Essential thrombocythemia

Definition

• Myelodysplastic disorder of the thrombocytopoeitic stem cells causing a clonal proliferation of thrombocytes

Clinical Manifestations

• History
  • History of thrombosis or bleeding
• Signs & Symptoms
  • Digital ischemia
  • Cerebrovascular ischemia
• High risk for vascular events if:
  • History of thrombosis or bleeding
  • Increased cardiovascular risk
  • Older than 60 years

Differential Diagnosis

• Must distinguish from other myelodysplastic disorders (especially polycythemia vera) as well as from secondary causes of thrombocytosis

Investigations

• CBC with peripheral blood film shows thrombocytosis with platelet anisocytosis
  • RBCs usually normochromic and normocytic, unless there is concurrent iron deficiency anemia
  • Leukoerythroblastic reaction suggests post-ET myelofibrosis
• Bone marrow aspiration and biopsy shows normal cellularity or moderate hypercellularity with large megakaryocytes
  • Findings that suggest an alternative diagnosis include highly atypical megakaryocytes, increased myeloblasts, myelodysplastic features, or significant reticulin fibrosis or collagen fibrosis
• Genetic testing
  • JAK2 in 60-65%
  • CALR in 20-25%
  • MPL in 5%
  • Triple-negative (all above negative) in 10-15%
• Send BCR-ABL testing to exclude CML

WHO Diagnostic Criteria

• Diagnosis require 4 major criteria or the first 3 major criteria plus the minor criterion
• Major criteria
  • Platelets ≥450
  • Bone marrow biopsy showing proliferation of megakaryocytes with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei; and no significant increase or left shift in neutrophil granulopoiesis or erythropoiesis and very rare minor increase in reticulin fibers
  • Not meeting WHO criteria for BCR-ABL1 CML, PV, PMF, myelodysplastic syndrome, or other myeloid neoplasms
  • Presence of JAK2, CALR, or MPL mutation
• Minor criterion
  • Presence of a clonal marker or abscence of evidence for reactive thrombocytosis

Management

• Acute
  • If digital or cerebrovascular ischemia, rapid cytoreduction with platelet pheresis
• Chronic
  • If high risk, requires cytoreduction and aspirin:
    • First-line: hydroxyurea
    • Alternative: anagrelide
    • Pregnancy: interferon alfa
  • If >1.5m platelets, requires cytoreduction alone