Thalassemia Flashcards
Definition
Autosomal recessive disorders due to defective globin chain production
Quantitive defect
a thalassemia syndromes
Impaired E chain production Due to deletion of one or more of the 4 a globin genes on chromosome 16
One gene missing p Silent carrier () (a)
Asymptomatic
Two gene missing ➡️a thalassemia trait
- Familial microcytic anemia ; commonly mistaken as iron deficiency
- Normal iron indices
- Normal Electrophoresis for age.
- Diagnosed by DNA analysis.
Three genes missing ➡️ Hemoglobin H disease
- Mild to moderate microcytic hemolytic anemia at birth
- Evidence of chronic hemolysis
- Electrophoresis shows: Hb H (4b chains).
Four genes missing → Fetal hydropes
- Severe intra uterine anemia and anemic heart failure
- Resulting in death in-utero or short after birth
- Electrophoresis shows: Dominant hemoglobin Bart (4 K globin chains )
with complete absence of normal fetal and adult hemoglobin
B-thalassemia syndromes
Impaired B chains production Due to mutation of one or more of the 2 F globin genes on chromosome 11
One gene mutation p F thalassemia trait ( Heterozygous F-thalassemia) B- minor
•BoB or B+B
Microcytic anemia with no evidence of overt hemolysis
• Differentiated from iron deficiency anemia by S Normal iron indices and Mentzer index <13 S Characteristic hemoglobin electrophoresis:
¿ Hb A 2 up to 3-7% in over 90% of cases.(diagnostic)
Normal (1-3%)
¿ HbF up to 1-3% in only 50% of cases.
Thalassemia intermedia
- Due to a combination of homozygous mild A and B thalassemia
- Moderate anemia (Hb 7–10 g/dL) doesn’t require regular transfusions
adult HB
- Two alpha
* Two beta
. Hb a2
• Two alpha
. Two delta
fetal
• Two alpha
Two gama
•
B Thalassemia Major
Pathophysiology
Impaired Bchain production
Impaired B chain production➡️⬇️ Production of Hb
Impaired B chain production➡️ Deposition of excess unmatched E chain inside the RBCs → hemolysis➡️anemia
Impaired B chain production➡️ Compensatory production of other Hb containing non Beta chains especially Hb F➡️⬆️ oHbF (⬆️ O 2 affinity)
-anemia +⬆️O2 affinity ➡️➡️ Tissue hypoxia ➡️➡️ Compensatory increased RBCs production ➡️➡️ Medullary hematopoiesis ➡️➡️ Bone marrow expansion (Skeletal changes) +++++ Extra medullary hematopoiesis ➡️➡️ Splenomegaly (s hepatomegaly
Iron overload due to
- Chronic hemolysis.
- Enhanced iron absorption.
- Repeated blood transfusion.
thalassemic facies
maxilla hyperplasia, flat nasal bridge, frontal bossing
Clinical picture
-General features of chronic hemolytic anemia (see before)
- Manifestations start insidiously after the 6 th month of age when switch from y to B chain production usually normally occur.
- Classic features: Progressive anemia, jaundice ,thalassemic facies,and organomegaly
Hemosiderosis p Iron deposition in:
Hemosiderosis p Iron deposition in: features
1-Skin • Bronzed skin
2-Pituitary → Short stature ,Hypogonadism
3- Heart • Restrictive cardiomyopathy Dysrhythmias • Heart failure 4-Liver • Liver cirrhosis • Liver cell failure Hepatitis 5- Pancreas 1. Diabetes mellitus
6-Thyroid and parathyriod → Hypothyroidism ,Hypoparathyriodism
7- Gonads → Hypogonadism • Delayed puberty
Complications and causes of death
- Heart failure
- Liver cell failure
- Diabetic keto acidosis
- Hypersplenism :
Sx\Pallor, purpura, pyrexia, and organomegaly S CBC: pancytopenia S Bone marrow\marrow hyperplasia , no malignant cells - Frequent blood transfusions carry risk of blood bone infections e.g. HBV, HCV, AIDS, and CMV
Investigations
a. For anemia → Low Hb% and Ht. value.
b. For chronic hemolysis
- Unconjugated hyperbilirubinemia
- Reticulocytosis (commonly <8%)
- Skull X-ray in children >3 years
“😱Hair on end” appearance
c. For the cause
1- Blood film → hypochromic, microcytic anemia with target cells.
2- Alkaline denaturation (Apt) test p Hb F resist denaturation by alkali
3- Hemoglobin electrophoresis:
• Markedly raised Hb F (80-90%)
• Slightly raised Hb A2
• Absent or near absent Hb A
4- Prenatal diagnosis is possible by chorionic villous sampling (CVS)
d. For diagnosis of iron overload
- Serum iron and ferritin
- Cardiac / hepatic MRI*
- Liver biopsy*
- Liver iron by Superconducting Quantum Interference Device (SQUID)
Chronic transfusion therapy
🌺 Indications for initiation of regular red cell transfusions include:
• Hemoglobin level 7 g/dl (on at least 2 measurements)
• Poor growth
• Facial bone changes
🌺 Aim: To keep pre transfusion Hb > 9.5- 10.5 gm/dl
🌺 Dose: 10-15 ml/kg packed RBCs monthly.
🌺 Benefits
• Allow normal growth and activity
• Decreases bone marrow activity ➡️⬇️ skeletal changes.
• Decreases extra medullary hematopoiesis ➡️⬇️ organomegaly.
Iron chelation therapy indications
🌼 Often deferred until age 3 to 4 years.
🌼 Indications:
• Cumulative transfusion load of 120 ml/kg or greater
• Serum ferritin level persistently >1,000 ng/ml
• Liver iron concentration .5–7 mg/g dry weight
. Drugs used chelation
A. Desferroxamine (Desferal)
- Dose: 25-50 mg/kg/day
- Route: IV or by continuous SC pump for 10 hours, 5-6 nights per week.
- Side effect: anaphylaxis, deafness, cataract, retinal damage , yerssinia sepsis and skeletal changes
- Ascorbic acid 200 mg daily enhance the chelating effect of Desferal
B. Recent Oral drugs
- Deferiprone (Ferriprox)
- Dose : 75-100 mg/kg
- Value: Effective in Reducing cardiac iron overload.
- Side effects: Gastric upset ,neutropenia and agranylocytosis
- Defrasirox (Exjade)
- As effective as desferal but oral with longer half life
- Once daily, 20-40 mg /kg
- Monitoring of liver enzymes and serum creatinine is essential
Supportive treatment
Low iron diet
Folic acid 1mg/day
Endorcine support as necessary. Hepatitis A and B vaccine
_ vit c+D
Splenectomy
y Indications
A. Hypersplenism suggested by:
- Increasing need for transfusion by u 50% than usual for > 6 months.
- Annual PRBCs > 250 ml/kg/year in face of uncontrolled iron overload
- Severe leucopenia and / or thrombocytopenia (Pancytopenia)
B. Huge spleen with pain or pressure symptoms.
y When: Preferably after the 5 th – 6 th year y Risk: Overwhelming sepsis (especially if done < 5 years) y Precautions: See before
