What is the next step in managing a patient with persistent erythrocytosis (elevated Red Blood Cell (RBC) count), hyperhemoglobinemia (elevated Hemoglobin (HGB)), hyperhematocrit (elevated Hematocrit (HCT)), and increased Red Blood Cell (RBC) distribution width?

Evaluation and Management of Erythrocytosis

The next step in managing a patient with persistent erythrocytosis (elevated RBC, hemoglobin, and hematocrit) should be to evaluate for underlying causes, particularly focusing on primary versus secondary erythrocytosis, while ensuring the patient is adequately hydrated. 1, 2

Initial Assessment

• Determine if this represents true erythrocytosis versus relative erythrocytosis (from dehydration) by ensuring adequate hydration status 1
• Assess for symptoms of hyperviscosity such as headache, visual disturbances, fatigue, or poor concentration 1
• Evaluate for potential underlying causes through targeted history and examination focusing on:
  • Cardiopulmonary symptoms suggesting hypoxemia 1
  • Smoking history 2
  • Sleep apnea symptoms 2
  • Family history of erythrocytosis 2

Diagnostic Workup

First-line Testing

• Measure serum erythropoietin (EPO) level - the critical first step to distinguish between primary and secondary erythrocytosis 2

  • Low EPO suggests primary erythrocytosis (e.g., polycythemia vera)
  • Normal or elevated EPO suggests secondary erythrocytosis

• Assess iron status with serum ferritin and transferrin saturation 1

  • Iron deficiency can mask the full extent of erythrocytosis and compromise oxygen transport 1

• Peripheral blood smear to evaluate red cell morphology 3

  • Look for microcytosis which may indicate iron deficiency or thalassemia 4

• Evaluate red cell distribution width (RDW) 1

  • Increased RDW may indicate underlying pathology affecting erythrocytes 1

Second-line Testing (Based on EPO Results)

• If EPO is low:

  • Test for JAK2 V617F mutation (for polycythemia vera) 2
  • Consider bone marrow biopsy if clinical suspicion for myeloproliferative neoplasm remains high 5, 2

• If EPO is normal or elevated:

  • Arterial blood gas to assess for hypoxemia 1
  • Sleep study if sleep apnea is suspected 2
  • Abdominal imaging to evaluate for renal or hepatic pathology 2
  • Hemoglobin electrophoresis if high-oxygen-affinity hemoglobinopathy is suspected 2

Management Approach

For All Patients

• Ensure adequate hydration as first-line therapy 1
• Avoid routine phlebotomy unless specific indications are present 1

Specific Management Based on Findings

• If secondary erythrocytosis is identified:

  • Treat the underlying cause (e.g., hypoxemia, sleep apnea) 1, 2
  • Monitor hemoglobin and hematocrit periodically 1

• If polycythemia vera is diagnosed:

  • Refer to hematology for specialized management 2
  • Consider cytoreductive therapy and low-dose aspirin 2

• If iron deficiency is present:

  • Cautious iron supplementation with close monitoring of hemoglobin levels 1
  • Iron deficiency in erythrocytosis can increase stroke risk and should be corrected 1

Indications for Therapeutic Phlebotomy

• Phlebotomy should only be considered if 1:

  • Hemoglobin >20 g/dL and hematocrit >65% AND
  • Patient has symptoms of hyperviscosity AND
  • No evidence of dehydration or anemia

• If phlebotomy is performed, always replace with equal volume of dextrose or saline 1

Important Considerations and Pitfalls

• Avoid routine phlebotomies as they can lead to iron depletion, decreased oxygen-carrying capacity, and increased stroke risk 1

• Do not assume all erythrocytosis is polycythemia vera - secondary causes are more common and require different management approaches 5, 2

• Recognize that iron deficiency can mask the full extent of erythrocytosis while still contributing to symptoms of hyperviscosity 1

• Be aware that microcytosis with elevated RBC count can occur in thalassemia minor, iron deficiency with polycythemia vera, or secondary polycythemia with coincidental iron deficiency 4

• Monitor renal function as chronic erythrocytosis can affect renal glomeruli and lead to reduced glomerular filtration rate 1