What is the management for elevated hemoglobin and hematocrit levels?

Management of Elevated Hemoglobin and Hematocrit

The management of elevated hemoglobin (17.5 g/dL) and hematocrit (54.0%) should focus on determining the underlying cause and implementing therapeutic phlebotomy to maintain hematocrit below 45% if a myeloproliferative disorder is diagnosed or if the patient has symptoms of hyperviscosity or risk factors for thrombosis. 1

Initial Diagnostic Evaluation

When encountering elevated hemoglobin and hematocrit levels, a systematic approach to diagnosis is essential:

1. Rule out relative erythrocytosis:

   • Dehydration
   • Diuretic use
   • Stress polycythemia (Gaisböck syndrome)

2. Evaluate for absolute erythrocytosis:

   • Laboratory studies:

     • Complete blood count with peripheral smear
     • Serum erythropoietin level
     • JAK2 V617F mutation testing (and exon 12 if V617F negative but high suspicion)
     • Iron studies (ferritin, transferrin saturation)
     • Arterial blood gas analysis

   • Secondary causes assessment:

     • Hypoxic conditions (COPD, sleep apnea, high altitude)
     • Smoking history
     • Renal disease or masses
     • Hepatocellular carcinoma
     • Androgen use

Diagnostic Criteria for Polycythemia Vera

According to the WHO diagnostic criteria, PV diagnosis requires 2:

Major criteria:

1. Elevated hemoglobin (>16.5 g/dL in men, >16.0 g/dL in women) OR hematocrit (>49% in men, >48% in women) OR increased red cell mass
2. Presence of JAK2 mutation (V617F or exon 12)

Minor criteria:

1. Bone marrow histology consistent with PV
2. Subnormal serum erythropoietin level
3. Endogenous erythroid colony formation

Diagnosis requires either both major criteria and one minor criterion, or the first major criterion and two minor criteria.

Treatment Approach

For Confirmed or Suspected Polycythemia Vera:

1. Therapeutic phlebotomy:

   • Target hematocrit <45% to reduce thrombotic risk 2, 3
   • Remove 350-500 mL of blood with saline replacement if symptomatic 1
   • Schedule follow-up hematocrit check in 1-2 weeks

2. Antiplatelet therapy:

   • Low-dose aspirin (81-100 mg daily) for all patients without contraindications 2

3. Cytoreductive therapy for high-risk patients (age >60 years and/or history of thrombosis):

   • Hydroxyurea (first-line)
   • Interferon-α (particularly for younger patients or pregnant women)
   • Ruxolitinib (if intolerant or inadequate response to hydroxyurea) 4

For Secondary Erythrocytosis:

1. Treat underlying cause:

   • CPAP for sleep apnea
   • Smoking cessation
   • Treatment of renal/hepatic tumors
   • Discontinuation of androgens or erythropoietin

2. Selective phlebotomy:

   • For symptomatic patients with hematocrit >65% or hemoglobin >20 g/dL 2
   • For patients with congenital heart disease with hematocrit >65% and hyperviscosity symptoms 2
   • Before non-cardiac surgery when hematocrit >65% 2

Monitoring and Follow-up

• Complete blood count every 2-4 weeks initially, then every 3 months once stable
• Monitor iron status periodically in patients undergoing regular phlebotomy
• Annual cardiovascular risk assessment
• Assess for symptoms of disease progression or complications

Important Considerations and Pitfalls

1. Avoid routine phlebotomy in asymptomatic secondary erythrocytosis with hematocrit <65%, as this can lead to iron deficiency without improving outcomes 2

2. Ensure adequate hydration before considering phlebotomy, as dehydration can cause relative erythrocytosis 2

3. Evaluate iron status before repeated phlebotomies, as iron deficiency can compromise oxygen delivery without lowering viscosity 2

4. Consider white blood cell count as an additional risk factor for thrombosis in PV patients (WBC ≥11 × 10^9/L significantly increases thrombotic risk) 5

5. Recognize that normal ranges vary by altitude - at 4000m elevation, normal hematocrit can range up to 61% in men and 56% in women 6

The evidence strongly supports maintaining hematocrit <45% in patients with PV, as demonstrated in the CYTO-PV study and subsequent real-world analyses showing a 61% higher risk of thrombotic events with hematocrit ≥45% 3. For patients with secondary erythrocytosis, the approach should be more conservative, with phlebotomy reserved for those with symptoms or very high hematocrit levels.