|
 
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| ORIGINAL ARTICLE |
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| Year : 2014 | Volume
: 27
| Issue : 1 | Page : 66-72 |
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Lipid profiles in β thalassemic children
Seham M. Ragab1, Manal A. Safan2, Asmaa S. Sherif3
1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menufia, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Menufia, Egypt
3 Department of Pediatris, Shebin Elkom Teaching Hospital, Shebin El-Kom, Egypt
| Date of Web Publication | 20-May-2014 |
Correspondence Address:
Seham M. Ragab
M.D., Pediatric Department, Faculty of Medicine, Menoufia University, Sheben El-Kom, Postal code: 32511
Egypt
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1110-2098.132749
Objectives
To study the pattern of serum lipids in β thalassemic children.
Background
β Thalassemia is a common chronic hemolytic anemia in Egypt. Iron overload is a common sequelae in these patients. Abnormal lipid profile patterns have been suggested to occur in thalassemic patients.
Materials and methods
Forty-two children with β thalassemia (22 thalassemia major and 20 thalassemia intermedia) were included in the present study with 30 matched controls. Complete blood count, kidney function tests (serum creatinine, blood urea), liver function tests (alanine aminotransferase, aspartate aminotransferase), serum ferritin, and 12-h overnight fasting Serum lipid profiles including total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) triglycerides were performed for patients and controls.
Results
The thalassemic children had significantly higher platelets count, WBCs count, serum ferritin, alanine aminotransferase, aspartate aminotransferase, and serum triglyceride levels, with significantly lower Hb level, RBCs count, total cholesterol, HDL-C, LDL-C levels, and LDL/HDL ratio compared with the control group.
Conclusion
β Thalassemic children are at risk of developing disturbed lipid profile patterns that could place them at risk for atherosclerosis and thromboembolic events. Keywords: High-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides, lipid profiles, total cholesterol, β thalassemia
How to cite this article:
Ragab SM, Safan MA, Sherif AS. Lipid profiles in β thalassemic children. Menoufia Med J 2014;27:66-72 |
| Introduction | |  |
Thalassemia is a hereditary anemia resulting from genetic disorders of hemoglobin synthesis. Thalassemia is caused by inherited defects in the rate of synthesis of one or more of the globin chains (͍ or β). The results are imbalanced globin chain production [1].
In β-thalassemia major (β-TM), the production of β-globin chains is severely impaired. This imbalance in globin chain synthesis results in ineffective erythropoiesis and severe hemolytic anemia [2] in which life can only be sustained by regular blood transfusions [3].
Thalassemia intermedia is a term used to define a group of patients with β thalassemia in whom the clinical severity of the disease is somewhere between the mild symptoms of β-thalassemia trait and the severe manifestations of β-TM [2]. The diagnosis is a clinical one made on the basis of the patient maintaining a satisfactory Hb level of at least 6-7 g/dl without the need for regular blood transfusions [4].
A high incidence of thromboembolic event has been observed in patients with β thalassemia. Thrombotic events are more frequent in β-thalassemia patients who are not receiving regular transfusions or in β-thalassemia patients who have undergone splenectomy, strongly supporting the procoagulant activity of circulating damaged red blood cells (RBCs) [5].
Vascular dysfunction with increased arterial stiffness and endothelial dysfunction have been found in patients with β thalassemia [6]. Endothelial dysfunction occurs in thalassemic children because of peroxidative tissue injury because of continuous blood transfusions [7].
Children with β thalassemia are at risk of developing premature atherosclerosis because of dyslipidemia [8]. Abnormal lipid profiles, including low total cholesterols, low high-density lipoprotein cholesterol (HDL-C), low low-density lipoprotein cholesterol (LDL-C), and high triglycerides, have long been observed in β thalassemia [9].
Thalassemic patients are subjected to peroxidative tissue injury. It has been documented that circulating LDL-C in thalassemic patients shows marked oxidative stress. Free radical production is increased in patients with iron overload. Iron-overloaded patients have elevated plasma levels of thiobarbituric acid reactants and increased hepatic levels of aldehyde protein adducts, indicating lipid peroxidation [10].
| Materials and methods | | |
Patients
Forty-two children with β thalassemia (22 TM and 20 thalassemia intermedia) were included in the present study. Their age ranged from 4 to 18 years, mean age 11.1 ± 5.8 years. Patients were selected from among the outpatients attending the pediatric hematology clinic Minoufia University Hospital. Thirty normal, healthy children were included as controls.
The participants were categorized into three groups:
Group I included 22 TM (13 males and nine females) patients. Their ages ranged from 4 to 18 years, mean 9.9 ± 5.5 years.
Group II included 20 thalassemia intermedia patients (10 males and 10 females). Their ages ranged from 4 to 18 years, mean 11.9 ± 4.7 years.
Group III included 30 healthy children matched for age (ranging from 3 to 18 years, mean 12.1 ± 7.4 years), sex (10 males and 20 females), and socioeconomic standard as a control group.
Informed consents were obtained from the parents of the children studied and the ethical committee in our medical school approved the study.
Exclusion criteria
None of the participants had any acute illness or diabetes mellitus.
All patients and controls were subjected to the following:
Full assessment of history.
Thorough clinical examination.
Laboratory investigations.
Five milliliter of venous blood was withdrawn from every child by sterile vein puncture after a 12 h overnight fasting. Four milliliter was transferred into plain tubes, allowed to clot, centrifuged for 15 min at 3000 rpm, and 1 ml was transferred into an EDTA tube for complete blood count.
- Determination of serum levels of total cholesterol [11], triglycerides [12], and HDL-C [13] was carried out using the precipitation method. Serum LDL-C levels were calculated using the Friedewald formula [14].
- Determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was carried out by the IFCC method without pyridoxal phosphate [15].
- Determination of urea was carried out using the enzymatic method [16] and creatinine using the Jaffe method [17].
- Serum level of ferritin was assessed using the ELISA technique from alpha diagnostic international company [18].
- Complete blood count was performed using the AC920 Autocounter (Boule Medical AB, Sweden).
- Hepatitis B surface antigen was determined using commercially available enzyme immunoassays and the presence of anti-hepatitis C virus (HCV) Ab was determined using a third-generation enzyme immunoassay.
Statistical method
Using Microsoft Excel 2010 and SPSS v18.0 (SPSS Inc., Chicago, IL, USA) for Microsoft Windows 7, the clinical and laboratory data were analyzed statistically.
Comparisons between means were made using an Unpaired student t-test for comparison between two groups with independent parametric data, the Mann-Whitney (U) test for comparison between two groups of independent nonparametric data, one-way analysis of variance for comparison between more than two groups of independent parametric data, the Kruskal-Wallis test for comparison between more than two groups of independent nonparametric data, the χ2 -test for comparison between two groups with qualitative, and Correlation statistics using the Pearson correlation coefficient between parametric data and Spearman correlation coefficient between nonparametric data. P-value, probability of chance, was considered significance at P less than or equal to 0.05 and highly significant at P less than or equal to 0.01.
| Results | | |
All the thalassemic groups and each of the thalassemic subgroups (TM and thalassemia intermedia) had significantly higher positive consanguinity, wasting, prevalence of HCV infection, and spleen abnormalities. Also, the TM group included a significantly higher percentage of stunted children, with a higher pulse rate compared with the control group and significantly higher positive consanguinity when compared with TI, without a significant difference between both groups in the other parameters tested [Table 1] and [Table 2]. | Table 1: Comparison between thalassemic patients (groups 1 and 2) and control (group3) group in demographic and clinical data
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 | Table 2: Comparison between both thalassemia major (groups 1) and thalassemia intermedia (group 2) patients and control (group 3) in demographic and clinical data
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The entire thalassemic group and each of the thalassemic subgroups (TM, TI) had significantly higher platelets, WBCs counts, serum ferritin level, ALT, AST, and serum triglycerides level, with significantly lower Hb level, RBCs count, serum total cholesterol, HDL-C, LDL-C, and LDL-C/HDL-C ratio compared with the control group. The TI group had significantly higher platelets counts and serum triglycerides levels compared with the TM group, without a significant difference between both groups in the other parameters tested [Table 3]. | Table 3: Comparison between both thalassemia major (groups 1) and thalassemia intermedia (group 2) patients and control (group 3) in laboratory data
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The serum total cholesterol had a significant positive correlation with serum triglycerides and LDL-C [Figure 1] and the serum triglycerides had a significant negative correlation with the RBCs transfusion index in thalassemic children [Figure 2]. No significant correlation was observed between serum ferritin and the other parameters [Table 4].
| Discussion | | |
Lipid abnormalities have been detected in β thalassemia and also in various hematological disorders including sickle cell disease, glucose-6-phosphate dehydrogenase deficiency, spherocytosis, aplastic anemia, and myelodysplastic syndrome [19].
This study showed that the prevalence of HCV infection among thalassemic children was significantly higher than that of the controls. This is in agreement with many studies for example Younus et al. [20] and Yaghobi et al. [21].
Blood transfusion is the main risk factor for transmission of viral hepatitis in patients with hematological diseases [22].
β-Thalassemic patients had significantly elevated liver enzymes ALT and AST compared with controls. This is in agreement with many studies such as Lil et al. [23], Younus et al. [20], and Yaghobi et al. [21]. This can be attributed to iron deposition and infection by hepatitis B and C [24].
Thalassemic children had significantly higher serum ferritin levels compared with the controls. No significant difference was found between TM and TI in serum ferritin. This is in agreement with Vladislav et al. [25] and Ali et al. [26].
The iron overload in thalassemic patients can be attributed to multiple life-long transfusions and enhanced iron absorption results in secondary hemosiderosis, with a resultant increase in serum ferritin [1].
A few studies have reported conflicting results on lipid profiles in thalassemic children. Some have reported atherogenic profiles such as Tantawy et al. [8], Dwivedi and Kumar [27], and others have reported antiatherogenic profiles in the thalassemic children studied such as Hartman et al. [28], Al-Quobaili and Abou Asali, [9] and Tselepis et al. [29].
The results of this study showed that the thalassemic children had significantly lower total serum cholesterol, LDL-C, and HDL-C level, with higher serum triglycerides, compared with the control group; this is in agreement with the results reported by Hartman et al. [28], Al-Quobaili and Abou Asali [9], and Tselepis et al. [29].
The pathogenesis of these abnormalities is caused by many mechanisms including plasma dilution because of anemia, accelerated erythropoiesis resulting in increased cholesterol uptake by macrophages and histiocytes of the reticuloendothelial system, defective liver functioning because of iron overload, macrophage system activation with cytokine release, and hormonal disturbances [9],[30],[31]. A reduced extrahepatic lipolytic activity could account for the increase in circulating triglyceride [9].
It seems that the main mechanism of dyslipidemia in β thalassemia is severe iron overload and oxidative stress [32] and in βTI the major mechanism is accelerated erythropoiesis and enhanced cholesterol consumption [28], [33].
The atherogenic ratio, LDL-C/HDL-C ratio, was significantly lower in both thalassemic groups compared with the control group. This is in agreement with Tselepis et al. [29]. Studies proved that the risk for myocardial infarction is high when HDL-C is low [34]. Thalassemic patients are at a much higher coronary risk than their matched controls because of the low HDL-C production; even total cholesterol is normal [35].
Our results showed that the only lipid profile parameter that differed between TM and TI was the serum triglycerides, being significantly higher in TI compared with TM children. This result is in contrast with that of Haghpanah et al. [36], who found no significant difference between TM and TI in lipid profiles. Ricchi et al. [19] found lower levels of TC and LDL-C in TI than TM.
The present study showed that the serum total cholesterol had a significant positive correlation with serum triglycerides and LDL-C. Al-Quobaili and Abou Asali [9] found a strong positive correlation between serum LDL-C and TC in thalassemic children.
The serum triglycerides had a significant negative correlation with RBCs transfusion index among thalassemic children. This means the anemia places the thalassemic patients at risk for decreased extrahepatic lipolytic activity, resulting in high serum triglycerides. In our study, no significant correlation was found between the lipid profiles and serum ferritin. However, Mansi and Aburjai [37] found that the triglyceride level correlated positively with the serum ferritin levels in thalassemic children.
| Conclusion | | |
Our study showed that thalassemia patients had a disturbed lipid profile in the form of lower serum total cholesterols, LDL-C levels, and HDL-C levels with higher serum triglycerides compared with healthy control participants. Thus, better evaluation of the cardiovascular risk factors should be carried out in these patients.
| Acknowledgements | | |
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
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