How is elevated hemoglobin (Hb) managed?

Management of Elevated Hemoglobin

Phlebotomy is the cornerstone of treatment for elevated hemoglobin, with a target hematocrit <45% to reduce thrombotic risk, and should be initiated immediately when hemoglobin exceeds 18.5 g/dL or when polycythemia vera is diagnosed. 1, 2, 3

Initial Diagnostic Workup

Before initiating treatment, determine the underlying cause of elevated hemoglobin:

• Obtain a complete blood count with differential to assess for thrombocytosis (suggesting polycythemia vera) or isolated erythrocytosis (suggesting secondary causes). 2
• Order JAK2 V617F mutation testing as >95% of polycythemia vera patients harbor this mutation, which distinguishes primary from secondary erythrocytosis. 2, 3, 4
• Evaluate for secondary causes including chronic hypoxemia (COPD, sleep apnea), smoking history, renal disease, and high-altitude exposure. 2
• Perform bone marrow examination if JAK2 mutation is positive to confirm morphologic diagnosis of polycythemia vera. 3, 4

Immediate Management Based on Hemoglobin Level

Hemoglobin >18.5 g/dL

• Initiate phlebotomy immediately to reduce viscosity and prevent thrombotic complications. 2
• Remove 250-500 mL of blood per session, which decreases hemoglobin by approximately 1.5 g/dL per 400 mL unit removed. 2
• Target hemoglobin <15 g/dL in men and <14 g/dL in women for secondary erythrocytosis. 2

Confirmed Polycythemia Vera

• Maintain hematocrit <45% through therapeutic phlebotomy, as this target significantly reduces thrombotic risk. 1, 3, 4
• Perform phlebotomy once or twice weekly as tolerated, removing one unit (300 mL) per session. 1
• Monitor hemoglobin/hematocrit before each phlebotomy to avoid reducing values to <80% of starting levels. 1

Antiplatelet Therapy

• Initiate low-dose aspirin 81-100 mg once or twice daily in all patients with polycythemia vera unless contraindications exist (bleeding history, extreme thrombocytosis ≥1000 × 10⁹/L with acquired von Willebrand disease). 2, 3, 4
• Consider twice-daily dosing for enhanced thrombosis prevention, though controlled studies are needed to confirm superiority over once-daily dosing. 5

Risk Stratification and Cytoreductive Therapy

High-Risk Patients (Require Cytoreductive Therapy)

High-risk criteria include:

• Age >60 years OR prior thrombosis history 3, 4, 5
• Persistent symptoms despite phlebotomy and aspirin 3
• Leukocytosis or high JAK2V617F allele burden (additional thrombotic risk factors) 4

First-line cytoreductive agent: Hydroxyurea 3, 4, 5

Second-line options:

• Pegylated interferon-α (preferred in younger patients or those desiring pregnancy) 3, 4, 5
• Busulfan (alternative second-line agent) 3, 4, 5
• Ruxolitinib (reserved for hydroxyurea-intolerant/resistant patients or those with severe pruritus or marked splenomegaly unresponsive to other agents) 3, 4, 6

Low-Risk Patients

• Phlebotomy plus aspirin alone is sufficient for patients <60 years without thrombosis history. 3, 4, 5

Monitoring During Phlebotomy

• Check serum ferritin every 10-12 phlebotomies (approximately every 3 months initially), targeting ferritin 50-100 μg/L to indicate adequate iron depletion without inducing iron deficiency. 1
• Transferrin saturation remains elevated until iron stores are depleted. 1
• Transition to maintenance phlebotomy once target hematocrit is achieved; frequency varies from monthly to 1-2 units per year based on individual iron reaccumulation rates. 1

Management of Secondary Erythrocytosis

• Address the underlying cause first: smoking cessation, CPAP for sleep apnea, oxygen therapy for COPD. 2
• Reserve phlebotomy for symptomatic patients or those with hemoglobin >18.5 g/dL despite treating the underlying condition. 2
• Do NOT perform phlebotomy in hereditary methemoglobinemia with compensatory polycythemia, as higher erythrocyte mass allows normal tissue oxygenation. 2

Critical Medication Considerations

IMMEDIATELY DISCONTINUE erythropoiesis-stimulating agents (ESAs) such as epoetin alfa and darbepoetin alfa if the patient is receiving them, as they worsen erythrocytosis and increase mortality risk. 2, 7

• ESAs are contraindicated in elevated hemoglobin states and should never be used to manage this condition. 2, 7
• If hemoglobin exceeds 12 g/dL during ESA therapy for anemia, ESA doses must be reduced by 25-50% or discontinued until hemoglobin falls below 12 g/dL. 7

Special Clinical Scenarios

Perioperative Management

• Optimize hematocrit to <45% before elective surgery to minimize thrombotic risk. 4
• Continue aspirin perioperatively unless bleeding risk is prohibitive. 4

Pregnancy

• Pegylated interferon-α is the cytoreductive agent of choice during pregnancy, as hydroxyurea is teratogenic. 4
• Continue phlebotomy and aspirin throughout pregnancy with careful monitoring. 4

Splanchnic Vein Thrombosis

• Initiate systemic anticoagulation in addition to phlebotomy and aspirin for patients with venous thrombosis history, particularly in unusual sites like splanchnic veins. 3, 4

Common Pitfalls to Avoid

• Do not target hemoglobin >12 g/dL in any patient with polycythemia vera, as this increases thrombotic risk and mortality. 7
• Do not induce iron deficiency by over-phlebotomizing; stop when ferritin reaches 50-100 μg/L. 1
• Do not use ruxolitinib as first-line therapy in polycythemia vera; reserve it for hydroxyurea-intolerant/resistant cases or refractory symptoms. 3, 4, 5
• Do not overlook cardiovascular risk factors (hypertension, diabetes, hyperlipidemia) that compound thrombotic risk in polycythemia vera patients. 4