Complications of Polycythemia Vera

Major Thrombotic and Hemorrhagic Complications

Myocardial infarction, stroke, and peripheral ischemic events represent the most common arterial complications, with suboptimal cerebral blood flow occurring with hematocrit values between 46-52% 1
Acquired von Willebrand Disease occurs in more than one-third of PV patients and is associated with bleeding diathesis, characterized by decreased large von Willebrand factor multimers due to abnormal adsorption to clonal platelets, exposing protein cleavage sites 2, 3
Poor platelet aggregation in response to multiple agonists and abnormally low intraplatelet levels of adenine nucleotides and serotonin contribute to bleeding risk 2, 3
Impaired binding to fibrinogen due to decreased GP IIb/IIIa expression also contributes to bleeding risk 2, 3

Erythromelalgia affects approximately 3-5% of PV patients, presenting as painful burning sensation in extremities, often associated with thrombocythemia, and typically responds to low-dose aspirin therapy 4

Approximately 10% risk of transformation to Myelofibrosis in the first decade, with a 20-year cumulative risk reaching 16% 4
Acute myeloid leukemia develops in approximately 6.8% of patients, with a 20-year cumulative risk of approximately 4%, and certain cytoreductive agents significantly increase leukemia risk 4
Diminished platelet adenylate cyclase response to prostaglandin D2 and increased baseline platelet production of thromboxane A2 contribute to prothrombotic mechanisms 3
Abnormal in vivo activation of leukocytes, endothelial cells, and platelets, and widespread activation of coagulation proteins with reduced levels of physiologic anticoagulants also contribute to prothrombotic mechanisms 3

Untreated polycythemia vera historically resulted in median survival of less than 2 years in non-phlebotomized patients, improving to >10 years with aggressive phlebotomy 1
Uncontrolled hematocrit >45% is a high-risk feature for complications, and accepting hematocrit targets of 45-50% increases thrombotic risk 1, 4
Inadequate fluid replacement during phlebotomy can precipitate hypotension, particularly in elderly patients with cardiovascular disease 4
Using aspirin in patients with extreme thrombocytosis (>1000 × 10⁹/L) requires caution due to bleeding risk from acquired von Willebrand disease 1

The endothelial displacement of platelets and leukocytes at low shear rates enhances thrombogenic interactions, contributing to the prothrombotic state in polycythemia vera 5

The National Comprehensive Cancer Network recommends cytoreductive therapy with hydroxyurea or interferon in addition to phlebotomy and aspirin for high-risk patients (age >60 years or prior thrombosis history) with polycythemia vera 6