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Stem
A 64-year-old man presents to the emergency department with a two-month history of headache, visual blurring, dizziness and intense generalised itching after hot showers. He also reports an episode of transient right-sided weakness last week. He is a non-smoker with no chronic lung disease. On examination he is plethoric with a ruddy complexion, blood pressure 156/92, and a spleen tip is palpable. Bloods: haemoglobin 198 g/L, haematocrit 0.61, white cells 16 x10^9/L, platelets 560 x10^9/L; oxygen saturation 98 percent on room air.
Questions
a) What is the most likely diagnosis, and which three features in the history point to it? (2 marks)
Most likely diagnosis is polycythaemia vera (PV), a BCR-ABL-negative myeloproliferative neoplasm. The three features are: (1) raised haematocrit (0.61, well over 0.52 in a man) with a plethoric/ruddy complexion; (2) aquagenic pruritus (itch after hot showers) — a classic hallmark of PV; and (3) hyperviscosity-related symptoms plus a thrombotic event (transient ischaemic attack) and splenomegaly.
b) Outline the investigations you would order to confirm the diagnosis and to distinguish it from secondary polycythaemia. (4 marks)
- Serum erythropoietin (EPO) level — the key discriminator: LOW in PV (autonomous JAK2-driven red-cell mass suppresses EPO) versus HIGH in secondary (hypoxic) polycythaemia.
- JAK2 V617F mutation screen — positive in about 95 percent of PV (JAK2 exon 12 if negative); confirms a clonal MPN.
- Full blood count and film — raised haematocrit, often leukocytosis and thrombocytosis; assess for tear-drop cells/leukoerythroblastic film if fibrosis suspected.
- Bone-marrow aspirate and trephine — hypercellular marrow with panmyelosis and pleomorphic megakaryocytes; reticulin stain to exclude early myelofibrosis.
- To exclude secondary causes: oxygen saturation / arterial blood gas (he is 98 percent, against hypoxic secondary polycythaemia), renal/hepatic imaging to exclude an EPO-secreting tumour (renal cell carcinoma, hepatocellular carcinoma), and serum urate/LDH (high in PV from cell turnover).
c) Describe the stepwise definitive management for this high-risk patient. (3 marks)
- Venesection to a target haematocrit below 0.45 — the ECLAP/Marchioli target that reduces cardiovascular death and major thrombosis (roughly 450 mL at a time, guided by iron studies).
- Low-dose aspirin 75 mg oral daily (unless contraindicated) to reduce thrombotic events.
- Cytoreduction with hydroxycarbamide because he is high-risk (age over 60 AND a recent thrombotic/embolic event); interferon-alpha or ruxolitinib are alternatives if resistant/intolerant, and interferon-alpha is preferred in younger patients and in pregnancy.
- Manage cardiovascular risk factors (blood pressure, lipids) and treat hyperuricaemia/gout (allopurinol) if needed.
d) State two diagnostic pitfalls specific to this disease group. (1 mark)
- Diagnosing "secondary" polycythaemia without checking serum EPO and JAK2 — a normal oxygen saturation does not exclude PV, which is clonal and has a LOW EPO.
- Missing an occult MPN behind splanchnic (Budd-Chiari, portal) vein thrombosis — always test JAK2 V617F even when the full blood count is normal, because occult MPN is a leading cause of splanchnic vein thrombosis.