When and how should emergent therapeutic phlebotomy be performed in a polycythemia vera patient presenting with acute hyperviscosity (hematocrit >55%) and symptoms such as headache, visual changes, chest pain, or neurologic deficits?

Emergent Therapeutic Phlebotomy in Polycythemia Vera with Acute Hyperviscosity

In polycythemia vera patients presenting with acute hyperviscosity symptoms (headache, visual changes, chest pain, or neurologic deficits) and hematocrit >55%, emergent therapeutic phlebotomy should be performed immediately by removing 300-450 mL of blood with simultaneous equal-volume replacement using isotonic saline or dextrose to prevent hemoconcentration, targeting hematocrit reduction to <45%. 1, 2, 3

Indications for Emergent Phlebotomy

Strict criteria must be met before proceeding:

• Confirmed polycythemia vera diagnosis with JAK2 mutation positivity (present in >95% of PV cases) 1
• Hematocrit >55% with documented hyperviscosity symptoms 1, 2
• Presence of acute symptoms including:
  • Visual disturbances (blurred vision, retinal vein occlusion) 2
  • Neurologic manifestations (headache, dizziness, confusion, altered mental status, seizures, cranial nerve palsies, limb weakness) 2, 4
  • Bleeding manifestations (epistaxis, mucosal bleeding, easy bruising) 2
  • Cardiovascular symptoms (chest pain, thrombotic events) 5

Critical distinction: These symptoms must represent true hyperviscosity rather than dehydration or iron deficiency, which produce identical symptoms but require opposite management. 2, 3

Pre-Procedure Assessment

Before performing phlebotomy, you must:

• Exclude dehydration first – rehydrate with oral fluids or IV normal saline as first-line therapy, as dehydration exacerbates symptoms and mimics true hyperviscosity 2, 3
• Assess iron status with serum ferritin and transferrin saturation (not MCV, which is unreliable in erythrocytosis) 1
• Rule out iron deficiency – if transferrin saturation <20%, iron supplementation is required rather than phlebotomy, as iron-deficient red cells have reduced oxygen-carrying capacity and deformability, paradoxically increasing stroke risk 1, 3
• Confirm adequate hydration status before proceeding 3

Phlebotomy Procedure Protocol

When emergent phlebotomy is indicated:

• Remove 300-450 mL of blood per session (approximately 1 unit) 1, 3
• Simultaneously replace with equal volume (750-1000 mL) of isotonic saline or dextrose – this is mandatory to prevent further hemoconcentration and reduce stroke risk 1, 3
• Monitor hemodynamic status carefully throughout the procedure 1
• Target hematocrit <45% as the therapeutic goal, with a slightly lower target of approximately 42% reasonable for women 1

The immediate benefit: Phlebotomy produces rapid improvement in small artery compliance and symptom relief within minutes to hours, though this effect is short-lived without ongoing management. 6, 7

Evidence-Based Hematocrit Targets

The CYTO-PV randomized trial provides the strongest evidence:

• Maintaining hematocrit strictly <45% reduced cardiovascular death or major thrombosis to 2.7% compared with 9.8% in patients maintained at 45-50% (HR 3.91; 95% CI 1.45-10.53; P=0.007) 1
• This represents a >3-fold reduction in thrombotic risk with aggressive hematocrit control 1
• The 45% threshold is absolute and evidence-based for PV patients 1

Long-Term Management After Emergent Phlebotomy

Following acute intervention:

• Continue therapeutic phlebotomy to maintain hematocrit strictly <45% 8, 1
• Initiate low-dose aspirin (81-100 mg daily) as the second cornerstone of therapy for thrombosis prevention 1
• Consider cytoreductive therapy (hydroxyurea, interferon alfa-2a, or ruxolitinib) if phlebotomy requirements are excessive or if thrombocytosis/leukocytosis is present 8
• Monitor complete blood count regularly and reassess iron status periodically 3

Critical Warnings and Common Pitfalls

Never perform repeated routine phlebotomies without volume replacement – this creates iron depletion, decreases oxygen-carrying capacity, produces rigid poorly deformable red cells, and paradoxically increases stroke risk. 1, 3

Do not rely on symptom severity alone to guide phlebotomy decisions, as symptoms do not correlate reliably with measured hematocrit or viscosity levels. 2

Do not overlook coexisting iron deficiency – it mimics hyperviscosity symptoms but requires iron supplementation, not phlebotomy. 1, 3

Distinguish PV from secondary erythrocytosis – in secondary causes (smoking, COPD, cyanotic heart disease), phlebotomy is indicated only when hemoglobin >20 g/dL AND hematocrit >65% with documented hyperviscosity symptoms after excluding dehydration and iron deficiency. 1, 3

When to Consult Hematology Urgently

Immediate hematology consultation is warranted for:

• JAK2-positive patients with acute hyperviscosity symptoms 1
• Hemoglobin >20 g/dL with symptoms 1
• Unexplained splenomegaly with erythrocytosis 1
• Concurrent cytopenias in other cell lines 1
• Diagnosis remains unclear after initial workup 1