What is the likely diagnosis and recommended management for a patient with a 7‑year history of isolated, stable erythrocytosis (hemoglobin rarely above 17 g/dL), normal white‑cell and platelet counts, negative JAK2 mutation, and no symptoms?

Likely Diagnosis: Idiopathic or Hereditary Erythrocytosis

For a patient with 7+ years of stable, isolated erythrocytosis (hemoglobin rarely touching 17 g/dL), normal white cell and platelet counts, negative JAK2 mutation, and no symptoms, the most likely diagnosis is idiopathic erythrocytosis or an undiagnosed hereditary erythrocytosis, and the recommended management is conservative observation with cardiovascular risk factor optimization—therapeutic phlebotomy is NOT indicated at these hemoglobin levels. 1, 2, 3

Diagnostic Reasoning

Why This Is NOT Polycythemia Vera

• JAK2 mutation testing (including exon 12) is negative, which excludes polycythemia vera in >97% of cases, as JAK2 mutations are found in virtually all PV patients. 4, 5
• Normal white cell and platelet counts argue strongly against PV, which typically shows trilineage myeloproliferation with elevated platelets and leukocytes. 4
• Seven-year stability without progression is inconsistent with PV, which is a progressive myeloproliferative neoplasm that would typically show worsening counts, splenomegaly, or transformation over this timeframe. 4

Classification as Mild, Stable Erythrocytosis

• Hemoglobin "hardly touching 17 g/dL" represents borderline elevation, as diagnostic thresholds for erythrocytosis are >18.5 g/dL in men and >16.5 g/dL in women. 4, 1
• Long-standing (7+ years) stable erythrocytosis strongly suggests either hereditary erythrocytosis or a benign idiopathic condition rather than an acquired secondary cause. 5, 6, 7
• The stability over 7 years indicates this is the patient's physiologic baseline rather than a progressive disease process. 5, 6

Recommended Diagnostic Workup

Essential Next Steps

• Obtain historical hemoglobin/hematocrit records from childhood or young adulthood if available, as lifelong elevation confirms hereditary erythrocytosis. 5, 6, 7
• Measure serum erythropoietin level to distinguish between EPO-driven (normal/elevated EPO) and EPO-independent (low EPO) mechanisms. 5, 6, 7
• Assess iron status with serum ferritin and transferrin saturation, as iron deficiency can mask the true degree of erythrocytosis. 1, 3
• Review medication list for erythrocytosis-inducing drugs including testosterone, SGLT-2 inhibitors, or erythropoiesis-stimulating agents. 5, 6

Secondary Evaluation Based on EPO Level

If EPO is low or normal:

• Consider hereditary EPO receptor mutations, particularly if family history is positive. 5, 6, 7
• Evaluate for PIEZO1 mutations or other rare hereditary causes. 5, 6

If EPO is elevated:

• Assess for hypoxic causes: overnight oximetry or sleep study for obstructive sleep apnea, pulmonary function tests for COPD, echocardiography for right-to-left shunting. 1, 5, 6
• Screen for EPO-producing tumors: renal ultrasound or CT to exclude renal cell carcinoma, hepatocellular carcinoma, or renal cysts. 5, 6
• Measure P50 (oxygen tension at 50% hemoglobin saturation) to detect high-oxygen-affinity hemoglobin variants or 2,3-BPG deficiency. 5, 6, 7

Genetic Testing Considerations

• Germline mutation screening for oxygen-sensing pathway genes (HIF2A, PHD2, VHL) should be considered if EPO is elevated with normal P50 and no secondary causes identified. 5, 6, 7
• Genetic testing is particularly indicated with positive family history of erythrocytosis. 5, 6, 7

Management Recommendations

Conservative Observation Is Appropriate

Therapeutic phlebotomy is absolutely NOT indicated at hemoglobin levels of 17 g/dL. 1, 2, 3

• Phlebotomy should only be performed when hemoglobin exceeds 20 g/dL AND hematocrit exceeds 65% AND the patient has documented symptoms of hyperviscosity (headache, fatigue, poor concentration) AND dehydration has been excluded. 4, 1, 2, 3
• Repeated routine phlebotomies are explicitly contraindicated in non-PV erythrocytosis because they cause iron depletion, decreased oxygen-carrying capacity, reduced red cell deformability, and paradoxically increase stroke risk. 4, 1, 2, 3

Recommended Interventions

• Cardiovascular risk factor optimization is the cornerstone of management: control hypertension, manage hyperlipidemia, encourage smoking cessation, optimize diabetes control. 5, 6
• Low-dose aspirin (81-100 mg daily) may be considered if cardiovascular comorbidities are present or if there is a history of thrombosis, though evidence is limited in non-PV erythrocytosis. 5, 8, 6
• Ensure adequate hydration to prevent relative polycythemia from volume depletion. 1, 3
• Correct iron deficiency if present, as iron-deficient red cells have reduced oxygen-carrying capacity and deformability, potentially increasing vascular complications. 4, 1, 3

Monitoring Strategy

• Serial complete blood counts every 6-12 months to confirm continued stability and detect any progression. 3, 5
• Monitor iron status periodically with serum ferritin and transferrin saturation to avoid iron deficiency. 1, 3
• Assess for development of symptoms including headache, visual disturbances, pruritus, erythromelalgia, or thrombotic events at each visit. 3, 5

Common Pitfalls to Avoid

• Do not perform phlebotomy based solely on hemoglobin/hematocrit numbers without meeting the strict criteria (Hgb >20 g/dL, Hct >65%, symptoms of hyperviscosity, no dehydration). 1, 2, 3
• Do not create iatrogenic iron deficiency through unnecessary phlebotomy, as this worsens oxygen delivery and increases stroke risk despite lowering hemoglobin. 4, 1, 2, 3
• Do not assume thrombotic risk is equivalent to PV—the evidence for increased thrombosis in non-clonal erythrocytosis is limited and does not justify aggressive cytoreduction. 5, 6
• Do not overlook secondary causes such as sleep apnea, smoking, or medication effects that may be readily treatable. 1, 5, 6
• Do not label as "idiopathic" without completing appropriate diagnostic evaluation including EPO level, P50 measurement, and screening for secondary causes. 5, 6

When to Refer to Hematology

• Hemoglobin persistently >18.5 g/dL (men) or >16.5 g/dL (women) despite evaluation for secondary causes. 1, 5
• Development of thrombocytosis, leukocytosis, or splenomegaly suggesting evolution to a myeloproliferative neoplasm. 4, 1
• Positive family history with suspected hereditary erythrocytosis requiring genetic counseling and germline mutation testing. 5, 6, 7
• Symptoms of hyperviscosity that may warrant consideration of therapeutic intervention. 2, 3, 5