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Thalassemia : summarized

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:

Hb A(α2β2)
Hb A22δ2)
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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