Slide 1

Report
22
96%
Hb A2
a22
3%
Hb F
a22
1%
Hb A
Chromosome 11-non-alpha globin
-Both beta proteins work( β / β)
-One works (trait/minor) (β/ β+, β/ β0)
-Both affected, but not absent (intermedia)
(β+/β+)
-Absent (major) (β0/ β0,β+/β0)
-One normal gene and one affected gene ( β / β + or β / β 0 )
-Often asymptomatic.
-CBC :mild or no anemia, MCV and MCH are usually low,
RBC count often high.
-Hb electrophoresis or Hb HPLC: HbA2 > 3.5% of total
hemoglobin) and usually HbF >1%.
-An elevated HbA2 is considered diagnostic of -thalassemia
trait.
Iron Deficiency
Anemia
Thalassemia Minor
p-value
RBC (x 106 /μL)
4.7634 ± 0.4313
5.9662 ± 0.5929
<0.001
Hemoglobin(g/dl)
11.0095 ± 1.2102
11.8103 ± 1.1617
0.004
MCV (fL)
72.4432 ± 5.8923
62.2794 ± 4.4002
<0.001
MCH (pg)
23.2351 ± 2.7320
19.8669 ± 1.7002
<0.001
-Both affected, but not absent (β+/β+)
-There is a moderate haemolytic anaemia
-Some haemoglobin A is present
-Varying increase in haemoglobin A2
-Distinct increase in haemoglobin F.
Thalassemia
Major
β+/β0 or β0/β0.
A decrease in the rate of
production of β
Imbalance with the normally
produced α globin chains.
α globin chains accumulates
Modifiers
May reduce the degree of globin chain imbalance
and typically ameliorate the symptoms of
thalassemia.
-Co-inheritance of α thalassemia
-Co-inheritance of determinants that increase gamma
chain production
-The presence of mild or silent -thalassemia alleles
Hb F production
advantages.
Binding some of
the excess alpha
chains
protect the
RBCs
provides
additional Hb
with oxygencarrying ability.
Hb F production
disadvantages
increases
oxygen
affinity
leading to
hypoxia
-It is characterize by severe anemia that can
begin months after birth
-Paleness
-Delays in growth and development
-Bone marrow expansion.
-Untreated Beta Thalassemia major can lead
to child death due to heart failure.
Diagnostic work of suspected BTM
Complete hemogram
-Hemoglobin: usually <7 gm/dl.
-MCV and MCHC are decreased unless recently transfused.
-Reticulocyte count is increased unless recently transfused.
-WBC ± increased
-Leucopenia and thrombocytopenia indicates Hypersplenism.
-Blood film: severe hypochromic microcytic anemia with
anisocytosis and poikilocytosis, numerous target cells,
nucleated red cells, and schistocytes may be seen. Moderate
basophilic stippling is common
Diagnostic work of suspected BTM
Hemoglobin electrophoresis
(HPLC)
-Hb A decreased or absent.
-Hb F invariably increased.
-HbA2 usually normal
VARIANT HEMOGLOBINS
co-inherited with Beta -thalassemia
The most common are Hemoglobin S,
Hemoglobin E, and Hemoglobin C.
-HbS/Beta-thalassemia
-HbE/Beta –thalassemia
-Hemoglobin C/Beta-thalassemia
DNA testing
-Presence of two severe beta Thalassemia mutations.
-Absence of readily detectable forms
of alpha Thalassemia.
- Absence of determinants that
increase gamma chain production
Observation Phase (Variable)
The decision to place a Thalassemia major
patient on regular blood transfusion program
is rarely urgent.
Hb drop
≥ 1gm/
week
lowest Hb less
than 6.5g/dl
on more than
2 occasions
signs of
ineffective
erythropiesis
Signs of
Growth
failure.
β- THALASSEMIA MAJOR DIAGNOSED
GENETIC COUNSELLING
OBSERVATION PHASE
BLOOD TRANSFUSION PROGRAM
IRON CHELATION THERAPY
MANAGEMENT OF IRON
OVERLOAD COMPLICATIONS
SPLENECTOMY
BONE MARROW
TRANSPLANATION
-1 unit of blood contains approximately
200 mg of iron
-Iron accumulates with repeated blood
transfusion
-iron absorption is increased
Pituitary gland
Heart
•
Iron overload results in non–
transferrin-bound
iron in the plasma
Pancreas
•
Increased iron uptake into
selective organs
Gonadal
•
Generation of free hydroxyl
radicals
Liver
Tissue damage
What is the ideal iron
chelator ?
Heart failure
is the leading cause of death
in patients with ß-thalassemia major
60%mortality
Iron cardiomyopathy
Iron cardiomyopathy
is preventable
is treatable
is reversible
We are no more powerless
to predict
WHO is at risk ??
MRI T2*
T2* - CARDIAC RISK RANGING
Below a myocardial T2* of 20 ms, there was a progressive and significant decline in LVEF ( P<0·0001)
High
Intermediate
Low
-Success is related to the pre transplantation clinical
conditions:
-The presence of hepatomegaly
-extent of liver fibrosis
-magnitude of iron accumulation.
-Disease-free survival is over 90% In HLA –Matched
sibling donor transplant In children who lack the
above risk factors.
-Cord blood transplantation from a related donor.
OPTIONS OFFERED FOR COUPLES AT GENETIC RISK
MOST IDEAL
Preconception
Conception
Preimplantation
PGD
Implantation
Embryogenesis
Prenatal
PRENATAL DIGNOSIS
ABORTION
Fetal Growth
Perinatal
IN UTERO BMT
Birth
Childhood
Postnatal
BMT
LEAST IDEAL
BLOOD TRANSFUSION PROGRAM AND IRON CHELATION THERAPY
-Remain Single
-Avoid Another Carrier as Partner
-Select as Usual but Remain Childless
-PND at Cost of 25% Abortion
-PGD if 1st PND Resulted in Abortion
-PGD from Onset
-PGD + HLA For Treating Affected Sibling
THANK YOU

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