What is the evaluation and management of elevated red blood cell (RBC) hemoglobin and hematocrit?

Evaluation and Management of Elevated Red Blood Cell, Hemoglobin, and Hematocrit

Initial Assessment

Therapeutic phlebotomy is indicated only when hemoglobin is greater than 20 g/dL and hematocrit is greater than 65%, associated with symptoms of hyperviscosity in the absence of dehydration or anemia. 1

• Confirm elevated values with repeat measurements, as a single measurement is not reliable for diagnosis 2
• True erythrocytosis is defined as hemoglobin >18.5 g/dL in men or >16.5 g/dL in women, or hematocrit >55% in men or >49.5% in women 2
• Initial laboratory evaluation should include complete blood count with red cell indices, reticulocyte count, differential blood cell count, serum ferritin, transferrin saturation, and C-reactive protein 2

Diagnostic Algorithm

Step 1: Distinguish between absolute and relative erythrocytosis

• Relative erythrocytosis: plasma volume contraction (dehydration) with normal red cell mass 2
• Absolute erythrocytosis: true increase in red blood cell mass 2

Step 2: If absolute erythrocytosis is confirmed, evaluate for:

• Primary erythrocytosis (polycythemia vera)

  • Test for JAK2 mutations (both exon 14 and exon 12) 2
  • According to WHO criteria, diagnosis requires either both major criteria (elevated hemoglobin/hematocrit/RBC mass AND presence of JAK2 mutation) plus at least one minor criterion, OR first major criterion plus at least two minor criteria 2

• Secondary erythrocytosis

  • Hypoxemia: sleep apnea, COPD, smoking, high altitude 2
  • Inappropriate erythropoietin production: renal disease, tumors 2
  • Exogenous factors: testosterone use 2

Management Approach

For Polycythemia Vera

• Maintain hematocrit below 45% through therapeutic phlebotomy to reduce thrombotic risk 3
• Low-dose aspirin (100 mg daily) unless contraindicated 3
• Cytoreductive therapy (hydroxyurea, interferon alfa) for high-risk patients 3

For Secondary Erythrocytosis

• Treat underlying condition (e.g., COPD, sleep apnea) 2
• Monitor testosterone users closely and consider dose adjustment if levels continue to rise 2

For Symptomatic Hyperviscosity

• Therapeutic phlebotomy only if hemoglobin >20 g/dL and hematocrit >65% with symptoms 1
• Remove 1 unit of blood with equal volume replacement of dextrose or saline 1
• Repeated routine phlebotomies are not recommended due to risk of iron depletion, decreased oxygen-carrying capacity, and stroke 1

For Iron Deficiency in the Context of Erythrocytosis

• Cautious iron supplementation with close monitoring of hemoglobin levels 1, 3
• Oral iron may result in rapid and dramatic increase in red cell mass; monitor hemoglobin closely 1
• Once serum ferritin and/or transferrin saturation is within normal range, discontinue iron supplementation 1

Special Considerations

• High RDW with normal or low MCV suggests possible iron deficiency coexisting with erythrocytosis 2
• In patients with cyanotic congenital heart disease, erythrocytosis is a compensatory response to improve oxygen transport 1
• Patients with renal dysfunction may require special consideration due to potential abnormal glomerular function 1
• For patients requiring transfusion (not the focus of this guidance), restrictive RBC thresholds (Hb trigger 70 g/L) should be used unless the patient has cardiovascular disease 1

Monitoring

• Regular follow-up with serial measurements for patients with borderline elevated values 2
• For polycythemia vera, monitor response using European LeukemiaNet criteria for clinicohematologic response 3
• For patients on testosterone therapy, monitor hematocrit closely 2

Common Pitfalls to Avoid

• Don't perform aggressive phlebotomy or allow blood loss without adequate volume replacement 1
• Don't assume a 3:1 ratio between hematocrit and hemoglobin; this relationship varies with age and clinical conditions 4
• Don't rely solely on point-of-care testing devices for treatment decisions, as they may have significant biases compared to laboratory measurements 5, 6
• Don't overlook the possibility of coexisting iron deficiency in patients with erythrocytosis 1, 2