Which iron supplement and dose should be given to a 15‑year‑old with thalassemia trait?

Do Not Give Iron Supplementation to a 15-Year-Old with Thalassemia Trait

Iron supplementation should be avoided in patients with thalassemia trait unless concurrent iron deficiency is documented by laboratory testing. 1 Thalassemia trait (thalassemia minor) does not cause iron deficiency—it causes microcytic anemia with normal or elevated iron stores—and inappropriate iron supplementation can lead to iron overload and organ damage. 2

Critical Distinction: Thalassemia Trait vs. Iron Deficiency Anemia

Why Iron Supplementation Is Contraindicated in Isolated Thalassemia Trait

• Thalassemia trait patients do not have iron deficiency by default; they have a genetic hemoglobinopathy causing microcytic red blood cells with normal or increased iron stores. 3

• Iron supplementation in the absence of true iron deficiency can cause iron overload, leading to hepatic cirrhosis, cardiac dysfunction, and endocrine disorders. 1, 2

• Guidelines explicitly state that iron supplementation should be avoided in hemochromatosis and iron overload conditions, and the same principle applies to thalassemia trait when iron stores are adequate. 1

When to Consider Iron Supplementation in Thalassemia Trait

Iron deficiency commonly coexists with thalassemia trait in approximately 31% of cases, particularly in adolescent females with menstrual blood loss. 3 Therefore, you must screen for concurrent iron deficiency before making any treatment decision.

Screening Algorithm for This 15-Year-Old:

1. Obtain complete iron studies: serum ferritin, serum iron, total iron-binding capacity (TIBC), transferrin saturation, and C-reactive protein (CRP) to exclude inflammation that falsely elevates ferritin. 4, 3

2. Check hemoglobin and red blood cell indices: hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red blood cell count. 3, 5

3. Apply age-appropriate ferritin cutoffs:

   • For adolescents aged 12-15 years, use a ferritin cutoff of 20 µg/L to diagnose iron deficiency. 4
   • For those aged >15 years, use a ferritin cutoff of 30 µg/L. 4

4. Use hemoglobin as a screening trigger: If hemoglobin is <11.5 g/dL in a patient with known thalassemia trait, screen for concurrent iron deficiency (sensitivity 79.8%, specificity 82.6%). 3

If Iron Deficiency Is Documented:

Only if ferritin is below the age-appropriate cutoff and transferrin saturation is low should you prescribe iron supplementation. 4, 3

• Oral iron therapy: Ferrous sulfate 28-50 mg elemental iron once daily, taken between meals to maximize absorption. 4

• Avoid excessive doses: Higher doses increase gastrointestinal side effects without improving efficacy. 4

• Recheck iron studies after 8-10 weeks: Hemoglobin should increase by ≥1 g/dL if iron deficiency was the cause. 1, 4

• If no response after 4 weeks despite compliance, consider malabsorption, ongoing blood loss, or misdiagnosis (the anemia may be solely due to thalassemia trait, not iron deficiency). 1, 5

If Iron Studies Are Normal or Elevated:

Do not prescribe iron supplementation. 1 The microcytic anemia is due to thalassemia trait alone, and iron therapy will not improve hemoglobin and may cause harm. 1, 2

Common Pitfalls to Avoid

Pitfall 1: Assuming All Microcytic Anemia Requires Iron

• Thalassemia trait causes microcytosis with normal or high iron stores, unlike iron deficiency anemia. 3, 5

• Do not reflexively prescribe iron based on low MCV alone; always check ferritin and iron studies first. 4, 3

Pitfall 2: Ignoring Coexistent Iron Deficiency

• Approximately one-third of thalassemia trait patients also have iron deficiency, especially menstruating adolescent females. 3

• Failure to screen for and treat documented iron deficiency in a thalassemia trait patient can perpetuate symptomatic anemia and fatigue. 3

Pitfall 3: Using Ferritin Alone Without Checking CRP

• Ferritin is an acute-phase reactant and can be falsely elevated during inflammation or infection, masking true iron deficiency. 4

• Always measure CRP concurrently; if elevated, ferritin may underestimate iron deficiency. 4

Pitfall 4: Prescribing Iron "Just in Case"

• Preventative iron administration in the presence of normal stores is inefficient, has side effects, and is potentially harmful. 4

• Long-term daily iron supplementation with normal or high ferritin is not recommended and may cause iron overload. 4, 2

Summary Algorithm

1. Confirm thalassemia trait diagnosis (hemoglobin electrophoresis showing elevated HbA2 or HbF, family history, ethnic background). 3

2. Obtain iron studies (ferritin, serum iron, TIBC, transferrin saturation, CRP) and complete blood count. 4, 3

3. If ferritin is below age-appropriate cutoff (<20 µg/L for ages 12-15, <30 µg/L for >15 years) and CRP is normal:

   • Prescribe oral ferrous sulfate 28-50 mg elemental iron once daily between meals. 4
   • Recheck hemoglobin and iron studies in 8-10 weeks. 4

4. If ferritin is normal or elevated:

   • Do not prescribe iron. 1
   • Reassure the patient that the microcytic anemia is due to thalassemia trait and does not require treatment. 3

5. If hemoglobin is <11.5 g/dL, strongly consider screening for iron deficiency even if not initially suspected. 3