Management of Elevated RBC and Hematocrit
Elevated RBC and hematocrit require immediate assessment to distinguish between relative polycythemia (hemoconcentration) and true polycythemia, as the management and implications differ dramatically—relative polycythemia requires rehydration while true polycythemia may necessitate urgent hematology referral and therapeutic phlebotomy to prevent life-threatening thrombotic complications. 1
Initial Diagnostic Approach
Verify the elevation with concurrent hemoglobin and hematocrit measurements, as RBC count alone may be misleading due to plasma volume variations 1. The first critical step is to assess hydration status by examining vital signs, mucous membranes, skin turgor, and recent fluid losses, as dehydration commonly causes spurious RBC elevation 1.
Review all medications that may cause hemoconcentration, including:
- Diuretics
- Testosterone
- Erythropoietin-stimulating agents 1
Diagnostic Algorithm for True Polycythemia
Once relative polycythemia is excluded, proceed systematically:
- Check oxygen saturation to identify hypoxia-driven erythrocytosis, as chronic hypoxemia triggers compensatory RBC production 1
- Obtain serum erythropoietin level to distinguish primary from secondary polycythemia 1
- Assess for renal pathology with renal ultrasound and creatinine, as renal cell carcinoma, polycystic kidney disease, and renal artery stenosis can cause inappropriate EPO production 1
Management Based on Etiology
Relative Polycythemia
Restore euvolemia with oral or intravenous isotonic crystalloid as the primary intervention 1. This is the most common scenario and resolves with appropriate fluid resuscitation.
Secondary Polycythemia
Optimize oxygenation as the primary treatment, targeting PaO2 60-100 mmHg to prevent further RBC overproduction 1. Do not assume all elevated RBC counts require phlebotomy, as appropriate secondary erythrocytosis may be physiologically necessary 1.
Primary Polycythemia
Refer urgently to hematology for definitive diagnosis with JAK2 V617F mutation testing and bone marrow biopsy 1. The American Society of Hematology recommends initiating therapeutic phlebotomy to maintain hematocrit <45% in men and <42% in women, as this reduces thrombotic risk 1.
Clinical Implications of Elevated Hematocrit
Thrombotic Risk
Elevated hematocrit significantly increases thrombotic risk through multiple mechanisms. Mice with elevated hematocrit form thrombi at a faster rate with shortened vessel occlusion time 2. This occurs because RBCs promote arterial thrombosis by enhancing platelet accumulation at sites of vessel injury—elevated hematocrit increases both the frequency and duration of platelet-thrombus interactions 2.
Monitor for thrombotic complications including deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction, as hyperviscosity significantly increases risk 1.
Hemostatic Effects
While elevated hematocrit increases thrombotic risk, it also affects hemostasis. Erythrocytes contribute to hemostasis by influencing platelet margination and supporting thrombin generation 3. An acute reduction of hematocrit results in increased bleeding time, with restoration upon re-transfusion 3. However, the optimal hematocrit required to sustain hemostasis in bleeding patients remains unclear 3.
Monitoring Parameters
Recheck hemoglobin and hematocrit weekly during initial phlebotomy until target levels are achieved 1. For patients undergoing therapeutic phlebotomy, maintain hematocrit <45% in men and <42% in women 1.
Critical Pitfalls to Avoid
Never transfuse RBCs in patients with elevated RBC counts, as this worsens hyperviscosity and increases thrombotic risk 1. This is a potentially fatal error that can precipitate acute thrombotic events.
Do not delay hematology referral when primary polycythemia is suspected, as untreated polycythemia vera carries significant morbidity and mortality from thrombotic complications 1.
Avoid assuming all elevated counts are pathologic—appropriate secondary erythrocytosis in response to chronic hypoxemia may be physiologically necessary and should not be treated with phlebotomy 1.