What could cause an elevated hemoglobin of 17.9 g/dL in an adult?

Elevated Hemoglobin at 17.9 g/dL: Differential Diagnosis and Workup

A hemoglobin of 17.9 g/dL requires immediate evaluation to distinguish between polycythemia vera (which carries significant thrombotic risk) and secondary causes, with JAK2 mutation testing as the critical first step. 1, 2

Initial Diagnostic Considerations

The hemoglobin of 17.9 g/dL falls into a diagnostic gray zone that requires context-dependent interpretation:

• In men: This value approaches but does not definitively meet the WHO major criterion for polycythemia vera (≥18.5 g/dL), though it exceeds the alternative threshold of ≥17 g/dL if there has been a sustained increase of ≥2 g/dL from baseline 3, 2
• In women: This clearly exceeds the WHO major criterion for polycythemia vera (≥16.5 g/dL) and warrants immediate JAK2 mutation testing 3, 2
• Critical caveat: Iron deficiency can mask polycythemia vera by lowering hemoglobin levels, so the diagnosis requires demonstrating WHO criteria AFTER iron replacement if deficiency is present 2

Primary Polycythemia (Polycythemia Vera)

Polycythemia vera must be ruled out first because it carries significant thrombotic risk requiring specific management to prevent morbidity and mortality. 1

Diagnostic Criteria

The WHO diagnostic algorithm requires either:

• Both major criteria (elevated Hb/Hct AND JAK2 mutation) plus ≥1 minor criterion, OR
• First major criterion (elevated Hb/Hct) plus ≥2 minor criteria 3, 2

Major criteria:

1. Hemoglobin ≥18.5 g/dL (men) or ≥16.5 g/dL (women), OR Hb ≥17 g/dL (men) or ≥15 g/dL (women) with sustained ≥2 g/dL increase from baseline 3, 2
2. Presence of JAK2 V617F (found in >90-95% of PV cases) or JAK2 exon 12 mutation 3, 1

Minor criteria:

1. Bone marrow biopsy showing hypercellularity with trilineage growth (panmyelosis) 3
2. Serum erythropoietin level below the reference range for normal 3
3. Endogenous erythroid colony formation in vitro 3

Immediate Testing Required

• JAK2 V617F mutation testing (exon 14) as first-line molecular testing—this captures >90% of PV cases 3, 1
• Complete blood count with differential to assess for thrombocytosis (≥450 × 10⁹/L) and leukocytosis (≥12 × 10⁹/L) which support the diagnosis 3, 4
• Serum erythropoietin level to distinguish primary (low/low-normal) from secondary (elevated) polycythemia 1, 4
• Serum ferritin and transferrin saturation to exclude iron deficiency masking the diagnosis 2, 4

Secondary Polycythemia (Hypoxia-Driven)

Common Causes to Evaluate

Obstructive sleep apnea (OSA):

• Polysomnography (sleep study) should be ordered to confirm OSA as the cause of chronic hypoxemia 1
• Nocturnal hypoxemia drives erythropoietin production 4
• Treatment with CPAP resolves the erythrocytosis 1, 4

Chronic obstructive pulmonary disease (COPD):

• Pulmonary function tests and chest imaging to assess for chronic lung disease 1, 4
• Treatment of underlying pulmonary condition is necessary 1, 4

Smoking ("smoker's polycythemia"):

• Carbon monoxide exposure causes tissue hypoxia and stimulates erythropoietin production 1, 4
• Smoking cessation should be implemented before ordering extensive blood volume studies 1
• Resolves with smoking cessation 4

High altitude residence:

• Hemoglobin thresholds must be adjusted for altitude of residence 3, 2
• At 4000 meters, normal male hemoglobin averages 17.3 g/dL (range 13-21 g/dL) and female hemoglobin averages 15.8 g/dL (range 12-19 g/dL) 5
• Physiologic adaptation increases hemoglobin by 0.2-4.5 g/dL depending on elevation (1000-4500 meters) 4

Secondary Polycythemia (Non-Hypoxia-Driven)

Erythropoietin-producing tumors:

• Renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, and meningioma can produce erythropoietin independently 1, 4
• Renal imaging (ultrasound or CT) should be performed to exclude these causes 4

Testosterone therapy:

• Prescribed or unprescribed testosterone can cause erythrocytosis 1, 4
• Dose adjustment or temporary discontinuation is necessary if causative 4

Relative Polycythemia (Plasma Volume Depletion)

• Dehydration, diuretic use, burns, and stress polycythemia (Gaisböck syndrome) cause relative polycythemia 4
• Confirm true polycythemia by repeating measurements after adequate hydration 4

Recommended Diagnostic Algorithm

1. Confirm elevation with repeat hemoglobin and hematocrit measurements, as single measurements are unreliable 4

2. Order immediate laboratory workup:

   • Complete blood count with red cell indices, reticulocyte count, and differential 4
   • Serum ferritin and transferrin saturation 4
   • JAK2 V617F mutation testing 1, 4
   • Serum erythropoietin level 1, 4

3. If JAK2 mutation is positive:

   • Bone marrow biopsy is required to confirm PV diagnosis and assess for trilineage myeloproliferation 4
   • Immediate referral to hematology 4

4. If JAK2 mutation is negative:

   • Systematically evaluate secondary causes:
     • Sleep study for OSA 1, 4
     • Pulmonary function tests and chest imaging for COPD 1, 4
     • Smoking history and cessation counseling 1, 4
     • Renal imaging for erythropoietin-producing tumors 4
     • Medication review for testosterone use 1, 4
     • Adjust thresholds for altitude of residence 2, 4, 5

Management Principles

For confirmed polycythemia vera:

• Maintain hematocrit strictly below 45% through therapeutic phlebotomy to reduce thrombotic risk 1, 4
• Initiate low-dose aspirin (81-100 mg daily) as second cornerstone of therapy for thrombosis prevention 1, 4

For secondary polycythemia:

• Treat the underlying condition (CPAP for OSA, smoking cessation, management of COPD, dose adjustment of testosterone) 1, 4
• Therapeutic phlebotomy is indicated ONLY if hemoglobin >20 g/dL and hematocrit >65% with symptoms of hyperviscosity, after excluding dehydration 4
• Avoid repeated routine phlebotomies due to risk of iron depletion, decreased oxygen-carrying capacity, and stroke 4

Critical Pitfalls to Avoid

• Do not overlook iron deficiency coexisting with erythrocytosis—this can cause microcytic polycythemia with elevated RBC count but reduced hemoglobin 4
• Do not use standard PV diagnostic thresholds at high altitude without adjustment for physiologic adaptation 4, 5
• Do not perform aggressive phlebotomy without adequate volume replacement, as this increases hemoconcentration and stroke risk 4
• Do not assume anemia is normal with aging—hemoglobin does not physiologically decline with age 6