Thromboembolic events in polycythemia vera

Abstract

Thromboembolic events and cardiovascular disease are the most prevalent complications in patients with polycythemia vera (PV) compared with other myeloproliferative disorders and are the major cause of morbidity and mortality in this population. Moreover, a vascular complication such as arterial or venous thrombosis often leads to the diagnosis of PV. The highest rates of thrombosis typically occur shortly before or at diagnosis and decrease over time, probably due to the effects of treatment. Important risk factors include age (≥ 60 years old) and a history of thrombosis; elevated hematocrit and leukocytosis are also associated with an increased risk of thrombosis. The goal of therapy is to reduce the risk of thrombosis by controlling hematocrit to < 45%, a target associated with reduced rates of cardiovascular death and major thrombosis. Low-risk patients (< 60 years old with no history of thrombosis) are managed with phlebotomy and low-dose aspirin, whereas high-risk patients (≥ 60 years old and/or with a history of thrombosis) should be treated with cytoreductive agents. Interferon and ruxolitinib are considered second-line therapies for patients who are intolerant of or have an inadequate response to hydroxyurea, which is typically used as first-line therapy. In this review, we discuss factors associated with thrombosis and recent data on current treatments, including anticoagulation, highlighting the need for more controlled studies to determine the most effective cytoreductive therapies for reducing the risk of thrombosis in patients with PV.

Hematocrit and incidence of venous thromboembolism

“…Hematocrit well above the normal range, found in polycythemia vera, is clearly associated with increased risk of VTE . The risk of VTE in the Tromsø and ARIC general population studies, however, appears to be increased at hematocrit levels much lower than for polycythemia vera.…”

“…Hematocrit well above the normal range, found in polycythemia vera, is clearly associated with increased risk of VTE. 1 The risk of VTE in the Tromsø and ARIC general population studies, however, appears to be increased at hematocrit levels much lower than for polycythemia vera. Mechanistically, high hematocrit increases TA B L E 3 Hazard ratios (95% CIs) of total, provoked, and unprovoked VTE by groups of Visit 1 hematocrit, ARIC, 1987-1989 through 2015 Hematocrit (percentiles based on sex-race specific cut points) platelet margination and adhesiveness.…”

“…Mechanistically, high hematocrit increases platelet margination and adhesiveness . However, a more important mechanism by which hematocrit may increase VTE risk is via increased blood viscosity and venous stasis …”

“…Patients with markedly elevated hematocrit due to polycythemia vera are at increased risk of arterial thrombosis and venous thromboembolism (VTE). This risk has been attributed in part to increased blood viscosity created by elevated hematocrit . Reduction of hematocrit to <45% reduces thrombotic risk in polycythemia vera .…”

“…This risk has been attributed in part to increased blood viscosity created by elevated hematocrit. 1 Reduction of hematocrit to <45% reduces thrombotic risk in polycythemia vera. 2 In contrast, raising hematocrit in anemic patients with renal disease or cancer using erythrocyte-stimulating agents increases thrombosis risk.…”