What is the appropriate management for a patient with elevated hemoglobin and hematocrit levels?

Management of Elevated Hemoglobin and Hematocrit

This patient requires confirmation of true erythrocytosis with repeat testing, followed by JAK2 mutation testing and evaluation for secondary causes before considering any therapeutic intervention. 1

Confirm True Erythrocytosis

• Repeat hemoglobin and hematocrit measurements, as a single elevated value (Hb 18.2 g/dL, Hct 54.0%) does not establish a diagnosis—borderline values require confirmation before proceeding with further workup. 1
• True erythrocytosis is defined as hemoglobin >18.5 g/dL in men or >16.5 g/dL in women, and hematocrit >55% in men or >49.5% in women. 1 This patient's values (Hb 18.2 g/dL, Hct 54.0%) are borderline and warrant repeat testing.
• Hemoglobin is more reliable than hematocrit for monitoring because hematocrit can falsely increase by 2-4% with prolonged sample storage and is affected by hyperglycemia, while hemoglobin remains stable. 1

Initial Laboratory Workup

Once erythrocytosis is confirmed, order the following tests immediately:

• Complete blood count with red cell indices (already available—shows normal MCV 99.1, normal RDW 13.6). 1
• Reticulocyte count to evaluate bone marrow response. 1
• Peripheral blood smear review by a qualified hematologist to assess red cell morphology. 1
• Serum ferritin and transferrin saturation to evaluate iron status—iron deficiency can coexist with erythrocytosis and must be identified before any phlebotomy consideration. 1
• C-reactive protein (CRP) as part of the minimum workup. 1

Test for Primary vs. Secondary Erythrocytosis

JAK2 Mutation Testing

• Order JAK2 mutation testing (both exon 14 and exon 12) to evaluate for polycythemia vera, which is found in up to 97% of PV cases. 1
• Polycythemia vera diagnosis requires either both major criteria (elevated Hb/Hct AND JAK2 mutation) plus one minor criterion, OR the first major criterion plus two minor criteria. 1
• Minor criteria include aquagenic pruritus, splenomegaly, or erythromelalgia. 1

Evaluate for Secondary Causes

If JAK2 is negative, systematically evaluate secondary causes:

• Smoking history and carbon monoxide exposure—"smoker's polycythemia" results from chronic tissue hypoxia stimulating erythropoietin production. 1
• Sleep study if nocturnal hypoxemia is suspected—obstructive sleep apnea produces nocturnal hypoxemia that drives erythropoietin production. 1
• Pulmonary function testing for chronic obstructive pulmonary disease or other chronic lung disease. 1
• Testosterone use (prescribed or unprescribed)—testosterone therapy can cause erythrocytosis and should be considered in the differential. 1
• Erythropoietin level to differentiate between primary and secondary causes. 1

Management Based on Diagnosis

If Asymptomatic with Borderline Values (Current Patient)

Do NOT perform therapeutic phlebotomy at this time. 1, 2 This patient's hemoglobin (18.2 g/dL) and hematocrit (54.0%) do not meet thresholds for intervention.

• Therapeutic phlebotomy is indicated ONLY when hemoglobin >20 g/dL AND hematocrit >65%, with associated symptoms of hyperviscosity (headache, dizziness, visual disturbances, fatigue), and only after excluding dehydration. 1, 3, 2
• Repeated routine phlebotomies are contraindicated due to risk of iron depletion, decreased oxygen-carrying capacity, and paradoxically increased stroke risk. 1, 2

If Polycythemia Vera is Diagnosed

• Maintain hematocrit strictly below 45% through therapeutic phlebotomy to reduce cardiovascular death and major thrombotic events from 9.8% to 2.7%. 2
• Phlebotomy protocol: Remove 250-500 mL per session, initially twice weekly if Hct >55% or weekly if Hct 50-55% until target achieved, then adjust frequency to maintain Hct <45% (typically every 2-3 months). 3
• Add low-dose aspirin 100 mg daily unless contraindicated to significantly reduce thrombotic events. 3, 2
• Consider cytoreductive therapy (hydroxyurea, interferon alfa, or pegylated interferon) if age ≥60 years, history of prior thrombosis, poor phlebotomy tolerance, symptomatic splenomegaly, platelet count >1,500 × 10⁹/L, or progressive leukocytosis. 3, 2

If Secondary Erythrocytosis is Diagnosed

• Treat the underlying condition: smoking cessation for smoker's polycythemia, CPAP for obstructive sleep apnea, management of COPD or chronic lung disease. 1, 2
• Dose adjustment or discontinuation of testosterone if causative. 1
• Avoid routine phlebotomy in secondary erythrocytosis—it can cause iron deficiency and compromise oxygen transport. 2

Critical Management Principles

Hydration First, Not Phlebotomy

• For suspected hyperviscosity symptoms, hydration is first-line therapy—administer oral fluids or intravenous normal saline before considering any other intervention. 2
• If phlebotomy is performed, it must be replaced with equal volume of dextrose or saline to prevent further hemoconcentration. 1

Evaluate and Manage Iron Status

• Iron deficiency should be evaluated before considering phlebotomy using serum ferritin, transferrin saturation, and iron levels—iron deficiency can mimic hyperviscosity symptoms and increases stroke risk. 1, 2
• If transferrin saturation <20%, treat with cautious oral iron supplementation until stores are replete, monitoring hemoglobin closely as rapid increases in red cell mass can occur. 1, 2
• Iron-deficient red blood cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk even in the presence of erythrocytosis. 1

Referral Indications

Refer immediately to a hematologist if:

• JAK2 mutation is positive. 1
• Hemoglobin >20 g/dL with symptoms of hyperviscosity. 1
• Unexplained splenomegaly. 1
• Progressive erythrocytosis over time requiring frequent monitoring. 1

Common Pitfalls to Avoid

• Do not perform aggressive phlebotomy based on a single elevated measurement—confirm with repeat testing first. 1
• Do not overlook iron deficiency in patients with erythrocytosis—it can coexist and requires specific evaluation. 1
• Do not perform routine phlebotomy in secondary erythrocytosis without clear indications—this can lead to iron deficiency and compromise oxygen transport. 2
• Do not ignore cardiovascular risk factors—aggressively manage smoking, hypertension, and diabetes regardless of diagnosis. 2