What is the management for a patient with polycythemia, as indicated by a hemoglobin level of 18.7 g/dL and a hematocrit of 56.7%?

Management of Polycythemia with Hemoglobin 18.7 g/dL and Hematocrit 56.7%

Immediately initiate therapeutic phlebotomy to reduce hematocrit below 45%, start low-dose aspirin 81-100 mg daily, and urgently evaluate for polycythemia vera versus secondary causes through JAK2 mutation testing and serum erythropoietin levels. 1, 2

Immediate Risk Assessment and Initial Management

Your patient's hematocrit of 56.7% places them at significantly elevated thrombotic risk. The landmark CYTO-PV trial demonstrated that maintaining hematocrit strictly below 45% reduces cardiovascular death and major thrombotic events from 9.8% to 2.7% (HR 3.91, P=0.007). 1, 2

Urgent Phlebotomy Protocol

Induction Phase:

• Remove 300-450 mL weekly or twice weekly until hematocrit drops below 45% 2
• Each phlebotomy session should remove the same volume with intervals determined by hematocrit monitoring 2
• This is first-line treatment regardless of whether the cause is polycythemia vera or secondary erythrocytosis 2

Maintenance Phase:

• Continue same volume per session with frequency adjusted based on hematocrit levels 2
• Monitor complete blood count every 2-4 weeks during induction, then every 3 months once stable 2

Antiplatelet Therapy

Start low-dose aspirin 100 mg daily immediately unless contraindicated. 1, 2 The ECLAP study demonstrated that aspirin significantly reduces the combined endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, pulmonary embolism, and major venous thromboembolism (RR 0.40,95% CI 0.18-0.91, P=0.03). 1

Diagnostic Workup to Determine Etiology

Essential Testing

Order immediately:

• JAK2 V617F mutation testing 1, 2
• Serum erythropoietin level 2, 3
• Complete metabolic panel to assess renal function 2
• Oxygen saturation measurement 1

If JAK2 positive: Diagnosis of polycythemia vera is confirmed. 1, 3

If JAK2 negative: Test for CALR and MPL mutations. 1, 2 If all mutations are negative and erythropoietin is elevated, investigate secondary causes including chronic lung disease, congenital heart disease, renal disease, or heavy smoking. 1, 2, 4

Risk Stratification and Cytoreductive Therapy Decision

High-Risk Criteria (Requires Cytoreductive Therapy)

Add cytoreductive therapy if any of the following are present: 1, 2

• Age ≥60 years
• History of prior thrombosis
• Poor phlebotomy tolerance (inability to maintain hematocrit <45% with phlebotomy alone after 3 months)
• Symptomatic or progressive splenomegaly
• Platelet count >1,500 × 10⁹/L
• Leukocyte count >15 × 10⁹/L
• Severe symptoms interfering with daily activities

First-Line Cytoreductive Agents

Hydroxyurea: 1

• Most commonly used first-line agent
• Start at 15-20 mg/kg/day, adjust based on response
• Target: hematocrit <45%, platelet count ≤400 × 10⁹/L, WBC count ≤10 × 10⁹/L

Interferon alfa or pegylated interferon: 1

• Preferred for younger patients (<60 years)
• Particularly effective for intractable pruritus
• Consider for pregnant patients requiring cytoreductive therapy

Ruxolitinib: 1, 5

• Reserved for patients with inadequate response to or intolerance of hydroxyurea
• Achieves hematocrit control in 88% of patients by 3 months 5
• Associated with lower thromboembolic event rates (1.8% vs 8.2% with best available therapy) 1

Special Considerations for Secondary Erythrocytosis

If secondary erythrocytosis is confirmed (elevated erythropoietin, negative JAK2/CALR/MPL):

Do NOT perform routine phlebotomy. 2 The patient's homeostatic processes generally achieve optimal red cell mass, and routine phlebotomy can cause iron deficiency, decrease oxygen-carrying capacity, and paradoxically increase stroke risk. 2

Phlebotomy in secondary erythrocytosis is ONLY indicated when ALL of the following are present: 2, 6

• Hematocrit >65%
• Symptoms of hyperviscosity (headache, dizziness, poor concentration, blurred vision, tinnitus)
• Patient is adequately hydrated
• No iron deficiency present (transferrin saturation >20%)

First-line treatment for suspected hyperviscosity: Hydration with oral fluids or intravenous normal saline, NOT phlebotomy. 2

Monitoring and Follow-Up

For Confirmed Polycythemia Vera:

• Complete blood count every 2-4 weeks during induction, then every 3 months 2
• Assess response using European LeukemiaNet criteria: complete response = hematocrit <45% without phlebotomy, platelet count ≤400 × 10⁹/L, WBC count ≤10 × 10⁹/L, no disease-related symptoms 1, 2
• Monitor for iron deficiency in patients undergoing repeated phlebotomy 2
• Evaluate for disease progression and transformation to myelofibrosis or acute leukemia 3, 7

For Secondary Erythrocytosis:

• Monitor hematocrit every 3-6 months 2
• Assess iron status regularly (serum iron, ferritin, transferrin saturation) 1, 2
• If transferrin saturation <20%, treat with iron supplementation until stores are replete 2
• Evaluate for progression of underlying disease 2

Critical Pitfalls to Avoid

Do not delay phlebotomy while awaiting diagnostic results. With hematocrit at 56.7%, thrombotic risk is immediate and substantial. 1, 2

Do not assume secondary erythrocytosis requires routine phlebotomy. This is a common error that can lead to iron deficiency and paradoxically worsen outcomes. 2

Do not overlook iron deficiency. Iron-deficient red cells are less deformable and have reduced oxygen-carrying capacity, which can mimic or worsen hyperviscosity symptoms at lower hematocrit levels. 2, 6

Do not withhold aspirin without clear contraindications. The thrombotic risk reduction is substantial and well-established. 1

Do not forget cardiovascular risk factor management. Aggressively manage smoking cessation, hypertension control, and diabetes regardless of the underlying diagnosis. 2