What to do when a patient has elevated Red Blood Cell (RBC) count, Hemoglobin (HGB), and Hematocrit (HCT) levels with normal liver enzymes?

Evaluation and Management of Elevated RBC, Hemoglobin, and Hematocrit with Normal Liver Enzymes

In a man with elevated RBC count, hemoglobin, and hematocrit but normal liver enzymes, you should first measure the hematocrit level and if it exceeds 50%, withhold any potential contributing factors (such as testosterone therapy) and investigate the underlying cause of polycythemia before proceeding further. 1

Immediate Assessment

Confirm the Degree of Elevation

• If hematocrit exceeds 54%, this warrants immediate intervention including dose reduction of any contributing medications or temporary discontinuation 1
• Hematocrit between 50-54% requires formal investigation of the etiology before any treatment decisions 1
• The normal liver enzymes effectively rule out hepatocellular injury as a contributing factor to the hematologic abnormalities 1

Critical History Elements to Obtain

• Testosterone therapy use: Injectable testosterone is associated with the greatest treatment-induced increases in hemoglobin/hematocrit 1
• Smoking history and chronic hypoxia risk factors (sleep apnea, COPD, high altitude residence) 1
• Symptoms of hyperviscosity: headaches, dizziness, visual disturbances, pruritus after bathing 1
• Family history of polycythemia or thrombotic events 1

Diagnostic Workup Algorithm

First-Line Testing

• Repeat complete blood count to confirm elevation and assess mean corpuscular volume 2
• Erythropoietin (EPO) level to distinguish primary from secondary polycythemia 1
• Arterial oxygen saturation to evaluate for hypoxemia-driven erythrocytosis 1
• JAK2 V617F mutation testing if primary polycythemia vera is suspected 1

Additional Considerations

• The presence of normal mean red cell volume helps distinguish true polycythemia from other causes of elevated hematocrit 2
• Unconjugated bilirubin measurement may reveal Gilbert's syndrome, which has been associated with relatively increased red cell mass 2
• In Gilbert's syndrome cases, hemoglobin, hematocrit, and red blood cell values are significantly higher compared to matched controls (P < 0.001) 2

Management Based on Etiology

If Testosterone-Related

• Prior to offering testosterone therapy, baseline hemoglobin/hematocrit measurement is mandatory 1
• If hematocrit >50% at baseline, withhold testosterone until etiology is investigated 1
• If hematocrit >54% while on therapy, reduce dose or temporarily discontinue 1
• Injectable testosterone formulations carry the highest risk for polycythemia compared to other delivery methods 1

If Primary Polycythemia Suspected

• Refer to hematology for bone marrow evaluation and JAK2 mutation analysis 1
• Consider therapeutic phlebotomy to maintain hematocrit <45% in men to reduce thrombotic risk 1

If Secondary Polycythemia Identified

• Address underlying hypoxemia (treat sleep apnea, optimize COPD management, smoking cessation) 1
• Monitor hematocrit every 3-6 months once stable 3

Monitoring Strategy

For Patients on Testosterone

• Measure hemoglobin/hematocrit at baseline before initiating therapy 1
• Recheck at 3 months after starting or changing dose 1
• Then monitor every 6-12 months if stable and hematocrit remains <50% 1

For Patients Not on Testosterone

• Recheck complete blood count in 2-4 weeks to establish trend (increasing, stable, or decreasing) 4
• If persistently elevated after addressing modifiable factors, refer to hematology 4, 3

Critical Pitfalls to Avoid

• Do not ignore hematocrit elevations >50%, as this significantly increases thrombotic risk and requires investigation 1
• Do not assume the elevation is benign simply because liver enzymes are normal—the two systems are independent 1
• Do not continue testosterone therapy in patients with hematocrit >54% without dose adjustment or discontinuation 1
• Do not overlook secondary causes of polycythemia (hypoxemia, renal tumors, testosterone use) before pursuing expensive hematologic workup 1