|Year : 2012 | Volume
| Issue : 4 | Page : 183-186
Lipid profile in children with β-thalassemia major
Samera Z. Sayed1, Sheren E. Maher1, Ghada Adel1, Lamea Hamdy2
1 Department of Pediatrics, Faculty of Medicine, El-Minia University, Cairo, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, El-Minia University, Cairo, Egypt
|Date of Submission||23-Feb-2012|
|Date of Acceptance||20-Mar-2012|
|Date of Web Publication||21-Jun-2014|
Sheren E. Maher
Department of Pediatrics, Faculty of Medicine, El-Menia University, P.O. Box 61519, Cairo
Source of Support: None, Conflict of Interest: None
β-Thalassemia major is a very serious blood condition, as affected patients are unable to synthesize enough healthy red blood cells and depend on blood transfusions throughout their life.
Aim of work
The aim of the study was to evaluate the lipid profile in patients with β-thalassemia major.
Patients and methods
Fifty patients with β-thalassemia major and 25 healthy controls were included in this study. They were subjected to complete history taking, a thorough clinical examination, and laboratory investigations including complete blood count, liver function test, and assessment of serum ferritin levels and fasting lipid profile including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs) levels.
Patients with β-thalassemia major showed significantly lower total cholesterol, HDL-cholesterol, and LDL-cholesterol when compared with controls. Serum TG levels of β-thalassemia major patients were found to be significantly higher than the levels in control individuals. Our results revealed that the lipid profile changed in patients with thalassemia major.
In thalassemic patients, adequate chelation therapy with normalization of serum ferritin level and monitoring of TGs is highly recommended, and they are treated aggressively if the levels are increased. Several interventions including antioxidant therapy and vitamin-lowering and lipid-lowering agents should be used in high-risk patients with β-thalassemia major to decrease the risk of atherosclerosis.
Keywords: lipid profile, serum ferritin, β-thalassemia major
|How to cite this article:|
Sayed SZ, Maher SE, Adel G, Hamdy L. Lipid profile in children with β-thalassemia major. Egypt J Haematol 2012;37:183-6
| Introduction|| |
Thalassemia is the most common heterogenous genetic disorder in which the production of normal hemoglobin is partly or completely suppressed because of defective synthesis of one or more globin chains, which vary widely in severity from asymptomatic forms to severe or even fatal entities 1. Patients with β-thalassemia major may go through several complications including transfusion-related infections such as HBV, HCV, and HIV. Iron overload complications are also noticed, which include endocrinopathies, heart and liver disease, chelation therapy complications, and bacterial infections 2.
Thalassemic patients are also subjected to peroxidative tissue injury. It has been documented that circulating low-density lipoprotein (LDL) in thalassemic patients shows marked oxidative modification that could represent an event leading to pathogenesis. Free-radical production is increased in patients with iron overload 3. Selimoglu et al. 4 suggested that both serum iron and triglycerides (TGs) are involved in the pathogenesis of LDL oxidation.
Aim of the work
The aim of this study was to assess whether there is any change in lipid profile in patients with β-thalassemia major that may predispose to early atherosclerotic changes, and hence whether there could be any medical intervention to delay or slow this process.
| Patients and methods|| |
Our study was conducted on 50 patients with β-thalassemia major who were regularly followed up in the Pediatric Hematology Outpatient Clinic, Suzan Mubark University Hospital, El-Minia University, from October 2009 to April 2010. There were 22 boys and 28 girls with ages ranging from 5 to 14 years. The control group consisted of 25 apparently healthy children with age and sex matched to the diseased group, which included 11 boys and 14 girls with ages ranging from 5 to 14 years. The studied children were classified as follows:
Group I: This group included 50 patients who were diagnosed as having β-thalassemia major.
Group II: This group included 25 apparently healthy children as the control group.
The studied groups were subjected to the following assessments:
Thorough history taking:
- age of the child and age at onset;
- manifestation of anemia;
- frequency of blood transfusion;
- history of medication (including iron chelation therapy, folic acid, and others);
- history of splenectomy;
- family history of a similar condition;
- history of consanguinity.
- General examination:
(i) measurement (weight, height, head circumference);
(ii) vital signs;
(iii) thalassemic feature.
- Systemic examination:
(iv) chest examination;
(v) heart examination;
(vi) abdominal examination.
Laboratory investigation included the following:
- Complete blood count using Sysmex (Sysmex Corporation, Kobe, Japan).
- Lipid profile: The serum levels of total cholesterol and TGs were determined with a fully automated clinical chemistry autoanalyzer system [Konelab (201); Thermo Electron Corporation, Vantaa, Finland].
- Liver enzymes: alanine transaminase (ALT) and aspartate transaminase (AST).
- Serum ferritin using enzyme-linked immunosorbent assay.
High-density lipoprotein (HDL)-cholesterol level was determined by means of the colorimetric method using Micro Lab 200 (Vital Scientific NV, DIERN, Netherland). Reagents were supplied by Human Gesellschaft für Biochemica and Diagnostica GmbH (Wiesbaden, Germany).
LDL-cholesterol level was calculated using the Friedewald equation 5.
The standard computer program SPSS for windows, release 13.0 (SPSS Inc., Chicago, Illinois, USA), was used for data entry and analysis. All numeric variables were expressed as mean±SD. Comparisons of different variables in various groups were made using the Student t-test and the Mann–Whitney test for normal and nonparametric variables, respectively. The χ2-test was used to compare the frequency of qualitative variables among the different groups. Pearson’s and Spearman’s correlation tests were used for correlating normal and nonparametric variables, respectively. Multiple regression analysis was also performed to determine the effect of various factors on a dependent variable. A P value less than 0.05 was considered significant. For all tests, a graphic presentation of the probability of the results was also made.
| Results|| |
The results of the present study are presented in [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6] and [Table 7].
|Table 3: Correlation between serum ferritin and liver function in the studied cases|
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|Table 5: Correlation between lipid profile and serum ferritin in the patient group|
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|Table 6: Correlation between frequency of blood transfusion and lipid profile in the patient group|
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|Table 7: Comparison of laboratory finding between patients treated with and those not treated with chelation|
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| Discussion|| |
Thalassemias are genetic disorders that encompass a wide variety of clinical phenotypes, ranging in severity from clinically silent heterozygous β-thalassemia to severe transfusion-dependent thalassemia major. Among others, clinical features of thalassemia include vascular complications, such as pulmonary thromboembolism, cerebral thrombosis, and leg ulcer. Consistent with the pathogenesis of such events, the data indicate that vascular endothelial cells are injured in thalassemia patients 6. Patients with β-thalassemia major may go through several complications such as transfusion-related infections like HBV, HCV, and HIV 2.
Iron overload complications are also noticed, which include endocrinopathies, heart and liver diseases, chelation therapy complications, and bacterial infection 7. There is increasing evidence suggesting that the oxidative modification of LDLs is the key step in the sequence of events leading to atherosclerosis-related vascular alterations. Modified LDL is internalized in monocyte-derived macrophages through cell surface scavenger receptors, an event that leads to foam cell formation. Infiltration and deposition of these cells in the arterial wall are considered the initiating steps to the development of atherosclerotic plaque 8.
Many reports have concluded that circulating LDL in thalassemia major patients is more susceptible to the oxidation of the iron load secondary to continuous blood transfusions. Nevertheless, the elevation of iron alone may lead to the free-radical reaction causing oxidative stress to LDL, but other factors are required, such as depletion of antioxidant defenses and decrease in HDL. In addition, an important role of unpaired hemoglobin chains and red blood cell hemolysis products is also under consideration, as it has been observed that the interaction between hemoglobin α-chain and LDL leads to the oxidative modification of LDL 8.
In this study, we tried to evaluate the lipid profile in β-thalassemia major patients. We found that there was a significant decrease in hemoglobin concentration in β-thalassemia major patients compared with the normal control group (P<0.0001). In contrast, ferritin concentration was very highly statistically significantly increased in these patients when compared with normal controls (P<0.0001). Furthermore, liver enzymes (AST and ALT) were statistically significantly higher in our thalassemic patients compared with normal controls (P<0.0001).
Our results are in agreement with the results obtained by Williams 9, who stated that thalassemic patients have iron overload, probably because of multiple blood transfusions, increased dietary iron absorption, or inadequate chelation therapy, and liver affection could occur as a direct consequence of iron toxicity.
In addition, our results agree with those of Lanzkowsky 10, who stated that iron overload in thalassemic patients is caused by excessive hemolysis, a decrease in the life span of red blood cells, and by blood transfusions. In addition, thalassemic patients absorb too much iron from food because of the abnormally low levels of a small peptide, hepcidin, which regulates iron uptake from the gut. Moreover, he stated that the majority of his patients were incompliant to chelation therapy.
We found that total cholesterol, HDL-cholesterol, and LDL-cholesterol were statistically significantly low in thalassemic patients when compared with normal controls (P<0.0001). However, serum TG levels were statistically significantly higher in our patients when compared with the normal control group (P<0.0001).
Our results are in agreement with the results obtained by Shalev et al. 11, who stated that the mechanism of hypocholesterolemia in thalassemia major includes increased erythropoietic activity, resulting in increased cholesterol requirements and liver injury due to iron overload. In addition, increased uptake of LDL by macrophages and histiocytes of the reticuloendothelial system is the main determinant of low plasma cholesterol levels in patients with β-thalassemia major.
In contrast, Mario et al. 12 reported that in thalassemic patients there were higher TG, LDL, and HDL concentrations compared with controls. They explained their results by the reduction in extrahepatic lipolytic activity, which could account for the rise in circulating TG in thalassemic patients. There are some clues that iron overload, steatosis, and chronic viral infections from repeated hemotransfusions may induce hepatic acute-phase response, which is associated with an enhanced LDL secretion.
We also found that there was a positive correlation between serum ferritin and liver enzymes in our thalassemic patients (P<0.0001). Our results are in agreement with those of Cohen et al. 13, who explained this by revealing the hepatic damage caused by iron deposition. Iron overload produces cellular injury with progression to fibrosis and cirrhosis. In addition, our results are in agreement with the results obtained by Hershko and Hoffbrand 14, who stated that liver disease or inflammation will result in high serum ferritin levels.
In this study, a significant statistical positive correlation between TG and age was detected (P<0.0001). In contrast, there was a negative correlation between cholesterol, HDL, and age, but of nonstatistical significant value. Our results are in agreement with the results obtained by Flavio 15, who found a positive correlation between TG levels and age among patients with the major form of β-thalassemia. In contrast, we disagree with Kamal and Talal 16 who reported that the lipid profile in thalassemia major patients is not influenced by age.
There was a significant positive correlation between serum ferritin and TG levels in our patients (P=0.03). In contrast, there was a negative correlation between serum ferritin and both total and LDL-cholesterol levels, but of nonstatistical significant value. In addition, we observed a nonstatistically significant positive correlation between serum ferritin and HDL levels.
Our results are in agreement with the results obtained by Selimoglu et al. 4, who stated that these results might support the hypothesis that both serum iron and TGs are involved in the pathogenesis of LDL oxidation. In contrast, Kamal and Talal 16 in their study found that the lipid profile in thalassemia major patients is not influenced by serum ferritin.
In the present study, we observed that there was a positive significant correlation between the frequency of blood transfusion and cholesterol levels (P=0.04). In contrast, there was a nonsignificant correlation between frequency of blood transfusion and both LDL and HDL in β-thalassemia cases. The increased level of cholesterol could be explained by the fact that liver affection could occur as a direct consequence of iron toxicity caused by massive blood transfusion, resulting in decreased cholesterol uptake by the liver and hence increased level in the blood.
In contrast, Giardini et al. 17 detected a negative correlation between the frequency of blood transfusions and cholesterol levels; they stated that low plasma cholesterol levels in β-thalassemia major patients was due to hepatic damage caused by iron overload as a result of massive blood transfusions, leading to lowered liver secretion of cholesterol.
Our study showed that there was a very high level of serum ferritin in most of the β-thalassemia major patients (84%) despite receiving chelation therapy, which could be attributed to inadequate chelation therapy, multiple blood transfusions, and increased dietary iron absorption. The remaining (16%) cases of β-thalassemia major did not receive any chelation therapy at all, as their serum ferritin level (535.8±305.6) was below the therapeutic level of chelation, which is 1000 μg/l according to Beutler 18.
With regard to the lipid profile, we observed that, although serum ferritin levels of chelated patients were highly significantly increased compared with those of nonchelated patients, the level of HDL was significantly increased (P=0.008) and the level of LDL was decreased (P=0.06). These observations point to the advantage of chelation therapy in the modification of lipid profile in β-thalassemia major patients in a manner that protects them against early atherosclerosis, or in other words slows down the process of atherosclerotic changes.
We observed that, although serum ferritin levels of chelated patients were highly significantly increased compared with those of nonchelated patients, their liver enzymes (AST and ALT) were statistically significantly lower than those of nonchelated patients (P=0.0001 and 0.004, respectively). These results refer to the advantage of chelating therapy on liver function. Our results were in agreement with the results obtained by Hershko and Hoffbrand 14, who stated that chelation therapy reduces hepatic iron toxicity and improves liver function.
| Conclusion|| |
β-Thalassemia major patients showed significantly lower total cholesterol, HDL-cholesterol, and LDL-cholesterol when compared with controls. Serum TG levels of β-thalassemia major patients were found to be significantly higher than the levels in control individuals. Our results revealed that the lipid profile changed in patients with thalassemia major.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]