely to have hypertension, hyperlipidemia, or to be active smokers.

“We confirm that a history of arterial and/or venous thrombosis is the most reliable risk factor for future arterial and venous event,” conclude the authors, adding that “a novel observation is the association of leukocytosis with increased risk of all thrombotic events, specifically venous thrombosis.”

Reference

Cerquozzi S, Barraco D, Lasho T, et al. Risk factors for arterial venous thrombosis in polycythemia vera: a single center experience in 587 patients. Blood Cancer J. 2017;7(12): 662. doi: 10.1038/s41408-017-0035-6.