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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 Summary, Conclusion and Recommendations 123 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 124 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 Summary, Conclusion and Recommendations 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). |