Thalassemia
Dr Zubair Bhutta
Group of inherited hemoglobinopathies that
affect the synthesis of adult hemoglobin tetramer ( Hb A).
Classification: based upon affecting the synthesis of α or β hemoglobin chains
1) α-thalassemia : major, intermedia or
minor 2)β-thalassemia: major,
intermedia or minor
Β-thalassemia major
·
Is a Clinical diagnosis
·
Results in variety of sign and
symptoms i-e severe anemia, growth retardation, hepatomegaly , bone marrow
expansion and bone deformity.
·
Transfusion therapy is necessary
to sustain life.
·
Symptoms starting during early
childhood , usually at age of 6 months
·
Newborn’s cord blood should be
screened for haemoglobinopathies with hemoglobin electrophoresis.
Antenatal consideration:
·
Preconception genetic counseling
is advised for couples at risk or other relatives of a thelassemia child.
·
Once pregnant , chorionic
villous sampling (CVS) at 10-11 weeks gestation or Amniocentesis at 15 weeks
gestation to detect point mutations or deletions with PCR technology.
Genetics:
·
autosomal recessive pattern of
inheritance
Diagnosis:
·
ON HISTORY:
pallor, Poor growth , excessive fatigue, cholelitheasis, pathologic fracture,
shortness of breath.
·
ON EXAMINATION:
Pallor, jaundice, maxillary hyperplasia/frontal bossing due to massive bone
marrow expansion and dental malocclusion, splenomegaly, delayed SMR, delayed
growth .
·
D/D: iron
deficiency anemia, lead toxicity, sideroblastic anemia, other hematological
anemia or hemoglobinopathies
Investigations: CBC Hb is 10-12 g/dl with thelassemia trait and 3-8 g/dl with
Thelassemia major before transfusion Hematocrit
28-40% in thalassemia trait and may fall to << 10% in β-thalassemia
major Peripheral Blood Picture Microcytosis(MCV
<70fl) ,Hypochromia(MCH<<20pg), High %age of target cells,
Reticulocytes count is elevated RDW(Red
Cell Distribution Width) always normal range 11.5-14.5 in thalassemia trait Mentzer index Mean corpuscular volume /
RBC count( interpretation:<<13 thalassemia or >13 suggestive for iron
deficiency anemia) DNA analysis screening tool for children and adults
Hemoglobin electrophoresis:
Hemoglobin electrophoresis:
|
|
Hb A(α2β2)
|
Hb A2(α2δ2)
|
Hb F(α2ϒ2)
|
|
Normal
|
>90%
|
2.5%
|
<2%
|
|
Thalassemia minor
|
Dec.
|
10%
|
7%
|
|
Thalassemia intermedia
|
20-40%
|
Increased
|
60-80%
|
|
Thalassemia major
|
Absent or Dec.
|
>3%
|
>90%
|
Management and
Treatment:
β-Thalassemia
Trait: No
therapy required
β-Thalassemia minor:1) NO therapy needed unless Hb
falls to level that causes symptoms 2)Iron supplementation should not be given
unless iron deficiency confirmed with low ferritin
β-Thalassemia
major:
·
Regular Transfusion scheduled
1)to increase post transfusion Hb to 13-14g/dl 2) mean Hb to pre transfusion
9.5-10.5 g/dl
·
Tx required every25-30 days.
·
Monitor serum ferratin levels in
regular transfusion child every 6 months.
·
Formula
for Required Transfusion: Req. Tx=(13-current Hb)X 3 X
Wt.
Iron Chelation Therapy:
·
Initiation of therapy: 1)age
>2 yrs and above 2)after 1st yr
of transfusion therapy 3)Serum Ferratin level ≥1,000ng/ml
·
Goal of Chelation therapy: Serum
ferritin level ≤1000ng/ml
·
3 Available iron chelator
agents:
1)Deferoxamine
2)Deferasirox 3)Deferiprone
·
Desferrioxamine:
(Inj.Desferal 500mg) Subcutaneous with infusion
pump, Dose starting with 30 mg/kg/day over 8-12hours, 5 days a week( gap for 2
days) and may increase to 50 mg/kg /day, starting not less than 5 years side
effects: ototoxicity, retinal changes,and bone dysplasia with truncal
shortening
·
Deferasirox:
(Tab.Asunra 400mg) Oral tablet,Dose starting
20mg/kg/day,regular without gap,may increase max. 40 mg/kg/day, side
effects: gastrointestinal damage, potential kidney damage,
thrombocytopenia.
·
Deferiprone:
oral tablet, starting 50 mg/kg/day in 3 divided
doses, regular and may inc. max to 75mg/kg/day, side effects: transient
agranulocytosis(required weekly CBC to screen this side effect)
REGULAR FOLLOW UP : should be on S/Ferritin,
Echocardiography, TFT’s,RFT’s,LFT’s,Hepatitis B,C screening. Growth monitoring.
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