What is the assessment protocol for an incidental finding of erythrocytosis (high red blood cell count) with elevated hematocrit and hemoglobin, and a high red cell distribution width?

Assessment Protocol for Incidental Erythrocytosis

The evaluation of an incidental finding of high red blood cell count (erythrocytosis) with elevated hematocrit, hemoglobin, and high red cell distribution width should follow a systematic diagnostic approach to determine if it represents true erythrocytosis and identify the underlying cause.

Initial Laboratory Evaluation

• The minimum workup should include complete blood count with red cell indices (MCV, RDW), reticulocyte count, differential blood cell count, serum ferritin, transferrin saturation, and C-reactive protein (CRP) 1
• Assess for true versus relative polycythemia by confirming elevated hemoglobin (>18.5 g/dL in men, >16.5 g/dL in women) or hematocrit (>55% in men, >49.5% in women) 1
• High RDW with normal or low MCV suggests possible iron deficiency coexisting with erythrocytosis 1
• Evaluate for dehydration as a potential cause of relative polycythemia by reviewing clinical signs and obtaining history of fluid intake and losses 2

Secondary Evaluation Based on Erythropoietin Level

• Measure serum erythropoietin (EPO) level to differentiate between primary and secondary causes 3
• Low EPO suggests primary erythrocytosis (e.g., polycythemia vera) 3
• Normal or elevated EPO indicates secondary erythrocytosis 3

Testing for Primary Erythrocytosis

• For suspected polycythemia vera (PV), test for JAK2 mutations (both exon 14 and exon 12) 1
• According to WHO criteria, PV 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 1
• Minor criteria include MPD-consistent bone marrow histology, serum erythropoietin level below reference range, and presence of endogenous erythroid colonies 1

Testing for Secondary Erythrocytosis

• Extended workup for normal/high EPO cases should include:
  • Arterial blood gas analysis to assess for hypoxemia 3
  • Overnight oximetry to evaluate for sleep apnea 3
  • Abdominal imaging (ultrasound or CT) to rule out renal or hepatic tumors 3
  • Genetic testing for congenital causes in younger patients or those with family history, including VHL, PHD2, and HIF2A mutations 4, 5

Additional Considerations

• Assess for iron deficiency which may mask the degree of erythrocytosis - iron studies should include serum ferritin, iron, TIBC, and transferrin saturation 1
• Evaluate vitamin B12 and folate levels if macrocytosis is present 1
• Consider bone marrow examination if diagnosis remains unclear after initial testing 3

Management Approach

• For patients with confirmed true erythrocytosis, the diagnostic pathway should be guided by erythropoietin levels, with subsequent testing tailored to distinguish between primary and secondary causes 3
• Therapeutic phlebotomy should be considered only if hemoglobin is greater than 20 g/dL and hematocrit greater than 65%, with associated symptoms of hyperviscosity 1
• Repeated routine phlebotomies should be avoided due to risk of iron depletion, decreased oxygen-carrying capacity, and stroke 1
• If iron deficiency is confirmed in the context of erythrocytosis, cautious iron supplementation with close monitoring of hemoglobin levels is recommended 1

Follow-up Recommendations

• Repeat CBC after ensuring adequate hydration if relative polycythemia is suspected 2
• For patients with unexplained erythrocytosis after standard evaluation, consider referral to a hematologist for further specialized testing 6
• Gene panel sequencing may be beneficial for patients with idiopathic erythrocytosis, as it can identify mutations missed by traditional sequential testing approaches 5