From the Guidelines
Yes, Polycythemia Vera (PV) is a hypercoagulable state.
Key Factors Contributing to Hypercoagulability
- High hematocrit levels, which increase blood viscosity and enhance thrombogenic interactions 1
- Qualitative cell defects, such as diminished response of platelet adenylate cyclase to prostaglandin D2 and increased baseline platelet production of thromboxane A2 1
- Abnormal activation of leukocytes, endothelial cells, and platelets 1
- Reduced levels of physiologic anticoagulants, such as antithrombin III, proteins C and S, and decreased fibrinolytic activity 1
Clinical Implications
- The European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study showed that low-dose aspirin significantly reduces the risk of thrombotic events in PV patients 1
- The CYTO-PV trial demonstrated that maintaining hematocrit levels strictly below 45% efficiently reduces the risk of thrombotic events 1
- Risk factors for thrombosis in PV include age ≥ 65, prior thrombosis, and leukocytosis 1
Management Recommendations
- Therapy to control hematocrit levels, such as phlebotomy, is essential in reducing the risk of thrombotic events 1
- Low-dose aspirin is recommended as a cornerstone of PV therapy to reduce the risk of thrombotic events 1
- Cytoreductive drugs, such as hydroxyurea, may be prescribed in high-risk PV patients to reduce the risk of thrombosis 1
From the Research
Hypercoagulable State in Polycythemia Vera
- Polycythemia Vera (PV) is associated with an increased frequency of thrombotic complications, suggesting a hypercoagulable state 2, 3, 4.
- Studies have shown that PV patients demonstrate abnormal hemostasis, with a major role played by platelets rather than plasma factors 2.
- The hypercoagulable state in PV patients is characterized by increased circulating procoagulant microparticles and phosphatidylserine-exposing erythrocytes/platelets 3.
- Neutrophils also play a significant role in thrombosis in PV patients, with activated PRKCD-mediated neutrophil extracellular traps pathway contributing to the hypercoagulable state 5.
Comparison with Other Conditions
- PV patients have a greater number of thromboembolic events per patient and more peripheral arterial thromboemboli compared to patients with secondary polycythemia caused by smoking 4.
- Whole blood rotational thromboelastometry (ROTEM) has been used to detect hypercoagulability in patients with myeloproliferative neoplasms, including PV and essential thrombocythemia 6.
Mechanisms and Factors Contributing to Hypercoagulability
- Platelet count is significantly higher in PV patients and is independently associated with ROTEM results, suggesting a key role in the hypercoagulable state 2, 6.
- Erythrocytapheresis, a procedure used to reduce red blood cell count, can augment the hypercoagulable state in PV patients, possibly due to hemodilution 2.
- Treatment with hydroxyurea is associated with a decrease in phosphatidylserine exposure and microparticle release, suggesting a potential therapeutic strategy to reduce hypercoagulability 3.