What to do with a patient having leukocytosis and elevated hemoglobin levels?

Management of Elevated Hemoglobin and Leukocytosis

The most appropriate next step for a patient with hemoglobin of 19 g/dL and WBC of 15×10⁹/L is to perform a diagnostic workup for polycythemia vera, including serum erythropoietin level and JAK2 mutation testing.

Initial Assessment

When encountering a patient with both elevated hemoglobin (Hb 19 g/dL) and leukocytosis (WBC 15×10⁹/L), a systematic approach is essential as these findings suggest a potential myeloproliferative disorder, particularly polycythemia vera (PV).

Key Diagnostic Steps:

1. Confirm true polycythemia:

   • Rule out relative polycythemia (dehydration, Gaisböck syndrome)
   • Check for signs of volume depletion
   • Review medication history for androgens, erythropoietin

2. Order immediate laboratory tests:

   • Serum erythropoietin level (low in PV)
   • JAK2 V617F mutation testing (positive in >95% of PV cases)
   • Complete blood count with peripheral smear
   • Comprehensive metabolic panel
   • Arterial blood gas (to rule out hypoxemia)

Diagnostic Algorithm for Polycythemia

According to Mayo Clinic guidelines, the diagnostic approach should follow this algorithm 1:

1. Serum erythropoietin level:

   • Low: Strongly suggestive of PV (specificity >90%)
   • Normal: PV still possible (sensitivity <70%)
   • Elevated: PV unlikely, consider secondary causes

2. If erythropoietin low or normal:

   • Proceed with bone marrow examination with cytogenetic studies
   • Test for JAK2 V617F mutation

3. If diagnosis remains unclear:

   • Consider specialized tests such as endogenous erythroid colony formation

Management Considerations

Immediate Management:

• Assess for symptoms of hyperviscosity (headache, blurred vision, dizziness)
• Evaluate for thrombotic complications
• Check for splenomegaly on physical examination

Treatment Options:

• If PV is confirmed:
  • Therapeutic phlebotomy to maintain hematocrit <45%
  • Consider cytoreductive therapy (hydroxyurea) if high thrombotic risk
  • Low-dose aspirin for thrombosis prevention

Differential Diagnosis

1. Polycythemia vera:

   • Most likely diagnosis with both elevated Hb and WBC
   • May present with splenomegaly, pruritus, thrombosis

2. Secondary polycythemia:

   • Due to chronic hypoxemia (COPD, sleep apnea)
   • High altitude exposure
   • Erythropoietin-secreting tumors
   • Typically normal WBC count

3. Stress leukocytosis with coincidental polycythemia:

   • Infection, inflammation
   • Corticosteroid use
   • Smoking

4. Other myeloproliferative neoplasms:

   • Essential thrombocythemia (check platelet count)
   • Myelofibrosis

5. Leukemoid reaction:

   • Severe infection
   • Malignancy

Important Caveats

• Avoid misdiagnosis: Spurious elevation of hemoglobin can occur with severe leukocytosis (>40×10⁹/L) due to analyzer interference, but this is unlikely at WBC of 15×10⁹/L 2

• Beware of Adult-Onset Still's Disease: Can present with leukocytosis, but typically not with elevated hemoglobin 1

• Consider acute promyelocytic leukemia: If there are abnormal cells on peripheral smear, as this requires emergency management 1

• Avoid leukapheresis: Not recommended for hyperleukocytosis unless there are signs of leukostasis with severe neurological or pulmonary symptoms 3

Follow-up

• If PV is confirmed, regular monitoring of blood counts is essential
• Assess cardiovascular risk factors and manage aggressively
• Monitor for progression to myelofibrosis or transformation to acute leukemia
• Evaluate for thrombotic and bleeding complications

The combination of elevated hemoglobin and leukocytosis strongly suggests a myeloproliferative disorder, with polycythemia vera being the most likely diagnosis. Prompt diagnostic workup and appropriate management are essential to prevent complications related to hyperviscosity and thrombosis.