What does it mean to have elevated red blood cell (RBC) and hematocrit levels?

Elevated RBC and Hematocrit: Meaning and Clinical Significance

Elevated red blood cell (RBC) count and hematocrit levels most commonly indicate polycythemia vera or secondary polycythemia, which require different management approaches and carry significant cardiovascular risks if left untreated.

Causes of Elevated RBC and Hematocrit

Elevated RBC and hematocrit can be categorized into three main types:

1. Primary Polycythemia (Polycythemia Vera)

   • Characterized by autonomous overproduction of red blood cells
   • Diagnostic criteria include:
     • Elevated hemoglobin (≥18.5 g/dL in men, ≥16.5 g/dL in women) or hematocrit >99th percentile
     • Presence of JAK2 V617F or JAK2 exon 12 mutation
     • Bone marrow showing hypercellularity with trilineage growth 1

2. Secondary Polycythemia

   • Physiologic response to hypoxemia or abnormal erythropoietin production
   • Common causes:
     • Chronic lung disease
     • Congenital heart disease
     • High altitude exposure
     • Smoking
     • Sleep apnea
     • Renal disease (including tumors)

3. Relative Polycythemia (Spurious Polycythemia)

   • Normal RBC mass with decreased plasma volume
   • Often associated with dehydration, diuretic use, or stress polycythemia

Clinical Significance and Risks

Elevated RBC and hematocrit levels significantly increase the risk of:

1. Thrombotic Events

   • Elevated hematocrit enhances platelet accumulation following vascular injury 2
   • Increased risk of venous thromboembolism (VTE) and arterial thromboembolism 3
   • Higher rates of major adverse cardiovascular events (MACE) 4

2. Hyperviscosity Syndrome

   • Symptoms include headache, dizziness, visual disturbances, and fatigue
   • Can lead to reduced tissue perfusion and end-organ damage

3. Disease Progression (in Polycythemia Vera)

   • Potential transformation to myelofibrosis or acute leukemia 1

Diagnostic Approach

When elevated RBC and hematocrit are identified:

1. Initial Evaluation

   • Complete blood count with peripheral blood smear
   • JAK2 V617F mutation testing
   • Serum erythropoietin level 1

2. Additional Testing Based on Initial Results

   • Bone marrow biopsy if polycythemia vera is suspected
   • Chest X-ray and oxygen saturation to evaluate for pulmonary causes
   • Sleep study if sleep apnea is suspected
   • Abdominal imaging to rule out renal tumors if erythropoietin is elevated

3. Differentiation Between Types

   • Measurement of red blood cell mass and plasma volume may be required to differentiate primary, secondary, and combined polycythemia 5, 6
   • Low erythropoietin levels suggest polycythemia vera
   • Normal/high erythropoietin levels suggest secondary causes

Management Considerations

Management depends on the underlying cause:

1. Polycythemia Vera

   • Therapeutic phlebotomy to maintain hematocrit <45%
   • Low-dose aspirin (81-100 mg daily) for thrombosis prevention
   • Cytoreductive therapy (hydroxyurea, interferon-α, or ruxolitinib) for high-risk patients 1

2. Secondary Polycythemia

   • Treatment of underlying cause (e.g., CPAP for sleep apnea, smoking cessation)
   • Phlebotomy may be considered if symptomatic or if hematocrit is significantly elevated

3. Relative Polycythemia

   • Hydration
   • Management of underlying causes (e.g., diuretic adjustment)

Monitoring and Follow-up

Regular monitoring is essential:

• CBC every 2-3 months during initial management, then every 3-6 months once stable
• Assessment for signs of disease progression or complications
• Evaluation of thrombotic and bleeding risk 1

Common Pitfalls to Avoid

• Overlooking masked polycythemia vera due to iron deficiency
• Attributing findings solely to inflammation
• Neglecting bone marrow examination when indicated
• Performing excessive phlebotomies leading to iron deficiency 1
• Failing to consider secondary causes when JAK2 mutation is absent

Elevated RBC and hematocrit require thorough evaluation to determine the underlying cause and appropriate management strategy to prevent serious cardiovascular complications.