Is platelet function altered in patients with polycythemia vera?

Platelet Function in Polycythemia Vera

Yes, platelet function is significantly reduced in polycythemia vera despite paradoxical platelet activation, creating a complex hemostatic environment that contributes to both thrombotic and bleeding complications. 1

Paradoxical Platelet Dysfunction in PV

Patients with polycythemia vera (PV) exhibit multiple pro-hemorrhagic platelet defects despite evidence of in vivo platelet activation, creating a paradoxical situation:

Platelet Activation

• Increased baseline platelet production of thromboxane A2 1
• Diminished response of platelet adenylate cyclase to prostaglandin D2 (a physiological inhibitor of platelet aggregation) 1
• Abnormal in vivo activation of platelets, leukocytes, and endothelial cells 1
• Shortened platelet survival and increased platelet activation markers 2

Platelet Function Defects

• Poor platelet aggregation in response to multiple agonists including:
  • Thrombin
  • ADP
  • Epinephrine
  • Collagen
  • Thromboxane A2
  • Platelet-activating factor 1
• Abnormally low intraplatelet levels of adenine nucleotides and serotonin 1
• Reduced platelet factor X-activating activity 1
• Defective platelet lipid peroxidation 1
• Impaired binding to fibrinogen due to decreased glycoprotein (GP) IIb/IIIa expression 1

Acquired von Willebrand Disease in PV

• Occurs in more than one-third of PV patients 1
• Associated with bleeding diathesis 1
• Characterized by decreased large von Willebrand factor multimers and increased cleavage products 1
• Particularly associated with extreme thrombocytosis 1
• Pathogenesis involves abnormal adsorption of large von Willebrand proteins to clonal platelets, exposing cleavage sites and enhancing proteolysis 1
• Reversible with normalization of platelet count 1, 2

Clinical Implications of Platelet Dysfunction

Thrombotic Risk

• Despite platelet dysfunction, PV patients have increased thrombotic risk 1, 3
• Genetic factors may influence thrombotic risk - presence of PIA2 allele of platelet glycoprotein IIIa is associated with increased arterial thrombosis risk 1
• Thrombotic risk persists as long as platelet counts are above normal (>400 × 10⁹/L) 2

Bleeding Risk

• At platelet counts exceeding 1000 × 10⁹/L, thrombotic tendency shifts to bleeding tendency due to acquired von Willebrand syndrome 2
• Bleeding complications are somewhat higher in PV than in the general population 4

Management Considerations

• Low-dose aspirin (81-100 mg daily) is recommended for all PV patients unless contraindicated 3
• Cytoreductive therapy may be needed to control platelet counts in high-risk patients 3
• Microvascular disturbances like erythromelalgia respond well to aspirin 3
• Regular monitoring of complete blood count every 2-3 months during initial management, then every 3-6 months once stable 3

Proposed Mechanism

The proposed concept is that platelets in PV are hypersensitive but functionally impaired:

1. Due to high shear stress in the microvasculature, platelets spontaneously activate
2. They secrete their products and form aggregates mediated by von Willebrand factor
3. These aggregates transiently plug the microcirculation
4. Platelets then deaggregate and recirculate as exhausted, defective platelets with secondary storage pool disease 2

This mechanism explains why ex vivo platelet function tests show impairment despite clear evidence of in vivo platelet activation and thrombotic tendency.

Practical Implications

• Platelet dysfunction contributes to both thrombotic and hemorrhagic complications in PV
• Therapeutic approaches must balance thrombotic and bleeding risks
• Maintaining hematocrit <45% through phlebotomy is recommended for all PV patients 3
• Cytoreductive therapy may be necessary to control platelet counts in high-risk patients 3