Polycythemia vera, essential thrombocythemia

1. Polycythemia vera (PV)

Definition & key concept

PV is an MPN characterized by excessive tri-lineage clonal proliferation — granulocytic, megakaryocytic, and erythrocytic — but most symptoms are driven by the absolute increase in red cell mass.

• Low EPO levels (growth factor-independent clone)
• Driven by JAK2 mutation
• Typically disease of late middle-aged patients

Morphology

• Hypercellular BM (tri-linear: all three myeloid lines proliferate)
• Hepatosplenomegaly → extramedullary hematopoiesis
• Hyperviscosity + vascular stasis → thromboses and infarctions (heart, spleen, kidneys)

Clinical features

• Hematocrit >60%; RBC count >6 million/µL
• Platelet count >400,000/µL
• Functionally inactive thrombocytes → bleeding tendency
• Pruritus (histamine from neoplastic basophils); excess histamine → peptic ulceration
• Median survival ~10 years
• After 10–15 years, myelofibrosis may develop

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2. Essential thrombocythemia (ET)

Definition

ET is an MPN involving the megakaryocytic lineage only (uni-linear).

Key features

• Proliferation of large atypical megakaryocytes in BM
• BM otherwise normocellular
• Thrombocytosis (>450 × 10⁹/L)
• Disease of young females (~30 years old)
• Driven by JAK2 or calreticulin mutation

Clinical features

• Long symptom-free intervals; often found incidentally
• High risk for thrombosis
• Erythromelalgia: throbbing and burning of hands and feet (platelet occlusion of small arterioles)
• Rarely transforms into myelofibrosis
• Median survival 10–15 years

Treatment

• Life-threatening complications: plasmapheresis to rapidly reduce platelet count

💡 High-yield: PV = tri-linear MPN + low EPO + JAK2 + hyperviscosity/thrombosis + pruritus. ET = megakaryocytes only + JAK2/calreticulin + thrombocytosis + erythromelalgia. Both driven by JAK2 pathway.