الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
thalassemia is considered a one of the most famous hemoglobinopathies, It is not
a single disease but a group of disorders, each resulting from an inherited abnormality of
globin production, and inherited defects in the globin chains production. Without
transfusion support, 85% of ß- thalassemia patients with homozygous or compound
heterozygous genotype may die by 5 years old because of severe anemia. However,
transfusions result in progressive iron overload due to inadequate excretory pathways.
Types of ß-thalassemia syndromes include: thalassemia major, thalassemia
intermediate, thalassemia trait (minor), and thalassemia in association with Hb variants.
Thalassemia major denotes the compound heterozygous or homozygous genotype of
the disorder, that are manifested by marked anemia (Hb=1-7 g/dL ), hemolysis that
necessitate regular blood transfusion and iron chelation.
Strategies for thalassemia management consist of prevention, the birth of new cases
control and offering the best management to thalassemia patients in form of regular blood
transfusion, iron chelators, treat complications of thalassemia or those of blood transfusion.
New modalities of drugs increase HbF and decrease splenic size, bone marrow
transplantation and gene therapy.
Regular and early packed RBCs transfusion therapy in homozygous β-thalassemia
patients decreases the marked anemia complications and increases survival
Complications of regular blood transfusion are iron overload, immune modulation,
infections and others. Recently the risk of ischemia reperfusion injury started to be studied
in acute coronary syndromes.
Restoration of blood flow to an acutely ischemic tissue is now recognized to initiate
a series of steps that cause significant vascular and tissue injury, thus exacerbating the
initial ischemic injury. The mechanisms of reperfusion-induced injury are multifactorial
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with biochemical events initiated during ischemia contributing to the injury. The reintroduction
of molecular oxygen with blood flow restoration can result in the generation
of toxic oxygen products that can cause tissue injury following ischemia and reperfusion.
Ischemia-reperfusion leads to the migration of neutrophils (PMN) into tissue upon
restoration of blood flow, and this accumulation occurs in response to chemoattractants
and other inflammatory mediators.
The activated PMNs adhere to endothelial cells where they can release toxic oxygen
products and proteases that can contribute to reperfusion-induced vascular injury. Once
adherent, PMNs then migrate extravascularly where they can provoke tissue damage by
similar mechanisms. Reperfusion of an ischemic tissue can also elicit a systemic
inflammation leading to injury and dysfunction of remote organs.
Clinical disorders involving ischemia-reperfusion include renal impairment,
pulmonary hypertension, hepatic dysfunction.
CD11/CD18 leukocyte adhesion molecules can be upregulated several fold from
intracellular granules by chemotactic factors such as C5a, interleukin-8, and platelet
activating factor
The C5a is a potent anaphylatoxin, it is a split product of the complement component
C5 during complement activation. it induces the release of inflammatory mediators as
cytokines and chemokines, upregulates the expression of adhesion molecule, and increases
vascular permeability
The aim of the present work was to study the expression of CD11b/CD18 and serum
level of complement 5a as markers of ischemia reperfusion injury in ß- thalassemia major
patients before and after blood transfusion
We collected forty (40) patients treated for ß- thalassemia major at the Department of
Hematology, Medical Research Institute, University of Alexandria, ten (10)ß-thalassemia
minor patients not receiving blood transfusion and followed up at the Department of
Hematology , Medical Research Institute, University of Alexandria were included, and ten
(10) healthy subjects sex and age matched were recruited as a control group.
Patients were subjected to the following:
1. Full history taking, with emphasis on history of transfusion and iron chelation.
2. Thorough clinical examination.
Summary, Conclusion and Recommendations
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3. Complete blood count (CBC).
4. CD11b/CD18 surface expression by flow cytometry.
5. Serum complement 5a level by ELISA.
Samples were drawn just before and 1 hour after packed RBCs transfusion patients
with ß- thalassemia major.
The statistically significant difference was observed between the three studied groups
as regards the following:
C5a (p = < 0.001) CD11b/CD18 (p = < 0.001) CRP (p = < 0.001) positive
consanguinity (p = < 0.001) elevated hepatic markers AST and ALT (p = < 0.001) indirect
bilirubin (p = < 0.001) serum ferritin (p = < 0.001) and monocyte count (p = < 0.001)
There was statistically significant correlation between C5a level change before and
after blood transfusion in B-thalassemia major patients (p = < 0.001) as well as between
change of CD11b/CD18 expression before and after transfusion in ß-thalassemia major
patients (p = < 0.001)
There was statistically significant correlation between Hb level change (p = < 0.001),
WBCs count including neutrophil count, monocyte count and lymphocyte count (p = <
0.001) before and after transfusion in ß-thalassemia major patients
There was statistically significant relation between C5a level change and female sex
(p=0.022) in ß-thalassemia major patients where females had higher levels compared to
males.
There was statistically significant relation between C5a level change and non washed
nor filtered transfused blood in ß-thalassemia major patients.
There was statistically significant relation between C5a level change and elevated
serum creatinine (p= 0.031), and osteopenia/osteonecrosis (p=.026)
There was statistically significant correlation between C5a level change and serum
ferritin level (p=0.006), and neutrophil/ lymphocyte ratio (p = < 0.001) in ß-thalassemia
major patients
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125
There was statistically significant relation between CD11b/CD18 change of
expression and hepatic markers as AST (p = < 0.001), ALT (p= 0.013), and indirect
bilirubin (p = < 0.001) in ß -thalassemia major patients
There was statistically significant relation between CD11b/CD18 change of
expression and pulmonary hypertension (p = < 0.001), endocrinopathy in form of DM,
short stature and amenorrhea (p=0.010), presence of viral hepatitis C (p = < 0.001)
There was statistically significant relation between CD11b/CD18 change of
expression and frequency of transfusion as change of CD11b/CD18 were higher in ßthalassemia
major patients who received only one packed RBCs per month(p = < 0.001)
than those received twice packed RBCs per month.
There was statistically significant relation between CD11b/CD18 change of
expression and non chelator therapy as change of CD11b/CD18 was higher in ß -
thalassemia major patients who did not use chelator therapy (p= 0.004).
There was statistically significant relation between CD11b/CD18 change of
expression and intravenous infusion of ranitidine as change of CD11b/CD18 was higher in
ß-thalassemia major patients who did not receive intravenous ranitidine infusion before
blood transfusion (p = < 0.001) .
There was statistically significant correlation between CD11b/CD18 change of
expression and increased neutrophil count post blood transfusion in ß-thalassemia major
patients (p=0.045).
There was statistically significant correlation between CD11b/CD18 change of
expression and neutrophil /lymphocyte ratio post blood transfusion in ß- thalassemia major
patients (p = < 0.001).