🩸 Myeloproliferative neoplasms (MPNs) are chronic clonal disorders of haematopoietic stem cells characterised by overproduction of one or more mature myeloid cell lines. They can cause thrombosis, bleeding, splenomegaly, constitutional symptoms, and in some cases progression to myelofibrosis or acute myeloid leukaemia (AML).

✅ UK guidance framing: NICE mainly helps with recognition and urgent referral, while detailed diagnosis and management of PV, ET, and myelofibrosis are guided mainly by British Society for Haematology (BSH) recommendations. CML also has NICE technology appraisals for specific tyrosine kinase inhibitors.

📖 What are MPNs?

Classical Philadelphia-negative MPNs: Polycythaemia vera (PV), Essential thrombocythaemia (ET), and Primary myelofibrosis (PMF).
BCR::ABL1-positive MPN: Chronic myeloid leukaemia (CML).
Other rarer MPNs: chronic neutrophilic leukaemia (CNL), chronic eosinophilic leukaemia (CEL-NOS), and MPN-unclassifiable (MPN-U).

🧬 Molecular Pathogenesis

JAK2 V617F is present in most PV cases and in a substantial proportion of ET and PMF.
CALR and MPL mutations are important driver mutations in JAK2-negative ET/PMF.
BCR::ABL1 fusion, caused by the Philadelphia chromosome t(9;22), defines CML.
These mutations lead to constitutive signalling, cytokine-independent proliferation, and increased thrombo-inflammatory risk.

🚩 When to suspect an MPN

Persistent erythrocytosis, thrombocytosis, or marked leukocytosis.
Splenomegaly, early satiety, or abdominal fullness.
Aquagenic pruritus, erythromelalgia, gout, or hyperviscosity symptoms.
Unusual-site thrombosis such as splanchnic vein thrombosis or cerebral venous sinus thrombosis.
Constitutional symptoms: fatigue, weight loss, night sweats.

🔎 Individual Subtypes

Subtype	🧪 Diagnosis & Key Features	💊 Usual First-line / Core Management
🩸 Polycythaemia vera (PV)	Erythrocytosis causing hyperviscosity and thrombosis risk; aquagenic pruritus, erythromelalgia, gout, splenomegaly. Usually JAK2-positive; serum EPO is often low.	Venesection to target haematocrit <0.45 plus low-dose aspirin unless contraindicated. Cytoreduction is considered in higher-risk patients; this is specialist-led.
🩸 Essential thrombocythaemia (ET)	Sustained thrombocytosis; headaches, visual disturbance, microvascular symptoms, thrombosis or bleeding. Driver mutations include JAK2, CALR, and MPL. Always exclude reactive thrombocytosis.	Aspirin may help microvascular symptoms if there is no acquired von Willebrand syndrome. Higher-risk disease may need cytoreduction; pregnancy and younger patients need specialist-tailored choices.
🩸 Primary myelofibrosis (PMF)	Marrow fibrosis causing anaemia, constitutional symptoms, tear-drop cells, leucoerythroblastic film, and often marked splenomegaly. Risk of progression to AML.	Symptom control, transfusion support, and splenic symptom management. Ruxolitinib is used for selected symptomatic patients. Allogeneic stem cell transplant is the only potentially curative option in suitable patients.
🧬 Chronic myeloid leukaemia (CML)	Leukocytosis with basophilia, often splenomegaly; chronic, accelerated, and blast phases. Defined by BCR::ABL1 detected by PCR/FISH/cytogenetics.	Tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, or nilotinib, with molecular monitoring. Change of TKI or transplant may be needed in resistant or advanced disease.

🩺 Clinical Presentation

🌙 Night sweats, ⚖️ weight loss, 😴 fatigue.
🍽️ Splenomegaly causing early satiety and abdominal discomfort.
🩸 Thrombosis and/or bleeding, especially in PV and ET.
🧪 Hyperviscosity symptoms in PV: headache, dizziness, blurred vision.
⚠️ Anaemia, constitutional symptoms, and massive spleen are especially suggestive of PMF.

🔬 Investigations

🧪 FBC, blood film, renal/liver profile, LDH, urate, ferritin, and inflammatory markers where relevant.
🧬 Molecular testing: JAK2, then CALR/MPL if indicated; BCR::ABL1 if CML is suspected.
🦴 Bone marrow biopsy for morphology, fibrosis grading, and integrated diagnosis where needed.
🖥️ Ultrasound or CT for splenomegaly and complications.
Always think about secondary causes of erythrocytosis or thrombocytosis before labelling an MPN.

💊 Management Principles

Management is specialist-led and based on subtype, symptoms, thrombosis risk, age, and molecular profile.
Main goals are to reduce thrombosis/bleeding, control symptoms, manage splenomegaly, and monitor for progression.
PV: venesection + aspirin are the backbone of treatment.
ET: aspirin and/or cytoreduction depending on risk and symptoms.
PMF: supportive care, JAK inhibition in selected patients, transplant assessment if fit.
CML: TKI therapy with regular molecular monitoring.

📊 Summary Table

Subtype	Driver Mutation	Key Features	Core Therapy
PV 🩸	JAK2	Raised Hb/Hct, aquagenic pruritus, thrombosis	Venesection + aspirin
ET 🩸	JAK2 / CALR / MPL	Platelets ↑, headaches, erythromelalgia, thrombosis/bleeding	Aspirin ± cytoreduction
PMF ⚠️	JAK2 / CALR / MPL	Fibrosis, anaemia, tear-drop cells, splenomegaly	Supportive care ± ruxolitinib ± transplant
CML 🧬	BCR::ABL1	Leukocytosis, basophilia, splenomegaly	TKI therapy

🧾 Clinical Pearls

🧠 High-yield clues:
– Itch after a hot shower → think PV.
– Very high platelets + bleeding → suspect acquired von Willebrand syndrome in ET.
– Unusual-site thrombosis (for example splanchnic vein thrombosis) → screen for an underlying MPN.
– Massive spleen + tear-drop cells → think myelofibrosis.
– Basophilia + marked leukocytosis → think CML, then confirm BCR::ABL1.

📚 References (UK)

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Myeloproliferative disorders ✅