What is the appropriate evaluation and treatment approach for a female patient with elevated hematocrit (Hct)?

Evaluation and Management of Elevated Hematocrit in a Female Patient

Initial Assessment

For a female patient with hematocrit of 48.2%, confirm this is true erythrocytosis by repeating the measurement and obtaining a complete blood count with red cell indices, reticulocyte count, serum ferritin, transferrin saturation, and C-reactive protein. 1

• This hematocrit exceeds the diagnostic threshold for erythrocytosis in women (>48-49%) and warrants systematic evaluation 1
• Hemoglobin is more reliable than hematocrit for monitoring because hematocrit can falsely increase by 2-4% with prolonged sample storage, while hemoglobin remains stable 1
• A single measurement is not reliable for establishing diagnosis; serial measurements are necessary 1

Distinguish Primary from Secondary Causes

Test for Polycythemia Vera First

Order JAK2 mutation testing immediately, as this distinguishes polycythemia vera from secondary causes and is positive in up to 97% of polycythemia vera cases. 1

• If JAK2 is positive, refer immediately to hematology for bone marrow biopsy to confirm diagnosis 1
• Polycythemia vera diagnosis requires both major criteria (elevated hemoglobin/hematocrit AND JAK2 mutation) plus one minor criterion, OR first major criterion plus two minor criteria 2, 1
• Minor criteria include bone marrow hypercellularity with trilineage growth, subnormal serum erythropoietin level, and endogenous erythroid colony formation 1

Evaluate Secondary Causes if JAK2 Negative

If JAK2 mutation is absent, systematically evaluate for secondary causes including hypoxic conditions (obstructive sleep apnea, chronic lung disease, smoking) and non-hypoxic causes (testosterone use, erythropoietin-producing tumors, renal disease). 1

• Obtain sleep study if nocturnal hypoxemia suspected 1
• Perform pulmonary function tests and chest imaging for chronic obstructive pulmonary disease 1
• Order renal imaging (ultrasound or CT) to exclude renal cell carcinoma, hydronephrosis, or cystic disease 1
• Review medications, particularly testosterone or erythropoietin therapy 1
• Measure serum erythropoietin levels to differentiate primary (low/normal) from secondary (elevated) causes 1

Consider Relative Polycythemia

Assess hydration status and cardiovascular risk factors, as relative polycythemia from plasma volume depletion is common, particularly in hypertensive patients. 3

• Hypertension is the most common disease association with spurious polycythemia 3
• Smoking and obesity are additional risk factors 3
• These findings are reversible when underlying conditions are treated 3

Management Based on Diagnosis

If Polycythemia Vera Confirmed

Maintain hematocrit strictly below 45% through therapeutic phlebotomy, as this reduces cardiovascular death and major thrombotic events from 9.8% to 2.7%. 2, 1, 4

• Phlebotomy protocol: Remove 300-450 mL weekly or twice weekly until hematocrit <45%, then maintain with same volume per session at intervals determined by monitoring 4
• Add low-dose aspirin 81-100 mg daily for all polycythemia vera patients unless contraindicated 2, 4
• Initiate cytoreductive therapy (hydroxyurea or interferon) if age ≥60 years, prior thrombosis history, poor phlebotomy tolerance, symptomatic splenomegaly, platelet count >1,500 × 10⁹/L, or progressive leukocytosis 2, 4

If Secondary Erythrocytosis

Treat the underlying condition rather than performing routine phlebotomy, as repeated phlebotomies cause iron depletion, decreased oxygen-carrying capacity, and paradoxically increase stroke risk. 1, 4

• For smoking-related erythrocytosis: Smoking cessation resolves the condition 1
• For obstructive sleep apnea: CPAP therapy addresses the hypoxemia 1
• For chronic lung disease: Optimize pulmonary management 1
• For testosterone-induced erythrocytosis: Reduce dose or temporarily discontinue 1

Phlebotomy in secondary erythrocytosis is indicated ONLY when all of the following are met: hemoglobin >20 g/dL AND hematocrit >65%, symptoms of hyperviscosity present, adequate hydration confirmed, and no iron deficiency. 1, 4

• First-line therapy for suspected hyperviscosity is hydration with oral or intravenous normal saline, NOT phlebotomy 4
• If phlebotomy is necessary, replace with equal volume of fluid to prevent hemoconcentration 1
• Target hematocrit of 55-60% may be appropriate in secondary erythrocytosis, as elevated hematocrit serves a compensatory physiological role 1

If Relative Polycythemia

Treat underlying hypertension, encourage smoking cessation, and address obesity rather than performing venesection. 3

• The peripheral blood findings are reversible when blood pressure is controlled 3
• The red cell pool is normal and shows no evidence of progression to polycythemia vera 3

Critical Management Principles

Iron Status Assessment

Evaluate and treat iron deficiency before considering phlebotomy, as iron deficiency mimics hyperviscosity symptoms but requires opposite treatment. 1, 4

• Check serum ferritin, transferrin saturation, and iron levels 1
• If transferrin saturation <20%, treat with iron supplementation until stores are replete 1, 4
• Iron-deficient red blood cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk 1
• Mean corpuscular volume is unreliable for screening iron deficiency in erythrocytosis 1

Monitoring Strategy

For borderline elevations without clear diagnosis, monitor with serial measurements every 3-6 months rather than immediate intervention. 1

• Regular monitoring is appropriate for patients with borderline elevated hematocrit 1
• Evaluate for signs of disease progression at each visit 2
• Assess cardiovascular risk factors and manage aggressively regardless of diagnosis 4

Common Pitfalls to Avoid

• Never perform routine phlebotomy in secondary erythrocytosis without meeting strict criteria, as this causes iron depletion and increases stroke risk 1, 4
• Never perform phlebotomy without adequate volume replacement, as this increases hemoconcentration and thrombotic risk 1
• Never overlook iron deficiency coexisting with erythrocytosis, particularly in women, as this requires iron supplementation not phlebotomy 1
• Never use standard polycythemia vera diagnostic thresholds at high altitude without adjustment, as physiologic adaptation increases hemoglobin by 0.2-4.5 g/dL depending on elevation 1