Thalassemia is Highly Likely with These Laboratory Findings
With low hemoglobin, normal TIBC, high serum iron, and low transferrin saturation, thalassemia trait is the most probable diagnosis after excluding iron deficiency anemia. This constellation of findings—microcytic anemia with normal or elevated iron stores—is characteristic of thalassemia rather than iron deficiency 1, 2.
Why This Pattern Suggests Thalassemia
Microcytic anemia with normal/high iron stores is the hallmark of thalassemia, distinguishing it from iron deficiency anemia where iron stores are depleted 1, 2.
Normal TIBC (total iron-binding capacity) excludes iron deficiency, as iron deficiency characteristically shows elevated TIBC (>400 mcg/dL) as the liver produces more transferrin to capture scarce iron 3, 4.
High serum iron with low transferrin saturation creates an apparent paradox that occurs in thalassemia due to ineffective erythropoiesis—the bone marrow cannot effectively utilize available iron for hemoglobin production 5, 6.
Thalassemia patients develop iron overload even without transfusions due to increased intestinal iron absorption triggered by ineffective erythropoiesis, resulting in elevated serum iron and ferritin 7, 6.
Essential Diagnostic Steps to Confirm Thalassemia
Check serum ferritin immediately—thalassemia carriers typically have normal or elevated ferritin (often >100 ng/mL), while iron deficiency shows ferritin <30 ng/mL 3, 2.
Obtain complete red blood cell indices: Mean corpuscular volume (MCV) is markedly reduced (60-70 fL) and mean corpuscular hemoglobin (MCH) is low (19-23 pg) in β-thalassemia carriers, with slightly less reduction in α-thalassemia 2.
Red blood cell count is characteristically elevated or high-normal in thalassemia despite low hemoglobin—this is a key distinguishing feature from iron deficiency where RBC count is reduced 8, 2.
Hemoglobin electrophoresis is the definitive diagnostic test: Elevated HbA2 (>3.5%) confirms β-thalassemia trait, while normal or low HbA2 suggests α-thalassemia trait 1, 2.
Genetic testing confirms the diagnosis and identifies specific mutations, which is essential for α-thalassemia diagnosis and for genetic counseling 1, 2.
Critical Pitfalls to Avoid
Do not assume iron deficiency based solely on low hemoglobin—the normal TIBC and high serum iron exclude this diagnosis 3, 4.
Low transferrin saturation does not always indicate iron deficiency—in thalassemia, this reflects ineffective iron utilization rather than iron depletion 5, 6.
Never initiate iron supplementation without confirming iron deficiency, as thalassemia patients already have iron overload and additional iron causes severe organ damage (cardiac, hepatic, endocrine) 1, 7.
Exclude iron deficiency definitively with ferritin <30 ng/mL before considering thalassemia, as concurrent iron deficiency can mask thalassemia's characteristic elevated HbA2 2.
Additional Considerations
Screen for celiac disease with tissue transglutaminase antibody if any uncertainty exists, as malabsorption can present with similar laboratory patterns 3, 8.
Check C-reactive protein (CRP) to exclude inflammation that might elevate ferritin and confound interpretation 3, 4.
Family history and ethnicity provide important clues—thalassemia is more common in Mediterranean, Middle Eastern, African, and Southeast Asian populations 1, 2.
Thalassemia trait is generally asymptomatic and requires only monitoring, not treatment, but genetic counseling is essential for reproductive planning 1, 2.