1. β thalassemia major

2. Seminar on
Diagnosis and treatment update of
thalassemia

3. Thalassemias:
• Inherited disorder charactarised by complete
absence or partial reduction of synthesis of
globin chain.
•B-thallassaemia- B chain production is either completely absent or reduced to a variable degree.
• a-thallassaemia- a chain production is either
completely absent or partially reduced.

4. Type Genotype Clinical status
β thalasamiya
Major β⁰/β⁰
β⁰/β
severe ,patient require regular
BT
Intermedia Moderate to severe , patient
may not required BT
Minor Asymptomatic with mild or
absent anaemia
Classification of b thalassemia

5. Type Genotype Clinical status
Hydrops fetalis Little in utero
HbH disease severe
α thallasemia trait Asymptomatic
Silent carrier Asymptomatic
Classification of b thalassemia

6. Hb E β thalassemia
• Combination of thallassaemia and Hb E. Most common type of thallassaemia in
Bangladesh.
• Claassified into 3 category
#Mild Hb EB thallassaernia #Moderately severe Hb E B thallassaemia
(like thallassaemia intermedia).
#Severe Hb EB thallassaemia(like thallassaemia major)

11. How to diagnose
• Clinical presentation:
#History:
*Age of presentation:
Thallassaemia major: <2 year.Commonty 2-6 month.
Thallassaemia intermedia: >2 year. *Progressive pallor *Intermittent mild
jaundice.
*Prone to develop infection.
*Failure to thrive, profound weakness, poor appettite.

12. Examination
● Pallor
● Mild Jaundice.
● Hepatosplenomegaly.
● Cachexia.
● Thallassaemic facies:
- Frontal bossing,
- Depressed nasal bridges,
- Maxillary prominences,
- Malocdusion of teeth.

15. Investigations
● Hb% :
β thalassemia major : markly reduced (3-5 gm/dl)
β thalassemia intermedia : (8-9 gm/dl)
β thalassemia trait : normal or mild reduced
● WBC (TC & DC) : normal
● PLATELET COUNT : normal , may be reduced if hypersplenism

17. ● Marked anisopoikilocytosis.
● Microcytosis.
● Hypochromia.
● Target cell.
● Schistocyte.
● Neucleated RBC.
● Basophillic stippling.
RBC INDICES:
● RBC COUNT: Reduced.
● MCV: Reduced.
● MCH: Reduced.

18. PBF :
● Marked anisopoikilocytosis.
● Microcytosis.
● Hypochromia.
● Target cell.
● Schistocyte.
● Neucleated RBC.
● Basophillic stippling.
RBC INDICES:
● RBC COUNT: Reduced.
● MCV: Reduced.
● MCH: Reduced.
●

19. ● MCHC:Reduced
● Reticulocyte count:Elevated, (5-10%) but inappropriately low compared to degree of
anaemia due to ineffective erythropoiesis.
● Hb electrophoresis/HPLC:Confirmatory test.
BOThallassaemia major:
HbA:absent
HbF:96-98.5%
HbA,:1.5-4%.
Thallassaemia major:
HbA:10-90%,
HbF:10-90%
HbA2:1.5-4%

20. B thallassaemia intermedia:
● HbA:20-40%
● HbF:60-80%
B thallassaemia trait:
● HbA:mild reduction(90-95%). HbF:normal or slight increase(1-5%)
● HbA2:increased(>3.5%)
HDE B thallassaemia :
● HbA:absent or reduced. HbF:Increased.
● HbE:40-60%.

21. Radiological findings:
● *X-ray skull:Hair on end appearance.
● *X-ray hand:Mosaic pattern, laey trabeulen #NESTROFT(Naked eye single
tube red cell
● Osmotic fragility test): *Decreased osmotic fragility
● *Effective test for screening of B thallassaemia trait.
● #Other investigations :
● *S.ferritin,/ron, *RFT G]6vd ve *S. bilirubin.
● *LFT

22. Differentiation of thalassemia major and
intermedia
Important for designing appropriate treatment *Accurate prediction of mild
phenotype helps to
avoid needless transfusion and transfusion related complcaton.
Timely diagnosis of thallassaemia major will allow earty start of transfusion
programme
thereby delaying/preventing hypersplenism and skeletal deformity.

24. Screening of thalassemia
and hemoglobinopathies

26. Management of thalassemia
Thalassemia major
● Transfusion therapy
● Iron chelation therapy
● Treatment of complications
● Splenectomy
● BMT (bone marrow transplantation)

27. Neocyte transfusion / cord blood transplantation
● Fetal Hb inducer
● Nutrition with suppliments
● Gene replacement therapy
● Prevention of disease by antenatal diagnosis and genetic counselling and
general awareness

28. Transfusion therapy
The decision to initiate transfusion therapy should be based on a definite
diagnosis of severe thalassaemia. Regular BT to maintain pre-transfusion Hb level
above 9-10.5 gm/dl but post-transfusion not exceed greater than 15 gm/dl and in
children as per normal Hb values corresponding to age.

29. How to transfuse ?
● Usual recommended dose:
● Packed RBC= 10-15 ml/kg over 3-4 hours every 2-5 weeks (3rd week) 3-4
weekly.
● Cardiac failure or Hb <5 gm/dl = 2-5 ml/kg/hr at slower rate
● Amount PCV required (ml) = wt(kg) x 4 x desired raise of Hb (gm/dl)

30. Iron Chelation Therapy
1. Desferrioxamione (DFO)
2. Deferiprone (L1)
3. Combination of Desferrioxamione and deferiprone
4. Deferasirox
When to start chelation?
● After 10-20 transfusion or
● S.ferritin >1000 micro gm/l or
● LIC >3.2 mg/ g dry wt. or
● Age >/= 3 years

33. Patient getting
DFO through
infusion pump

34. DFO in pregnancy and lactation
● Pregnancy:
Avoid in 1st trimester but extremly high iron load or serious heart problem treat
with low dose DFO (20-30 mg/kg/day) in late stage pregnancy
● Lactation:
DFO can be resumed while breast feeding.
Deferasirox is not recommended in pregnancy and lactation

35. When restart L1 ?
● WBC >/= 3,000/mm³
● Neutrophil >/= 1,000/mm³
Evalution of effectiveness of chelation therapy
● FBC (TC,DC) : S.ferritin : 24 hrs urine exam
● LFT : Zn level : LIC : S.Creatinine
● Auditory, Opthalmic exam and Growth monitoring

36. Splenectomy :
1. An oversized spleen> 6 cm in length and resulting in discomfort
2. When amount of blood required increase 1.5 times or more than 200 - 220
ml/kg/yr of BRBC
3. age of pt > 5 years old
4. Hypersplenism
5. Increasing iron store despite good chelation therapy.
6. Possibility of spleenic rupture in massive spleenomegaly

37. Complication of spleenectomy :
● Risk of infection (streptococcus ,N.meningitidis , pnemococcus , H.inluenzae)

38. How preventing/minimizing the risk of Infection ?
● Immunoprophylaxis against HI, Pneumococcal,Meningococcal vaccine 2
weeks before surgury.
● Chemoprophylaxis =Oral penicillin or alternatives
● <2yrs=125 mg BD ; >2yrs=250 mg BD (life long or untill 18 yrs or 2 yrs after
operation)
● Education about infection ; planning to travel in different infectious disease of
the world
● Attention to raise the platelet count=(i.e.,>800000/mm³) treatment: aspirin
50-100mg/daily till normal

39. BMTcurative
Choice of recipient(pt) depends on 3 risk factors :
Choice of the recipient (pt) depend on 3 risk factor
● Enlarge liver >/= 3cm
● Liver damage = fibrosis or scarring of liver
● Poor control of iron chilation
According to the number of risk factor pts. are classified into 3 categories
● Class 1= no risk factor -93% disease free survival
● Class 2= 1 or 2 risk factor - 85% disease free survival
● Class 3= all 3 risk factor - 58%
Another independent risk factor = age > 16 yrs (poor result)

40. Complication of BMT
● Infection
● GVHD
● Graft rejection

41. ● Neocyte transfusion/ Cord blood transplantation
● Fetal Hb inducer
5 azacytidine, Cytosine arabinoboside, hydroxy urea(TI)
Erythropoietin, Butyric acid derivatives (arginine is the most effective)
Dose 200-400 mg/kg/days over 6-8 hrs IV drip slowly.
● Oral analog - Na butyrate

42. ● Treatment complications :
1. Febrile reaction = antipyretics, antihistamine, leukocyte filtration for
neutrophil elimination
2. Hemolytic transffusion reaction = Stop BT
3. Transmission transmitted disease=hepatitis B & C, HIV, syphilis, malaria, CMV
B19

43. Nutrition with supplements :
● Very I don't reach food should be avoided
Liver or drinks, Multivitamin, baby food containing added iron.
● Patient should drink black tea with meals and diet containing calcium
● Vit C -2-3 mg/kg/day PO. or, <10yr=50 mg/day PO. or, >10 yrs = 100 mg/day
PO.
● Folic acid - 10 mg/day
● Vitamin E - BD

44. ● Gene replacement therapy: final cure
● Prevention of disease by antinatal diagnosis genetic counselling and general awareness
Antenatal diagnosis:
FBS : at 16-18/20 week of IU life (estimation of global synthesis)
Fetal blood sampling
DNA analysis by PCR
CVS : at 8-9/10-12 week or later (preferable)
Amniocentasis: at 15 week onwards

45. Genetic counselling
● Correct diagnosis
● Risk eliminatiocn
● Career identifications-RBC indicies (MCV, MCH, MCHC) NESTROFT, HbA2
DNA mutation analysis.
● Marriage counseling
● Reproductive choice
● Prenatal Diagnosis

46. What are the problem associate with thalassemia and
with treatment ?
● Heart and endocrine complication (BVF arrythmia, slow growth, delayd
growth, hypogonadism, diabetes, hypothyroidism, hypoparathyroidism.
● Fibrosis of liver, cirrhosis of liver, specially HBV & HCV
● Osteoporosis
● Infection
● Psychological problem

47. Management of endocrine and bone disorder
● Measure height quarterly /year
● Sexual development =Tanner stitching 6 monthly from 10 year
● FSH & LH = 6 monthly
● Estradiol, testosterone = 6 monthly
● Glucose (blood & urine) = at any visit
● GTT = yearly
● Hypothyroidism = 6 monthly
● Hypoparathyroidism = 3 monthly
● Bone = yearly
● Bone age = X-Ray (knee, wrist) DEXA Scan, X-Ray spine.

48. Management of TI
To maintain HB level between 6-9 gm/dl,
patient suffer mild anaemia 8-10 gm/dl and
rarely requireing BT if at all.

49. When to BT therapy ?
The following condition from chronic anaemia to initiate blood transfusion
therapy.
● Delayed growth
● Pathological bone fracture
● Hyper splenism
● Cardiac complication
● Facial deformity
● Decrease normal physical activity

50. Iron chilation
Like TM
But SC not more than 2-3 days/week.

51. What are the problems of TI ?
● Bone changes - expansion of bone marrow
● Gall stone
● Leg ulcer
● Kidney complication
● Thrombophalia
● EME (chest area, near spine)
● Hot and liver complications

52. Thalassemia trait :
● No treatment is usually required but mile anaemia treated with iron and
genetic counselling should be offered.
HbE β thalassemia management :
● Mild - no treatment
● Moderately severe like - TI treatment
● Severe - like TM treatment
HbE disease - like T minor
HbE carrier - asymptomatic

53. Prognosis
● Iron load is commonest cause of death
● Date usually occur towards the end of second or
early 3rd decade
● No transffusion death within 2 to 5 years
● Inadequately transferred = poor outcome
● Lohemoglobin throughout the childhood death
within early childhood

54. Psychosocial existence
● Physical demand of the disease and lack of public awareness both
patient parents and families experience emotional difficulties in
trying to cope with thalassemia.
● Patient frustration disappointment depression fare to death
helplessness and feelings of being unloved.
● Positive emotion courage sense of challenge and endiorence.

55. ● Patient similar positive and negative emotions are experienced
● Patient and parents feels with painful reality of long term treatment
● Information from -NTA, ITF, doctors and nurse.

56. The End