Hemolytic anemia can be caused by thalassemias, the most common genetic blood disorders worldwide characterized by reduced or absent globin chain production leading to anemia. The main types are beta thalassemia major requiring lifelong blood transfusions, and alpha thalassemia including trait, HbH disease, and rare hydrops fetalis. Treatment focuses on blood transfusions, iron chelation therapy, and in severe cases bone marrow transplantation.

1. Hemolytic anemia
By: TING LEE YING

2. 1. Thalassaemias
a)B-Thalassaemia-> 1. Major
2. Intermedia
3. Minima and minor
4. Trait
b) A-Thalassaemia->1. Major
2. HbH
3. TraiT
4. Silent

3. Introduction
 1. Thalassemia comes from the Greek word
"thalassemia" which means "anemia by-the-sea."
 2. The most common genetic disorder worldwide
 3.Children with thalassemia:
 a) shorter red cell life
 b) HbF until older age
 c) red cell prone to oxidative stress

4. Epidemiology
 Worldwide- 3% for B-Thalassemia
 SEA- 5-10% for A-Thalassemia

5. Anaemia
 Neonate: Hb< 14g/dl
 1-12 months: Hb< 10g/dl
 1-12 years : Hb <11g/dl

9. Thalassemia Major ( Cooley’s
anemia)
1.Hb- Bo/Bo
2. Chromosome 11
3. Epidemiology:
- Indian subcontinent, Mediterranean, Middle East
 The estimated carrier rate for beta-
thalassemia in
Malaysia is 3.5-4%. There were 4768 transfusion
dependent thalassemia major patients as of
May 2010 (Data from National Thalassemia
Registry).

10. B- Thalassaemia Major
 1. Autosomal Recessive

11. Pathophysiology
Mutation of B- globin chain
deficiency of B-globin chain
Increase in gamma and delta chain
Increase in HbF and HbA2, excess A4
Precipitation of globin chain
Ineffective erythropoiesis(cell death)

12. Clinical manifestations:
1. Presenting Age: 4- 6 months of life
2. Presented with : a) Weakness
b) Cardiac decompensation
3.Hb level : </=4g/dl
4. General symptoms(b4 transfusion)
1. Fatigue
2. Poor appetite
3. Failure to thrive

13. Classical presentations
1. Thalassemic facies
2. Pathologic fractures
3. Marked hepatosplenomegaly
4. Cachexia
5.Greenish brown complexion

14. I’m innocent T.T
Chipmunk face >.<

16. Complications of hemosiderosis
 1. Hepatic- fibrosis and cirrhosis
 2. Pancreas- DM (beta cells)
 3. Pituitary, testis and ovaries- growth
retardation, hypogonadotrophic hypogonadism
 4. Parathyroid- hypocalcemia, osteoporosis
 5. Heart- arrhythmias, myocarditis, cardiac failure.

17. Lab Findings and investigations
 1. Hb Electrophoresis/ HPLC- a) Increased HbF
b)Decreased or
absent HbA
c) HbA2 variable
 2. FBC , peripheral blood film– anemia, high
reticulocytes, numerous nucleated
cell, microcytosis
 3. Unconjugated bilirubin- increased
 4. Serum ferritin and transferrin – elevated ( even
b4 transfusion)
 5. Red cell phenotyping (ideal)–transfusion
 6.X- ray- bone marrow hyperplasia

18.  7. DNA analysis (optional)- confirm, prenatal
diagnosis, detection of carrier
 8.Liver function test
 9.Infection screen- HIV, Hepatitis B and C, VDRL
(before first transfusion)
 10. HLA typing ( for all patient with unaffected
siblings)

19. Hair on end sign

21. Treatment
?When- completed blood investigation to confirm
diagnosis:
1. Blood transfusion ( life-long)
Indication:
a)Hb<7g/dl ( 2times, 2 weeks apart with no other factor
eg infection)
b) Hb>7g/dl if impaired growth, bones
changes, hepatosplenomegaly.
Goal : Hb – 9.5 g/dl( Post)
Maintain : Hb 12-12.5g/dl and <15.5g/dl (mean post)
Interval : 2-6 weekly interval( mean 4)
Volume : 15-20mls/kg (max) over 4 hours.

22. 2. Assess Iron Overload via :
a) Liver biopsy
b) Ferritometry
c) Serum Ferritin
3. Iron Chelation ( Prevent
hemosiderosis, haemochromatosis)
- Deferoxamine( Desferal) / Deferiprone

23.  4. Splenectomy
Indications: a)T. Intermediate- falling steady state
Hb
b) Transfused- Rising transfusion
needs
Blood consumption volume of PRBC >1.5x normal
or >200-220ml/kg/year in those >5 years age to
maintain norm level
* Prophylaxis
5. Bone marrow transplant(cure!)
HLA- matched siblings

24. Iron chelation therapy
?When- > 2years old and serum ferritin reaches
1000ng/ml (10-20 tranfusions)
A) Deferoxamine(Desferal) given:
 -> SC over 10-12 hours via continuous infusion
pump
 -> 5-7 days per week (severity dependent)
Aim: Serum ferritin <1000ng/ml.
 Side effects:
 1. Local skin irritation
 2. Yersinia infection (fever, abdominal
pain, diarrhea)

25. Toxicity >50mg/kg/day in low serum ferritin
 1. Ototoxicity
 2. Retinal changes
 3. Bone dysplasia
 B) Deferiprone/L1( Kelfer/Ferriprox)
 Given: oral
 Dosage : 75-100mg/kg/day in 3 doses/daily
(combination)
-Less effective and side effects
a) Neutropenia
b) Arthritis
c) Hepatic fibrosis

26.  3. Deferasirox (Exjade)-new
 Targets: >2years
 Dosage: 20-30mg/kg/day in liquid dispersible
tablet ( once!)

27. Monitor
Each time
1. Clinical assessment : Height, Weight, Liver and
Spleen size
2. Pre transfusion Hb, platelet , Post
transfusion(half hour)
3. Volume transfused
Every 3-6 months
1 Growth &Development
2.Serum Ferritin
3.LFT

28.  Every year (/more)
1. Growth &Development
2. Endocrine assessment( RBS,T4/TSH,Ca(PTH
and vit D,Po4)
3. Pubertal and Sexual (>10years)
4. FSH,LH,Estrogen and testosterone
5. Infection screen (Hep B and C , HIV, VDRL) (6
monthly)
6. Cardiac assessment- ECG, Echo
7. Liver Iron store

29. Thalassemia intermedia
1. Combination of B- thalassaemia mutation (
Bo/B+, Bo/B variant, E/Bo)
2. Late onset (> 2 years of age)
2. HB level – >7g/dl
Controversy whether to transfuse

30. Thalassaemia minima or minor
 HB- heterozygotes (Bo/B, B+/B+)
 ( more severe than trait but less severe than
intermediate
 Investigate phenotype and monitor iron
accumulation

31. B- Thalassemia trait
 Misdiagnosed as iron deficiency
 Test:
 1.Presistent red cell distribution width
 2. Hb electrophoresis- Increased HBF and HBA2.

32. Alpha- Thalassemia
 Epidemiology:
Malaria area especially in SEA.
Intro
1. 4 A-globin chain and therefore 4 deletional A
Thalssaemia phenotype.
2. Chromosome 16

33. A- Thalassaemia Deletion of A-globin Clinical manifestations
gene
Silent Trait 1 Diagnosed after birth
with 2 gene deletion of
Hb H ( B4)- Africa-
American
A- Thalassaemia trait 2 Microcytic anemia, Hb
elctrophoresis norm, (
eliminate Fe def and
conf DNa testing
Hb H disease 3 Marked microcytosis and
anemia, HB
electrophoresis. ( may
be assymtomatic)
A- Thalassaemia Major 4( Transfusion Hydrop fetalis ( epsilon
(Hb Barts Syndrome) dependent) globin gene must be
present to survive, with
mainly Barts’s , Gower 1,
2, Portland)

34. Hemoglobin Bart's

35. Hb B -mild to moderate
anaemia, hepatosplenomegaly, and jaundice. Some
affected individuals also have bone
changes(overgrowth of the upper jaw and an
unusually prominent forehead).
Alpha Thalassaemia Major
 Additional signs and symptoms:
severe anaemia, hepatosplenomegaly, heart
defects, and abnormalities of the urinary system or
genitalia.
 serious complications for women during pregnancy:
preeclampsia) premature delivery, and abnormal
bleeding.

36. Treatment
 1. Folate supplementation
 2. Splenectomy
 3. Transfusion- Intermittent for severe anemia (Hb
H)
 Chronic transfusion (survivors of
Hydrop fetalis)
 4. Bone marrow transplant

37. Reference
 Nelson Textbook for Paediatrics, 17th Edition
 Illustrated Paediatrics, 3rd edition, Lissauer
Clayden.
 Paediatric Protocols Malaysia, 2nd Edition
 CPG Malaysia
 www.Emedicine.com