Thalassemia: Clinical Case Discussion & Key Learning Points
Model Case Presentation
Patient Demographics
Name: Master Arjun, Age: 3 years, Gender: Male, Informant: Mother (Reliable), Ethnicity: Gujarati
Chief Complaints
- Progressively increasing pallor since 6 months of age
- Abdominal distension – 1 year
- Poor weight gain and delayed milestones – 2 years
- Repeated blood transfusions – on regular transfusion program since 10 months of age
History Summary
Child was apparently normal till 6 months of age. Gradually noticed increasing pallor, lethargy, and poor feeding. Abdomen progressively distended. Two episodes of jaundice noticed. Child was transfused first at 10 months of age for severe pallor; now requires transfusion every 3–4 weeks to remain active. Between transfusions, child becomes pale, irritable, and lethargic (pretransfusion Hb drops to ~5–6 g/dL).
No cyanosis, no bleeding from any site. Parents are consanguineous (first cousins). Elder sibling died in infancy with "blood problem." Born at term, NVD, cried immediately. Birth weight 2.9 kg. No antenatal complications noted.
Examination Summary
| Parameter | Finding | Significance |
|---|---|---|
| Weight | 10 kg | Failure to thrive (expected ~14 kg) |
| Height | 85 cm | Short stature (expected ~96 cm) |
| Pallor | Severe (all grades) | Chronic severe anemia |
| Jaundice | Mild icterus | Hemolysis |
| Cyanosis | Absent | — |
| Frontal bossing | Present | Marrow expansion / ineffective erythropoiesis |
| Malar prominence | Present | Facial bones expanded — "Thalassemic facies" |
| Spleen | Massive — 10 cm BCM | Extramedullary hematopoiesis + sequestration |
| Liver | 5 cm BCM | Extramedullary hematopoiesis, iron overload |
Skin: Brownish discoloration (bronze skin) — iron deposition. Dental: Dental malocclusion and maxillary prominence. Cardiovascular: Tachycardia; no murmur; no features of heart failure currently.
✅ Complete Diagnosis
Beta Thalassemia Major (Cooley's Anemia) — on regular transfusion program — with massive splenomegaly, hepatomegaly, thalassemic facies, failure to thrive, and features of iron overload (bronze discoloration).
📝 History — Exam Q&A
Thalassemia is a group of inherited autosomal recessive hemoglobinopathies characterized by reduced or absent synthesis of one or more globin chains of hemoglobin, leading to chronic hemolytic anemia.
- Beta thalassemia: Reduced (β+) or absent (β⁰) production of beta-globin chains → excess unpaired alpha chains → precipitation in RBC precursors → ineffective erythropoiesis + hemolysis
- Alpha thalassemia: Deletion of alpha-globin genes → excess beta chains → HbH (β4) or Hb Barts (γ4)
Beta Thalassemia:
| Type | Genotype | Clinical Features |
|---|---|---|
| Thalassemia Minor (Trait) | β/β⁰ or β/β+ | Mild microcytic anemia; asymptomatic |
| Thalassemia Intermedia | β+/β⁰ or β+/β+ | Moderate anemia; may need occasional transfusions |
| Thalassemia Major (Cooley's) | β⁰/β⁰ or β⁰/β+ | Severe anemia from 6 months; transfusion-dependent |
Alpha Thalassemia (gene deletions):
| Genes Deleted | Type | Clinical Features |
|---|---|---|
| 1 gene (-α/αα) | Silent carrier | Normal; no anemia |
| 2 genes (-α/-α or --/αα) | Alpha Thal Trait | Mild microcytic anemia |
| 3 genes (--/-α) | HbH disease | Moderate-severe hemolytic anemia; splenomegaly |
| 4 genes (--/--) | Hb Barts / Hydrops Fetalis | Intrauterine death / stillbirth |
At birth and during fetal life, the predominant hemoglobin is HbF (α2γ2), which does not require beta-globin chains. The infant is protected by HbF.
Between 3–6 months of age, there is a physiological switch from gamma-globin to beta-globin production (hemoglobin switching). In beta thalassemia, the defective beta-globin production becomes manifest only at this point → HbA cannot be produced → severe anemia develops.
- Beta thalassemia is most common in the "thalassemia belt" — Mediterranean, Middle East, Indian subcontinent, Southeast Asia
- In India, carrier frequency is ~3–4%; in some communities (Sindhis, Gujaratis, Punjabis) up to 10–17%
- ~10,000–12,000 new cases of thalassemia major born in India each year
- Alpha thalassemia is most common in Southeast Asia and Africa
History of presenting complaints:
- Age of onset of pallor — onset after 6 months suggests beta thalassemia major
- History of blood transfusions — frequency, first transfusion age, pretransfusion Hb
- Jaundice — suggests hemolysis
- Abdominal distension (splenomegaly / hepatomegaly)
- Growth and developmental history — failure to thrive, delayed milestones
- Infections — recurrent respiratory or other infections (hypersplenism)
Family history (critical):
- Consanguinity in parents
- Siblings with similar illness or deaths in infancy
- Known thalassemia trait in parents
Pertinent negatives: No bleeding (rules out bleeding disorders), no cyanosis (rules out cyanotic CHD), no fever/weight loss (rules out leukemia)
Thalassemia major follows autosomal recessive inheritance.
When both parents are thalassemia trait (carriers):
- 25% chance of thalassemia major in each pregnancy
- 50% chance of thalassemia trait (carrier)
- 25% chance of completely normal child
💡 Pearl
Thalassemia trait is NOT a disease — it protects against malaria (evolutionary advantage — explains its high prevalence in malaria-endemic regions).
The central defect is imbalance of alpha-to-beta globin chain production:
- Reduced/absent beta chain production → excess free alpha chains accumulate
- Free alpha chains are insoluble and toxic → precipitate inside RBC precursors in bone marrow → destruction of erythroid precursors = Ineffective erythropoiesis
- Surviving RBCs are abnormal (microcytic, hypochromic, fragile) → undergo hemolysis in spleen → anemia + jaundice
- Chronic anemia stimulates erythropoietin → massive marrow expansion → bone changes (frontal bossing, thalassemic facies, "hair-on-end" skull X-ray)
- Extramedullary hematopoiesis in liver, spleen → hepatosplenomegaly
- Ineffective erythropoiesis → increased intestinal iron absorption + each transfusion adds ~200 mg iron → progressive iron overload → damage to heart, liver, endocrine glands
| Hemoglobin | Composition | Normal % |
|---|---|---|
| HbA (Adult) | α2β2 | 95–97% |
| HbA2 | α2δ2 | 2–3.5% |
| HbF (Fetal) | α2γ2 | <1% (adult) |
| HbH (abnormal) | β4 | Absent (seen in HbH disease) |
| Hb Barts (abnormal) | γ4 | Absent (seen in alpha thal) |
In beta thalassemia major: HbA absent or markedly reduced; HbF elevated (compensatory).
🩺 Examination — Exam Q&A
The classic "thalassemic facies" (also called "Mongoloid facies" due to resemblance) includes:
- Frontal bossing — expansion of frontal bone marrow
- Prominent malar eminences (high cheekbones)
- Maxillary hypertrophy — upper teeth protrude (rodent facies)
- Dental malocclusion — Class II most common (Angle)
- Flat or depressed nasal bridge
- Mongoloid slant of eyes
Mechanism: Chronic severe anemia → high erythropoietin → massive erythroid hyperplasia → bone marrow expansion → cortical thinning and remodeling of facial and skull bones. Seen mainly in inadequately transfused patients.
Massive splenomegaly — often the most prominent finding; smooth, non-tender, firm; crosses the midline in severe cases.
Hepatomegaly — firm, smooth; due to extramedullary hematopoiesis and iron deposition.
Distended abdomen — protuberant due to organomegaly.
💡 Pearl
Splenomegaly in thalassemia occurs due to: (1) extramedullary erythropoiesis, (2) sequestration and destruction of abnormal RBCs. Hypersplenism worsens anemia, thrombocytopenia, and leucopenia — a key indication for splenectomy.
Iron overload (hemosiderosis) affects multiple organs:
- Skin: Bronze or brownish-grey pigmentation (melanin + hemosiderin deposition)
- Heart: Cardiomegaly, signs of CCF (tachycardia, gallop), arrhythmias — leading cause of death
- Liver: Hepatomegaly → cirrhosis → portal hypertension
- Endocrine glands: Short stature (GH deficiency), delayed puberty (hypogonadism), diabetes mellitus (pancreatic damage), hypothyroidism, hypoparathyroidism
- Joints/Bones: Arthropathy
Hypersplenism — overactive spleen destroys blood elements excessively:
- Worsening anemia (increased RBC destruction) → increased transfusion requirement
- Thrombocytopenia → bleeding tendency
- Leucopenia → recurrent infections
Clinical indicator: Rising transfusion frequency (needing transfusion every <3 weeks) suggests hypersplenism → indication for splenectomy.
| Condition | Key Distinguishing Features |
|---|---|
| Thalassemia Major | Thalassemic facies, pallor from 6 months, transfusion history, positive HbEP, family history |
| Sickle Cell Disease | Crisis, dactylitis, priapism; HbS on electrophoresis; NOT microcytic |
| Kala-azar (Visceral Leishmaniasis) | Prolonged fever, travel history, rK39 antigen positive, no thalassemic facies |
| Chronic Malaria | Fever, thick smear positive, hyper-reactive malarial splenomegaly (HMS) |
| Leukemia | Bleeding, lymphadenopathy, bone pain, blast cells on smear, pancytopenia |
| Gaucher's Disease | Storage disorder, Erlenmeyer flask deformity on X-ray, glucocerebrosidase deficiency |
Thalassemia intermedia is a milder phenotype — patients have significant anemia but can maintain Hb 7–10 g/dL without regular transfusions.
- Presents later — often after 2 years of age
- Less severe facial changes (milder marrow expansion)
- Significant splenomegaly (extramedullary hematopoiesis is the main compensatory mechanism)
- Leg ulcers and thrombotic events (due to hypercoagulable state) — more common than in major
- Iron overload still occurs (from gut absorption due to ineffective erythropoiesis) — without regular transfusions
- Extramedullary hematopoietic masses (e.g., paravertebral — can cause spinal cord compression)
🔬 Investigations — Exam Q&A
| Parameter | Finding |
|---|---|
| Hemoglobin | Severely low (3–7 g/dL pretransfusion) |
| MCV (Mean Corpuscular Volume) | Low — Microcytic (<80 fL) |
| MCH (Mean Corpuscular Hb) | Low — Hypochromic |
| MCHC | Normal or low |
| RBC count | Low but relatively preserved (compared to Hb level) |
| RDW | High — anisocytosis |
| WBC, Platelets | Low if hypersplenism; otherwise normal or elevated (leukocytosis due to NRBCs counted) |
| Reticulocyte count | Elevated — but low for degree of anemia (due to ineffective erythropoiesis) |
💡 Important Index: Mentzer Index
Mentzer Index = MCV / RBC count
- <13 → Thalassemia trait (RBC count is relatively high)
- >13 → Iron deficiency anemia (RBC count is low)
- Microcytes and hypochromia (small pale cells)
- Target cells (Codocytes) — pathognomonic; due to excess membrane relative to Hb
- Nucleated RBCs (NRBCs / Normoblasts) — released from hyperplastic marrow; hallmark of thalassemia
- Poikilocytosis — teardrop cells, elliptocytes, schistocytes
- Anisocytosis — variation in RBC size
- Basophilic stippling — precipitated ribosomes in RBCs
- In thalassemia intermedia: smear changes are less severe; in trait: only mild microcytosis + target cells
Hemoglobin Electrophoresis (HbEP) is the confirmatory investigation — it identifies and quantifies different hemoglobin fractions.
| Condition | HbA | HbA2 | HbF |
|---|---|---|---|
| Normal | 95–97% | 2–3.5% | <1% |
| Beta Thal Major (β⁰/β⁰) | 0% | 2–5% | 95–98% (compensatory) |
| Beta Thal Major (β+/β+) | Reduced | 2–5% | Elevated (50–90%) |
| Beta Thal Minor (Trait) | Normal to mildly ↓ | >3.5% (key finding) | Normal or mildly ↑ |
| Alpha Thal Trait | Normal | Normal | Normal (normal HbEP!) |
💡 Key Diagnostic Points
- In beta thalassemia trait: HbA2 > 3.5% is the hallmark
- In alpha thalassemia trait: HbEP is normal — diagnosis requires DNA analysis / gene studies
- Modern method: HPLC (High Performance Liquid Chromatography) — more accurate; used in newborn screening
Skull X-ray (lateral view):
- "Hair-on-end" or "sunray" appearance — perpendicular trabeculation of expanded outer table of skull; pathognomonic
- Thinning of outer cortex of skull bones
- Widened diploic space
Spine/Long bones:
- Cortical thinning and medullary expansion
- Erlenmeyer flask deformity of long bones (also seen in Gaucher's)
- Osteoporosis / pathological fractures
- Vertebral collapse in severe cases
Chest X-ray: Cardiomegaly (iron overload cardiomyopathy), rib expansion (extramedullary)
| Feature | Thalassemia Trait | Iron Deficiency Anemia |
|---|---|---|
| Anemia severity | Mild (Hb rarely <10) | Can be severe |
| RBC count | Normal or elevated | Low |
| MCV | Low | Low |
| RDW | Normal | High (anisocytosis) |
| Serum iron / ferritin | Normal or high | Low |
| TIBC | Normal | High |
| HbA2 | > 3.5% | Normal or low (iron depletion reduces HbA2) |
| Mentzer Index | < 13 | > 13 |
| Response to iron | No response | Hb rises in 2–4 weeks |
| Family history | Often positive | Usually negative for hemoglobinopathy |
🚨 Critical Point
Do NOT give iron supplements to thalassemia trait patients — it causes harmful iron accumulation. Always confirm diagnosis before treating microcytic anemia as IDA.
- Serum Ferritin — indirect marker; normal <300 ng/mL; target in thalassemia <1000 ng/mL; cheap and most widely used. (Caution: elevated in inflammation too)
- Liver Iron Concentration (LIC) — via liver biopsy or MRI; most accurate measure of total body iron. Target LIC <7 mg/g dry weight
- MRI T2* (cardiac and hepatic) — gold standard for non-invasive assessment of myocardial and liver iron. Cardiac T2* <20 ms indicates cardiac iron overload; <10 ms = severe risk of heart failure
- Transferrin saturation — elevated (>70%) indicates iron loading
Monitoring schedule: Serum ferritin every 3 months; cardiac MRI T2* annually once on chelation.
- Liver function tests — baseline and every 6–12 months (iron overload hepatitis, viral hepatitis from transfusions)
- Hepatitis B & C serology — transfusion-transmitted infection screening; Hepatitis B vaccine mandatory
- HIV testing — transfusion risk
- Echocardiography — annual; detect iron overload cardiomyopathy, pulmonary hypertension
- Thyroid function (TSH), blood glucose, serum calcium, PTH — monitor endocrine complications
- Bone density (DEXA scan) — osteoporosis screening
- Ophthalmology / Audiology — deferoxamine toxicity monitoring (retinal degeneration, hearing loss)
- HLA typing — if BMT is being considered
- Chorionic Villus Sampling (CVS) — at 10–12 weeks gestation; preferred (earliest)
- Amniocentesis — at 15–18 weeks (later, higher fetal loss)
- Material is used for DNA analysis / molecular genetics — to identify specific beta-globin mutations (e.g., IVS1-5 G→C common in India)
- Preimplantation Genetic Diagnosis (PGD) — in IVF, embryos tested before implantation; allows selection of unaffected embryo
- Prerequisite: Both parents must be known carriers and their specific mutations identified
💊 Management — Exam Q&A
Hypertransfusion regime (currently standard):
- Blood product: Leucoreduced, packed red blood cells (PRBCs)
- Target: Maintain pretransfusion Hb ≥ 9–10 g/dL
- Frequency: Every 2–4 weeks
- Volume: 10–15 mL/kg per transfusion; infuse over 3–4 hours
Goals of regular transfusion:
- Correct anemia and improve tissue oxygenation
- Suppress endogenous erythropoiesis → prevent bone marrow expansion → prevent skeletal changes and organomegaly
- Allow normal growth and development
Transfusion criteria for first transfusion: Hb <7 g/dL on two occasions at least 2 weeks apart (excluding acute infections), confirmed diagnosis.
🚨 Why leuco-reduced?
Leucocyte depletion prevents: febrile non-hemolytic transfusion reactions, HLA alloimmunisation (important if BMT is planned), CMV transmission.
Chelation is started when serum ferritin >1000 ng/mL (usually after 10–20 transfusions) or when LIC is elevated.
| Drug | Route | Dose | Advantage | Toxicity |
|---|---|---|---|---|
| Deferoxamine (DFO) | SC/IV (8–12 hr infusion, 5–7 days/week) | 25–50 mg/kg/day | Most evidence, cardiac iron clearance | Local site reactions, retinal/hearing toxicity, growth retardation |
| Deferasirox (DFX, Exjade/Jadenu) | Oral (once daily) | 20–40 mg/kg/day | Convenient, oral; good for liver iron | GI upset, renal impairment, hepatotoxicity, rash |
| Deferiprone (DFP, Ferriprox) | Oral (3 times daily) | 75–100 mg/kg/day | Best cardiac iron clearance; oral | Agranulocytosis (weekly CBC monitoring mandatory) |
💡 Combination Chelation
DFO + Deferiprone in combination gives superior cardiac iron clearance than monotherapy — used in patients with severe myocardial iron overload (T2* <10 ms).
Indications:
- Annual transfusion requirement >200–250 mL/kg/year (suggests hypersplenism)
- Symptomatic massive splenomegaly causing pain, early satiety
- Leucopenia or thrombocytopenia causing clinical problems
- Progressive splenomegaly causing risk of rupture
Preferred age: Delay until after age 5–6 years (higher risk of overwhelming post-splenectomy sepsis in younger children).
Before splenectomy: Vaccinate with Pneumococcal, Meningococcal, Hib vaccines (at least 2 weeks prior).
After splenectomy: Lifelong penicillin prophylaxis (especially <5 years) to prevent overwhelming post-splenectomy infection (OPSI).
Complications of OPSI: Fulminant sepsis — most commonly by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis.
Hematopoietic Stem Cell Transplantation (HSCT) / Bone Marrow Transplantation (BMT) — the only established cure.
- Best outcomes: Young children (<7–10 years), Class I/II patients (no hepatomegaly, no portal fibrosis, regular chelation), HLA-matched sibling donor
- Overall survival rate: ~90%; Thalassemia-free survival: ~80–85% (with matched sibling)
- Lucarelli Classification determines transplant risk:
- Class I: No hepatomegaly, no portal fibrosis, regular chelation → best prognosis
- Class II: One or two risk factors
- Class III: All three risk factors → higher transplant-related mortality
- Unrelated / matched unrelated donor: feasible but higher risk of GvHD
- Folic acid: 5 mg/day — to support erythropoiesis (increased demand due to high cell turnover)
- Avoid iron supplements — contraindicated; worsens overload
- Hepatitis B vaccination — all patients before first transfusion
- Hepatitis C screening — annual
- Endocrine surveillance: Annual thyroid function, blood sugar, growth assessment
- Calcium and Vitamin D: For bone health (osteoporosis prevention)
- Hydroxyurea: Used in thalassemia intermedia to stimulate HbF production — reduces transfusion requirement in some patients
- Psychological support / counseling — chronic disease burden on family
- Iron overload (transfusional hemosiderosis) — most serious; cardiac failure is the leading cause of death
- Alloimmunization — formation of antibodies against donor RBC antigens → hemolytic transfusion reactions, difficulty in future cross-matching
- Transmission of infections — Hepatitis B, Hepatitis C, HIV, CMV, malaria
- Febrile non-hemolytic transfusion reactions — reduced by leuco-depletion
- Transfusion-associated circulatory overload (TACO)
- Autoimmune hemolytic anemia
- Hypersplenism — progressive with repeated transfusions if splenomegaly not controlled
- Screening: Premarital and antenatal screening for thalassemia trait (CBC + HbEP) — identify carriers before starting a family
- If both parents are carriers: 25% risk of affected child in each pregnancy → offer prenatal diagnosis (CVS/amniocentesis + DNA analysis)
- If affected fetus detected at prenatal diagnosis — parents counseled about options including medical termination (as per law)
- Extended family screening — siblings of known carriers should be screened
- National programs: India has National Health Mission thalassemia screening initiatives; several states have mandatory premarital screening
- Explain: Thalassemia trait is NOT a disease — carriers lead normal lives; discourage stigma
🔭 Recent Advances — Exam Q&A
Gene therapy aims to cure thalassemia by introducing a functional globin gene into the patient's own hematopoietic stem cells (HSCs). Two FDA-approved therapies (2022–2023):
- Betibeglogene autotemcel (Zynteglo / beti-cel) — FDA approved 2022 for transfusion-dependent beta thalassemia. Uses a lentiviral vector to insert a modified functional beta-globin gene (βA-T87Q) into autologous CD34+ HSCs. One-time IV infusion after myeloablation. ~89% of patients achieved transfusion independence in phase 3 trials.
- Exagamglogene autotemcel (Casgevy / exa-cel) — FDA approved 2023. Uses CRISPR-Cas9 gene editing to reactivate fetal hemoglobin (HbF) production by disrupting the BCL11A gene (a suppressor of HbF). First CRISPR-based therapy approved for a genetic disease.
💡 Key concept — Why reactivate HbF?
HbF (α2γ2) does not require beta-globin chains. Increasing HbF compensates for the lack of HbA in beta thalassemia — essentially re-creating a "fetal" hemoglobin pattern. This is the basis of both hydroxyurea and CRISPR gene editing therapy.
Luspatercept (Reblozyl) — an erythroid maturation agent; FDA approved for adults with transfusion-dependent beta thalassemia (2020).
- Mechanism: Recombinant fusion protein that binds TGF-β superfamily ligands (GDF-11, activin B) → inhibits Smad2/3 signaling → promotes late-stage erythroid differentiation and maturation → reduces ineffective erythropoiesis
- Administration: Subcutaneous injection once every 3 weeks
- In BELIEVE trial: ~21% of patients had a ≥33% reduction in transfusion burden over 12 weeks
- Does not cure the disease; used as a disease-modifying agent to reduce transfusion frequency
MRI T2* is a specialized magnetic resonance technique that measures tissue iron concentration non-invasively.
- Iron causes loss of MRI signal → shorter T2* value = more iron
- Cardiac T2* < 20 ms: Significant myocardial iron deposition; risk of cardiac dysfunction
- Cardiac T2* < 10 ms: Severe iron overload; high risk of heart failure and arrhythmias; intensify chelation (combination therapy)
- Liver T2*: Used alongside LIC (liver iron concentration) to guide chelation dose
- Replaced liver biopsy as the gold standard for iron monitoring
- Recommended annually once patient is on regular transfusions and chelation (TIF guidelines)
Hydroxyurea (HU) is a HbF inducer — it increases gamma-globin gene expression → more HbF produced → compensates for deficient HbA.
- Most useful in: Beta thalassemia intermedia and some cases of sickle cell disease
- In thalassemia intermedia: can raise Hb by 1–2 g/dL, reduce transfusion frequency
- Response depends on genotype — patients with β+ mutations or coinheritance of hereditary persistence of HbF (HPFH) respond better
- Less useful in thalassemia major (β⁰/β⁰) where no beta chain production exists
- Side effects: Myelosuppression, teratogenicity, GI upset (generally well tolerated in children)
Previously, BMT required a fully HLA-matched sibling donor — available for only ~25–30% of patients.
Haploidentical (half-matched) BMT: Uses a parent or other half-matched relative as donor. With T-cell depletion or post-transplant cyclophosphamide (PTCy) protocols:
- Extends BMT to patients without matched siblings — most patients have a haploidentical parent
- Results improving but GvHD and graft failure rates remain higher than matched sibling
- Combined with gene therapy advances, this represents a major expansion of curative options
⚡ Key Points — Quick Revision
One-Liners for Exam
- Basic defect in beta thal major: Reduced/absent beta-globin → excess alpha chains → ineffective erythropoiesis + hemolysis
- Why presents at 6 months: HbF (fetal) is protective; symptoms appear when gamma→beta switch occurs
- Most common beta thal mutation in India: IVS1-5 (G→C)
- Thalassemia facies: Frontal bossing + malar prominence + maxillary hypertrophy + dental malocclusion
- Skull X-ray finding: "Hair-on-end" or "sunray" appearance
- Peripheral smear hallmark: Target cells + NRBCs (nucleated RBCs)
- HbEP in thal major: HbF ↑↑, HbA absent or markedly reduced, HbA2 normal/slightly elevated
- HbEP in thal trait (minor): HbA2 >3.5% is the hallmark
- Alpha thal trait: Normal HbEP — diagnosis by DNA analysis
- Mentzer Index <13: Thalassemia; >13 = IDA
- Iron supplementation: CONTRAINDICATED in thalassemia trait — worsens iron overload
- Transfusion target: Pre-transfusion Hb ≥9–10 g/dL; leucoreduced PRBCs every 2–4 weeks
- Chelation start: Ferritin >1000 ng/mL (after ~10–20 transfusions)
- Deferiprone risk: Agranulocytosis — weekly CBC monitoring mandatory
- Deferoxamine toxicity: Retinal degeneration + sensorineural hearing loss
- Cardiac MRI T2* <10 ms: Severe iron overload — combination chelation urgently
- Leading cause of death: Iron overload cardiomyopathy (cardiac failure)
- Only cure: Bone marrow transplant (HSCT) — best outcome with HLA-matched sibling, age <7–10 years, Class I Lucarelli
- Splenectomy age: Preferably after age 5; vaccinate 2 weeks before; lifelong penicillin prophylaxis after
- OPSI organisms: Pneumococcus, H. influenzae, Meningococcus
- Hydroxyurea: Useful in thal intermedia (HbF inducer); not in β⁰/β⁰ major
- First approved CRISPR gene therapy: Exagamglogene autotemcel (Casgevy) for beta thal — 2023
- Luspatercept: Erythroid maturation agent; reduces transfusion burden in adults
- Prenatal diagnosis: CVS at 10–12 weeks + DNA analysis for mutations
- Folic acid: 5 mg/day — given to all thalassemia patients (high cell turnover)
🧬 Hemoglobin Electrophoresis — Quick Summary Table
| Condition | HbA | HbA2 | HbF |
|---|---|---|---|
| Normal | 95–97% | 2–3.5% | <1% |
| Beta Thal Major (β⁰/β⁰) | 0% | 2–5% | 95–98% |
| Beta Thal Intermedia | Reduced | 2–5% | 20–60% |
| Beta Thal Trait | Normal | >3.5% | Normal/slightly ↑ |
| HPFH | Reduced | Normal | 15–35% (uniform ↑) |
| Alpha Thal Trait | Normal | Normal | Normal |