Management of Elevated RBC Count (6.48 million cells/μL)
Your first priority is to determine whether this represents true erythrocytosis versus relative erythrocytosis by ensuring adequate hydration, then distinguish between primary (clonal) and secondary (non-clonal) causes through JAK2 mutation testing and serum erythropoietin measurement. 1, 2
Initial Diagnostic Approach
Step 1: Confirm True Erythrocytosis
- Ensure the patient is adequately hydrated, as dehydration can cause relative erythrocytosis with falsely elevated RBC counts 1, 3
- Assess hemoglobin and hematocrit levels alongside the RBC count to confirm absolute erythrocytosis 4
Step 2: Order First-Line Testing
- Measure serum erythropoietin (EPO) level as your initial test: low or low-normal EPO suggests primary erythrocytosis (polycythemia vera), while normal or elevated EPO indicates secondary erythrocytosis 3, 2, 4
- Test for JAK2 mutation (JAK2V617F or exon 12) in peripheral blood to identify polycythemia vera, which accounts for most primary acquired erythrocytosis 2, 5
Step 3: Assess for Symptoms
- Evaluate for hyperviscosity symptoms including headache, visual disturbances, fatigue, and poor concentration 1, 3
- Check iron status with serum ferritin and transferrin saturation, as iron deficiency can mask the full extent of erythrocytosis while paradoxically worsening hyperviscosity symptoms 3
Management Based on Etiology
If JAK2 Mutation Positive (Polycythemia Vera)
- Refer to hematology for specialized management 4
- Target hematocrit below 45% in men through phlebotomy 6
- Consider cytoreductive therapy based on risk stratification 7
If EPO Normal/Elevated (Secondary Erythrocytosis)
- Identify and treat underlying causes: hypoxemia, sleep apnea, cyanotic heart disease, chronic lung disease, renal pathology, or erythropoietin-secreting tumors 1, 5
- Ensure adequate hydration as first-line therapy for all patients 1, 3
- Monitor hemoglobin and hematocrit periodically without routine phlebotomy 3
If Young Patient or Family History Present
- Suspect congenital causes and pursue genetic testing for germline mutations affecting EPO receptor (EPOR), oxygen-sensing pathways (VHL, EGLN1, EPAS1), or hemoglobin oxygen affinity (HBB, HBA1, HBA2, BPGM) 2, 8
Therapeutic Phlebotomy: When and How
Strict Indications (All Must Be Present)
- Hemoglobin exceeds 20 g/dL AND hematocrit exceeds 65% 6, 1
- Symptoms of hyperviscosity present (headache, fatigue, poor concentration) 6, 1
- No evidence of dehydration or anemia 6
Phlebotomy Protocol When Indicated
- Remove one unit of blood (400-500 mL) per session 6, 1
- Replace with equal volume of isotonic saline or dextrose (750-1000 mL) administered simultaneously 6, 1
- Perform weekly or fortnightly until target levels reached 6
Critical Pitfalls to Avoid
Do Not Perform Routine Phlebotomy
- Repeated routine phlebotomies without meeting strict criteria cause iron depletion, decreased oxygen-carrying capacity, reduced red cell deformability, and paradoxically increase stroke risk 6, 1, 3
- Myelosuppressive drugs should be avoided in idiopathic erythrocytosis as they are associated with evolution to acute leukemia in approximately 10% of patients 9
Monitor for Iron Deficiency
- Iron deficiency in the setting of erythrocytosis is particularly dangerous as it reduces oxygen-carrying capacity while increasing stroke risk 6, 1
- Regular monitoring through peripheral blood smear and iron studies is essential 6, 3
- If iron deficiency develops, cautious supplementation with close hemoglobin monitoring is warranted 3
Ongoing Monitoring
- Follow complete blood counts regularly to track hemoglobin, hematocrit, and RBC count 1, 3
- Assess iron status periodically to prevent iron deficiency from excessive phlebotomy 6, 1
- Monitor for symptoms of hyperviscosity or thrombotic complications at each visit 1, 3
- Evaluate renal function as chronic erythrocytosis can affect glomerular filtration rate 1, 3