What is the follow-up for elevated red blood cell (RBC) count?

Follow-up Approach for Elevated Red Blood Cell Count

The most appropriate follow-up for elevated red blood cell count requires a systematic diagnostic approach to identify the underlying cause, with initial focus on ruling out polycythemia vera and secondary causes of erythrocytosis.

Initial Diagnostic Workup

Essential First-Line Investigations

• Complete blood count with peripheral smear examination to evaluate for:

  • Presence of other cytopenias or cytoses
  • Abnormal cell morphology
  • Evidence of dysplastic changes 1

• Hemoglobin concentration measurement (preferred over hematocrit due to greater reproducibility) 1

• Reticulocyte count to assess bone marrow response 1

• Upper abdominal ultrasonography to evaluate for splenomegaly 2

• Arterial oxygen saturation measurement to differentiate between primary and secondary causes 2

Second-Line Investigations (Based on Initial Results)

• Serum erythropoietin level to differentiate between primary and secondary erythrocytosis 2
• Leukocyte alkaline phosphatase (LAP) score if polycythemia vera is suspected 2
• Iron studies including ferritin and transferrin saturation 1
• Vitamin B12 and folate levels to rule out deficiencies 1
• Hemolysis panel (haptoglobin, LDH, indirect bilirubin) if hemolysis is suspected 1

Diagnostic Algorithm

Step 1: Confirm True Erythrocytosis

• Rule out relative erythrocytosis (dehydration, stress erythrocytosis)
• Confirm increased red cell mass

Step 2: Evaluate for Primary vs. Secondary Causes

• If splenomegaly present with normal oxygen saturation:

  • High suspicion for polycythemia vera 2
  • Proceed with JAK2 mutation testing

• If spleen is not enlarged:

  • Check if leukocyte or platelet count is elevated (suggests polycythemia vera) 2
  • Measure serum erythropoietin level 2
    • Low: Suggests polycythemia vera
    • Normal/elevated: Suggests secondary erythrocytosis

Step 3: Investigate Secondary Causes

• Hypoxia-driven causes:

  • Chronic lung disease
  • Sleep apnea
  • High altitude
  • Smoking (smoker's polycythemia) 2
  • Congenital heart disease

• Pathologic erythropoietin production:

  • Renal disease/tumors
  • Hepatocellular carcinoma
  • Cerebellar hemangioblastoma
  • Pheochromocytoma

Special Considerations

Polycythemia Vera Diagnosis

• Consider diagnosis if:
  • Spleen is enlarged AND arterial oxygen saturation is normal 2
  • Spleen is not enlarged BUT leukocyte or platelet count is increased 2
  • LAP score is elevated (in absence of fever or inflammation) 2

Secondary Polycythemia Evaluation

• Smoker's polycythemia should be considered and excluded 2
• Erythropoietin assay and culture of erythroid stem cells may be necessary 2
• Consider cardiopulmonary evaluation if hypoxia is suspected

Management Principles

• Treatment should target the underlying cause
• For polycythemia vera:
  • Phlebotomy to maintain hematocrit <45% in men and <42% in women
  • Consider cytoreductive therapy in high-risk patients
• For secondary erythrocytosis:
  • Address underlying condition (e.g., CPAP for sleep apnea, smoking cessation)
  • Phlebotomy only if symptomatic hyperviscosity

Common Pitfalls to Avoid

• Do not attribute elevated RBC count to vitamin deficiency without checking vitamin levels 1
• Do not overlook medication history as certain drugs can affect RBC production 1
• Do not miss myelodysplastic syndrome by attributing abnormalities solely to vitamin deficiency 1
• Recent transfusion can mask the true nature of blood cell abnormalities 1
• Do not initiate treatment without proper diagnosis, as this may delay identification of underlying conditions 1

Follow-up Recommendations

• Follow-up frequency should be individualized based on the underlying cause
• For polycythemia vera: regular monitoring of complete blood counts every 2-3 months
• For secondary causes: follow-up based on the specific condition being treated
• Monitor for complications such as thrombosis, bleeding, and progression to myelofibrosis in cases of polycythemia vera