This is slide regarding Thalassemia, prepared for Paediatric Posting. Introduction, clinical features and management of the condition (Paediatric Protocol of Malaysia).

1. β-Thalassemia
Introduction
• Common among population in Indian subcontinent,
Middle East and Mediterranean.
• Prevalence is 16% in people from Cyprus and 3-8% in
populations from Bangladesh, China, India, Malaysia
and Pakistan
• Severe reduction in production of β-globin,
therefore reduce in HbA production.
• Disease severity depends on amount of residual HbA
and HbF production.

2. β-Thalassemia
Types of β-Thalassemia
• Two types β-Thalassemia Major and β-Thalassemia
Intermedia.
β-Thalassemia
Major
• Severe form
• Abnormal β-globin gene, HbA cannot be
produced.
β-Thalassemia
Intermedia
• Milder form
• Variable severity
• β-globin gene mutation, small HbA
production, high HbF production.

3. β-Thalassemia
Β-Thalassemia Traits
• Heterozygous is always asymptomatic
• Anemia is either mild or absent
• Hypochromic, microcytic anemia, with high
ferritin which differentiate from iron deficiency
anemia.

4. β-Thalassemia
Clinical Features
• Severe Anemia
• Jaundice
• Failure to thrive, growth failure
• Extra-medullary hemopoiesis (in absence of regular
blood transfusion)
- hepatosplenomegaly
- bone marrow expansion
- classical facies maxillary overgrowth, skull bossing

5. β-Thalassemia
Clinical Features

6. β-Thalassemia
Clinical Features

7. β-Thalassemia
Prenatal Diagnosis
• Heterozygous for β-Thalassemia is 1 in 4 is in risk.
• DNA analysis for chorionic villus samples
• Genetic Counseling
• To make decision whether to continue or terminate
the pregnancy

8. β-Thalassemia
Management
• Lifelong monthly transfusion of red blood cells
• Maintain Hemoglobin concentration above
10 g/dL.
• Prevent growth failure, by preventing bone
deformation.
• Iron Chelation with SC Desferrioxamine
• Iron Chelation with Oral Deferasirox
• Bone Marrow Transplantation (for Beta Thalassemia
Major which with HLA identical siblings)

9. β-Thalassemia
Complication of Long Term Blood Transfusion in
Children
• Iron deposition
- Total stores 3-4 grams.
- Each units of blood
200-250 mg iron
- Risk increase once
10 transfusions
received.
Heart Cardiomyopathy
Liver Cirrhosis
Pancreas Diabetes
Skin Hyperpigmentation
Pituitary
gland
Delay growth, sexual
maturation

10. β-Thalassemia
Complication of Long Term Blood Transfusion in Children
• Antibody formation (10%)
- Allo antibodies to transfused red cells make
finding compatible difficult.
• Infection (< 10%)
- Hepatitis A,B & C, HIV, Malaria, Prions
• Venous access
- Difficult in pediatric age group
- May need Portacath, which increase risk of infection.

11. β-Thalassemia
Prognosis
• If compliance, 90% live beyond age of 40 years
old.
• Poor compliance is high.
• Leads to high mortality in early adulthood due to
iron overload complications.

12. α-Thalassemia
Introduction
• Healthy individual have four α-globin genes.
• The manifestation depends on number of function α-
globin genes.

13. α-Thalassemia
Types
α-Thalassemia
Major
(Hb Barts Hyrops
Fetalis)
• Most severe form of disease
• Deletion of all 4 α-globin genes, thus no
HbA production.
• Presented in mid-trimester with fetal
hydrops (edema, ascites) from fatal
anemia.
HbH Disease • Deletion of 3 α-globin genes.
• Mild to moderate anemia

14. α-Thalassemia
Types
α-Thalassemia
traits
• Deletion of one or two α-globin genes.
• Asymptomatic or mild anemia
• Microcytic hypochromic anemia which to
differentiate with iron deficiency anemia.

15. α-Thalassemia
Management
α-Thalassemia
Major
• Diagnosis
- Hb Electrophoresis
- Hb High Performance Liquid
Chromatography (HPLC)
• Intrauterine transfusion monthly
• Continue lifelong monthly transfusion
after birth
HbH Disease • Occasional blood transfusion dependent

16. Sickle Cell Disease
Introduction
• Commonest genetic disorder in children in many
European countries.
• Patient with parents whose are black, from tropical
Africa or Caribbean and Middle East.
• Collective name given to haemoglobinopathies in
which HbS is inherited.
• HbS forms as a result of point mutation in codon 6 of
the β-globin gene, lead to change in amino acid
encoded from glutamine to valine.

17. Sickle Cell Disease
Types
Sickle Cell Anemia
(HbSS)
• Sickle mutation in both beta globin genes
• Severe form of disease.
• All hemoglobin is HbS
• Variable amount HbF (1 – 15%) , no HbA
HbSC Disease
(HbSC)
• Inherit HbS from one parent
• Inherit HbC from another parent
• HbC as a result of different point mutation
in beta globin)
• No HbA

18. Sickle Cell Disease
Types
Sickle β-
Thalassaemia
• Inherit HbS from one parent
• Inherit β-Thalassaemia trait from another.
• No HbA production
Sickle Trait • Inherit HbS from one parent
• Normal β-globin from another parent
• 40% HbS, 60% normal Hb
• Asymptomatic
• Carriers of HbS

19. Sickle Cell Disease
Pathogenesis
HbS
polymerizes
within RBC
Forming rigid
tubular spiral
bodies
Deformed RBC
into sickle
shape
Trapped in
micro-
circulation
Ischemia of
Organ or Bone
Exacerbated by dehydration, cold, low
oxygen tension
Shorter lifespan

20. Sickle Cell Disease
Clinical Manifestations
Anemia
Jaundice
• Moderate anemia
• Hemoglobin 6 – 10 g/dL
Infection • Chronic sickling lead to Hyposplenism
• Micro-infarction in spleen in infancy
• Risk of overwhelming sepsis
• Encapsulated organisms infection like
Pneumococci, H. Influenza
• Osteomyelitis by Salmonella and others.

21. Sickle Cell Disease
Clinical Manifestations
Painful crises • Vaso-occlusive crises causing pain
• Hand-Foot Syndrome which dactylitis with
swelling and pain of finger and/or feet
from vaso-occlusive.
• Bones of limbs and spines most common.
• Acute Chest Syndrome with Hypoxia
• Avascular necrosis of femoral heads.
Acute Anemia • Sudden drop of hemoglobin from
(a) Hemolytic crises
(b) Aplastic crises
(c) Sequestration crises

22. Sickle Cell Disease
Clinical Manifestations
Priapism • Need immediate transfusion
• Prevent fibrosis of corpora cavernosa
which may lead to erectile dysfunction.
Splenomegaly • Common in young children, less frequent
in older children.

23. Sickle Cell Disease
Long Term Problems
(a) Short stature and delayed puberty
(b) Strokes
- 1 in 10 have strokes
- More are having subtle neurological damage with
poor concentration and school performances.
(c) Adenotonsillar hypertrophy and sleep apnea
(d) Cardiac enlargement
(e) Heart failure

24. Sickle Cell Disease
Long Term Problems
(f) Pigment gallstones
(g) Leg ulcers (uncommon in children)
(h) Psychosocial problems

25. Sickle Cell Disease
Prenatal Diagnosis and Screening
(a) Prenatal diagnosis on chorionic villus sampling at the
end of first trimester
(b) Neonatal screening on dried blood spots (Guthrie Test)
- so Penicillin can be started earlier
- but not all place has this routine test.

26. Sickle Cell Disease
Management
(a) Prophylaxis against Infection
- full immunization
- daily oral Penicillin for all subgroup of Pneumococcal
(b) Treatment for Chronic Hemolytic Anemia
- once daily folic acid
(c) Minimized Vaso-Occlusive Crises
- prevent exposure to cold, dehydration, excessive
exercise, undue stress by practical measures.

27. Sickle Cell Disease
Management
(d) Treatment for Acute Crises
- Good hydration either oral or intravenously
- Oxygen given if its saturation is low
- Antibiotics for infection
- Analgesia (sometime opiates) for pain
- Exchange transfusion for acute chest syndrome, stroke,
and priapism.

28. Sickle Cell Disease
Management
(e) Treatment of Chronic Problem
- for recurrent admission due to painful vaso-occlusive
crises or acute chest syndrome.
- Hydroxyurea
- Increase the HbF production, prevent further crises.
- Watch for side effects : white cells suppression.
- Bone Marrow Transplantation
- those with stroke, not respond with Hydroxyurea
- with HLA-identical siblings
- 90% cure rate, 5% fatal due to transplant complications.

29. Sickle Cell Disease
Prognosis
• Cause of premature death due to one or more of severe
complications.
• 50% with most severe form of the disease die before 40
years old.
• Mortality rate during childhood is around 3% due to
bacterial infection.