What is the evaluation and management approach for a patient with elevated hemoglobin (hgb) and hematocrit (hct) levels?

Evaluation of Elevated Hemoglobin and Hematocrit

Begin evaluation when hemoglobin exceeds 18.5 g/dL in men or 16.5 g/dL in women, or when hematocrit exceeds 55% in men or 49.5% in women. 1

Initial Diagnostic Workup

Confirm true erythrocytosis by repeating measurements, as a single elevated value is unreliable for establishing diagnosis. 1 Hemoglobin is the preferred measurement over hematocrit because it remains stable during sample storage, whereas hematocrit can falsely increase by 2-4% with prolonged storage and is affected by hyperglycemia. 2, 1

Essential Laboratory Tests

Order the following tests immediately to differentiate primary from secondary causes: 1

• Complete blood count with red cell indices to assess mean corpuscular volume (MCV) and red cell distribution width (RDW) 2, 1
• Reticulocyte count to evaluate bone marrow response 2, 1
• Serum ferritin and transferrin saturation to identify coexisting iron deficiency, which can occur even with erythrocytosis 1
• C-reactive protein (CRP) to assess for inflammatory conditions 1
• Peripheral blood smear review by a qualified hematologist to identify abnormal morphology 1

High RDW with normal or low MCV suggests iron deficiency coexisting with erythrocytosis, a common pitfall that can mask the true severity of polycythemia. 1 MCV alone is unreliable for screening iron deficiency in erythrocytosis; serum ferritin, transferrin saturation, and iron levels are required for accurate diagnosis. 1

Distinguish Primary from Secondary Erythrocytosis

Test for Polycythemia Vera

Order JAK2 mutation testing (both exon 14 and exon 12) as the next step, since up to 97% of polycythemia vera cases carry this mutation. 1

Polycythemia vera diagnosis requires: 1

• Both major criteria (elevated hemoglobin/hematocrit/RBC mass AND JAK2 mutation) plus at least one minor criterion, OR
• First major criterion plus at least two minor criteria

Minor criteria include bone marrow hypercellularity with trilineage growth, subnormal serum erythropoietin level, and endogenous erythroid colony formation. 1

If JAK2 is positive, bone marrow biopsy is required to confirm diagnosis and assess for trilineage myeloproliferation. 1

Evaluate Secondary Causes if JAK2 Negative

Systematically evaluate the following secondary causes: 1

Hypoxic causes:

• Sleep study for obstructive sleep apnea, which produces nocturnal hypoxemia driving erythropoietin production 1
• Pulmonary function tests and chest imaging for chronic obstructive pulmonary disease 1
• Smoking history and carbon monoxide exposure, which causes "smoker's polycythemia" through chronic tissue hypoxia 1
• Echocardiography for cyanotic congenital heart disease with right-to-left shunting 1

Non-hypoxic causes:

• Renal imaging (ultrasound or CT) to exclude renal cell carcinoma, hydronephrosis, or cystic disease that can produce erythropoietin 1
• Medication review for testosterone use (prescribed or unprescribed), which commonly causes erythrocytosis in young adults 1
• Erythropoietin level measurement to differentiate primary (low/normal) from secondary (elevated) causes 1

Consider altitude of residence when interpreting results, as physiologic adaptation increases hemoglobin by 0.2-4.5 g/dL depending on elevation (1000-4500 meters). 1 Do not use standard diagnostic thresholds at high altitude without adjustment. 1

Management Based on Etiology

For Confirmed Polycythemia Vera

Maintain hematocrit strictly below 45% through therapeutic phlebotomy to reduce thrombotic risk, as demonstrated by the CYTO-PV trial showing significantly reduced thrombotic events (2.7% vs 9.8%, P=0.007). 1 A lower target of 42% is reasonable for women and African Americans due to physiological differences in baseline hematocrit. 1

Initiate low-dose aspirin (81-100 mg daily) as the second cornerstone of therapy for thrombosis prevention. 1

Refer immediately to hematology for ongoing management and consideration of cytoreductive therapy. 1

For Secondary Erythrocytosis

Treat the underlying condition rather than performing phlebotomy: 1

• Smoking cessation for smoker's polycythemia 1
• CPAP therapy for obstructive sleep apnea 1
• Management of chronic lung disease 1
• Dose adjustment or discontinuation of testosterone if causative 1

Therapeutic phlebotomy is indicated ONLY when: 1

• Hemoglobin exceeds 20 g/dL AND hematocrit exceeds 65%, AND
• Patient has symptoms of hyperviscosity (headache, dizziness, visual disturbances), AND
• Dehydration has been excluded

When phlebotomy is performed, replace with equal volume of dextrose or saline to prevent further hemoconcentration. 1

Critical Management Pitfalls to Avoid

Never perform repeated routine phlebotomies in secondary erythrocytosis, as this causes iron depletion, decreased oxygen-carrying capacity, and paradoxically increases stroke risk. 1 The elevated hematocrit in secondary erythrocytosis serves a compensatory physiological role. 1

Avoid iron deficiency even in the presence of erythrocytosis, as iron-deficient red blood cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk. 1 If iron deficiency is confirmed, provide cautious oral iron supplementation with close hemoglobin monitoring, as rapid increases in red cell mass can occur. 1

Never perform aggressive phlebotomy without adequate volume replacement, as this increases hemoconcentration and stroke risk. 1

Special Populations

In patients with cyanotic congenital heart disease, evaluate for intercurrent issues such as dehydration, iron deficiency, or infection rather than performing phlebotomy, as the erythrocytosis is a compensatory mechanism to optimize oxygen transport. 1 Phlebotomy is indicated only if hematocrit exceeds 65% with symptoms of hyperviscosity after excluding dehydration. 1

For patients on testosterone therapy, closely monitor hematocrit levels with consideration for dose adjustment or temporary discontinuation if levels continue to rise. 1