While most GPs won’t see large numbers of patients with myeloproliferative neoplasms (MPNs), they will see symptoms that can point to one. Persistent fatigue, recurrent headaches, troublesome itching after a shower, or a platelet count that’s been mildly elevated for months may be the earliest signs of an MPN for some patients. However, because these symptoms are common and non-specific, MPNs are often missed in primary care.

MPNs are chronic blood cancers in which the bone marrow produces excess blood cells. The major Philadelphia chromosome‑negative (“classic”) MPNs include:

• Polycythaemia vera (PV), characterised by excess red blood cell production
• Essential thrombocythaemia (ET), characterised by elevated platelet counts
• Pre-fibrotic primary myelofibrosis (pre-PMF), an early form of myelofibrosis that can resemble ET
• Primary myelofibrosis (PMF), characterised by progressive bone marrow scarring and abnormal blood cell production

Most cases are driven by acquired mutations involving the JAK2, CALR or MPL genes.

Chronic myeloid leukaemia (CML) is also classified as an MPN but is characterised by the Philadelphia chromosome and is generally considered separately from the classic MPNs discussed here.

While MPNs are considered rare, they are not exceptionally uncommon. International studies estimate an incidence at approximately 6 cases per 100,000 people annually, and prevalence continues to increase as patients live longer with these chronic conditions.

MPNs tend to develop slowly and often look like much more common problems encountered every day in primary care. In women, symptoms may also overlap with those commonly attributed to perimenopause and menopause.

Depending on the subtype, patients may experience:

• Stroke, TIA, heart attack and other arterial thrombotic events
• Deep vein thrombosis, pulmonary embolism and other venous thrombotic events
• Significant bleeding
• Progressive splenomegaly
• Progression to myelofibrosis
• Transformation to acute myeloid leukaemia (AML)

Unfortunately, some patients are diagnosed only after one of these complications has already occurred.

Early diagnosis allows timely referral, risk stratification and treatment. In PV, for example, controlling haematocrit levels can significantly reduce thrombotic risk. Earlier recognition also provides access to specialist monitoring, symptom management and support services.

Why MPNs are easy to miss in general practice

Symptoms are rarely specific and may appear in clusters.

Constitutional symptoms

• Fatigue
• Reduced exercise tolerance
• Night sweats
• Unintentional weight loss
• Low-grade fevers

Microvascular symptoms

• Headaches
• Dizziness
• Visual disturbances
• Tinnitus
• Erythromelalgia (burning pain and redness of the hands or feet)

Other clues

• Aquagenic pruritus (itching after bathing or showering)
• Ruddy complexion
• Early satiety
• Left upper quadrant discomfort
• Splenomegaly
• Unexplained thrombosis, especially at unusual sites

Individually, these findings may not seem particularly concerning, but when several occur together, especially alongside abnormal blood counts, they should prompt further evaluation.

Diagnosis frequently begins with a routine full blood count showing a mild but persistent abnormality. A platelet count that remains elevated across several tests months apart may be more significant than a single markedly abnormal result during an acute illness.

Red flags by subtype:

Polycythaemia vera

• Elevated haemoglobin
• Elevated haematocrit
• Persistent erythrocytosis without an obvious cause

Essential thrombocythaemia or pre-PMF

• Platelet counts that remain elevated on repeat testing

Primary myelofibrosis

• Unexplained anaemia
• Abnormal blood film findings
• Variable white cell and platelet abnormalities

MPNs aren’t confined to older adults

The median age at diagnosis is around 60 years but clinicians are increasingly encountering patients diagnosed in their 20s, 30s and 40s, thanks to improved recognition and access to molecular testing. This is important to keep in mind since younger patients may face decades of exposure to disease-related complications if diagnosis is delayed.

If an MPN is a possibility, follow these steps:

1. Repeat abnormal blood counts to confirm persistence
2. Review historical pathology whenever possible
3. Consider secondary causes of erythrocytosis or thrombocytosis
4. Ask specifically about itching after showering, headaches, visual symptoms, thrombotic history and constitutional symptoms
5. Examine for splenomegaly where appropriate
6. Refer to haematology when abnormalities remain unexplained or suspicion persists

 
Specialist assessment will often include molecular testing for JAK2, CALR and MPL mutations, alongside other investigations.

MPNs can hide behind apparently minor abnormalities

The patient with “borderline” thrombocytosis and fatigue may ultimately have ET or pre-fibrotic PMF.

The patient repeatedly seeking help for unexplained itching may have PV.

The patient presenting with an apparently unprovoked thrombotic event, especially in an unusual site such as the splanchnic veins, may have an underlying MPN driving their risk.

Not every abnormal blood count signals a blood cancer, but persistent unexplained abnormalities deserve an explanation. A mildly abnormal result that stays abnormal matters.

Key takeaways

• Persistent abnormalities in blood counts are often the earliest sign of an MPN
• Fatigue, headaches, aquagenic pruritus and unexplained thrombosis should raise suspicion, particularly when pathology is abnormal
• MPNs can occur in younger adults and should not be excluded based on age alone
• Earlier diagnosis can reduce complications and improve long-term outcomes
• Persistent unexplained erythrocytosis, thrombocytosis or other abnormal blood count abnormalities warrant haematology referral

Further Reading

MPN Alliance Australia – Information for GPs
https://www.mpnallianceaustralia.org.au/understanding-mpn/general-practitioners-information/

Leukaemia Foundation Australia
https://www.leukaemia.org.au/

Cancer Council Australia: Optimal Care Pathway for People with Myeloproliferative Neoplasms
https://www.cancer.org.au/assets/pdf/myeloproliferative-neoplasms

NCCN Guidelines: Myeloproliferative Neoplasms
https://www.nccn.org/professionals/physician_gls/