thalassemia

1. Presenter: Hazman Rafiq bin Hamidon
Siti Atiqah Binti Khaled
Mentor: Dr. Tracy

2.  Thalassemia is a group of hemoglobin disorder in which production of hemoglobin is
partly suppressed as a result of defective synthesis of one or more globin chain.

4. Normal Haemoglobin
 Embryonic Hb: 3rd to 10th week of pregnancy
-
 i.e: Hb Portland-2 (ζ2β2) < Hb Portland-1
(ζ2γ2) ≅ Hb Gower-1 (ζ2ɛ2) < Hbb Gower-2
(α2ɛ2) < HbF1 < HbF (α2γ2) < HbA2 (α2δ2)
 Fetal Hb : HbF (α2γ2)
 Adult Hb : 98% HbA (α2β2), 2% HbA2 (α2δ2)

7. Two basic groups of Thalassemia
 Alpha Thalassemia :
 Alpha genes are deleted – either loss of one gene (α-/α) or both genes (α-/α-) from
each chromosome 16 may occur, in association with the production of some or no
alpha globin chains
 Beta Thalassemia :
 Defective production – results from disabling point mutations causing no (βo) or
reduced (β-) beta chain production.

8.  Deficient/ absent alpha subunit
 Excess beta subunits
 Each cells has 4 copies of alpha globin
gene
 Each gene responsible for production of ¼
alpha globin

10.  HbH
 Hb constant spring (non-deletional HbH)
 Deletional HbH
 Non- Deletional HbH more severe than deletional HbH (Hb 2g/dL lesser)

11.  Each cell contains 2 genes of beta dlobin
 Suppression of gene more likely than deletion
 βo refers to complete absence of production of beta globin
 β+ refers to reduction of beta globin

12. Classification Genotype Clinical severity
β thal minor/trait β/β+ , β/βo Silent
β thal intermedia β+/β+, β+/βo Moderate
β thal major Βo/βo, β+/β+ Severe

13.  Thalassemia minor – characterized by mild anemia
 β thalassemia major appear in the first 2 years of life :
 Fatigue and weakness
 Pale skin or jaundice
 Protruding abdomen with hepatosplenomegaly

16. Siti Atiqah Binti Khaled

17.  Suppress extramedulary hemopoiesis while minimising complications
(hepatosplenomegaly, iron overload)
 Maintaining normal wellbeing (normal growth, corrects anemia)

18.  Blood transfusion
 Iron chelation therapy
 Splenectomy
 Bone Marrow transplant
 Follow ups and Monitoring - complications
 Nutritions and Supplements

19.  Thalassemia Major
 once diagnosis confirmed or if Hb less than 7 g/dl on 2 occasion more
than 2 weeks apart
 Thalassemia Intermedia
 Hb less than 8 g/dl if there is evidence of growth retardation attributed
to anemia after exclusion of other causes (dietary, constituitional)
 Bone Changes (maxillary/mandibular prominence), enlarging liver, spleenomegaly
 Alpha Thallasemia - transfuse if Hb persistently <7g/dl or symptomatic chronic anemia

20.  Before 1st Transfusion
 RBC genotyping (ABO, Rh [C,c,D,E,e] and Kell)
 Viral markers (HBsAg, Anti-HCV, Anti-HIV)
 TFT, RBS, LFT, RP
 Before Each Transfusion
 Pre transfusion Hb
 After Each Transfusion
 post transfusion Hb

21.  usually 4 weekly
 rate decline 1g/dl/week
 Interval varies depending on patient (range 3-6 weekly)

22.  after presentation, patient should be monitored closely to ascertain ability to maintain Hb above 7g/dl over 2 weeks
period.
 Transfusion interval - depend on pre and post transfusion Hb can be 2-4 weeks apart
 Regular transfusion
 confirmed thal major
 unable to maintain Hb >7g/dl
 poor growth
 extramedullary masses, bone deformity
 once decided for regular transfusion, regime should be similar to the one adopted for thal major
 Target Hb
 pre transfusion Hb: 9-10 g/dl
 post transfusion Hb: 13.5-15.5 g/dl
 Keep mean Hb 12-12.5
 the above target allow for normal physical activity and growth, abolishes chronic hypoxemia and reduces
compensatory marrow hyperplasia which causes irreversible facial bone changes and paraspinal masses.

23.  15 – 20 mls/kg packed red cells (leucodepleted packed cell < 2 weeks old)
 Volume required
(14-current Hb) X weight (kg) X 4
 In the presence of cardiac failure or Hb < 5g/dl
- Low volume PRBC (~ 5-10 ml/kg), slow infusion rate over > 4 hours with IV
Frusemide 1 mg/kg (20 mg maximum dose) in between transfusion

26.  monthly packed RBC will result in iron intake of 0.3-0.5 mg/kg/day
 >10-20 transfusion = most pt have serum ferritin >1000 μg/l
 serum ferritin should be monitored every 3-6 months

27.  received more than 10 units of blood
 serum ferritin >1000 mcg/L (in 2 occasions, at least 2 weeks apart)
 >3 years old

28.  Deferoxamine / DFO
 Deferiprone / DFP
 Deferasirox / DFX

29.  First line
 Brand name: Desferal
 Dosage : 20-40 mg/kg/day (children) up to 50-60 mg/kg/day (adult)
 Route: slow subcutaneous infusion using portable pump over 8-10 hours daily, 5-7
nights a week / IV
 Side Effects : oculotoxicity, local skin reaction, reduced vision, visual field defect, night
blindness, skeletal lesion i.e vetebral growth retardation.

31.  Alternative to DFO
 Brand name: Exjade
 Dosage: 20-30 mg/kg/day once daily
dosing
 Route: Oral
 Expensive
 Side effects: increase in serum
creatinine (reversible, dose related and
non progressive increase), GI sx

32.  is an alternative if iron chelation is ineffective/
inadequate despite optimal Desferal use or if Desferal
use is contraindicated
 Brand name : Ferriprox / Kelfer
 Dosage : 75-100mg/kg/day in 3 divided doses (TDS)
 Can be used in combination with desferal, using a lower
dose of 40-50 mg/kg/day
 Route: Oral
 Side Effects: Agranulocytosis, arthritis,

33.  Serum ferritin < 2500 mcg/kg/l
 T2* heart >20ms
 LIC (liver iron concentration) <7mg Fe/g DW

34.  Indications
 hypersplenism
 increasing transfusion requirement (1.5X than usual - 200-220ml/kg/year)
 massive splenomegaly causing discomfort and risk of infarct or rupture from
trauma
 complications
 sepsis
 gram positive ( strep pneumoniae, Haemophilus, Neiserria ), gram negative (E.coli,
Klebsiella, P. aeroginosa)
 Immunoprophylaxis - pneumococcal and HIB vaccination 4-6 weeks prior splenectomy,
meningococcal vaccination
 Chemoprophylaxis - oral penicillin for life (esp 1st 2 years after splenectomy) or IM
benzathine penicllin 3-4 weekly (alternative)
 thrombocytosis
 Tx : low dose of aspirin 75mg daily if thrombocytosis >800, 000

35.  Potential curative option when there is an HLA-compatible
sibling marrow donor
 Results from donor or cord blood transplant are inferior to
matched sibling bone marrow transplant with higher
morbidity, mortality and rejection rate
 Classification of patient into Pesaro risk groups based on
the presence of 3 risk factors: hepatosplenomegaly > 2cm,
irregular iron chelation and presence of liver fibrosis
 Best result if performed at the earliest age possible in
Class 1 pt

36.  During Each Transfusion
Height & weight
Liver and spleen size
Compliance to iron chelation theraphy and other medications
and its side effects
Observe for blood transfusion reaction

37. 6 MONTHLY
Height and weight
charting
- growth failure (less than 3rd centile for age and gender, significantly short for
the family, slow growth rate over 6 months-1year)
-Need to exclude desferoxamine toxicity-vetebral growth retardation , check
adequacy of blood transfusion, look for nutritional status
- Ix- TFT,sex hormone, zinc,calcium, ALP, OGTT, IGF-1, IGFBP-3, bone age
assessment
refer endocrinologist for assessment if suspect endocrine/ growth hormone
deficiency
Sexual development
(from age 10 in girls
and 12 in boys)
- to detect delayed puberty, hypogonadism and arrested puberty
- Tanner stage of breast and genitalia
- Ix: TFT, LH, FSH, estradiol, testosterone and bone age, pelvic usg to assess
ovarian and uterine size, if result abnormal need to perform GnRH stimulation
test
Infection screening - Ix: Hep B, Hep C, HIV, VDRL
Evaluate iron status - Ix: Ferritin
Bone - skeletal abnormality and osteoperosis
Others FBC, RP, LFT, TFT
YEARLY
ENT and Opthal
assessment
if pt on desferal

40.  Vitamin E supplementation
 helps to reduce platelet hyperactivity and reduce oxidative stress
 protect erythrocyte from early lysis due to oxidative stress
 Vitamin C
 help to mobilize iron from intracellular store and effectively increase the
efficacy of chelation of desferoxamine
 Folic Acid
 Take less iron rich food
 examples: liver, chicken, beef, egg yolk, oyster, clams, tuna, soy bean, tofu,
 Zinc supplement
 Dairy product