Elevated Hemoglobin and Hematocrit in a Female Patient
This female patient has elevated hemoglobin (16.3 g/dL) and hematocrit (47.6%) that exceed the diagnostic threshold for erythrocytosis in women and warrant immediate evaluation for polycythemia vera and secondary causes.
Clinical Significance
These values are significantly elevated compared to normal ranges for adult females:
- Normal menstruating female: Hgb 14.0 ± 2.0 g/dL, Hct 41 ± 5% 1
- Normal post-menopausal female: Hgb 15.5 ± 2.0 g/dL, Hct 47 ± 6% 1
- This patient: Hgb 16.3 g/dL, Hct 47.6%, RBC 5.51
The 2016 WHO diagnostic criteria for polycythemia vera define erythrocytosis as hemoglobin >16.0 g/dL in women or hematocrit >48% in women 1. This patient meets the hemoglobin criterion and is at the borderline for hematocrit, making polycythemia vera a critical diagnostic consideration.
Immediate Diagnostic Workup Required
Essential Laboratory Tests
Order the following tests immediately to determine the etiology 2:
- Complete blood count with differential to assess white blood cell count, platelet count, and red cell indices (MCV, MCH, MCHC) 1
- Reticulocyte count to evaluate bone marrow response 1, 2
- Serum ferritin and transferrin saturation to identify concurrent iron deficiency, which can mask more severe erythrocytosis 1, 2
- C-reactive protein (CRP) to assess for inflammatory conditions 2
- Peripheral blood smear reviewed by a hematologist to identify morphological abnormalities 2
JAK2 Mutation Testing
JAK2 mutation testing (both V617F and exon 12) must be performed immediately 1, 2. The JAK2 V617F mutation is present in up to 97% of polycythemia vera cases 2, and a positive result combined with these hemoglobin/hematocrit values would meet WHO diagnostic criteria for polycythemia vera 1.
Differential Diagnosis Framework
Primary Erythrocytosis (Polycythemia Vera)
If JAK2 mutation is positive, the diagnosis of polycythemia vera requires 1:
- Major criteria: Hemoglobin >16.0 g/dL in women (met in this case) AND presence of JAK2 mutation AND bone marrow biopsy showing hypercellularity with trilineage growth
- Minor criterion: Subnormal serum erythropoietin level
Bone marrow biopsy is required if JAK2 is positive to confirm the diagnosis and assess for myelofibrosis 2.
Secondary Erythrocytosis
If JAK2 mutation is negative, systematically evaluate for secondary causes 2:
Hypoxic causes:
- Obstructive sleep apnea - order sleep study if nocturnal symptoms present 2
- Chronic obstructive pulmonary disease - obtain pulmonary function tests and chest imaging 2
- Smoking history - "smoker's polycythemia" from chronic carbon monoxide exposure 2
- Cyanotic congenital heart disease - echocardiography if cardiac symptoms 2
Non-hypoxic causes:
- Testosterone use (prescribed or unprescribed) - particularly important in reproductive-age women 2
- Erythropoietin-producing tumors - renal cell carcinoma, hepatocellular carcinoma, uterine leiomyoma 2
- Renal disease - obtain renal imaging (ultrasound or CT) to exclude masses or cysts 2
Relative Polycythemia
Consider plasma volume depletion from 2:
- Dehydration
- Diuretic use
- Stress polycythemia (Gaisböck syndrome)
Critical Management Principles
When NOT to Perform Phlebotomy
Therapeutic phlebotomy is indicated ONLY when hemoglobin exceeds 20 g/dL AND hematocrit exceeds 65% with symptoms of hyperviscosity, after excluding dehydration 2. This patient does not meet these criteria.
Repeated routine phlebotomies are explicitly contraindicated due to risk of iron depletion, decreased oxygen-carrying capacity, and paradoxically increased stroke risk 2.
If Polycythemia Vera is Confirmed
Maintain hematocrit strictly below 45% through therapeutic phlebotomy to reduce thrombotic risk 2. The CYTO-PV trial demonstrated that maintaining hematocrit <45% significantly reduces thrombotic events (2.7% vs 9.8%, p=0.007) 2.
Initiate low-dose aspirin (81-100 mg daily) as the second cornerstone of therapy for thrombosis prevention 2.
If Secondary Erythrocytosis is Confirmed
Treatment of the underlying condition is necessary 2:
- Smoking cessation for smoker's polycythemia
- CPAP therapy for obstructive sleep apnea
- Management of chronic lung disease
- Dose adjustment or discontinuation of testosterone if causative
Common Pitfalls to Avoid
Do not assume this is "normal" for a post-menopausal woman - while the hematocrit of 47.6% falls within the upper range of normal for post-menopausal females (47 ± 6%), the hemoglobin of 16.3 g/dL exceeds the WHO threshold of 16.0 g/dL for women and requires investigation 1
Do not overlook coexisting iron deficiency - iron deficiency can mask more severe erythrocytosis by reducing hemoglobin synthesis despite elevated RBC count 2. Check serum ferritin and transferrin saturation.
Do not perform phlebotomy at these levels - this patient's values do not meet the threshold (Hgb >20 g/dL, Hct >65%) for therapeutic phlebotomy 2
Do not delay JAK2 testing - a single elevated measurement meeting WHO criteria warrants immediate JAK2 mutation testing rather than waiting for repeat measurements 2
Referral Indications
Refer immediately to hematology if 2:
- JAK2 mutation is positive
- Hemoglobin >20 g/dL with symptoms of hyperviscosity
- Unexplained splenomegaly on examination
- Diagnosis remains unclear after initial workup