What is the diagnosis and management for a patient with elevated RBC count and symptoms of fatigue, dizziness, and mental fog?

Evaluation of Elevated RBC with Fatigue, Dizziness, and Mental Fog

Primary Diagnosis: Secondary Erythrocytosis vs. Polycythemia Vera

The most likely diagnosis is secondary erythrocytosis from an underlying hypoxic or non-hypoxic cause, though polycythemia vera must be excluded given the elevated RBC count (5.16) with symptoms of hyperviscosity. 1, 2

The elevated RBC count (5.16) with normal hemoglobin and hematocrit suggests either early erythrocytosis or relative polycythemia from hemoconcentration (supported by elevated albumin 5.3). 1 The symptoms of fatigue, dizziness, and mental fog are consistent with hyperviscosity syndrome or tissue hypoxia. 2

Immediate Diagnostic Workup

Order the following tests urgently to establish the diagnosis:

• JAK2 V617F mutation testing - Present in >95% of polycythemia vera cases and is the single most important test to differentiate primary from secondary erythrocytosis 1, 3
• Serum erythropoietin level - Will be low or low-normal in polycythemia vera, but elevated in secondary causes 3, 2
• Repeat CBC when adequately hydrated - The elevated albumin (5.3) suggests hemoconcentration, which can cause relative polycythemia 1, 3
• Peripheral blood smear - Essential to evaluate red cell morphology and identify abnormalities 2
• Reticulocyte count - Evaluates bone marrow response 1

The mildly elevated bilirubin (1.3) and elevated MPV (11.5) warrant consideration of hemolysis, though the normal hemoglobin argues against significant hemolytic anemia. 4

Secondary Causes to Evaluate

Systematically assess for these common secondary causes:

• Smoking history and carbon monoxide exposure - "Smoker's polycythemia" from chronic tissue hypoxia stimulates erythropoietin production 1
• Obstructive sleep apnea - Nocturnal hypoxemia drives erythropoietin production; order sleep study if symptoms suggest this 1, 2
• Chronic lung disease (COPD) - Chronic hypoxemia is a common secondary cause 1
• Testosterone use - Either prescribed or unprescribed can cause erythrocytosis in young adults 1
• Renal dysfunction - Check creatinine and consider renal ultrasound for erythropoietin-producing tumors 1

Management Algorithm

If JAK2 Mutation is Positive (Polycythemia Vera):

• Refer immediately to hematology for definitive diagnosis and management 3
• Initiate low-dose aspirin (81-100 mg daily) to reduce thrombotic risk 1
• Target hematocrit <45% through therapeutic phlebotomy to reduce thrombotic events 1

If JAK2 Mutation is Negative (Secondary Erythrocytosis):

• Treat the underlying condition:

  • Smoking cessation for smoker's polycythemia 1, 2
  • CPAP therapy for obstructive sleep apnea 1, 2
  • Management of chronic lung disease 2
  • Dose adjustment or discontinuation of testosterone if causative 1

• Ensure adequate hydration as first-line therapy for all patients with erythrocytosis 2

• Monitor hemoglobin and hematocrit periodically 2

Critical Management Principles

Avoid routine phlebotomy unless specific criteria are met:

• Therapeutic phlebotomy is indicated only when hemoglobin >20 g/dL AND hematocrit >65% with symptoms of hyperviscosity, after excluding dehydration 1, 2
• Repeated routine phlebotomies are contraindicated due to risk of iron depletion, decreased oxygen-carrying capacity, and increased stroke risk 1, 2

If phlebotomy is performed:

• Replace with equal volume of dextrose or saline to prevent further hemoconcentration 1

Iron Status Considerations

The normal iron panel is reassuring, but iron deficiency can coexist with erythrocytosis and mask its full extent. 1, 2

• Iron deficiency in erythrocytosis increases stroke risk and should be corrected 2
• If iron deficiency develops, cautious oral iron supplementation with close hemoglobin monitoring is necessary, as rapid increases in red cell mass can occur 1

Common Pitfalls to Avoid

• Don't assume dehydration alone explains the findings - The elevated RBC count persisting after hydration requires full workup 1
• Don't overlook sleep apnea - This is a frequently missed cause of secondary erythrocytosis in patients with fatigue and mental fog 1
• Don't delay JAK2 testing - This is the key test to differentiate primary from secondary causes 3
• Don't perform aggressive phlebotomy without meeting specific criteria, as this can worsen outcomes 1, 2

Referral Indications

Refer immediately to hematology if:

• JAK2 mutation is positive 3
• Hemoglobin >20 g/dL with symptoms of hyperviscosity 1
• Diagnosis remains unclear after initial workup 1
• Unexplained splenomegaly is present 1