الفهرس 
Beta ThalassemiaOnly 14 pages are availabe for public view
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Abstract
β-thalassemia major is an inherited disease resulting from reduction or total lack of beta globin chains. Patients with this disease need repeated blood transfusion for survival. This may cause oxidative stress and tissue injury due to iron overload. Ischemia modified albumin (IMA) is an altered type of serum albumin that forms under conditions of oxidative stress. ROS resulting from conditions such as ischemia, hypoxia, acidosis, free radicals, and free iron can decrease the ability of the N-terminus to bind with transition metals. Under such conditions, the structure of human serum albumin is modified in such a way that permits for excessive production of IMA.
The aim of this work was to measure the levels of IMA in β-thalassemia patients as a marker of oxidative stress, and to assess its relation to lipid peroxidation as well as the effect on vascular complications and the efficacy of iron chelation.
This study included 45 β-TM patients (25 males and 20 females) recruited from the regular attendants of the Pediatric Hematology Clinic, Pediatric Hospital, Ain Shams University. Patients were compared with 30 age- and sex-matched healthy subjects (18 males and 12 females) enrolled as controls. The mean age of thalassemia patients was 14.3 ± 2.9 years (range: 6-18 years) while that of controls was 13.1 ± 1.9 years (range: 10-17 years). All included patients were subjected to detailed medical history and thorough clinical examination with special emphasis on anthropometric measures, disease duration, evidence of thrombosis, hepatic or cardiac disease, history of splenectomy, transfusion history and chelation therapy. Compliance was assessed by reviewing patient self-report. IMA levels were measured by enzyme linked immunosorbent assay (ELISA) and MDA was assessed by measuring the production of Thiobarbituric Acid Reactive Substances (TBARS). Echocardiography was performed and carotid intima media thickness (CIMT) was measured using Doppler ultrasound.
In this study, the mean disease duration was 12.9 ± 3.2 years (range: 3-16 years). It was observed that 53.3% of patients were splenectomized and 53.3% had hepatitis viral infection. Pulmonary hypertension risk (elevated TRV >2.5 m/sec) was found in 22.2% while heart disease (a systolic LV dysfunction; LV shortening fraction <30% or LV ejection fraction < 55%) was found in 20% of patients.
Comparison between β-thalassemia major patients with mean serum ferritin ≥2500 µg/L and those with serum ferritin <2500 µg/L revealed significantly higher transfusion index as well as elevated TRV and CIMT with lower EF in patients with serum ferritin ≥2500 µg/L.
In the current work, IMA and MDA levels were significantly higher in β-TM patients compared with control group. IMA was significantly higher among patients with heart disease and pulmonary hypertension risk than those without. ROC curve analysis revealed that the cutoff value of IMA at 17.5 U/mL could differentiate patients with and without heart disease with high sensitivity and specificity. In addition, ROC curve analysis revealed that the cutoff value of IMA at 75 U/mL could differentiate patients with and without PH risk with high sensitivity and specificity.
Serum IMA and MDA levels were elevated among patients with serum ferritin ≥2500 µg/L compared with patients below this cutoff while patients compliant to chelation had significantly lower IMA and MDA levels than non-compliant ones.
Significant positive correlations were found between IMA levels and disease duration, WBC count, serum ALT and AST. Both IMA and MDA levels were positively correlated there was a significant positive correlation between these two markers and mean serum ferritin in last 2 years prior to the study among TM patients.
As regards radiological variables, there was a significant positive correlation between IMA levels and TRV. Moreover, significant negative correlations between were found between both IMA and MDA levels and each of ejection fraction and fractional shortening. Both markers were positively correlated to CIMT.
Multiple linear regression analysis revealed that mean serum ferritin, MDA, TRV, ejection fraction and CIMT were independently related to IMA levels among thalassemia patients. Multiple linear regression analysis using CIMT as the dependent variable revealed that disease duration, serum ferritin, IMA and MDA were the significant independent factors among thalassemia patients.