Definition and epidemiology
Polycythaemia vera (PV) is a chronic BCR::ABL1-negative myeloproliferative neoplasm driven by clonal proliferation of erythroid, and to a lesser extent megakaryocytic and granulocytic, precursors. It is overwhelmingly a disease of older adults (median age at diagnosis ~60 years) and is very rare in children. The central clinical hazard is arterial and venous thrombosis; over years a minority transform to myelofibrosis or acute leukaemia.
Crucially for paediatric practice, true PV must be distinguished from the far commoner causes of a raised haematocrit in children: neonatal polycythaemia (delayed cord clamping, twin–twin transfusion, infant of a diabetic mother, intrauterine growth restriction) and secondary polycythaemia (cyanotic congenital heart disease, chronic hypoxaemia, high altitude, EPO-secreting tumours, congenital high-affinity haemoglobins). These are physiologically and genetically different entities and are not diagnosed with the WHO PV criteria.
Clinical features
- Hyperviscosity / vascular symptoms — headache, dizziness, visual disturbance, tinnitus, and a plethoric facies.
- Aquagenic pruritus — itch after warm water, a classic PV symptom.
- Erythromelalgia — burning, erythematous extremities, often relieved by aspirin.
- Thrombosis — arterial (stroke, MI) or venous, including splanchnic vein thrombosis (Budd–Chiari, portal vein); an unprovoked splanchnic thrombus should prompt JAK2 testing.
- Splenomegaly, fatigue, and a bleeding tendency from acquired von Willebrand disease at very high platelet counts.
Diagnosis
WHO 2016 diagnosis rests on three major criteria (raised haemoglobin/haematocrit — Hb >16.5 g/dL [men] or >16.0 g/dL [women], or Hct >49%/>48%, or raised red-cell mass; trilineage bone-marrow hypercellularity with pleomorphic mature megakaryocytes; and a JAK2 V617F or JAK2 exon 12 mutation) plus one minor criterion — a subnormal serum erythropoietin level. The diagnosis is met by all three major criteria, or by the first two major criteria plus the minor criterion. A subnormal EPO plus JAK2 positivity is highly suggestive even before marrow histology.
See the full criteria: Polycythemia Vera
Red flags
- New thrombosis at an unusual site (splanchnic, cerebral venous) — a recognised PV presentation.
- Haematocrit not controlled to target despite therapy.
- Rising white count, progressive splenomegaly, anaemia, or blasts — concern for transformation to myelofibrosis or acute leukaemia.
- In a neonate or child with a high haematocrit, look first for secondary causes; do not anchor on PV. A normal/raised EPO and absent JAK2 mutation point away from PV.
Management overview
Goals are to reduce thrombotic risk and control symptoms. The cornerstones are therapeutic phlebotomy to a haematocrit target (<45%) and low-dose antiplatelet therapy unless contraindicated. Cytoreductive therapy (a hydroxyurea-class agent or interferon-class agent) is added for high-risk disease — older age, prior thrombosis, or poor haematocrit control; JAK-inhibitor therapy is an option in hydroxyurea-resistant/intolerant disease. Cardiovascular risk-factor control and avoidance of iron supplementation (which can drive erythropoiesis) are adjuncts. Drug classes only are named here — dosing is outside the scope of this reference and any cytoreductive agent in a child should be directed by paediatric haematology.
References
- Arber DA, et al. Blood. 2016;127(20):2391–2405 (WHO 2016 classification).
- Barbui T, et al. Am J Hematol. PV update on diagnosis and management.
- Nelson Textbook of Pediatrics, 21st ed.
Decision support for qualified clinicians only — verify against current primary guidelines and your clinical judgement.