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Haematology & Oncology

Myeloproliferative neoplasms

A family of clonal stem-cell disorders in which a driver mutation (most often JAK2 V617F) constitutively activates JAK-STAT signalling, so one or more mature myeloid lineages are overproduced; the classic Philadelphia-negative trio is polycythaemia vera, essential thrombocythaemia and myelofibrosis, which share a mechanism but differ in which cell line dominates.

In a nutshell

MPNs are clonal myeloid disorders with different dominant risks: thrombosis and hyperviscosity in PV, thrombosis/bleeding in ET, and marrow failure, splenomegaly and constitutional symptoms in MF.

Classic presentation

Persistent erythrocytosis, thrombocytosis or splenomegaly with constitutional symptoms, pruritus, thrombosis, bleeding or an incidental abnormal FBC.

Key points

  • Exclude secondary or reactive causes before diagnosing an MPN.
  • JAK2, CALR and MPL testing, marrow morphology and clinical phenotype define the entity.
  • PV management is centred on haematocrit control and vascular-risk reduction.
  • ET treatment is risk- and bleeding-adapted, not platelet-count-only.
  • MF needs prognostic assessment, symptom control and transplant consideration in selected people.

First-line investigation

Repeat FBC and blood film, assess secondary/reactive causes, then use mutation testing and specialist marrow assessment where indicated.

Management

Confirm the MPN phenotype

  • Confirm persistent erythrocytosis, thrombocytosis or marrow/splenic features through specialist haematology, excluding reactive or secondary causes and using mutation and marrow assessment where indicated.1,3,7,2

Prevent thrombosis and bleeding

  • Individualise antiplatelet, venesection and cytoreductive treatment by vascular history, blood counts, bleeding risk, age, symptoms, pregnancy and mutation/diagnostic context.1,3,8,9

Treat the entity

  • Use venesection and cytoreduction for PV, risk-adapted antithrombotic/cytoreductive therapy for ET, and prognostic- and symptom-adapted treatment for MF.1,3,4,5,12

Control symptoms and complications

  • Address pruritus, constitutional symptoms, splenomegaly, iron status, infection, tumour lysis risk and cardiovascular risk with specialist and BNF-supported plans.8,4,13,9

Monitor transformation and response

  • Follow blood counts, symptoms, spleen, thrombosis/bleeding, treatment toxicity and progression to MF, MDS or AML.1,2,4

Exam traps

  • Do not call every high platelet count ET.
  • A high haemoglobin may be relative or secondary, not PV.
  • Extreme thrombocytosis can cause bleeding as well as thrombosis.
  • Ruxolitinib, momelotinib and fedratinib have defined MF populations and are not interchangeable blanket treatments.

Illustrations

Chronic myeloid leukaemia on peripheral blood filmPeripheral blood film showing marked granulocytic proliferation with myeloid cells at multiple stages of maturation, typical of chronic myeloid leukaemia.Paulo Henrique Orlandi Mourao, Wikimedia Commons · CC-BY-SA-3.0

Key sources

  1. BSH: Diagnosis and management of polycythaemia vera (UK BSH diagnostic, risk-stratification and management guidance for PV.)Published 27 Nov 2018
  2. BSH: Diagnosis and evaluation of prognosis of myelofibrosis (Current UK BSH diagnosis and prognostic evaluation guidance for primary and secondary MF.)Published 6 Nov 2023
  3. BSH: Guideline for investigation and management of adults and children presenting with thrombocytosis (UK BSH diagnostic and management guidance relevant to thrombocytosis and ET.)Published 1 Nov 2010
  4. BSH: The management of myelofibrosis (Current UK BSH management guideline for primary and secondary MF.)Published 1 Dec 2023 | Updated 22 Jul 2024
  5. NICE TA386: Ruxolitinib for myelofibrosis-related splenomegaly or symptoms (NICE recommendation for ruxolitinib in selected intermediate-2 or high-risk MF.)Published 23 Mar 2016
  6. NHS Salisbury: Myeloproliferative neoplasms (UK NHS overview of MPNs and specialist pathways.)
  7. BSH: Investigation and management of thrombocytosis without JAK2, CALR or MPL mutations (Current UK BSH guidance for mutation-negative thrombocytosis and differential diagnosis.)Published 4 Dec 2025
  8. BSH: Management of specific situations in polycythaemia vera and secondary erythrocytosis (UK BSH guidance for PV-specific situations and secondary erythrocytosis.)Published 13 Nov 2018
  9. BNF online (Check current antiplatelet, cytoreductive, JAK-inhibitor and supportive prescribing.)
  10. NICE TA957: Momelotinib for myelofibrosis-related splenomegaly or symptoms (NICE recommendation for momelotinib in selected intermediate-2 or high-risk MF with moderate-to-severe anaemia.)Published 20 Mar 2024
  11. NICE TA1018: Fedratinib for myelofibrosis-related splenomegaly or symptoms (Current NICE appraisal for fedratinib in selected MF after ruxolitinib when momelotinib is unsuitable.)Published 20 Nov 2024
  12. NICE TA921: Ruxolitinib for treating polycythaemia vera (NICE appraisal of ruxolitinib for adults with PV who are resistant to or intolerant of hydroxycarbamide.)Published 9 Aug 2023
  13. BSH: Updated guidelines for tumour lysis syndrome (Current UK tumour-lysis guidance.)Published 3 Sept 2025 | Updated 8 Dec 2025

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.