What is the best management approach for a patient with iron deficiency anemia, elevated hemoglobin (Hb) and hematocrit (Hct) levels, and normal Total Iron-Binding Capacity (TIBC), percentage saturation, total iron, and Comprehensive Metabolic Panel (CMP) levels?

Management of Paradoxical Iron Deficiency Anemia with Elevated Hemoglobin/Hematocrit

This clinical presentation is internally contradictory and requires immediate reassessment of the diagnosis.

The scenario described—iron deficiency anemia with simultaneously elevated hemoglobin and hematocrit alongside normal iron studies (TIBC, % saturation, total iron)—is physiologically incompatible and indicates either laboratory error, misdiagnosis, or an alternative underlying condition that must be identified before treatment.

Diagnostic Reassessment Required

Verify Laboratory Accuracy

• Repeat complete blood count (CBC) with peripheral smear examination immediately to confirm hemoglobin, hematocrit, mean corpuscular volume (MCV), and red cell distribution width (RDW) 1.
• Recheck serum ferritin, as this is the most powerful test for iron deficiency; ferritin <12-15 μg/dL is diagnostic of iron deficiency, while ferritin >100 μg/dL makes iron deficiency almost certainly absent 1.
• Hemoglobin and hematocrit are late indicators of iron deficiency and should decrease, not increase, in true iron deficiency anemia 1.

Evaluate for Alternative Diagnoses

• If MCV is <75-76 fL with normal ferritin, consider thalassemia trait (typically with elevated red cell count), hemoglobinopathies, or anemia of chronic disease 1, 2.
• If MCV is normal or elevated, iron deficiency anemia is unlikely; consider combined deficiencies (folate/B12), which may be recognized by elevated RDW 1.
• Transferrin saturation <30% may support iron deficiency diagnosis when ferritin is equivocal, but a therapeutic trial of oral iron for 3 weeks or bone marrow aspiration are definitive confirmatory tests 1.

Clinical Context Considerations

Rule Out Polycythemia or Hemoconcentration

• Elevated hemoglobin/hematocrit with normal iron studies suggests polycythemia vera, secondary polycythemia, or hemoconcentration rather than iron deficiency 1.
• Assess for dehydration, chronic hypoxia, smoking history, sleep apnea, or erythropoietin-producing tumors 1.

Assess for Functional Iron Deficiency

• In chronic kidney disease or inflammatory conditions, functional iron deficiency can occur with normal or elevated ferritin due to iron sequestration and hepcidin upregulation 1.
• However, this typically presents with low hemoglobin, not elevated levels 1.

Management Algorithm Once Diagnosis is Clarified

If True Iron Deficiency Anemia is Confirmed (Low Hb/Hct, Low Ferritin)

• Initiate oral iron supplementation with ferrous sulfate 200 mg three times daily to correct anemia and replenish body stores 1.
• Continue iron therapy for 3 months after hemoglobin normalization to replenish iron stores 1.
• Investigate underlying cause with upper GI endoscopy (including small bowel biopsies for celiac disease, present in 2-3% of IDA cases) and colonoscopy, as dual pathology occurs in ~10% of patients 1.

If Elevated Hb/Hct Persists with Normal Iron Studies

• Do not administer iron supplementation, as iron overload risk exists without documented deficiency 1.
• Investigate causes of polycythemia with erythropoietin level, JAK2 mutation testing, and oxygen saturation assessment 1.

Critical Pitfalls to Avoid

• Never assume dietary deficiency alone explains anemia; full gastrointestinal investigation is required even with positive dietary history 1.
• Do not rely on serum iron studies alone (iron, TIBC, saturation) for diagnosis, as they have poor predictive value in differentiating iron deficiency from anemia of chronic disease 2.
• Avoid treating with iron when ferritin >100 ng/mL unless transferrin saturation is definitively low and functional iron deficiency is documented 1.
• Recognize that normal hemoglobin/hematocrit does not exclude early iron depletion, but elevated levels contradict iron deficiency anemia diagnosis 1, 3.

Follow-Up Protocol

• Monitor hemoglobin and MCV every 3 months for one year, then annually once normalized 1.
• Repeat ferritin if hemoglobin or MCV falls below normal to guide additional iron therapy 1.
• Further investigation is only necessary if hemoglobin and MCV cannot be maintained with appropriate iron supplementation 1.