What is the likely diagnosis for a patient with microcytic anemia, indicated by a Mean Corpuscular Volume (MCV) of 65.7, Mean Corpuscular Hemoglobin Concentration (MCHC) of 29.8, Red Cell Distribution Width (RDW) of 17.5, and normal ferritin levels?

Thalassemia Trait is the Most Likely Diagnosis

With microcytic anemia (MCV 65.7), elevated RDW (17.5), and normal ferritin, the most likely diagnosis is thalassemia trait, though iron deficiency cannot be completely excluded and requires additional testing to definitively distinguish between these two conditions. 1, 2

Why This Pattern Suggests Thalassemia Over Iron Deficiency

The Diagnostic Dilemma

• Your laboratory pattern creates a diagnostic challenge because both iron deficiency and thalassemia cause microcytic anemia with low MCV 1
• The elevated RDW (17.5) typically points toward iron deficiency, as RDW >14-16.9% strongly distinguishes iron deficiency from thalassemia trait, which usually presents with normal or only slightly elevated RDW 1, 2
• However, the normal ferritin argues against iron deficiency, as ferritin <30 μg/L is diagnostic of iron deficiency in the absence of inflammation 1, 2

The Severely Low MCV is Key

• Your MCV of 65.7 is remarkably low, which is more characteristic of thalassemia trait than typical iron deficiency 3
• Thalassemia patients often have very low MCV with elevated red cell counts, creating a distinctive pattern 1
• The degree of microcytosis is disproportionate to what would be expected from early iron deficiency alone 3

Essential Next Steps for Definitive Diagnosis

Immediate Laboratory Testing Required

• Obtain complete iron studies immediately: serum iron, total iron-binding capacity (TIBC), and transferrin saturation 1, 2
• Transferrin saturation <30% would confirm iron deficiency despite normal ferritin 1
• Measure CRP or inflammatory markers to determine if inflammation is falsely elevating ferritin, as ferritin up to 100 μg/L may still indicate iron deficiency in the presence of inflammation 1, 2, 3

Hemoglobin Electrophoresis is Critical

• Order hemoglobin electrophoresis to diagnose thalassemia trait definitively, as this will identify hemoglobinopathies that cannot be diagnosed by routine labs alone 1
• This test is mandatory before presuming thalassemia as the cause, as microcytosis in certain ethnic groups should not be assumed to be thalassemia without laboratory confirmation 1

Consider a Therapeutic Trial

• If iron studies show any evidence of deficiency (transferrin saturation <30%), initiate oral iron supplementation for 3 weeks 1
• A therapeutic response to iron confirms iron deficiency, as this is one of the definitive ways to establish the diagnosis 1
• Continue iron for 3-6 months after hemoglobin normalizes to replete iron stores if response occurs 2

Critical Pitfall: Combined Deficiency

Don't Miss Coexisting Conditions

• You may have both thalassemia trait AND iron deficiency simultaneously 1, 3
• The elevated RDW suggests heterogeneous red cell populations, which can occur when iron stores become progressively depleted even in patients with underlying thalassemia 2
• Combined deficiency (iron plus thalassemia) can present with confusing laboratory patterns where the microcytosis is more severe than either condition alone 1

When to Investigate for Gastrointestinal Blood Loss

If Iron Deficiency is Confirmed

• All adult men and post-menopausal women with confirmed iron deficiency require complete gastrointestinal evaluation, regardless of symptoms 2
• This includes upper endoscopy with mandatory small bowel biopsies (to exclude celiac disease) and colonoscopy 1, 2
• 2-3% of patients with iron deficiency anemia have celiac disease, making small bowel biopsy essential 1
• Gastrointestinal malignancy is the most common source of occult blood loss in these populations 2

Document Medication History

• NSAID use is a common cause of occult gastrointestinal blood loss leading to iron deficiency 1, 3
• Stop NSAIDs whenever possible, though their use should not deter investigation 1

Rare Genetic Causes to Consider if Standard Workup is Negative

When to Suspect Genetic Iron Disorders

• If ferritin is elevated and/or transferrin saturation is abnormal, or anemia is refractory to iron supplementation, consider genetic disorders of iron metabolism 3
• Iron-refractory iron-deficiency anemia (IRIDA) presents with microcytic anemia, remarkably low transferrin saturation, and low-to-normal ferritin, with failure to respond to oral iron 3

Sideroblastic Anemia

• Consider X-linked sideroblastic anemia (XLSA) in patients with pyridoxine-responsive or unresponsive mild microcytic anemia 2
• Sideroblastic anemias present with elevated ferritin and transferrin saturation even before transfusions, requiring bone marrow examination showing ring sideroblasts 3
• Initial treatment with pharmacologic doses of pyridoxine (50-200 mg per day) may be effective 2