What does an elevated hematocrit (Hct) indicate in a female patient?

Elevated Hematocrit in a Female Patient

A hematocrit of 50.9% in a female patient indicates erythrocytosis (polycythemia) and requires immediate evaluation to distinguish between primary causes (polycythemia vera), secondary causes (hypoxia, smoking, sleep apnea, tumors), and relative polycythemia (dehydration). 1

Clinical Significance

This hematocrit level is significantly elevated above the normal range for women:

• Normal hematocrit for menstruating females: 41 ± 5% (range 36-46%) 2
• Normal hematocrit for post-menopausal females: 47 ± 6% (range 41-53%) 2
• Erythrocytosis threshold in women: Hematocrit >49.5% 1

A hematocrit of 50.9% places this patient above the diagnostic threshold for erythrocytosis and carries significant clinical implications. Elevated hematocrit is an independent risk factor for thrombosis, with women in the upper 20th percentile having increased risk of venous thromboembolism. 3 Additionally, higher hematocrit levels, even within the upper normal range, are associated with increased risk of developing heart failure. 4

Immediate Diagnostic Workup

Confirm True Polycythemia

Repeat the hematocrit measurement and obtain a complete blood count with red cell indices, as a single measurement is not reliable for establishing diagnosis. 1 Simultaneously measure:

• Hemoglobin level (should be >16.5 g/dL in women for true erythrocytosis) 1
• Red blood cell count and indices (MCV, MCH, MCHC) 1
• White blood cell count and differential 1
• Platelet count 1
• Reticulocyte count 1

Assess for Relative vs. Absolute Polycythemia

Evaluate hydration status clinically to exclude relative polycythemia from plasma volume depletion (dehydration, diuretic use, stress polycythemia). 1 If the patient is dehydrated, rehydrate and recheck hematocrit before proceeding with extensive workup.

Initial Laboratory Panel

Order the following tests immediately: 1

• Serum ferritin and transferrin saturation (iron deficiency can coexist with erythrocytosis, causing microcytic polycythemia) 1
• C-reactive protein (to assess for inflammatory conditions) 1
• Peripheral blood smear review (to identify abnormal red cell morphology) 1

Differential Diagnosis Algorithm

Primary Erythrocytosis (Polycythemia Vera)

Test for JAK2 mutations (both exon 14 and exon 12) as the next critical step. 1 JAK2 mutations are present in up to 97% of polycythemia vera cases. 1

Look for associated clinical features: 5, 1

• Splenomegaly
• Aquagenic pruritus (itching after water exposure)
• Erythromelalgia (burning pain in hands/feet)
• Elevated white blood cell count (>10 × 10⁹/L)
• Elevated platelet count (>400 × 10⁹/L)

WHO diagnostic criteria for polycythemia vera require: 1

• Both major criteria (elevated Hct >49.5% in women AND JAK2 mutation) plus one minor criterion, OR
• First major criterion plus two minor criteria

Secondary Erythrocytosis (Hypoxia-Driven)

Evaluate systematically for: 1

Smoking history:

• "Smoker's polycythemia" from chronic carbon monoxide exposure stimulates erythropoietin production 1
• Resolves with smoking cessation 1

Nocturnal hypoxemia:

• Order sleep study if obstructive sleep apnea is suspected (snoring, daytime somnolence, witnessed apneas) 1
• Sleep apnea produces nocturnal hypoxemia driving erythropoietin production 1

Chronic lung disease:

• Assess for COPD, interstitial lung disease, or other pulmonary conditions 1
• Consider pulmonary function tests and arterial blood gas if clinically indicated 1

Cyanotic congenital heart disease:

• Right-to-left shunting causes compensatory erythrocytosis 1
• Echocardiography if cardiac shunt suspected 1

Secondary Erythrocytosis (Hypoxia-Independent)

Screen for: 1

• Erythropoietin-producing tumors: renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, meningioma
• Exogenous erythropoietin therapy (if patient has chronic kidney disease)
• Measure serum erythropoietin level to differentiate primary (low/normal EPO) from secondary (elevated EPO) causes 1

Physiological Variations to Consider

Altitude adaptation: 1

• If patient lives at altitude >1,000 meters, hemoglobin and hematocrit naturally increase
• At 2,000m: expected increase of +0.8 g/dL hemoglobin
• At 3,000m: expected increase of +1.9 g/dL hemoglobin
• Normal hematocrit at 4,000m altitude in women: 41-56% 6

Management Based on Etiology

If Polycythemia Vera Confirmed

Maintain hematocrit strictly below 45% through therapeutic phlebotomy to reduce thrombotic risk. 5, 1 The CYTO-PV study demonstrated that maintaining hematocrit <45% significantly reduces thrombotic events in women (0 events with Hct <45% vs. 9 events with Hct 45-50%). 5

Initiate low-dose aspirin (81-100 mg daily) as the second cornerstone of therapy for thrombosis prevention. 5

Refer immediately to hematology for consideration of cytoreductive therapy (hydroxyurea) if patient has high-risk features (age >60 years or prior thrombosis). 5

If Secondary Erythrocytosis

Treat the underlying condition: 1

• Smoking cessation for smoker's polycythemia
• CPAP therapy for obstructive sleep apnea
• Optimize management of chronic lung disease
• Discontinue or reduce testosterone if causative (testosterone therapy commonly causes erythrocytosis) 5, 1

Therapeutic phlebotomy is indicated ONLY if: 5, 1

• Hematocrit exceeds 65% (this patient at 50.9% does NOT meet this threshold)
• Patient has symptoms of hyperviscosity (headache, dizziness, visual disturbances)
• Dehydration has been excluded

Avoid repeated routine phlebotomies as they risk iron depletion, decreased oxygen-carrying capacity, and paradoxically increase stroke risk. 1

Special Consideration: Iron Deficiency

If iron deficiency is confirmed (ferritin low, transferrin saturation <20%), cautious oral iron supplementation with close hemoglobin monitoring is necessary. 1 Iron-deficient red blood cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk even in the presence of erythrocytosis. 1

Mean corpuscular volume (MCV) is unreliable for screening iron deficiency in erythrocytosis—serum ferritin and transferrin saturation are required for accurate diagnosis. 1

Critical Thresholds and Monitoring

At hematocrit 50.9%, this patient requires intervention but NOT emergent phlebotomy. The key is determining the underlying cause:

• Hematocrit >54% on testosterone therapy: warrants dose reduction or temporary discontinuation 5
• Hematocrit >65% with hyperviscosity symptoms: warrants therapeutic phlebotomy 5, 1
• Female patients with hematocrit >55%: always have absolute polycythemia (not relative) 7

Common Pitfalls to Avoid

Do not perform aggressive phlebotomy without determining the underlying cause. 1 In secondary erythrocytosis (especially cyanotic heart disease), the elevated hematocrit is a compensatory mechanism to optimize oxygen transport, and phlebotomy can be harmful. 1

Do not overlook coexisting iron deficiency. 1 High red blood cell count with low hemoglobin and low MCV suggests microcytic polycythemia from iron deficiency, which requires iron supplementation, not phlebotomy. 1

Do not assume anemia is impossible with elevated hematocrit. 1 Relative polycythemia from dehydration can mask underlying anemia—always recheck after adequate hydration.

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, 2

Referral Indications

Refer immediately to hematology if: 1

• JAK2 mutation is positive
• Hemoglobin >20 g/dL with symptoms of hyperviscosity
• Unexplained splenomegaly
• Elevated white blood cell count or platelet count suggesting myeloproliferative disorder
• Diagnosis remains unclear after initial workup