Laboratory Tests for Evaluating Elevated Red Blood Cell Count, Hematocrit, and Hemoglobin
When evaluating elevated red blood cell count, hematocrit, and hemoglobin levels, a comprehensive panel including complete blood count with red cell indices, reticulocyte count, serum ferritin, transferrin saturation, and JAK2 mutation testing should be ordered to determine the underlying cause. 1
Initial Laboratory Evaluation
- Complete blood count (CBC) with red cell indices should be performed using an automated cell counter to provide standardized results and additional information on white blood cells and platelets 2
- Reticulocyte count should be measured to assess new red blood cell formation and potential causes of erythrocytosis 1, 3
- Serum ferritin and transferrin saturation to evaluate iron status and rule out concurrent iron deficiency 2, 1
- C-reactive protein (CRP) to assess for inflammatory conditions that may affect erythrocyte parameters 1
- Confirm true erythrocytosis by verifying elevated hemoglobin (>18.5 g/dL in men, >16.5 g/dL in women) or hematocrit (>55% in men, >49.5% in women) 1
Testing for Primary Erythrocytosis
- JAK2 mutation testing (both exon 14 and exon 12) is essential for evaluating suspected polycythemia vera 1
- According to WHO criteria, diagnosis of polycythemia vera requires either:
- Both major criteria (elevated hemoglobin/hematocrit/RBC mass AND presence of JAK2 mutation) plus at least one minor criterion, OR
- First major criterion plus at least two minor criteria 1
Additional Specialized Tests
- Red cell distribution width (RDW) - high RDW with normal or low MCV may suggest possible iron deficiency coexisting with erythrocytosis 1
- Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) to evaluate red cell characteristics 2, 4
- Sleep study if nocturnal hypoxemia is suspected as a secondary cause 1
- Evaluation for potential secondary causes such as smoking, COPD, or testosterone use 1
Important Considerations
Hemoglobin is a more accurate measure than hematocrit for assessing red blood cell abnormalities because:
- Hemoglobin remains stable when blood samples are stored, while hematocrit can increase by 2-4% due to MCV changes 2
- Hyperglycemia can falsely elevate MCV and calculated hematocrit but does not affect hemoglobin measurement 2
- There is less variability in automated analyzer measurements of hemoglobin compared to hematocrit 2
Multiple measurements should be taken to confirm persistent elevation, as single measurements may not be reliable 1
Common Pitfalls to Avoid
- Don't overlook the possibility of coexisting iron deficiency in patients with erythrocytosis 1
- Don't perform aggressive phlebotomy without adequate volume replacement 1
- Don't assume all cases of erythrocytosis are primary - secondary causes like COPD, sleep apnea, or testosterone use are common 1
- Don't rely solely on hematocrit values, especially if blood samples are stored for extended periods before testing 2
- Don't miss potential genetic factors - certain mutations like MTHFR C677T and Factor 13 have been associated with elevated hematocrit and hemoglobin values in patients with thrombosis history 5