Uncontrolled production of abnormal platelets

Aetiology

• Median age of diagnosis ~65 but can affect younger patients

Pathophysiology

• Platelet function is abnormal, leading to thrombosis
  • At high levels can also cause bleeding due to acquired von Willebrand disease

Clinical features

• Asymptomatic
• Increased cellular turnover - gout, fatigue, weight loss, sweats
• Symptoms/signs due to splenomegaly
• Marrow failure - fibrosis or leukaemic transformation (transformation risk is low)
• Thrombosis - arterial or venous including TIA, MI, abdominal vessel thrombosis, claudication, erythromelalgia
• Bleeding - unpredictable risk

Investigations

• Exclude reactive thrombocytosis - blood loss, inflammation, malignancy, iron deficiency
• Exclude CML
• Bloods: genetics
  • JAK2 mutations in approx. 50-60%
  • CALR mutation in approx 25%
  • MLP mutation in approx 5%
  • 10-20% of patients will be ‘triple negative’
• Bone marrow biopsy

Management

• Antiplatelet agents - aspirin
• Cytoreductive therapy to control proliferation - hydroxycarbamide, anagrelide, interferon alpha