What is the management for an adult patient with hyperhemoglobinemia (elevated hemoglobin) and elevated hematocrit (Hct)?

Management of Elevated Hemoglobin (17.3 g/dL) and Hematocrit (51.5%)

These values require immediate diagnostic evaluation to differentiate between polycythemia vera and secondary erythrocytosis, as management differs fundamentally between these conditions and inappropriate phlebotomy can cause harm. 1

Immediate Diagnostic Workup

Order the following tests now:

• JAK2 mutation testing (exon 14 and exon 12) to evaluate for polycythemia vera, which is present in up to 97% of PV cases 1, 2
• Complete blood count with differential to assess white blood cell and platelet counts (thrombocytosis or leukocytosis suggests PV) 1, 2
• Serum ferritin and transferrin saturation to identify iron deficiency, which commonly coexists with erythrocytosis and can mimic hyperviscosity symptoms 1, 2
• Erythropoietin level to distinguish primary (low/normal EPO) from secondary causes (elevated EPO) 2
• Reticulocyte count and peripheral blood smear to assess bone marrow response and red cell morphology 2

Critical Management Decision Points

If JAK2 Mutation is POSITIVE (Polycythemia Vera):

Maintain hematocrit strictly below 45% through therapeutic phlebotomy - this is the single most important intervention, reducing cardiovascular death and major thrombotic events from 9.8% to 2.7% (HR 3.91) 1. The current hematocrit of 51.5% places this patient at significantly elevated thrombotic risk.

Phlebotomy protocol: 1

• Induction phase: Remove 300-450 mL weekly or twice weekly until hematocrit <45%
• Maintenance phase: Same volume per session with intervals determined by hematocrit monitoring
• Always replace with equal volume of dextrose or saline to prevent hemoconcentration 1

Add low-dose aspirin 100 mg daily unless contraindicated - this is the second cornerstone of therapy for thrombosis prevention 1

Consider cytoreductive therapy if: 1

• Age ≥60 years
• History of prior thrombosis
• Poor phlebotomy tolerance
• Symptomatic or progressive splenomegaly
• Platelet count >1,500 × 10⁹/L
• Leukocyte count >15 × 10⁹/L

First-line cytoreductive agents are hydroxyurea or pegylated interferon 1

If JAK2 Mutation is NEGATIVE (Secondary Erythrocytosis):

Do NOT perform routine phlebotomy - this is contraindicated and can cause iron depletion, decreased oxygen-carrying capacity, and paradoxically increase stroke risk 1. The elevated hematocrit is a compensatory physiological response.

Identify and treat the underlying cause: 1, 2

• Smoking history: "Smoker's polycythemia" from chronic carbon monoxide exposure - requires smoking cessation
• Sleep study: Evaluate for obstructive sleep apnea causing nocturnal hypoxemia - treat with CPAP
• Pulmonary function tests: Assess for COPD or other chronic lung disease
• Medication review: Testosterone therapy (prescribed or unprescribed) commonly causes erythrocytosis - requires dose reduction or discontinuation 3, 2
• Imaging: Consider renal ultrasound or CT to exclude erythropoietin-secreting tumors (renal cell carcinoma, hepatocellular carcinoma)

Phlebotomy in secondary erythrocytosis is ONLY indicated when ALL of the following are present: 1, 4

• Hemoglobin >20 g/dL AND hematocrit >65%
• Symptoms of hyperviscosity (headache, dizziness, blurred vision, tinnitus, paresthesias)
• Patient is adequately hydrated
• No iron deficiency present

This patient with Hb 17.3 and Hct 51.5% does NOT meet criteria for phlebotomy if secondary erythrocytosis.

Iron Status Management - Critical Consideration

If transferrin saturation <20%, treat with iron supplementation until stores are replete, even in the presence of erythrocytosis 1. Iron-deficient red cells have reduced oxygen-carrying capacity and deformability, which increases stroke and myocardial ischemia risk 1, 4. Monitor hemoglobin closely during supplementation as rapid increases in red cell mass can occur 1.

Testosterone Therapy Consideration

If this patient is on testosterone therapy: 3

• Hematocrit >50% warrants investigation of etiology before continuing therapy
• Hematocrit >54% mandates intervention - dose reduction or temporary discontinuation 3
• Injectable testosterone is associated with the greatest treatment-induced increases in hematocrit 3

Common Pitfalls to Avoid

Never perform aggressive phlebotomy without equal volume replacement - this increases hemoconcentration and stroke risk 1

Never assume elevated hematocrit requires phlebotomy - in secondary erythrocytosis, routine phlebotomy is harmful and contraindicated 1

Never overlook iron deficiency - it commonly coexists with erythrocytosis and causes symptoms at lower hematocrit levels because iron-deficient red cells are less deformable 1, 4

Never use hematocrit alone for monitoring - hemoglobin is more accurate as hematocrit can falsely increase by 2-4% with sample storage and is affected by hyperglycemia 2

Monitoring Strategy

For suspected PV (pending JAK2 results):

• Monitor CBC every 2-4 weeks during induction phlebotomy
• Once stable, monitor every 3 months 1
• Assess for disease progression and transformation

For confirmed secondary erythrocytosis:

• Monitor hematocrit every 3-6 months 1
• Assess iron status regularly
• Evaluate for progression of underlying disease

Immediate hematology referral if: 2

• JAK2 mutation positive
• Hemoglobin >20 g/dL with hyperviscosity symptoms
• Unexplained splenomegaly
• Diagnosis remains unclear after initial workup