RBC Indices in Thalassemia
Thalassemia characteristically presents with low MCV (microcytosis), low MCH (hypochromia), elevated RBC count, and a normal or only mildly elevated RDW, distinguishing it from iron deficiency anemia which shows similar microcytosis but with markedly elevated RDW. 1
Characteristic RBC Index Pattern
Primary Distinguishing Features
- MCV (Mean Cell Volume): Markedly decreased, typically <80 fL, reflecting significant microcytosis 1
- RBC Count: Elevated or high-normal despite anemia, a key distinguishing feature from iron deficiency 2
- RDW (Red Cell Distribution Width): Normal to mildly elevated (≤14-16%), significantly lower than in iron deficiency 1, 3
- MCH (Mean Corpuscular Hemoglobin): Decreased, reflecting hypochromia 4
- MCHC (Mean Corpuscular Hemoglobin Concentration): More preserved relative to iron deficiency 2, 4
Differential Diagnosis: Thalassemia vs Iron Deficiency
The CDC guidelines establish that when MCV is low and RDW is ≤14%, thalassemia minor is the likely diagnosis, whereas low MCV with RDW >14% indicates iron deficiency anemia 1. This distinction is critical because the two conditions require fundamentally different management approaches.
- Microcytic-Hypochromic Ratio: In thalassemia trait, the percentage of microcytes (mean 33.1%) exceeds the percentage of hypochromic cells (mean 13.9%), with a ratio >0.9 having 92.4% discriminant efficiency 2
- Iron deficiency pattern: Percentage of hypochromic cells (mean 34.6%) exceeds microcytes (mean 12.8%), with ratio <0.9 2
- RDW behavior: In thalassemia minor, 52% maintain normal RDW even with low hemoglobin, whereas 94% of iron deficiency cases show elevated RDW of approximately 23% 3
Critical Pitfall to Avoid
Do not assume normal RDW excludes thalassemia with concurrent iron deficiency. When thalassemia trait coexists with iron deficiency (beta-THID), RDW elevates to levels similar to isolated iron deficiency (mean 20.62), potentially masking the underlying thalassemia diagnosis 5. In these cases, England's index (MCV²×RBC/Hb×100) with cutoff values can help: values suggesting thalassemia despite elevated RDW warrant hemoglobin electrophoresis 5.
Management Implications Based on Diagnosis
For Transfusion-Dependent Thalassemia
Once thalassemia is confirmed (not based solely on indices but requiring hemoglobin electrophoresis), the American College of Hematology recommends:
- Transfusion protocol: Maintain pre-transfusion hemoglobin 9-10 g/dL and post-transfusion 13-14 g/dL with regular transfusions every 3-4 weeks 6, 7
- Immediate iron chelation: Start deferasirox 20-30 mg/kg/day, deferoxamine 50 mg/kg/day subcutaneously, or deferiprone 75 mg/kg/day orally as each transfused unit contains 200-250 mg iron with no physiologic excretion mechanism 7
- Cardiac monitoring: Annual cardiac MRI T2* to detect iron overload before symptomatic cardiomyopathy develops, as cardiac iron is the leading cause of death in thalassemia 6, 7
Monitoring During Chelation
- Serum ferritin: Target <1000 mcg/L, checked every 3 months, though MRI liver iron concentration is more accurate 6, 8
- Renal function: Monitor eGFR closely; deferasirox is contraindicated if eGFR <40 mL/min/1.73 m² and requires 50% dose reduction if eGFR 40-60 mL/min/1.73 m² 9
- Hepatic assessment: Liver function tests every 3 months; reduce deferasirox dose by 50% in moderate hepatic impairment (Child-Pugh B) and avoid in severe impairment (Child-Pugh C) 9
Special Consideration: Deferiprone and Neutropenia
Exercise caution with deferiprone as it increases neutropenia risk, particularly during concurrent antiviral therapy for hepatitis. The American Society of Hematology recommends switching to deferoxamine during HCV treatment rather than continuing deferiprone 8. Monitor complete blood counts more frequently if deferiprone is necessary 8.