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Myeloproliferative disorders

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Myeloproliferative Neoplasms are a group of chronic blood cancers characterised by abnormal overproduction of blood cells. They may transform into acute myeloid leukaemia (AML) and carry variable prognoses depending on subtype and molecular profile.

📖 What are MPNs?

Classic types: Polycythaemia Vera (PV), Essential Thrombocythaemia (ET), Primary Myelofibrosis (PMF), and Chronic Myeloid Leukaemia (CML).
Other rarer types: Chronic neutrophilic leukaemia (CNL), Chronic eosinophilic leukaemia (CEL-NOS), MPN-unclassifiable (MPN-U).

🧬 Molecular Pathogenesis

JAK2 V617F mutation: Found in ~95% of PV and ~50% of ET/PMF.
CALR & MPL mutations: Important in JAK2-negative cases.
BCR-ABL1 fusion: Defines CML, caused by the Philadelphia chromosome t(9;22).

🔎 Individual Subtypes

Subtype	🧪 Diagnosis & Key Features	💊 First-line Management
🩸 Polycythaemia Vera (PV)	• Erythrocytosis → hyperviscosity, thrombosis; aquagenic pruritus, erythromelalgia, gout • ↑ Hb/Hct (≈ Hct ≥0.52 men / ≥0.48 women); JAK2 V617F (~95%) or exon 12 • Low EPO, hypercellular trilineage marrow	• Venesection to Hct <0.45 + low-dose aspirin • Cytoreduction if high-risk (≥60y, prior thrombosis): hydroxycarbamide • Peg-interferon if younger/pregnant; manage CV risk, consider allopurinol
🩸 Essential Thrombocythaemia (ET)	• Sustained platelets >450×10⁹/L; microvascular sx (headache, visual change, erythromelalgia) • Mutations: JAK2 (~50%), CALR (~25–30%), MPL (~5–10%) • Exclude reactive causes; check vWF if platelets >1,000–1,500	• Aspirin for microvascular sx (avoid if acquired vWD) • High-risk (≥60y, thrombosis, or JAK2+): hydroxycarbamide • Peg-interferon if younger/pregnant; anagrelide if intolerant
🩸 Primary Myelofibrosis (PMF)	• BM fibrosis → anaemia, constitutional sx, massive splenomegaly; risk AML transformation • Film: tear-drop cells; driver mutation (JAK2/CALR/MPL) • Prognosis by DIPSS-plus	• Ruxolitinib for symptoms/spleen • Transfusion support ± ESAs; infection/bleeding optimisation • Allogeneic transplant if fit (only curative)
🧬 Chronic Myeloid Leukaemia (CML)	• Leucocytosis with basophilia; splenomegaly; phases: chronic → accelerated → blast crisis • BCR-ABL1 (t(9;22)) by PCR/FISH	• TKIs (imatinib/dasatinib/nilotinib) + qPCR monitoring to major molecular response • Switch TKI if intolerance/resistance; transplant if refractory/advanced

🩺 Clinical Presentation

Constitutional symptoms: 🌙 night sweats, ⚖️ weight loss, 😴 fatigue.
Splenomegaly: 🍽️ early satiety, abdominal fullness.
🩸 Thrombosis/bleeding risk in PV and ET.
Fibrosis and cytopenias in PMF.

🔬 Investigations

🧪 Bloods: FBC, film, LDH, uric acid.
🧬 Molecular: JAK2, CALR, MPL, BCR-ABL1 testing.
🦴 Bone marrow biopsy for morphology and fibrosis grading.
🖥️ Imaging: Ultrasound/CT for splenomegaly.

📊 Summary Table

Subtype	Driver Mutation	Key Features	First-line Therapy
PV 🩸	JAK2 V617F	Raised Hb/Hct, pruritus, thrombosis	Phlebotomy + Aspirin
ET 🩸	JAK2/CALR/MPL	Platelets ↑, headaches, thrombosis	Aspirin ± Hydroxycarbamide
PMF ⚠️	JAK2/CALR/MPL	Fibrosis, anaemia, splenomegaly	Ruxolitinib ± Transplant
CML 🧬	BCR-ABL1	Leukocytosis, splenomegaly	TKIs (Imatinib)

🧾 Clinical Case Examples – Myeloproliferative Neoplasms

Case 1 – Polycythaemia Vera (PV) 🩸 A 58-year-old man has headaches, facial plethora, and intense itch after hot showers. Exam: splenomegaly. FBC: Hb 200 g/L, Hct 0.60, mild leukocytosis/thrombocytosis. 👉 Dx: PV (likely JAK2 V617F+). 👉 Mgmt: Venesection to Hct <0.45, low-dose aspirin; risk-adapt cytoreduction (e.g., hydroxycarbamide) if >60 y or prior thrombosis.

Case 2 – Essential Thrombocythaemia (ET) 🔢 A 45-year-old woman has recurrent headaches and burning palms/soles (erythromelalgia). Platelets 950 ×10⁹/L; Hb/WBC normal. 👉 Dx: ET (JAK2/CALR/MPL mutation). 👉 Mgmt: Low-dose aspirin for microvascular symptoms; cytoreduction (hydroxycarbamide or interferon if pregnancy/younger) if high-risk.

Case 3 – Primary Myelofibrosis (PMF) 🌲 A 65-year-old man reports night sweats, weight loss, and early satiety. Massive splenomegaly; film shows tear-drop cells. 👉 Dx: PMF. 👉 Mgmt: Ruxolitinib for symptoms/spleen; transfusions/ESAs for anaemia; consider allogeneic transplant if fit (curative).

Case 4 – Chronic Myeloid Leukaemia (CML) 🧬 A 50-year-old man with fatigue and early satiety. WBC 110 ×10⁹/L with basophilia/eosinophilia; spleen palpable. 👉 Dx: CML (BCR-ABL1 fusion). 👉 Mgmt: Start TKI (imatinib/dasatinib/nilotinib); molecular response monitoring (qPCR).

Case 5 – Splanchnic Vein Thrombosis ⚠️ A 42-year-old woman presents with abdominal pain and hepatomegaly. Imaging: hepatic vein thrombosis (Budd–Chiari). FBC: high Hct, platelets 600 ×10⁹/L. 👉 Dx: Underlying MPN (often PV/ET) presenting with Budd–Chiari. 👉 Mgmt: Anticoagulation, manage PV/ET (venesection/cytoreduction), hepatology input.

Case 6 – ET with Bleeding at Extreme Platelet Counts 🩸🛑 A 63-year-old with ET (platelets 1,800 ×10⁹/L) has mucocutaneous bleeding and easy bruising. VWF activity reduced. 👉 Dx: Acquired von Willebrand syndrome in ET. 👉 Mgmt: Hold aspirin; reduce platelets (cytoreduction), consider VWF concentrate/DDAVP for procedures.

Case 7 – Hyperuricaemia & Gout in PV 🦶 A 59-year-old man with PV develops acute podagra. Uric acid elevated. 👉 Dx: Gout from high cell turnover. 👉 Mgmt: Treat flare (NSAID/colchicine; avoid NSAIDs if contraindicated), start urate-lowering therapy once flare settles; continue PV control.

Case 8 – Pregnancy with ET 🤰 A 32-year-old pregnant woman with ET (CALR+) asks about risks. Platelets 750 ×10⁹/L; no thrombosis history. 👉 Issues: Maternal thrombosis/haemorrhage, fetal loss. 👉 Mgmt: Low-dose aspirin; consider LMWH per risk; interferon-α if cytoreduction needed (avoid hydroxycarbamide/anagrelide).

Case 9 – Post-ET/PMF Transformation to AML 🔥 A 71-year-old with long-standing ET develops anaemia, thrombocytopenia, circulating blasts (25%). 👉 Dx: Secondary AML (“blast phase” of MPN). 👉 Mgmt: High-risk; consider intensive chemo/venetoclax-based regimens and transplant assessment if eligible; palliative focus if frail.

Case 10 – CML Blast Crisis 🚨 A 55-year-old with poorly followed CML presents febrile and anaemic with bone pain; blasts 35% in blood. 👉 Dx: Myeloid blast crisis. 👉 Mgmt: Urgent TKI escalation + AML-type induction; transplant consult.

🧠 Teaching pearls: – Itch after hot shower (aquagenic pruritus) → think PV (JAK2). – Very high platelets + bleeding → suspect acquired vWD in ET (stop aspirin, cytoreduce). – Unusual site thrombosis (splanchnic/cerebral venous) → screen for MPN. – Massive spleen + tear-drop cells → PMF. – Basophilia + very high WBC → CML; confirm BCR-ABL1 and start TKI.

PLEASE NOTE LEGAL ADVICE: The contents are under continuing development and improvements and may contain errors of omission or fact. Feedback vital and always welcome at drokane at gmail.com. This is not to be used for the assessment, diagnosis or management of patients. It should not be regarded as medical advice. It is only for educational purposes. Please adhere to your local protocols. If you are unwell please seek healthcare advice from your doctor. This does not replace senior or specialist advice. If you do not accept this then please do not use the website. If you need medical advice, please consult a doctor or other appropriate medical professional. If you are a medical professional and you need advice then speak to your senior or colleagues.

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