How to manage a patient with erythrocytosis and elevated hemoglobin?

Management of Erythrocytosis in a 53-Year-Old Patient

This patient with hemoglobin 16.6 g/dL and RBC count 5.91 does NOT meet criteria for therapeutic intervention and requires diagnostic workup to determine the underlying cause rather than immediate treatment. 1

Initial Diagnostic Confirmation

• Repeat hemoglobin and hematocrit measurements to confirm true erythrocytosis, as a single measurement is unreliable for establishing diagnosis. 1 The current hemoglobin of 16.6 g/dL is borderline elevated for women (>16.5 g/dL) but within normal range for men (>18.5 g/dL). 1

• Obtain a complete blood count with red cell indices, reticulocyte count, differential blood cell count, serum ferritin, transferrin saturation, and C-reactive protein (CRP) to distinguish true polycythemia from relative polycythemia and assess for iron deficiency. 1

• Hemoglobin is the preferred measurement over hematocrit because it remains stable during sample storage, whereas hematocrit can falsely increase by 2-4% with prolonged storage and is affected by hyperglycemia. 1

Determining Primary vs. Secondary Erythrocytosis

• Measure serum erythropoietin level as the critical first step: a low level indicates primary erythrocytosis (likely polycythemia vera), while normal or elevated levels suggest secondary causes. 1, 2

• If erythropoietin is low, test for JAK2 mutations (both exon 14 and exon 12) as up to 97% of polycythemia vera cases carry this mutation. 1 The World Health Organization diagnostic criteria require either both major criteria (elevated hemoglobin/hematocrit AND JAK2 mutation) plus one minor criterion, OR first major criterion plus two minor criteria. 1

Evaluating Secondary Causes (If Erythropoietin Normal/Elevated)

• Assess for hypoxic causes systematically: 1

  • Smoking history and carbon monoxide exposure (causes "smoker's polycythemia" that resolves with cessation) 1, 3
  • Obstructive sleep apnea (order sleep study if nocturnal hypoxemia suspected) 1, 3
  • Chronic obstructive pulmonary disease or other chronic lung disease 1
  • Cyanotic congenital heart disease with right-to-left shunting 1, 3

• Screen for non-hypoxic secondary causes: 1

  • Testosterone use (prescribed or unprescribed) - particularly relevant in this age group 1
  • Erythropoietin-producing tumors (renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, meningioma) 1
  • Renal dysfunction with abnormal glomerular function 1

• Consider physiological variations: altitude adaptation (if living at elevation >1,000 meters), gender differences (males have higher baseline hemoglobin due to testosterone effects). 1

Critical Management Thresholds

Therapeutic phlebotomy is indicated ONLY when ALL of the following criteria are met: 1, 3

• Hemoglobin >20 g/dL AND hematocrit >65% 1, 3
• Presence of hyperviscosity symptoms (headache, visual disturbances, fatigue, poor concentration, dizziness, tinnitus, blurred vision, paresthesias) 3, 4
• Dehydration has been excluded 1, 3

This patient does NOT meet these criteria and should NOT undergo phlebotomy. 1, 3

Critical Pitfalls to Avoid

• Never perform routine or repeated phlebotomies without meeting established criteria as this causes iron deficiency, which paradoxically worsens symptoms by reducing oxygen-carrying capacity and red cell deformability, and increases stroke risk. 3, 4 Iron-deficient microcytosis is the strongest independent predictor for cerebrovascular events—not the severity of erythrocytosis itself. 4

• Ensure adequate hydration as first-line therapy for all patients with erythrocytosis, as dehydration can cause relative polycythemia from plasma volume depletion. 1, 3

• Monitor iron status regularly using serum ferritin, transferrin saturation, and iron levels (not just MCV, which is unreliable in erythrocytosis). 1 If iron deficiency is confirmed despite erythrocytosis, cautious oral iron supplementation with close hemoglobin monitoring is necessary, as rapid increases in red cell mass can occur. 1, 3

Referral Indications

Refer immediately to hematology if: 1

• JAK2 mutation is positive
• Hemoglobin >20 g/dL with hyperviscosity symptoms
• Unexplained splenomegaly
• No identifiable secondary cause after complete workup

Monitoring Recommendations

• Follow up with serial complete blood counts to monitor hemoglobin and hematocrit trends. 3
• Periodically assess iron status to avoid iron deficiency. 3
• Monitor for symptoms of hyperviscosity or thrombotic complications (cerebrovascular accidents, coronary events, peripheral vascular disease). 3, 4
• Evaluate renal function as chronic erythrocytosis can affect renal glomeruli. 3

Treatment of Underlying Conditions

Once the cause is identified, treat the underlying condition rather than the erythrocytosis itself: 1, 3

• Smoking cessation for smoker's polycythemia 1, 3
• CPAP therapy for obstructive sleep apnea 1, 3
• Management of COPD or other chronic lung disease 1, 3
• Dose adjustment or discontinuation of testosterone if causative 1
• For confirmed polycythemia vera, maintenance of hematocrit strictly below 45% through phlebotomy plus low-dose aspirin 1