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العنوان
Phospholipase Lipoprotein-associated A2 and relation to premature atherosclerosis in β-thalassemia children \
المؤلف
Issa, Hanan Mabruk Ayad.
هيئة الاعداد
باحث / حنان مبروك عياد عيسى
مشرف / محسن صالح الألفي
مشرف / وليد محمد الجندي
مشرف / هبة جمعة عبد الرحيم
تاريخ النشر
2018.
عدد الصفحات
250 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
طب الأطفال ، الفترة المحيطة بالولادة وصحة الطفل
تاريخ الإجازة
1/1/2018
مكان الإجازة
جامعة عين شمس - كلية الطب - طب الاطفال
الفهرس
Only 14 pages are availabe for public view

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Abstract

beta-thalassemia is an autosomal recessive hereditary hemoglobinopathy that affects the production of the β-
globin chains of the hemoglobin.
Thalassemia is becoming a major health problem in the world, especially in Mediterranean region β-thalassemia encompasses a group of monogenic diseases that have in common defective synthesis of β-globin. The defects involved are extremely heterogeneous and give rise to a large phenotypic spectrum, with patients that are almost asymptomatic to cases in which regular blood transfusions are required to sustain life. The patients suffer from chronic anemia due to a process called ineffective erythropoiesis (IE). The sequelae of IE lead to extramedullary hematopoiesis (EMH) with massive splenomegaly.
Vascular endothelial abnormalities together with vasomotor dysfunctions and increased arterial stiffness were documented in β- TM as early predisposing pathological abnormalities for atherosclerosis. Thromboembolic events especially strokes are considered One of the serious β-thalassemia complications Suggesting a pro-atherogenic liability in these patients.
Atherosclerosis in β-thalassemia major patients may be the result of iron-overloaded state causing oxidative modification of lipids, altered lipid profile and vascular dysfunction. Studies have
also shown relation between iron load and risk of atherosclerosis which is an important pathologic cause of cardiovascular (CV) and cerebrovascular diseases in these patients.
Carotid ultrasound provides quantitative measurements of carotid intima–media thickness (CIMT) that can be used to assess cardiovascular disease (CVD) risk in individuals and monitor ongoing disease progression and regression. It is non- invasive, rapid, reproducible, and carries no risk. Numerous epidemiological studies have established that CIMT is a marker of subclinical atherosclerosis and is associated with established CVD risk factors and with both prevalent and incident CVD.
Lipoprotein-associated phospholipase A2 is a member of the intracellular and secretory phospholipase enzyme family secreted by activated macrophages. Lp-PLA2 is involved in the development of atherosclerosis, an observation that has prompted interest as a possible therapeutic target.
The objective of the current study was to measure the level of lipoprotein-associated phospholipase A2 in patient with β thalassemia and its relation to premature arteriosclerosis by using carotid intima thickness. Furthermore, to correlate the level of lipoprotein-associated phosphlipaseA2 and premature arteriosclerosis in β thalassemia in relation to iron overload and lipid profile.
For this purpose the study was conducted on 30 children with beta thalassemia (22 β-thalassemia major and 8 β- thalassemia intermedia patients) attended the Hematology Unit, Pediatrics Hospital, Ain-Shams University (diseased group) and 30 healthy children with matched age and sex (control group).
The study populations were grouped into 3 groups; β- thalassemia major group comprised 22 patients, They were (12) males and (10) females, M: F ratio (1.2: 1), their ages ranged from 10 to 18 years with a mean value of (14.87 ± 2.31SD) years. β-thalassemia intermedia group Comprised 8 patients, They were (3) males and (5) females, M: F ratio (1: 1.6), their ages ranged from 11 to 15 years with a mean value of (13.00 ± 1.51SD) years. Control group Comprised 30 healthy children and adolescents with matched age and sex. They were 6 males (20%) and 24 females (80%), with a male to female ratio of (1: 4). their ages ranged from 10 to 18 years with a mean value of (15.53 ± 2.52 SD)
All patients were subjected to the following:
i) Full history includes, age, sex, duration of the illness since the first blood transfusion, the frequency of blood transfusion, transfusion index (amount of PRBCS in mL ⁄ kg ⁄ year) and history of intake of iron chelating agents (type, duration and compliance).
ii) Thorough clinical examination including, anthropometric measurements: Weight, height, standard deviation score (SDS), BMI, Blood pressure, Hepatosplenomegally, cardiac examination, chest examination and Tanner scoring.
iii) Laboratory investigations including, Hb electrophoresis, Mean blood hemoglobin over the last year, Viral markers including hepatitis B&C, Complete blood count, ALT, T. BILI., D.BILI., S.Ferritin, Lipid profile and Lipoprotein- associated phospholipaseA2.
iv) Imaging: CIMT measurement using B mode ultrasound.
Results of the hematologic and biochemical investigations of our beta thalassemia patients displayed very peculiar metabolic pattern with; significant anemia, high increase in serum ferritin, and dyslipidemia which presented as high triglyceride level but associated with low cholesterol, LDL and HDL level than controls.
Results of our study revealed that the mean level of CIMT was (0.39±0.02/0.45±0.02/0.45±0.02) with range (0.35-
0.41/0.4-0.47/0.4-0.47) in control, β-thalassemia major and β- thalassemia intermedia respectively. Considering CIMT as an excellent marker of subclinical atherosclerosis, the significant increased CIMT in patient groups compared to the controls provides a good evidence of the presence of premature atherosclerosis in vascular-free TM and TI patients.
The median level of serum Lp-PLA2 was (0.6, 5, 2.75 ng/ml) with range (0-12.5, 1.5-77, 2-41) in control, β- thalassemia major and β-thalassemia intermedia respectively.
In our results, correlation studies show significant positive correlations between PhLA2 and CIMT in all study group as P<0.05.
High level of Lp-PLA2 was detected in patients with high liver span with positive correlation between them in β- thalassemia major patients (P=0.000).
However, no significant correlation was found comparing Lp-PLA2 and any of the other studied clinical parameters in all patients as sex, weight, height SD score, BMI, age at diagnosis, interval of disease, spleen span at present status, transfusion index, start of age transfusion and duration of chelation, Ejection fraction, compliance, splenectomy and types of chelations.
Correlation studies between Lp-PLA2 level and the laboratory variables of the studied patients revealed significant positive correlation between Lp-PLA2 and ALT (P-value=0.019), TG level (P-value=0.000), ferritin (P-value=0.003) and CHOL (P- value=0.016) in patients with β-thalassemia major.
No significant correlation was found comparing Lp- PLA2 and any of laboratory data in all patients as HGB, Mean HGB, TLC, PLT, HCT, T.BIL, D.BIL, HgA, HgA2, HgF, LDL
and HDL.
Positive correlation between CIMT level and Diastolic BP (P-value=0.030) in patients with β-thalassemia major. There was negative correlation between CIMT level and age of diagnosis (P-value=0.449), Ejection fraction (P-value=0.006) in patients with β-thalassemia intermedia.
However, no significant correlation was found comparing CIMT level and any of the other studied clinical parameters in all patients as sex, weight, height SD score, BMI, age at diagnosis, interval of disease, spleen span at present status, transfusion index, start of age transfusion and duration of chelation, Ejection fraction, compliance, splenectomy and types of chelations.
Correlation studies between CIMT level and the laboratory variables of the studied patients revealed significant positive correlation between CIMT and Lp-PLA2 in all studied patients (P-value= 0.012), ferritin (P-value=0.000), TG (P- value=0.000) and CHO (P-value=0.000).
Significant positive correlation between CIMT and Lp- PLA2 in patients with β-thalassemia major (P-value= 0.022), LDL (P-value=0.0147), ferritin (P-value= 0.006), TG (P- value=0.004) and CHO (P-value=0.022).
Significant positive correlation between CIMT and PhLA2 in patients with β-thalassemia intermedia (P-value= 0.003), ferritin (P-value=0.000), TG (P-value=0.002) and CHO (P- value=0.000).
On the other hand CIMT was negatively correlated with D.Bil. (P-value=0.040) in β-thalassemia major.
No significant correlation was found comparing CIMT and any of laboratory data in all patients as HGB, Mean HGB, TLC, PLT, HCT, T.BIL, HgA, HgA2, HgF and HDL.