What is the most likely diagnosis for a male patient with a stable hemoglobin of 15.8–17 g/dL over seven years, a low erythropoietin level, a normal spleen on examination, and otherwise normal complete blood count parameters?

Normal Hemoglobin with Low Erythropoietin: Diagnostic Approach

A male patient with stable hemoglobin of 15.8-17 g/dL over seven years, low erythropoietin, normal spleen, and otherwise normal blood counts most likely has polycythemia vera or an early myeloproliferative neoplasm, though the hemoglobin is at the upper end of normal rather than frankly elevated.

Understanding the Clinical Picture

This presentation requires careful interpretation because the hemoglobin values fall within the normal range for adult males (>12 g/dL per guideline definitions) 1. However, several features warrant investigation:

Key Diagnostic Considerations

The combination of "high-normal" hemoglobin with suppressed erythropoietin is physiologically inappropriate and suggests:

• Primary polycythemia (polycythemia vera) - The bone marrow produces red cells independent of erythropoietin signaling, leading to suppressed EPO levels even when hemoglobin is in the normal-high range 2
• Early myeloproliferative neoplasm - JAK2 mutation testing should be performed as this is present in >95% of polycythemia vera cases
• Physiologic high-normal variant - Less likely given the suppressed EPO, as normal individuals maintain consistent EPO levels across the normal hemoglobin range 2

Critical Laboratory Evaluation Needed

Order the following tests immediately:

• JAK2 V617F mutation - This is the definitive test for polycythemia vera
• Complete iron studies (ferritin, transferrin saturation, serum iron, TIBC) - Iron deficiency can mask polycythemia by preventing the hemoglobin from rising further 3
• Red blood cell mass measurement - If available, this directly measures true erythrocytosis versus relative polycythemia
• White blood cell and platelet trends - Review the seven-year history for subtle increases that might indicate myeloproliferation
• Peripheral blood smear - Assess for morphologic abnormalities 4

Why Low EPO Matters

Erythropoietin levels remain remarkably consistent across the normal hemoglobin range and only increase markedly when hemoglobin falls below 12 g/dL 2. Therefore:

• A suppressed EPO with hemoglobin of 15.8-17 g/dL is not physiologically normal
• This suggests EPO-independent red cell production
• The bone marrow is producing red cells autonomously, characteristic of polycythemia vera

Ruling Out Secondary Causes

Before concluding primary polycythemia, exclude:

• Hypoxic conditions - Check oxygen saturation, consider sleep apnea evaluation, pulmonary function tests
• Renal pathology - Renal ultrasound to exclude cysts or tumors that produce EPO
• Hepatic lesions - Liver imaging if clinically indicated
• Exogenous testosterone or anabolic steroids - Medication and supplement history

The Seven-Year Stability Factor

The seven-year stability with hemoglobin consistently 15.8-17 g/dL suggests:

• This is not acute or transient
• If polycythemia vera, it may be in a very early or "masked" phase
• Iron deficiency could be limiting the full expression of the disease 3
• Serial monitoring has been appropriate, but definitive testing is now warranted

Common Pitfalls to Avoid

Do not dismiss this as "normal" simply because hemoglobin is <18 g/dL:

• Polycythemia vera can present with hemoglobin in the high-normal range, especially with concurrent iron deficiency 3
• The suppressed EPO is the key abnormal finding that demands explanation
• Waiting for hemoglobin to rise further delays diagnosis and increases thrombotic risk

Do not assume normal spleen size excludes myeloproliferative disease:

• Early polycythemia vera often presents without splenomegaly
• Splenomegaly develops later in the disease course

Next Steps Algorithm

1. Order JAK2 V617F mutation testing immediately - This is the single most important diagnostic test
2. Check complete iron studies - Ferritin, transferrin saturation, iron, TIBC 3
3. Review seven-year CBC trends - Look for subtle increases in WBC or platelets
4. If JAK2 positive - Refer to hematology for bone marrow biopsy and management
5. If JAK2 negative but suspicion remains - Check for JAK2 exon 12 mutations and other myeloproliferative markers
6. If all negative - Consider red cell mass measurement to distinguish true versus relative polycythemia

The suppressed erythropoietin in the context of high-normal hemoglobin is the critical abnormality that cannot be ignored and requires hematologic evaluation.