Screen for hyperviscosity syndrome, acute arterial or venous thrombosis, and extreme polycythaemia requiring urgent venesection.
Hct >0.60 (60%) causes severe hyperviscosity. Blood viscosity increases exponentially above Hct 0.55. At Hct 0.60, blood is 5× more viscous than normal, causing sluggish flow, cerebral hypoperfusion, and thrombosis. Urgent venesection (remove 400-500 mL) reduces Hct by 3-5% within hours, preventing stroke.
Hyperviscosity syndrome: Headache, blurred vision, tinnitus, dizziness, confusion. Cerebral blood flow reduced by 30-40% at Hct >0.55. Retinal vein engorgement visible on fundoscopy. Stroke risk is 10-15% per year if Hct >0.55 untreated. Emergency venesection is life-saving.
Polycythaemia vera (PV) is the commonest cause of true polycythaemia (95% JAK2 V617F positive). Thrombosis risk is 5% per year (arterial > venous). Budd-Chiari syndrome (hepatic vein thrombosis) occurs in 1-2% of PV patients, presenting with ascites + hepatomegaly + abdominal pain.
Pruritus after bathing (aquagenic pruritus) is pathognomonic for PV. Occurs in 40% of PV patients. Caused by mast cell histamine release triggered by temperature change. Relieved by antihistamines. This symptom does NOT occur in secondary polycythaemia.
Confirm true polycythaemia (raised red cell mass) and exclude relative polycythaemia (reduced plasma volume). A single raised Hct may be dehydration or lab error.
Relative polycythaemia (pseudopolycythaemia) is common. Affects 5% of middle-aged men. Caused by reduced plasma volume (dehydration, diuretics, obesity). Hct typically 0.52-0.56 (mild elevation). No splenomegaly, no thrombocytosis, no symptoms. JAK2 negative. Does NOT require venesection; treat hypertension and cardiovascular risk factors.
Smoking causes pseudopolycythaemia via two mechanisms: (1) carboxyhaemoglobin (CO bound to Hb) falsely elevates measured Hb; (2) chronic hypoxia stimulates erythropoietin. Smoking cessation normalizes Hct within 3-6 months. Always measure Hct in smokers, not just Hb.
Haematocrit >0.52 (men) or >0.48 (women) on two occasions is diagnostic for polycythaemia. Single elevated Hct can be dehydration, stress polycythaemia, or lab error. Repeating at 1-2 weeks differentiates true from relative polycythaemia.
Red cell mass measurement (chromium-51 labeling) is gold standard but rarely performed now. Reserved for borderline cases (Hct 0.50-0.52 in men) where distinguishing true from relative polycythaemia changes management. JAK2 testing has largely replaced red cell mass studies.
Classify polycythaemia as primary (PV, JAK2+ myeloproliferative neoplasm) or secondary (erythropoietin-driven). This determines investigation pathway and treatment.
Polycythaemia vera (PV) is a JAK2-driven myeloproliferative neoplasm. Uncontrolled red cell, platelet, and white cell production. 95% have JAK2 V617F mutation (activates JAK-STAT signaling). Median age 60. Thrombosis is leading cause of death (5% per year). 10-20% progress to myelofibrosis or acute leukaemia over 10-20 years.
Secondary polycythaemia is reactive, driven by erythropoietin (EPO). Chronic hypoxia (COPD, OSA, altitude) causes physiological EPO elevation. Renal disease and tumors cause inappropriate EPO secretion. Treating the underlying cause normalizes Hct in 50-70% of cases.
EPO levels differentiate PV from secondary. PV has low/normal EPO (autonomous red cell production, no EPO needed). Secondary polycythaemia has high EPO (driving red cell production). JAK2 mutation is 95% sensitive for PV; if JAK2 negative but clinical suspicion high, measure EPO and request bone marrow biopsy.
Thrombocytosis + leucocytosis alongside polycythaemia strongly suggests PV (trilineage proliferation). Secondary polycythaemia affects only red cells; platelets and WCC are normal. Splenomegaly occurs in 70% of PV, 0% of secondary polycythaemia.
Examine for signs of PV (splenomegaly, plethora, thrombosis) and secondary causes (cyanosis, clubbing, hypertension).
Splenomegaly is the single most discriminating clinical sign for PV. Present in 70% of PV patients, absent in secondary polycythaemia. Spleen size correlates with disease burden. Massive splenomegaly (>8 cm) suggests transformation to post-PV myelofibrosis (15-20% of PV patients over 10-20 years).
Plethora (ruddy complexion) is due to raised Hct (>0.55). Red palms, injected conjunctivae, facial flushing. More pronounced in PV than secondary polycythaemia (higher Hct in PV typically). Plethora reduces post-venesection as Hct falls to target (<0.45).
SaO₂ <92% on room air indicates chronic hypoxia. This is the hallmark of secondary polycythaemia (COPD, OSA, altitude, cyanotic heart disease). Overnight oximetry diagnoses OSA (>15 desaturations/hour = moderate OSA). CPAP therapy normalizes Hct in 50% of OSA patients within 6 months.
Aquagenic pruritus (itching after hot bath/shower) is pathognomonic for PV. Occurs in 40% of PV patients. Caused by basophil/mast cell histamine release triggered by temperature change. Relieved by antihistamines (cetirizine 10 mg OD). Does NOT occur in secondary polycythaemia.
Investigate to differentiate PV from secondary polycythaemia. JAK2 mutation is diagnostic for PV; EPO level guides further workup.
JAK2 V617F mutation is diagnostic for PV. Positive in 95% of cases. Sensitivity and specificity both >99% for myeloproliferative neoplasm. If JAK2 positive, no further testing needed to confirm PV (haematology will risk-stratify and initiate treatment). 3-5% of PV have JAK2 exon 12 mutations instead (test if V617F negative but high clinical suspicion).
EPO level is the key discriminator when JAK2 is negative. PV has low/normal EPO (<15 IU/L, typically <5 IU/L) because red cell production is autonomous, not EPO-driven. Secondary polycythaemia has high EPO (>20 IU/L) driving reactive erythrocytosis. EPO <5 IU/L is 90% specific for PV even if JAK2 negative.
Overnight oximetry diagnoses obstructive sleep apnoea (OSA). Apnoea-hypopnoea index (AHI) >15/hour = moderate OSA. Oxygen desaturations during sleep stimulate EPO, causing polycythaemia. CPAP therapy normalizes SaO₂ and reduces Hct by 0.05-0.10 within 6 months in 50% of patients.
Renal ultrasound is mandatory in secondary polycythaemia with high EPO and no hypoxia. Detects polycystic kidney disease (10% of secondary polycythaemia), renal cell carcinoma (paraneoplastic EPO secretion), post-transplant erythrocytosis (native kidneys secrete EPO), and renal artery stenosis (ischaemia → EPO).
Refer based on Hct level, JAK2 status, thrombosis risk, and underlying cause. PV requires specialist management; secondary polycythaemia may be managed in primary care if mild.
Hct >0.60 requires same-day haematology even if asymptomatic. Blood viscosity at this level causes cerebral hypoperfusion, stroke risk 10-15% within weeks. Emergency venesection (remove 400-500 mL) reduces Hct to <0.55 within hours, preventing thrombotic events. Delay risks stroke, MI, or Budd-Chiari syndrome.
JAK2 V617F positive is diagnostic for PV and mandates 2WW haematology referral (NICE NG12 suspected haematological cancer pathway). Haematology confirms diagnosis with bone marrow biopsy (WHO criteria), risk-stratifies (age, thrombosis history), and initiates venesection + aspirin ± cytoreduction.
Relative polycythaemia (Gaisböck syndrome) does NOT require haematology referral or venesection. Treat cardiovascular risk factors (weight loss, BP control, smoking cessation). Hct normalizes in 30-40% of patients with 10% weight loss. Venesection is contraindicated (does not improve outcomes, increases cardiovascular risk).
Secondary polycythaemia with Hct <0.56 and asymptomatic can be managed in primary care. Treat underlying cause (CPAP for OSA, oxygen therapy for COPD). Venesection only if Hct >0.56 symptomatic (headache, dizziness). Target Hct <0.52. Haematology referral not needed unless cause unclear.
Treatment depends on cause. PV: venesection + aspirin ± cytoreduction. Secondary polycythaemia: treat cause, venesection only if symptomatic. Gaisböck syndrome: cardiovascular risk reduction, no venesection.
PV treatment ladder (haematology-managed):
Venesection to Hct <0.45 is the cornerstone of PV treatment. CYTO-PV trial showed Hct <0.45 reduces cardiovascular events by 79% vs Hct 0.45-0.50 (HR 0.21, p<0.001). Target is <0.45 for BOTH men and women (not <0.52 as previously). Venesection removes iron, limiting erythropoiesis; patients become iron-deficient but this is therapeutic.
Aspirin 75 mg reduces arterial thrombosis (stroke, MI) by 60% in PV. Mechanism: irreversible COX-1 inhibition preventing platelet aggregation. All PV patients require aspirin unless bleeding risk (acquired vWD if platelets >1500, prior GI bleed). PPI co-prescription if gastritis risk.
Hydroxycarbamide (hydroxyurea) is first-line cytoreductive agent for high-risk PV (age >60, prior thrombosis). Inhibits DNA synthesis, reducing Hct, platelets, WCC. Reduces thrombosis by 85%. Well-tolerated; main side effect is myelosuppression. Target Hct <0.45, platelets <400 × 10⁹/L.
Secondary polycythaemia treatment targets the underlying cause. CPAP for OSA normalizes Hct in 50% of patients. Oxygen therapy for COPD improves Hct modestly. Venesection is reserved for symptomatic Hct >0.56 (headache, dizziness). Routine venesection in asymptomatic secondary polycythaemia does NOT improve outcomes and may worsen tissue hypoxia.
Lifestyle interventions reduce thrombotic events in PV and improve Hct control in secondary polycythaemia. Cardiovascular risk factor control is as important as venesection.
Hydration reduces blood viscosity. At Hct 0.55, 2% dehydration increases viscosity by 15%, worsening cerebral perfusion and thrombosis risk. PV patients should drink 2.5-3 L/day (30-40 mL/kg). Urine should be pale yellow; dark urine indicates inadequate hydration.
Smoking cessation is critical in secondary polycythaemia. Smoking worsens COPD hypoxia (↑ EPO), raises carboxyhaemoglobin (falsely elevated Hb), and damages endothelium (↑ thrombosis). Quitting improves Hct by 0.03-0.05 within 6 months. NNT to prevent one thrombotic event = 15 smokers quit for 5 years.
Weight loss improves Gaisböck syndrome and OSA. 10 kg weight loss reduces Hct by 0.02-0.04 in Gaisböck (plasma volume expands). Weight loss also improves OSA severity (AHI reduces by 30% with 10% weight loss), lowering EPO and Hct. Mediterranean diet is evidence-based (PREDIMED trial).
CPAP therapy for OSA normalizes nocturnal SaO₂, reducing EPO secretion. Hct falls by 0.05-0.10 within 3-6 months in 50% of OSA patients. CPAP compliance >4 hours/night is essential. Side effects (nasal congestion, mask discomfort) improve with humidifier and mask re-fitting.
Monitor Hct trajectory, watch for thrombotic events, and re-refer if Hct rising or new symptoms. Chronic polycythaemia requires long-term surveillance.
Hct target <0.45 for BOTH men and women. CYTO-PV trial proved Hct <0.45 reduces thrombosis by 79% vs Hct 0.45-0.50. Previous target was <0.52 for men, but this was too high. Every 0.01 rise in Hct above 0.45 increases thrombosis risk by 10%. Strict Hct control is as important as aspirin for thrombosis prevention.
Thrombotic events on treatment indicate inadequate control or high-risk disease. If stroke/MI/DVT occurs despite Hct <0.45 + aspirin, haematology escalates to hydroxycarbamide or ruxolitinib, adds anticoagulation, or intensifies venesection frequency. Primary care role is early recognition and urgent referral.
Transformation risk: 10-20% of PV evolves to post-PV myelofibrosis over 10-20 years. Signs: progressive splenomegaly, tear-drop cells, rising LDH, anaemia, thrombocytopenia. 5-10% transform to acute myeloid leukaemia (AML) over 20 years. Ruxolitinib may slow progression to myelofibrosis.
Annual cardiovascular review is mandatory. PV patients have 2-5× higher CVD mortality than general population. Controlling BP, lipids, diabetes, smoking status, and weight reduces cardiovascular events by 50%. QRISK underestimates risk in PV (does not include polycythaemia as variable).