I have had borderline high hemoglobin for over 5 years, normal white‑blood cell and platelet counts, a subnormal erythropoietin (EPO) level, no pruritus after warm showers or night sweats, and my hemoglobin fluctuates spontaneously; what is the likely diagnosis and what work‑up and management should I pursue?

Borderline High Hemoglobin with Fluctuating Levels and Low EPO

Your presentation—borderline high hemoglobin fluctuating spontaneously over 5+ years, normal white blood cells and platelets, subnormal EPO, and absence of classic polycythemia vera symptoms—most likely represents either early/masked polycythemia vera or a secondary polycythemia that requires systematic exclusion before definitive diagnosis.

Immediate Diagnostic Workup Required

First-Line Testing (Order Now)

JAK2 V617F mutation testing is mandatory as your first diagnostic step, since this mutation is present in >95% of polycythemia vera cases and will definitively distinguish primary from secondary causes 1, 2, 3. The combination of borderline-high hemoglobin with subnormal EPO has >90% specificity for polycythemia vera, making this diagnosis highly likely 4, 2.

• If JAK2 V617F is negative, proceed immediately to JAK2 exon 12 mutation testing, which captures the remaining ~3% of polycythemia vera cases 2, 5
• Repeat complete blood count to confirm sustained elevation and check for microcytosis (low MCV), which suggests iron deficiency that can mask true polycythemia 1, 5
• Check serum ferritin and iron studies because iron deficiency can suppress hemoglobin levels and create fluctuating values that obscure the diagnosis 1, 5

Critical Diagnostic Pitfall You're Facing

Your fluctuating hemoglobin levels do NOT exclude polycythemia vera—in fact, this pattern is characteristic of iron-deficient polycythemia vera, where hemoglobin rises when iron is adequate and falls when iron stores are depleted 1. The Mayo Clinic warns that iron deficiency can mask true polycythemia and must be excluded before dismissing the diagnosis 2.

Why Your EPO Level Doesn't Rule Out Polycythemia Vera

Subnormal EPO strongly suggests polycythemia vera (specificity >90%), but you need to understand that EPO interpretation has important nuances 4, 2:

• Low EPO reflects autonomous, JAK2-driven erythropoiesis that suppresses normal EPO feedback mechanisms 4
• EPO sensitivity for polycythemia vera is only 64-70%, meaning normal EPO levels don't exclude the diagnosis 4, 5
• In your case, subnormal EPO combined with borderline-high hemoglobin makes polycythemia vera the leading diagnosis until proven otherwise 4, 2

Secondary Causes to Systematically Exclude

If JAK2 mutations are negative, you must evaluate for secondary polycythemia through this algorithmic approach 1, 4:

Hypoxia-Driven Causes (Check These First)

• Smoking history and carboxyhemoglobin level: Smoker's polycythemia from chronic carbon monoxide exposure is the most common secondary cause and resolves with smoking cessation 1, 4
• Sleep study for obstructive sleep apnea: Nocturnal hypoxemia drives compensatory erythrocytosis 1, 2
• Arterial oxygen saturation and chest X-ray: Rule out chronic lung disease (COPD) or right-to-left cardiopulmonary shunts 1, 4

Hypoxia-Independent Causes (If Above Are Negative)

• Abdominal ultrasound or CT: Screen for EPO-producing tumors including renal cell carcinoma, hepatocellular carcinoma, uterine leiomyomas, pheochromocytoma 1, 4
• Medication review: Check for exogenous testosterone, anabolic steroids, or erythropoietin use 1, 4
• Renal function tests: Evaluate for post-renal transplant erythrocytosis if applicable 1

Why Your Lack of Symptoms Doesn't Exclude Polycythemia Vera

The absence of pruritus and night sweats does NOT rule out polycythemia vera—these symptoms are present in only 33% and a minority of patients, respectively 3, 6. Many patients with polycythemia vera are asymptomatic at diagnosis 3, 7.

• Pruritus occurs in approximately one-third of polycythemia vera patients, meaning two-thirds lack this symptom 3
• Splenomegaly is present in only 36% at diagnosis 3
• Your presentation of isolated erythrocytosis without other symptoms is actually common in early polycythemia vera 7, 8

What Happens If JAK2 Is Positive

Immediate referral to hematology is mandatory if JAK2 mutation is positive, as this confirms polycythemia vera and requires specialist management 2, 5.

Treatment You Would Need

• Therapeutic phlebotomy to maintain hematocrit <45% in men or <42% in women to reduce thrombosis risk 3, 8
• Low-dose aspirin (81 mg daily) unless contraindicated, to prevent arterial thrombosis 3, 8
• Risk stratification based on age >60 years or prior thrombosis history determines if you need cytoreductive therapy with hydroxyurea or interferon 1, 8

Critical Next Steps

Do not wait or continue observing—a sustained increase of ≥2 g/dL hemoglobin from baseline, even within normal ranges, warrants immediate investigation 2, 5. Your 5+ year history of borderline-high hemoglobin with subnormal EPO represents a diagnostic emergency for thrombosis prevention.

Order These Tests This Week

1. JAK2 V617F mutation testing 2, 3
2. Complete blood count with differential and red cell indices 1, 5
3. Serum ferritin, iron, and transferrin saturation 1, 5
4. Comprehensive metabolic panel 4

If JAK2 Is Negative

1. JAK2 exon 12 mutation testing 2, 5
2. Carboxyhemoglobin level (if smoker) 1, 4
3. Arterial oxygen saturation 1, 4
4. Abdominal imaging for EPO-producing tumors 1, 4

The combination of borderline-high hemoglobin, subnormal EPO, and 5+ year duration makes polycythemia vera highly likely until proven otherwise—your fluctuating hemoglobin pattern suggests iron-deficient polycythemia vera rather than a benign condition 1, 2.