Can a 39-year-old female with thalassemia trait and mild anemia receive an iron infusion?

Iron Infusion in Thalassemia Trait with Low Ferritin

No, this patient should NOT receive an iron infusion despite the low ferritin of 22 ng/mL, because thalassemia trait patients have normal or increased iron stores in their bone marrow even when serum ferritin appears low, and iron supplementation does not improve their hemoglobin levels. 1

Understanding the Clinical Picture

This patient presents with classic thalassemia trait laboratory findings that must be distinguished from true iron deficiency:

• Elevated RBC count (5.68 × 10^12/L) with low MCV (67 fL) and low MCH (21.0 pg) 2
• Mild anemia (Hb 119 g/L) with disproportionately low MCV for the degree of anemia 2
• The combination of high RBC count with severe microcytosis is pathognomonic for thalassemia trait, not iron deficiency 1, 2

Why Iron Supplementation is Contraindicated

Bone Marrow Iron is Normal in Thalassemia Trait

The critical distinction is that bone marrow hemosiderin is present in normal amounts in patients with thalassemia minor, but absent in true iron deficiency anemia. 1 The low serum ferritin of 22 ng/mL does not reflect actual iron stores in thalassemia trait patients.

Iron Therapy Does Not Improve Hemoglobin

If therapy with iron does not restore hemoglobin values to normal, thalassemia minor is strongly suspect. 1 Even in thalassemia trait, there may be small fluctuations in hemoglobin values, particularly in pregnancy, but these should not be mistakenly ascribed to iron therapy. 1

Risk of Iron Overload

Patients with thalassemia trait who receive inappropriate iron supplementation risk developing:

• Cardiac disease from iron overload, which is the leading cause of death in chronically iron-loaded patients 3
• Liver disease with fibrosis and cirrhosis from iron deposition 3
• Endocrine dysfunction including hypothyroidism and diabetes 3

The Diagnostic Pitfall: Concurrent Iron Deficiency

When Thalassemia Trait Masks True Iron Deficiency

A critical caveat: Patients with thalassemia trait CAN develop concurrent true iron deficiency, which creates a diagnostic challenge. 4 Iron deficiency anemia reduces the synthesis of HbA2, so patients with both conditions may have normal HbA2 levels and be misdiagnosed. 4

How to Identify Concurrent Iron Deficiency

In this patient with confirmed thalassemia trait and ferritin 22 ng/mL, you must determine if there is additional iron deficiency:

• Check transferrin saturation: True iron deficiency shows TSAT <15% 5
• Assess for blood loss: Menorrhagia, GI bleeding, or other sources 4
• Review dietary history: Inadequate iron intake 4
• Consider trial of oral iron: If Hb increases significantly (>1 g/dL), concurrent iron deficiency was present 1, 4

Recommended Management Approach

Step 1: Confirm the Diagnosis

Before any iron therapy:

• Measure HbA2 levels to confirm beta-thalassemia trait (should be >3.5%) 4
• Check transferrin saturation to assess functional iron availability 5
• Evaluate for blood loss if ferritin is genuinely low for reasons beyond thalassemia 4

Step 2: If Concurrent Iron Deficiency is Suspected

Only if there is clear evidence of additional iron deficiency (active bleeding, TSAT <15%, dietary deficiency):

• Start with oral iron supplementation (ferrous sulfate 325 mg daily) for 8-10 weeks 5, 6
• Monitor response: Recheck Hb and ferritin after 8-10 weeks 5
• If oral iron fails or is not tolerated, then consider intravenous iron 5

Step 3: Intravenous Iron Criteria (If Truly Needed)

Intravenous iron is indicated ONLY when: 5

• Oral iron is poorly tolerated or ineffective
• There is insufficient time before surgery
• Functional iron deficiency is confirmed with low hepcidin levels 5

If IV iron is given, use ferric carboxymaltose 1 g as a single dose over 15 minutes, and allow >2 weeks before surgery for optimal Hb response. 5, 7

Common Pitfalls to Avoid

• Do not reflexively treat low ferritin in thalassemia trait patients without confirming concurrent iron deficiency 1
• Do not use ferritin alone to diagnose iron deficiency in thalassemia trait; it is unreliable 1, 4
• Do not give iron infusions without first trying oral iron unless there are specific contraindications 5, 6
• Do not ignore the elevated RBC count (5.68 × 10^12/L), which strongly suggests thalassemia trait rather than pure iron deficiency 2

Monitoring if Iron is Given

If you determine concurrent iron deficiency exists and treat with iron:

• Recheck Hb after 8-10 weeks, not earlier, as ferritin levels are falsely elevated immediately after IV iron 5
• Expect modest improvement only: Thalassemia trait limits the Hb response even with iron repletion 1
• Stop iron if no response: Lack of Hb improvement confirms thalassemia trait as the primary cause 1