(Based on standard pediatric approach as in Nelson Textbook of Pediatrics)
Table of Contents
1️⃣ Definition
Thalassemia = inherited disorder of decreased synthesis of α or β globin chains, leading to:
- Imbalanced globin chain production
- Ineffective erythropoiesis
- Chronic hemolytic anemia
- Marrow expansion + iron overload
2️⃣ Classification
A. Based on Globin Chain Affected
Alpha (α) Thalassemia
Chromosome 16 — 4 α genes (αα/αα)
| No. of gene deletions | Genotype | Clinical Type |
|---|---|---|
| 1 | -α/αα | Silent carrier |
| 2 | -α/-α or –/αα | α-thal trait |
| 3 | –/-α | HbH disease |
| 4 | –/– | Hydrops fetalis (Hb Bart’s) |
Beta (β) Thalassemia
Chromosome 11 — 2 β genes (one each parent)
| Mutation Type | Effect |
|---|---|
| β⁰ | No β production |
| β⁺ | Reduced β production |
Clinical types:
- β-thalassemia minor (trait)
- β-thalassemia intermedia
- β-thalassemia major (Cooley anemia)
3️⃣ Pathophysiology (Very Important for Exams)
Beta Thalassemia
↓ β-chain production → excess unpaired α chains
→ Precipitate in RBC precursors
→ Severe ineffective erythropoiesis
→ Intramedullary destruction
→ Hemolysis
→ Marrow expansion
→ Iron overload
Alpha Thalassemia
↓ α-chain production → excess γ or β chains
→ Hb Bart’s (γ4) in fetus
→ HbH (β4) in children/adults
4️⃣ Clinical Features
Beta Thalassemia Major
Onset: 6 months (after HbF falls)
Features:
- Severe pallor
- Failure to thrive
- Irritability
- Hepatosplenomegaly
- Recurrent infections
- Bone changes:
- Frontal bossing
- Maxillary hypertrophy
- Chipmunk facies
- Growth retardation
- Delayed puberty
If untreated → death by early childhood
Beta Thalassemia Intermedia
- Moderate anemia
- Splenomegaly
- Bone changes milder
- May not need regular transfusion
Beta Thalassemia Minor
- Asymptomatic
- Mild microcytic anemia
- Often mistaken as iron deficiency
Alpha Thalassemia
HbH disease
- Moderate hemolytic anemia
- Jaundice
- Splenomegaly
- Episodic worsening with infections
Hb Bart’s (Hydrops fetalis)
- Severe anemia
- Hydrops
- Intrauterine death
5️⃣ Laboratory Findings
CBC
| Parameter | Finding |
|---|---|
| Hb | Low |
| MCV | Very low |
| MCH | Low |
| RBC count | Normal or high |
| RDW | Usually normal |
Key point: RBC count normal/high despite low MCV (helps differentiate from IDA)
Peripheral Smear
- Microcytosis
- Hypochromia
- Target cells
- Anisopoikilocytosis
- Nucleated RBCs
- Basophilic stippling
Hemoglobin Electrophoresis
Beta Thalassemia Major
- ↑ HbF
- ↑ HbA2
- ↓/absent HbA
Beta Thalassemia Minor
- ↑ HbA2 (>3.5%)
- Mild ↑ HbF
Alpha Thalassemia
- Usually normal electrophoresis in trait
- HbH detectable in HbH disease
- Hb Bart’s in newborn
Iron Studies
- Serum ferritin normal or increased
- Important to rule out iron deficiency
6️⃣ Diagnosis
- CBC + smear
- Hb electrophoresis
- HPLC
- Molecular testing (definitive)
- Prenatal diagnosis:
- CVS (10–12 weeks)
- Amniocentesis
7️⃣ Management
Beta Thalassemia Major
A. Regular Transfusion Program
Goal:
- Maintain Hb 9–10 g/dL
- Suppress ineffective erythropoiesis
- Prevent bone deformities
Usually every 3–4 weeks
B. Iron Chelation Therapy
Indicated after:
- ~10–20 transfusions OR
- Ferritin >1000 ng/mL
Drugs:
- Deferoxamine (SC infusion)
- Deferasirox (oral)
- Deferiprone (oral)
C. Splenectomy
Indications:
- Hypersplenism
- Increased transfusion requirement
After 5 years preferred
Vaccination required prior
D. Curative Treatment
✅ Hematopoietic stem cell transplantation (HSCT)
Best in:
- Young age
- HLA matched sibling
E. Emerging Therapy
- Gene therapy (experimental in many settings)
8️⃣ Complications
From Disease:
- Bone deformities
- Growth failure
- Extramedullary hematopoiesis
From Iron Overload:
- Cardiomyopathy (leading cause of death)
- Liver cirrhosis
- Endocrinopathies:
- Diabetes
- Hypothyroidism
- Hypogonadism
- Hypoparathyroidism
From Transfusion:
- Alloimmunization
- Viral infections (HBV, HCV)
- Iron overload
9️⃣ Prevention (Very Important in South Asia)
- Carrier screening
- Premarital counseling
- Antenatal screening
- Prenatal diagnosis
- Genetic counseling
High prevalence in:
- Mediterranean
- Middle East
- South Asia (including Nepal)
🔟 Differentiating Thalassemia Trait vs Iron Deficiency
| Feature | Thalassemia Trait | Iron Deficiency |
|---|---|---|
| RBC count | Normal/high | Low |
| RDW | Normal | High |
| HbA2 | Increased | Normal |
| Ferritin | Normal | Low |
| Mentzer index (MCV/RBC) | <13 | >13 |
Viva Pearls
- Severe anemia at 6 months → think β-thal major
- Very low MCV with normal RBC count → think thalassemia
- HbA2 >3.5% → diagnostic of β-thal trait
- Most common cause of death → iron-induced cardiomyopathy
- HSCT = only definitive cure
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