Myeloproliferative Neoplasms

What MPN means — in plain words

Where MDS is a marrow that makes too few cells, MPN is the opposite — a marrow that makes too many. There are three classical types, and although they look different, they share an underlying problem: a single mutation that switches on a growth signal which should normally be tightly regulated.

The three classical types

The driving mutations — JAK2, CALR, MPL

One of the great discoveries of the last two decades is that most MPNs are driven by one of three mutations in a signalling pathway called JAK-STAT.

• JAK2 V617F — found in nearly all patients with PV and in roughly half with ET and MF.
• CALR mutations — found in many JAK2-negative ET and MF patients.
• MPL mutations — found in a small minority of ET and MF patients.
• "Triple-negative" — a small group of patients without any of the three; we look at other criteria.

Identifying the driver helps confirm the diagnosis, refines the outlook, and — in myelofibrosis — guides risk scoring and transplant decisions.

"These are conditions where the most important treatment is often the simplest — keeping the blood thin enough and the counts in a safe range. Patients live with these diagnoses for decades."

How MPNs tend to present

• Unexplained high haemoglobin or haematocrit on a routine CBC — PV's commonest entry point.
• A persistently high platelet count — ET's commonest entry point.
• An unexplained clot — sometimes in unusual places (the portal vein, the hepatic veins, cerebral veins) — that turns out to have an underlying MPN.
• Itching after a hot shower (aquagenic pruritus) — classic in PV.
• A burning, red, painful sensation in the hands and feet (erythromelalgia) — sometimes seen in ET and PV.
• Fatigue, drenching night sweats, early satiety, weight loss, bone pain — more typical of myelofibrosis.
• An enlarged spleen noticed on examination or imaging — especially in MF.

How we diagnose MPN

1. Full blood count, with repeated measurements to confirm the abnormality is sustained, not a one-off.
2. JAK2, CALR, MPL mutation testing on a blood sample.
3. BCR-ABL testing to rule out CML when platelets or white cells are high.
4. Erythropoietin level — often low in PV, which helps distinguish it from secondary causes of high haemoglobin.
5. Ferritin, iron studies, oxygen saturation, kidney function, liver function to exclude reversible or secondary causes.
6. Abdominal ultrasound to assess spleen size.
7. Bone marrow aspirate and biopsy — particularly important for confirming ET and for diagnosing myelofibrosis (where the scarring is graded). What the procedure is like →

Treatment — by type

Polycythaemia Vera

The two cornerstones, for almost everyone:

• Phlebotomy (venesection) — removing blood at intervals to bring the haematocrit below 45%. Mechanically lowers thickness and clot risk.
• Low-dose aspirin — for most patients without bleeding risk.

In addition, cytoreductive treatment is added for patients over 60, those with a previous clot, or those with a very high cell count:

• Hydroxyurea — an oral tablet, well-tolerated, widely used.
• Interferon (pegylated interferon alfa, or ropeginterferon) — particularly attractive for younger patients and during pregnancy; can produce deep molecular responses.
• Ruxolitinib — a JAK inhibitor used when hydroxyurea fails or is not tolerated.

Essential Thrombocythaemia

Treatment depends on risk. We assess your age, your platelet count, your JAK2 status, and whether you've had a clot. Many low-risk patients need only observation, or aspirin alone. Higher-risk patients receive cytoreduction — hydroxyurea, anagrelide, or interferon — alongside aspirin. Very high platelet counts can paradoxically increase bleeding risk; we adjust aspirin use accordingly.

Myelofibrosis

The hardest of the three. Treatment is tailored to the dominant problem:

• For splenomegaly and constitutional symptoms — ruxolitinib, an oral JAK inhibitor, often produces dramatic relief: spleen shrinks, sweats settle, weight returns, fatigue lifts. Newer JAK inhibitors (fedratinib, momelotinib, pacritinib) cover patients whose counts make ruxolitinib difficult.
• For anaemia — supportive transfusions, erythropoiesis-stimulating agents in selected cases, danazol, luspatercept (where available), or momelotinib (which can improve anaemia).
• Allogeneic stem cell transplant — the only curative option, reserved for fitter patients with intermediate-2 or high-risk disease by DIPSS-plus or MIPSS70 scoring. The decision balances real risks against the chance of cure. Read more →

Special situations — pregnancy, surgery, fasting

MPN in pregnancy is a specialist situation — interferon is generally safe, hydroxyurea is not — and we plan early with our obstetric colleagues. Before any surgery, we adjust aspirin and cytoreductive therapy on a case-by-case basis. Fasting during Ramadan is often safe in stable MPN, with attention to hydration (particularly in PV) — we'll discuss it with you.

What outcomes look like — honestly

PV and ET, well-managed, are compatible with a near-normal lifespan for most patients. The main aim of treatment is preventing clots; with good control, the great majority never have one. A small proportion of PV and ET patients transform over many years to myelofibrosis, and a smaller proportion to acute leukemia — we watch for early signs.

Myelofibrosis prognosis varies more — from many years of stable disease in low-risk patients, to a more demanding course in higher-risk patients. JAK inhibitors have substantially improved quality of life. For transplant-eligible higher-risk patients, cure is possible.

Daily life with an MPN

Most patients live very normally. The main adjustments are regular clinic visits (every few months when stable), attention to cardiovascular risk factors (blood pressure, smoking, cholesterol — these matter even more in MPN), and awareness of clot warning signs. Many patients ask whether they can travel, exercise, work — almost always yes, with sensible hydration and movement on long flights, and a clear plan if symptoms arise.