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.

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Myeloproliferative disorders