Presentation: Polycythaemia

High haemoglobin

Polycythaemia (erythrocytosis) means an increase in absolute red cell mass, recognised in practice by a raised haemoglobin or haematocrit/PCV against age- and sex-specific reference ranges.

A raised Hb/PCV can instead reflect a contracted plasma volume (“relative” or spurious polycythaemia) rather than a true rise in red cell mass — from dehydration (vomiting, diarrhoea), diuretics, or the smoking/hypertension/obesity cluster sometimes called Gaisböck syndrome.

True polycythaemia is either primary (an intrinsic marrow disorder — polycythaemia vera, or rare congenital familial polycythaemia; serum erythropoietin low) or secondary (erythropoietin-driven).

Secondary causes include chronic hypoxaemia (COPD, obesity hypoventilation, cyanotic congenital heart disease with right-to-left shunt, high altitude, obstructive sleep apnoea), heavy smoking (raised carboxyhaemoglobin), erythropoietin-secreting lesions (renal cell carcinoma, renal cysts, hepatocellular carcinoma, cerebellar haemangioblastoma, uterine leiomyoma), drugs (testosterone and anabolic steroids, exogenous erythropoietin, SGLT2 inhibitors), post-renal-transplant erythrocytosis, and rare high-oxygen-affinity haemoglobinopathies.

Confirming and working up

Unless the Hb/PCV is very high, repeat the count after ensuring adequate hydration. Confirm a PCV > 0.52 in men or > 0.47 in women on a specimen taken without venous occlusion.

Because plasma volume expansion can mask a true red cell mass rise — especially in women, who may present with a normal haematocrit and hepatic vein thrombosis — an elevated red cell count is a more reliable marker of erythrocytosis than haemoglobin alone, and microcytic erythrocytosis is a hallmark of polycythaemia vera.

A confirmed PCV above these thresholds without an obvious secondary cause needs haematology referral. Workup is sequential: FBC and film, then serum erythropoietin.

• A low or low-normal EPO points to primary polycythaemia and prompts JAK2 V617F testing (exon 14 mutation in about 90–95%; JAK2 exon 12 in about 5%; CALR rarely).
• A raised or inappropriately normal EPO points to a secondary cause — check arterial oxygen saturation, carboxyhaemoglobin in smokers, and image the abdomen (and CNS) for an EPO-secreting tumour.

Untreated polycythaemia vera carries a high risk of arterial and venous thrombosis, including stroke.

Polycythaemia vera

A chronic myeloproliferative neoplasm with clonal proliferation of red cells (the hallmark) and usually white cells and platelets as well, almost always driven by a JAK2 mutation causing erythropoietin-independent erythropoiesis. See Myeloproliferative Disorders for the broader classification this sits within.

Mean age at diagnosis is about 60, though women can present decades earlier. Roughly 10–15% progress to myelofibrosis, and a smaller proportion transform to acute myeloid leukaemia.

Clinical features: often asymptomatic early; fatigue, headache, dizziness, visual disturbance, tinnitus; aquagenic pruritus (itch after a hot bath or shower), often the earliest symptom; facial plethora; splenomegaly (over 30%); erythromelalgia (red, warm, painful hands or feet); epistaxis or gastrointestinal bleeding; thrombosis, sometimes at unusual sites (Budd–Chiari syndrome, portal vein). Platelet counts above 1000 × 10⁹/L can cause an acquired von Willebrand syndrome and paradoxical bleeding.

Investigations: FBC and film; serum EPO (low or low-normal); JAK2 V617F, then JAK2 exon 12 and CALR if negative. Bone marrow biopsy typically shows panmyelosis with clustered atypical megakaryocytes, forms part of the WHO criteria, but is not by itself diagnostic. Secondary erythrocytosis — far commoner than polycythaemia vera — must be excluded first in anyone with an isolated raised haematocrit.

Management (haematology-led):

• Phlebotomy is the mainstay, targeting haematocrit < 0.45 in men and < 0.42 in women (< 0.35 in pregnancy); the CYTO-PV randomised trial showed fewer cardiovascular deaths and thromboses at the < 0.45 target than at 0.45–0.50.
• Low-dose aspirin (around 100 mg daily) unless contraindicated, for microvascular symptoms and thrombosis risk.
• Cytoreduction for high-risk or phlebotomy-intolerant disease: hydroxyurea, peginterferon alfa or ropeginterferon (interferon is safe in pregnancy), or the JAK inhibitor ruxolitinib when hydroxyurea is not tolerated or effective.
• Treat complications: allopurinol for symptomatic hyperuricaemia; antihistamines, SSRIs, interferon or ruxolitinib for pruritus; standard anticoagulation after a thrombotic event.

Thrombosis is the leading cause of death, followed by the complications of myelofibrosis and leukaemic transformation.