What is the next step in managing a patient with elevated Hemoglobin (Hb) and Hematocrit (Hct) levels?

Management of Elevated Hemoglobin and Hematocrit Levels

For patients with elevated hemoglobin (Hb) and hematocrit (Hct) levels, the next step should be a diagnostic workup for polycythemia vera, including JAK2 mutation testing, serum erythropoietin level, and bone marrow biopsy if indicated. 1

Initial Assessment

When evaluating elevated Hb and Hct, consider:

• Normal reference ranges:

  • Adult males/post-menopausal females: Hb 15.5 ± 2.0 g/dL, Hct 47 ± 6% 2
  • Menstruating females: Hb 14.0 ± 2.0 g/dL, Hct 41 ± 5% 2

• Ensure adequate hydration before interpreting results, as dehydration can cause falsely elevated values 1

• Repeat measurements to confirm persistent elevation, as initial Hb/Hct values may not accurately reflect true status 2

Diagnostic Algorithm

1. Complete Blood Count with Differential

   • Assess for concurrent abnormalities in white blood cell and platelet counts that might suggest a myeloproliferative disorder 2
   • Check red cell indices (MCV, MCH, MCHC) for clues to etiology

2. Iron Studies

   • Serum iron, total iron binding capacity (TIBC), ferritin, and transferrin saturation
   • Iron deficiency is unlikely with elevated Hb/Hct but should be ruled out

3. JAK2 V617F Mutation Testing

   • Essential for diagnosing polycythemia vera, the most common pathologic cause of elevated Hb/Hct 1

4. Serum Erythropoietin Level

   • Low in polycythemia vera
   • Elevated in secondary polycythemia (hypoxic conditions, inappropriate EPO production) 1

5. Arterial Blood Gas Analysis

   • To assess for hypoxemia as a cause of secondary polycythemia
   • Check oxygen saturation and carboxyhemoglobin levels

6. Abdominal Ultrasound

   • To evaluate for splenomegaly, which is common in polycythemia vera
   • Also to screen for renal or hepatic masses that might produce erythropoietin

7. Bone Marrow Biopsy

   • Consider if clinical suspicion for polycythemia vera is high, especially if JAK2 mutation is positive 1

Management Based on Etiology

If Polycythemia Vera is Diagnosed:

1. Therapeutic Phlebotomy

   • Remove 450-500 mL of blood per session
   • Initially 2-3 times weekly until target Hct is reached
   • Goal: reduce Hct to <45% in men and <42% in women 1
   • Maintenance phlebotomy every 2-3 months as needed 1

2. Risk Stratification

   • Low-risk: age <60 years and no history of thrombosis
   • High-risk: age ≥60 years or history of thrombosis 1

3. Cytoreductive Therapy

   • Consider if >5 phlebotomies per year are required
   • Options include hydroxyurea (first-line in older patients) or interferon-α (preferred in younger patients) 1

4. Low-dose Aspirin

   • 81-100 mg daily to reduce cardiovascular events
   • Avoid in patients with extreme thrombocytosis due to bleeding risk 1

If Secondary Polycythemia:

1. Treat Underlying Cause

   • Address hypoxic conditions (sleep apnea, COPD, high altitude)
   • Investigate and manage inappropriate EPO production (renal cysts, tumors)

2. Phlebotomy

   • Consider if symptomatic or Hct >54%
   • Less aggressive schedule than for polycythemia vera

If Relative Polycythemia (Dehydration):

1. Hydration
   • Intravenous or oral fluid replacement
   • Recheck Hb/Hct after adequate hydration

Clinical Pearls and Pitfalls

• Measurement Considerations: Hb is a more accurate measure than Hct, as Hct can be falsely elevated with sample storage or hyperglycemia 2

• Relationship Between Hb and Hct: While traditionally Hct ≈ 3 × Hb, this ratio can vary in certain conditions. In alpha-thalassemia, the ratio may be higher (3.5) 3

• Cardiovascular Risk: Both high and low levels of Hb/Hct are associated with increased cardiovascular risk. Maintaining Hct <45% significantly reduces cardiovascular death and thrombotic events 1, 4

• Avoid Assuming Dehydration: While dehydration is a common cause of elevated Hb/Hct, don't delay appropriate workup for more serious conditions like polycythemia vera

• Monitor for Symptoms: Watch for hyperviscosity symptoms (headache, blurred vision, fatigue) that may necessitate more urgent intervention

By following this systematic approach, you can efficiently diagnose the cause of elevated Hb/Hct and implement appropriate management to reduce morbidity and mortality associated with polycythemia.