Laboratory Workup for Elevated Hemoglobin and Hematocrit
Order a complete blood count with differential, serum erythropoietin level, and comprehensive metabolic panel as your initial laboratory evaluation for elevated hemoglobin and hematocrit. 1
Initial Laboratory Tests
Essential First-Line Tests
Complete Blood Count (CBC) with differential: Evaluate white blood cell count, platelet count, and red blood cell indices to identify associated features of polycythemia vera (thrombocytosis, leukocytosis) or other myeloproliferative disorders 1
Serum Erythropoietin (EPO) level: This is the critical discriminating test—a low EPO level has >90% specificity for polycythemia vera, though sensitivity is only approximately 70% 1
- Low EPO strongly suggests primary polycythemia (polycythemia vera)
- Normal EPO does not exclude polycythemia vera
- Elevated EPO indicates secondary polycythemia from hypoxia or other causes 1
Comprehensive metabolic panel: Including serum electrolytes, blood urea nitrogen, creatinine, liver function tests, and glucose to identify secondary causes and assess organ function 1
Additional Recommended Tests
Arterial blood gas or oxygen saturation: To evaluate for hypoxemia as a cause of secondary polycythemia 1
Iron studies: Including serum ferritin and transferrin saturation, as iron deficiency commonly accompanies polycythemia vera and can mask the true elevation in red cell mass 1
Vitamin B12 level or unbound B12 binding capacity: Elevated in polycythemia vera, though this lacks sensitivity and specificity 1
Clinical Context Matters
Confirm the elevation is real: Hemoglobin/hematocrit must be above the 95th percentile adjusted for sex and race, OR show documented increase from baseline, OR be accompanied by polycythemia vera-related features (thrombocytosis, leukocytosis, splenomegaly, aquagenic pruritus, unusual thrombosis, erythromelalgia) even if borderline elevated 1
Important Caveats
Repeat testing in 3 months if isolated borderline elevation without associated features 1
Serial measurements are crucial: A single normal-range value may mask early bleeding or iron deficiency in a patient with underlying polycythemia vera 1
The hematocrit/hemoglobin ratio is typically 3:1 in normal individuals; deviations may suggest specific conditions like thalassemia (ratio >3.5) 2, 3
When to Proceed to Bone Marrow Examination
If EPO is low or normal AND clinical suspicion for polycythemia vera remains high based on associated features, proceed to bone marrow biopsy with cytogenetic studies 1. Bone marrow histology shows characteristic hypercellularity and can help distinguish polycythemia vera from other myeloproliferative disorders.
Red Cell Mass Measurement
Avoid routine red cell mass (RCM) measurement as it is costly and rarely changes management 1:
- RCM is redundant when hematocrit >60% without obvious hemoconcentration
- Normal RCM doesn't exclude polycythemia vera (patients at left tail of distribution)
- More practical tests (EPO, bone marrow) provide better diagnostic yield 1
Secondary Causes to Investigate
Based on EPO results and clinical context, consider:
- Pulmonary function tests and chest imaging: For chronic lung disease 1
- Sleep study: For obstructive sleep apnea 1
- Renal imaging: For renal artery stenosis or renal tumors 1
- Carboxyhemoglobin level: For carbon monoxide exposure or smoking 1
- Thyroid-stimulating hormone: Thyroid disorders can affect red cell production 1