No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Abnormal low and high density lipoproteins in homozygous beta-thalassemia
British Journal of Haematology
Abstract
The levels, structure and composition of plasma lipoproteins were determined in 67 patients with homozygous beta-thalassaemia and compared to healthy or heterozygous members of the same families and to patients with either sickle cell or iron deficiency anaemia. Plasma total and LDL and HDL cholesterol levels were low in patients with homozygous beta-thalassaemia and with sickle cell anaemia. Plasma triglycerides did not differ between subjects. The low plasma and lipoprotein cholesterol was independent of age, transfusion requirements and splenectomy.
Abnormal structure and composition of lipoproteins was found in homozygous beta-thalassaemia. The LDL was of higher density and was triglyceride-rich and cholesterol ester-poor. HDL separated to three populations. HDL2 was prominent (in spite of low plasma HDL cholesterol). HDL2–3 was of normal density and an intermediate HDL population, not found in normal subjects, was identified and designated HDL2–3. All three HDL populations were enriched with triglycerides and poor in cholesterol ester content. The modified LDL and HDL particles may then be possibly cleared rapidly from the plasma by activated monocytes and macro-phages.
... The results have been reported to be consistent with previous findings in patients with altered lipid profile of beta thalassemia major patients in different populations. This alteration may possibly lead to increase level of circulating TG due to decrease extrahepatic lipolytic activity and additionally may reduce hepatic synthesis due to iron overload in patients with anemia [4]. Considering the heterogeneity of beta-thalassemia mutations in different regions of the World as well as different environmental factors might mislead physicians for preventive medicine, we decided to investigate the lipid profiles in patients with TM and TI and examine the possible association with dyslipidemias causing susceptibility PPAR-α gene variants in the population of Turkish Cypriots, where the prevalence of thalassemia and carriers are very high. ...
... To our knowledge, this is the first study in the relevant literature to look the PPARA gene polymorphisms in Turkish Cypriot beta-thalassemia major, intermediate, and trait subjects and better understand the effect on serum lipid profile. Goldfard et al., [4]. demonstrated that homozygous beta-thalassemia patients have abnormal structure and composition of lipoproteins including high density of LDL was of higher density with rich for triglyceride and poor in cholesterol ester. ...
... demonstrated that homozygous beta-thalassemia patients have abnormal structure and composition of lipoproteins including high density of LDL was of higher density with rich for triglyceride and poor in cholesterol ester. Hepatic damage, low hepatic and extrahepatic lipase enzyme activity are causing modified HDL and LDL's (by triglyceride-rich and poor in cholesterol ester) therefore monocytes and macrophages are responsible for disrupting those molecules [4]. Additionally, there are many factors for serum lipid changes in children with beta-thalassemia, such as iron overload, liver damage, and hormonal disorders [6]. ...
... The results have been reported to be consistent with previous findings in patients with altered lipid profile of beta thalassemia major patients in different populations. This alteration may possibly lead to increase level of circulating TG due to decrease extrahepatic lipolytic activity and additionally may reduce hepatic synthesis due to iron overload in patients with anemia [4]. Considering the heterogeneity of beta-thalassemia mutations in different regions of the World as well as different environmental factors might mislead physicians for preventive medicine, we decided to investigate the lipid profiles in patients with TM and TI and examine the possible association with dyslipidemias causing susceptibility PPAR-α gene variants in the population of Turkish Cypriots, where the prevalence of thalassemia and carriers are very high. ...
... To our knowledge, this is the first study in the relevant literature to look the PPARA gene polymorphisms in Turkish Cypriot beta-thalassemia major, intermediate, and trait subjects and better understand the effect on serum lipid profile. Goldfard et al., [4]. demonstrated that homozygous beta-thalassemia patients have abnormal structure and composition of lipoproteins including high density of LDL was of higher density with rich for triglyceride and poor in cholesterol ester. ...
... demonstrated that homozygous beta-thalassemia patients have abnormal structure and composition of lipoproteins including high density of LDL was of higher density with rich for triglyceride and poor in cholesterol ester. Hepatic damage, low hepatic and extrahepatic lipase enzyme activity are causing modified HDL and LDL's (by triglyceride-rich and poor in cholesterol ester) therefore monocytes and macrophages are responsible for disrupting those molecules [4]. Additionally, there are many factors for serum lipid changes in children with beta-thalassemia, such as iron overload, liver damage, and hormonal disorders [6]. ...
... The results have been reported to be consistent with previous findings in patients with altered lipid profile of beta thalassemia major patients in different populations. This alteration may possibly lead to increase level of circulating TG due to decrease extrahepatic lipolytic activity and additionally may reduce hepatic synthesis due to iron overload in patients with anemia [4]. Considering the heterogeneity of beta-thalassemia mutations in different regions of the World as well as different environmental factors might mislead physicians for preventive medicine, we decided to investigate the lipid profiles in patients with TM and TI and examine the possible association with dyslipidemias causing susceptibility PPAR-α gene variants in the population of Turkish Cypriots, where the prevalence of thalassemia and carriers are very high. ...
... To our knowledge, this is the first study in the relevant literature to look the PPARA gene polymorphisms in Turkish Cypriot beta-thalassemia major, intermediate, and trait subjects and better understand the effect on serum lipid profile. Goldfard et al., [4]. demonstrated that homozygous beta-thalassemia patients have abnormal structure and composition of lipoproteins including high density of LDL was of higher density with rich for triglyceride and poor in cholesterol ester. ...
... demonstrated that homozygous beta-thalassemia patients have abnormal structure and composition of lipoproteins including high density of LDL was of higher density with rich for triglyceride and poor in cholesterol ester. Hepatic damage, low hepatic and extrahepatic lipase enzyme activity are causing modified HDL and LDL's (by triglyceride-rich and poor in cholesterol ester) therefore monocytes and macrophages are responsible for disrupting those molecules [4]. Additionally, there are many factors for serum lipid changes in children with beta-thalassemia, such as iron overload, liver damage, and hormonal disorders [6]. ...
Beta-thalassemiais one of most common autosomal recessive hematologic disorder. Alterations in the lipid profile have been reported consistent with β-thalassemia, but the pathogenesis is not clear. Genetics variations within in both the coding and noncoding regions of the PPAR-alfa gene locus contribute to dyslipidemias and imply hematologic risks. Therefore, this study is designed to investigate the lipid profiles in patients with β-thalassemia major and intermediate and examine the possible association with dyslipidemias causing susceptibility PPAR-α gene variants in the population of Turkish Cypriots, where the prevalence of thalassemia and carriers are very high. Our results showed the strong association with the PPAR-α rs4253778 CC genotype and triglyceride in beta-thalassemia major and intermediate patient. It is tempting to speculate here that the PPAR-α gene rs4253778 CC genotype could possibly impair triglyceride metabolism more effectively in beta thalassemia major and intermediate subjects. Overall, the results from our study establish the homozygous wild-type C allele at the PPAR-α rs4253778 locus as a genetic risk factor with a riglyceride-elevating effect in a population of Turkish Cypriot β-thalassemia patients.
... [3] reported significantly lower levels of TC, HDL-C, LDL-C and TG in TM patients receiving regular DFO therapy, as compared to controls. Similar findings in TM patients, except that TG was not significantly different [11,12] or was significantly high [4, [13][14][15][16] were also reported. Similar findings regarding HDL-C and TC in TM patients on DFO [17,18] were also reported; TG did not significantly differ between study groups in another study [19]. ...
... Goldfarb et al. [12] reported lower TC and LDL-C and higher HDL-C levels in TI compared to TM patients. Hartman et al. ...
... Oxidative stress seen in TM leads to increased uptake of LDL-C and HDL-C by macrophage/ monocyte system [4,5]. In TM, LDL and HDL particles themselves have abnormal lipid composition with low cholesterol and high TG [3,5,12]. A protective factor in TM patients is chelation therapy with DFO, because this treatment was shown to inhibit LDL oxidation independent of its iron chelation property [4,20]. ...
Abstract
Objectives: (a) To determine the differences in lipid profile parameters between thalassemia major (TM) patients not taking desferroxamine (DFO) who show signs of iron overload (IOL) and those well-controlled TM patients on DFO therapy.
(b) To determine the effects of age and BMI on measured parameters in both groups.
Subjects and Methods: The study was conducted in Thalassemia Center at Ibn-Al-Atheer Pediatric Hospital in Mosul from October 2007 to April 2008. Twenty patients with TM were selected as follows: Ten patients on DFO therapy with no signs of IOL and ten TM patients not on DFO therapy and showing signs of IOL. Data were presented as mean ± SD; independent samples t-test was used in comparing both groups, while effects of age and BMI on measured parameters were determined by using Pearson correlation.
Results: Total cholesterol (TC), triglyceride (TG), Very low density lipoprotein (VLDL-C), low density lipoprotein (LDL-C) and atherogenic index (AI) showed significant increase in IOL group, while serum high density lipoprotein (HDL-C) showed significant reduction in IOL group, when compared to the second group. Age and BMI show no significant correlation with measured parameters in well-controlled group, while in IOL group, BMI showed positive correlation with LDL-C and AI.
Conclusion: Significant changes in lipid profile parameters were seen in TM patients not taking DFO therapy and showing signs of IOL compared to those well-controlled patients on DFO therapy
... The low cholesterol levels were related to depletion of vitamin E and severity of thalassemia [10,13]. Oxidative modification of thalassemic LDL had been reported [14,15] which was related to the increased protein and triglyceride (TG) content but decreased cholesterol and vitamin E content [14]. Circulating malondialdehyde (MDA) is an oxidative stress marker and tissue injury via lipid peroxidation. ...
... The low cholesterol levels were related to depletion of vitamin E and severity of thalassemia [10,13]. Oxidative modification of thalassemic LDL had been reported [14,15] which was related to the increased protein and triglyceride (TG) content but decreased cholesterol and vitamin E content [14]. Circulating malondialdehyde (MDA) is an oxidative stress marker and tissue injury via lipid peroxidation. ...
... In our study, all b-TM patients had iron overload, elevated serum liver profiles (TB, DB, AST, ALT, and ALP), increased oxidative stress, decreased TAC level and decreased TC, LDL-C and HDL-C levels [14] were commonly occurred in b-TM patients. Both increased lipid peroxidation and decreased TAC mean that all circulating antioxidant defenses are overwhelmed and organs, HDL-C and other antioxidant agents are no longer protected and undergo oxidative damage. ...
Blood transfusion can be a life-saving therapy for β-thalassemia major and β-thalassemia/HbE (β-TM) patients with chronic anemia, major caused severe iron overload particularly in β-TM patients received only blood transfusion therapy. We aim to evaluate the association of iron overload with oxidative stress, liver damage, and elevated very low density lipoprotein cholesterol (VLDL-C) in transfusion-dependent β-TM patients. Serum ferritin, malondialdehyde (MDA), liver profiles, triglycerides levels, and VLDL-C were significantly higher while total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and total antioxidant capacity were lower in β-TM than controls. Serum ferritin was significantly correlated with MDA, liver enzymes and lipid profiles (p < 0.05). Multiple forward stepwise linear regression analyses of the significant variables showed that in these β-TM patients, independent predictors of iron overload were MDA (β = 0.410, r
2 = 0.671, p < 0.001), ALT (β = 0.493, r
2 = 0.578, p < 0.001), and VLDL-C (β = 0.253, r
2 = 0.711, p < 0.001). In conclusion, iron overload associated with increased oxidative stress, lipid peroxidation, liver damage, decreased TC, LDL-C, HDL-C and over production of VLDL-C, is significantly problem in transfusion-dependent β-TM patients. These appeared the major cause of future morbidity and mortality in β-TM patients.
... The low cholesterol levels were related to depletion of vitamin E and severity of thalassemia [10, 13]. Oxidative modification of thalassemic LDL had been reported [14, 15] which was related to the increased protein and triglyceride (TG) content but decreased cholesterol and vitamin E content [14]. Circulating malondialdehyde (MDA) is an oxidative stress marker and tissue injury via lipid peroxidation. ...
... The low cholesterol levels were related to depletion of vitamin E and severity of thalassemia [10, 13]. Oxidative modification of thalassemic LDL had been reported [14, 15] which was related to the increased protein and triglyceride (TG) content but decreased cholesterol and vitamin E content [14]. Circulating malondialdehyde (MDA) is an oxidative stress marker and tissue injury via lipid peroxidation. ...
... MDA in thalassemic erythrocytes was substantially greater compared to controls (p \ 0.001), which accords with previous work [27]. This increased MDA reaffirms the assumption that it reacts with membrane polyunsaturated fatty acid leading to hemolysis [14, 22]. A similarly membrane labiality may contribute to cell death in other tissues. ...
... TC and LDL-C seemed similarly decreased in i-trait carriers compared to controls [13] , whereas HDL-C and TG concentration were usually unmodified. Only limited data are available on lipoprotein percentage composition in homozygotes [10] , while i-trait carriers have been completely overlooked . We have previously suggested that low TC and LDL-C levels in homozygous i-thalassemic patients are largely ascribable to a diminished hepatic function [8,9] , while a faster LDL catabolic rate could be involved in heterozygotes whose liver activity and synthetic capacity is largely normal [13]. ...
... TG concentrations, on the other hand, were higher than control levels and all lipoprotein classes were TG-enriched. To our knowledge , only one other study examined the lipoprotein composition of i-thalassemia major patients in some detail [10] and, in spite of the larger number of subjects we analyzed our results confirm this. An impaired liver function might be a likely explanation for the decreased lipoprotein levels [27], while a reduced extrahepatic lipolytic activity (as we have already demonstrated) [28] could account for the rise in circulating TG and their quickened interchange from VLDLs to other plasma lipoproteins through neutral-lipid transfer activities [29]. ...
... The same mechanism could determine an LDL-class shift towards protein-rich, denser particles [31], and our findings of an increased LDL-protein content and higher apo B:LDL-C ratio in Cooley's patients, corroborates this hypothesis. Goldfarb et al. have similarly found, by zonal ultracentrifugation, that LDLs eluted later in patients with thalassemia major, that is they were heavier than in control subjects [10]. i-Trait carriers showed borderline reductions in TC and LDL-C, thus confirming our previous observation in a larger group [13]; they also had significantly lower apolipoprotein levels than control subjects. ...
Patients with homozygous beta-thalassemia show an abnormal lipoprotein profile. In asymptomatic heterozygotes the lipid pattern is less markedly affected but interestingly related to a diminished cardiovascular risk. The extent and significance of these findings are still a matter of debate and no data are available on lipoprotein(a) plasma levels. Seventy patients with homozygous beta-thalassemia (HT-P), 70 beta-thalassemia trait carriers (TT-C) and 70 sex and age-matched controls were investigated and their plasma lipoprotein profile and apo(a) phenotypes determined. In a subgroup of these same subjects (12 HT-P, 12 TT-C and 24 controls) and in 12 bone marrow-transplanted homozygous beta-thalassemic patients (BMT-P) plasma lipoprotein composition was assessed. HT-P disclosed significantly lower total-cholesterol, LDL-cholesterol, HDL-cholesterol, apo A-I, apo B plasma levels and higher triglyceride concentration than TT-C (-7, -11, -8, -8, -13 and +11%, respectively) or controls (-39, -50, -46, -32, -30 and + 35%, respectively). All lipoprotein subclasses were triglyceride-enriched, while LDLs were also protein-enriched and HDLs protein-depleted. TT-C disclosed a small but significant reduction in apo A-I and apo B plasma levels but only minor lipoprotein abnormalities with respect to the controls. BMT-P lipoprotein composition was intermediate between HT-P and normal subjects. Apo(a) plasma levels did not differ among the groups. A higher prevalence of 'small' apo(a) isoforms was present in HT-P. Within the same 'isoform group', apo(a) plasma levels were significantly lower in HT-P than in TT-C or controls. Since liver cirrhosis is almost always present in HT-P, it is conceivable that an altered hepatic apo(a) synthesis or catabolism due perhaps to diminished apolipoprotein glycation may be involved. In TT-C a partially improved cardiovascular risk profile was apparent (low hematocrit, low LDL-cholesterol and apo B), thus justifying the claim for a low prevalence of ischemic heart disease, but no Lp(a) plasma level modification could be detected.
... The inputting and analyzing data were done by using SPSS (20). All results were readout as Mean±SD and ANOVA one step test was used to find out the significance among the studied groups for each parameter. ...
... The lipoprotein particles are measured with a lipid profile. It is divided by their density into high-density lipoproteins (HDL), low-density lipoproteins (LDL), and very lowdensity lipoproteins (VLDL) [11].Hypocholesterolemia in all phenotype of thalassemia patients has been reported since the beginning of the20th century [12][13][14][15][16][17][18][19][20][21]. Our result agree with the study of Hartman et al., that explain TI patients showed significantly lower TC, HDL-C and LDL-C compared with TM, and TM lower than control group. ...
β-Thalassemia is hereditary blood disorders characterized by reduced synthesis of the beta chains of hemoglobin resulting to microcytic hypochromic anemia. Hypocholesterolemia is reported in recent studies in other countries. We estimated the level of triglyceride (T.G.), total cholesterol, high density lipoprotein (H.D.L) and low density lipoprotein (L.D.L) for seventy three patients with β-Thalassemia major(TM), (42 male and 31 female) and twenty patients with β-Thalassemia intermedia (TI), (10 Male and 10 Female) with thirty healthy participants (15 Male and 15 Female) as a control in Iraq, Their ages range was 18-30 years. The results show the level of all cholesterol species for TI is significantly decrease as comparison with TM and the last one is significantly decreases as comparison with control group. We found no association of serum lipid profile with age, sex, Hb and platelets.
... There are a few theories to explain the possible mechanisms involved in the regulation of plasma lipids by the spleen [7][8][9][10][11] . There is evidence that there would be a splenic factor able to determine the occurrence of hypocholesterolemia in hypersplenism, the spleen being compared to a lipid reservoir, which rises in cases of hypersplenism [7][8][9] . ...
... The splenic macrophages accumulate large amounts of fat through increased phagocytosis, with subsequent hypolipidemia. Another explanation for the lipidlowering effect would be the immune action of the mononuclear phagocyte system against structures found in the high density lipoprotein (HDL) and LDL, resulting in their clearance 10,11 . Caligiuri et al. 12 stated that the spleen influenced lipid metabolism through the B lymphocytes, which were capable of producing anti-oxidized-LDL antibodies. ...
Objective:
To elucidate the role of the spleen and splenic allograft in lipid control and evaluate its effect on the lipid profile of rats.
Method:
32 male Wistar rats were randomly assigned into four groups: control group (1), total splenectomy group (2), splenectomy and implantation of allograft group (3) and double spleen group (4). Each group was subdivided into two subgroups: A and B, based on the death of the animals after 30 or 120 days of monitoring. The procedures in groups 2, 3 and 4 were made simultaneously, and splenectomized animals, groups 2 and 3 were donors, respectively, for the animals of groups 3 and 4. In group 4 the spleen was preserved and the animals received implants from the spleens of rats from group 3. The regeneration of splenic tissue was evaluated by macroscopic and microscopic analyzes of the grafts and own spleens, as well as with measurements of VLDL, HDL, LDL, total cholesterol and triglycerides.
Results:
after 120 days, Group 4 showed levels of total cholesterol and LDL lower than the other groups. Group 1 had higher levels of lipids.
Conclusion:
The technique of double spleen was effective in the control of lipid metabolism, corroborating the function of the spleen as a reserve of lipids.
... Abnormal lipid profile has been repeatedly reported in all clinical phenotypes of β-thalassemia including thalassemia major, thalassemia intermedia and thalassemia minor [7][8][9][10][11]. Patients with β-thalassemia trait have been found to have lower plasma concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), but unmodified plasma levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) [12,13]. ...
... Previous studies have consistently shown a higher rate of aggression, violence and impulsivity as well as suicidal behaviors in individuals with low cholesterol level [15][16][17][18][19][20][21][22][23], due to reduction of serotonergic activity in the brain [27][28][29][30]. Given that thalassemia patients (major, minor and intermedia) have lower cholesterol levels [7][8][9][10][11][12][13][32][33][34][35][36] one may assume that carrier state may represent a risk factor for these behaviors [37]. Considering the high prevalence of carrier individuals in our population, we were concerned about the emerging problem of the increase of emotional distress, unstable interpersonal relationships and marriage difficulties. ...
Psychology is an international journal dedicated to the latest advancement of psychology. The goal of this journal is to provide a platform for doctors and academicians all over the world to promote, share, and discuss various new issues and developments in psychology related problems. All manuscripts must be prepared in English, and are subject to a rigorous and fair peer-review process.
... Lipid abnormality has been frequently reported in thalassemia, but its pathophysiology is not totally clear. [32][33][34][35][36][37][38][39][40] In our study we found that serum TG was significantly higher in patients compared to controls and correlated well with serum glucose, cholesterol, AST, ALT, iron, ferritin, and age. Hypertriglyceridemia was observed in 34.6% of the patients while it was seen in 6.6% of the controls. ...
... Maioli and colleagues in their studies published from 1984 to 1997 suggested that liver damage, accelerated erythropoiesis, and an increased uptake of low-density lipoprotein (LDL) by macrophages and histiocytes of the reticuloendothelial system are the main determinants of low plasma cholesterol in thalassemia. 37,38 In 1991 Goldfarb and colleagues found low plasma cholesterol and abnormality in structure and composition of lipoproteins in TM. 39 They found that all 3 high-density lipoprotein (HDL) populations were enriched with TG and poor in cholesterol ester contents. It is said that anemia, activating the macrophage system and liver dysfunction, interrelates to the final serum lipoprotein pattern. ...
Objectives: The aim of this study was the evaluation of glycometabolic function, lipid profile, and liver function in patients with (3 thalassemia major (TM) and their relationship with serum iron and ferritin Methods: Fasting serum glucose, insulin, cholesterol, triglyceride (TG), and liver enzymes were evaluated for 78 homozygous TM patients and 122 normal control subjects Serum iron, ferritin, and insulin resistance index (IRI) were determined for them Results: Fasting serum glucose, TG, aspartate transaminase (AST) levels, alanine transaminase (ALT) levels, and IRI were significantly higher in the homozygous TM patients than in the controls (P<0 0001 for all). Serum cholesterol was significantly lower in patients (P=0 003), and 5 1% of cases had diabetes mellitus. Conclusions: Impaired glucose and lipid metabolism, and also liver dysfunction were observed in about 18%, 30%, and 20% of the patients, respectively. Normoinsulinemia and a high IRI suggest beta cell failure. Better evaluation of iron toxicity can protect patients from complications associated with treatment.
... A person with this condition simply carries the genetic trait for beta thalassemia and will usually experience no health problems other than a mild anemia 2. It is well established that beta thalassemia has a major impact on plasma lipids and lipoproteins 3 . In severe beta thalassemia (thalassemia major and intermedia), hypocholesterolemia caused by a marked reduction of both LDL and HDL has been consistently reported [3][4][5][6][7] ; in parallel, in beta thalassemia carriers (thalassemia minor), total cholesterol and LDL levels tend to be lower than those found in age and sex-matched controls 6,7 . A wide study conducted in the Sardinian population not only proved that beta thalassemia carriers have a lower total and LDL cholesterol level than do controls but also showed a small but significant reduction of apoB and apoA-I levels and borderline changes in lipid and protein composition in LDL and HDL 8,9 . ...
... A person with this condition simply carries the genetic trait for beta thalassemia and will usually experience no health problems other than a mild anemia 2. It is well established that beta thalassemia has a major impact on plasma lipids and lipoproteins 3 . In severe beta thalassemia (thalassemia major and intermedia), hypocholesterolemia caused by a marked reduction of both LDL and HDL has been consistently reported [3][4][5][6][7] ; in parallel, in beta thalassemia carriers (thalassemia minor), total cholesterol and LDL levels tend to be lower than those found in age and sex-matched controls 6,7 . A wide study conducted in the Sardinian population not only proved that beta thalassemia carriers have a lower total and LDL cholesterol level than do controls but also showed a small but significant reduction of apoB and apoA-I levels and borderline changes in lipid and protein composition in LDL and HDL 8,9 . ...
Minor beta thalassemia is a disorder without any special symptom which only causes mild anemia. In thalassemic patients accelerated erythropoiesis and enhanced cholesterol consumption have been suggested as the dominant mechanism for low level of lipoproteins. Hyperlipidemia is a risk factor for cardiovascular diseases and hence, low level of serum lipids can act as a protective factor. Because of the differences between social, economic, cultural conditions, dietary habits and genetics patterns among Iranians with other nations, this survey was conducted to verify these parameters among our thalassemia minor subjects. This study was carried out on 100 thalassemia carriers and 200 normal controls. Blood samples were collected and the biochemical evaluation was performed for measuring serum total cholesterol, LDL, HDL, TG, VLD. Descriptive statistical tables, independent t-test, Mann-Whitney and Chi-square were used for analyzing the data. The average values of serum total cholesterol, TG, LDL, HDL and VLDL in thalassemia minor subjects were 163.63 +/- 34.28, 159.74 +/- 157.54, 90.97 +/- 23.94, 34.97 +/- 8.07 and 73.44 +/- 72.43 mg/dl respectively. Moreover, the mean levels of total cholesterol, TG, LDL, HDL and VLDL in normal subjects were 192.77 +/- 37.27, 155.67 +/- 109.58, 123.42 +/- 33.57, 38.02 +/- 15.6 and 71.57 +/- 50.5 mg/dl respectively. The amount of serum total cholesterol and LDL in thalassemia carriers was significantly lower than normal subjects that shows the potential decline of cardiovascular and brain vessels diseases among thalassemia minor subjects compared to control group while other factors between the two groups did not show any significant difference.
... 13 Oxidative modification of thalassemic LDL had been reported, which was related to the increased protein and triglyceride (TG) content, but decreased cholesterol and vitamin E content. 14 Hartman et al. 15 described the mechanisms of hypocholesterolemia in TDT patients as hemodilution due to anemia, excessive requirement of cholesterol due to erythroid hyperplasia, increased cytokine release due to the activated macrophage system, increased cholesterol uptake by the activated reticuloendothelial system and hepatic damage secondary to iron overload. Research by Sharif et al. 16 also showed similar increase in serum TG levels similar to our study. ...
Objective:
This study endeavored to assess the lipid profile and atherogenic lipid indexes in children with transfusion-dependent thalassemia (TDT) and to compare them with matched healthy children.
Method:
The study group consisted of a total of 72 TDT patients aged 3 to14 years, while the control group had 83 age- and sex-matched healthy children. The fasting lipid profile and lipid indexes were estimated and the atherogenic index of plasma (AIP), Castelli's risk indexes I and II, atherogenic coefficient were calculated and compared between the two groups.
Result:
Compared to the control group, the mean LDL, HDL and cholesterol levels were significantly lower among the case group (p-value < 0.001). The mean VLDL and triglycerides were significantly higher in the case group (p-value < 0.001). Lipid indexes, including the atherogenic index of plasma (AIP), Castelli's risk indexes I and II and atherogenic coefficients were significantly higher in TDT children.
Conclusion:
Dyslipidemia and increased risk of atherosclerosis were found in TDT children, as they had elevated atherogenic lipid indexes. Our study underlines the importance of the routine use of these indexes in TDT children. Future studies should focus on lipid indexes in this high-lipid group of children so that preventive strategies can be planned accordingly.
... This alteration is likely due to diminished hepatic biosynthesis as of anemia and iron overload, while a reduced extra hepatic lipolytic activity could account for the rise in circulating TG. Iron-loading and the effects of repeated blood transfusions induce a hepatic acute-phase response, which could determine an LDL-class shift towards protein-rich, denser particles 7,8 Some authors [10][11][12] suggested that accelerated erythropoiesis and increased uptake of LDL by macrophages and histiocytes of the reticulo endothelial system are the main determinants of low plasma cholesterol levels in beta thalassemia major. ...
Background: To study lipid profile in Beta-Thalassemia Major Patients. Methods: A cross-sectional was done on 30 diagnosed Cases of beta-thalassemia major in the age group of 1 year to 18 years receiving regular blood transfusions; not suffering from any ailment or any other disease leading to deranged lipid profile were included. Results: Lipid analyses of controls and thalassemic children. It is clear from the results that beta thalassemia major patients had significantly lower total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and low-density lipoprsotein cholesterol (LDL) compared with controls. Conclusion: Lipid profile in Beta thalassmia patients show significantly low levels of total cholesterol, LDLC and HDL-C. Keywords: Beta Thalassemia Major, Lipid Profile, LDL, HDL.
... Iron-loading and the effects of repeated blood transfusions induce a hepatic acute-phase response, which could determine an LDL-class shift towards protein-rich, denser particles [14,17]. Some authors [15,[20][21][22][23][24] suggested that accelerated erythropoiesis and increased uptake of LDL by macrophages and histiocytes of the reticulo endothelial system are the main determinants of low plasma cholesterol levels in beta thalassemia major. Factors such as iron overload (high ferritin level), liver injury, and hormonal disturbances affects lipids pattern among patients with major form of beta-thalassemia, while some researchers observed that the lipid profile in thalassemia major patients is not influenced by age, sex, liver injury, and hemoglobin or ferritin levels [15]. ...
Beta-thalassemia is considered to be the most frequent hereditary blood disorder worldwide. Lipid abnormalities have been detected in different types of beta-thalassemia.This was a cross sectional case control study in which 100 diagnosed cases of Beta thalassemia major were enrolled. 100 healthy children of same age group consisted of control group. The blood samples of study and control groups were examined for lipid profile test and values were evaluated. The tests were done using Olympus AU400 Auto analyser and values were evaluated. Statistical analysis was done by using IBM SPSS version 20. The mean values of serum HDL-C, LDL-C, total cholesterol, TG and VLDL in controls were 47.6±4.3, 76.8 ±15.4, 76.8 ±15.4, 74.64±16.23, 22.63±6.6715 mg/dl respectively. Total cholesterol to HDL-C ratio was4.57±1.55 and 2.66±0.39 in cases and controls respectively. Total cholesterol, HDL-C, LDL-C were significantly lower (p<0.05); triglycerides and total cholesterol & HDL ratio were significantly higher (p<0.05) compared with controls.This study concludes that children suffering from beta thalassemia major may possess increased risk of thrombotic and atherogenic complications. Early detection of these patients with deranged lipid profile is required to avoid these complications. It is also important to do routine periodical screening.
... This alteration is likely due to diminished hepatic biosynthesis as of anemia and iron overload, while a reduced extra hepatic lipolytic activity could account for the rise in circulating TG. Iron-loading and the effects of repeated blood transfusions induce a hepatic acute-phase response, which could determine an LDL-class shift towards protein-rich, denser particles 7,8 Some authors [10][11][12] suggested that accelerated erythropoiesis and increased uptake of LDL by macrophages and histiocytes of the reticulo endothelial system are the main determinants of low plasma cholesterol levels in beta thalassemia major. ...
Background: Beta-thalassemia is the commonest single-gene disorder in the Indian population. Beta thalassemia major is caused by complete absence of beta globin chain production resulting from reduced synthesis of one or more globin chains which can be caused by different globin gene mutation resulting in ineffective hematopoiesis, increased hemolysis and early onset anemia. Methods: A cross-sectional; case control study was done on 50 diagnosed Cases of beta-thalassemia major in the age group of 1 year to 18 years receiving regular blood transfusions; not suffering from any ailment or any other disease leading to deranged lipid profile were included. In controls; 50 normal healthy children were included. Results: Lipid analyses of controls and thalassemic children. It is clear from the results that beta thalassemia major patients had significantly lower total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and low-density lipoprsotein cholesterol (LDL) compared with controls (p<0.001). Conclusion: Lipid profile in Beta thalassmia patients show significantly low levels of total cholesterol, LDLC and HDL-C. Keywords: Beta Thalassemia Major, Lipid Profile, Hypocholesterolemia.
... This alteration is likely due to diminished hepatic biosynthesis as of anemia and iron overload, while a reduced extra hepatic lipolytic activity could account for the rise in circulating TG. Iron-loading and the effects of repeated blood transfusions induce a hepatic acute-phase response, which could determine an LDL-class shift towards protein-rich, denser particles 7,8 Some authors [10][11][12] suggested that accelerated erythropoiesis and increased uptake of LDL by macrophages and histiocytes of the reticulo endothelial system are the main determinants of low plasma cholesterol levels in beta thalassemia major. Factors such as iron overload (high ferritin level), liver injury, and hormonal disturbances affects lipids pattern among patients with major form of beta-thalassemia, while some researchers observed that the lipid profile in thalassemia major patients is not influenced by age, sex, liver injury, and hemoglobin or ferritin levels. ...
Background: To study lipid profile in Beta-Thalassemia Major Patients. Methods: A cross-sectional was done on 50 diagnosed Cases of beta-thalassemia major in the age group of 1 year to 18 years receiving regular blood transfusions; not suffering from any ailment or any other disease leading to deranged lipid profile were included. Results: Lipid analyses of controls and thalassemic children. It is clear from the results that beta thalassemia major patients had significantly lower total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and low-density lipoprsotein cholesterol (LDL) compared with controls. Conclusion: Lipid profile in Beta thalassmia patients show significantly low levels of total cholesterol, LDLC and HDL-C. Keywords: Beta Thalassemia Major, Lipid Profile, Hypocholesterolemia.
... However, several small studies demonstrated the preservation of splenic function after surgical splenic artery ligation based on the absence of Howell-Jolly bodies and normal uptake of technetium-99 on scintigraphy. [23,24] cOnclusiOns Our results showed SHL can be used in the management of traumatic splenic injuries. SHL has been shown to be safe and effective in increasing rates of splenic salvage in rats. ...
Background: The aim of this study was to compare the outcome of splenic hilum ligation (SHL) and splenectomy in spleen trauma in rat model. Methods: This interventional study was performed on 38 rats with spleen injuries. Rats were randomly divided into SHL and splenectomy groups. After 7 days of surgery, IgG, IgA, IgM, and IgE were measured. At this time, blood smear was prepared to evaluate Howell–Jolly bodies, target cells, schistocyte, poikilocyte, and anisocyte. Three months after the surgery, the spleen viability was evaluated by relaparotomy. Results: After 7 days, white blood count was significantly lower in SHL group as compared to control group (P = 0.024). All variables in peripheral blood smear were significantly lower in SHL group as compared to control group, except Howell–Jolly bodies (P = 0.461). In the SHL group, all spleens were viable in second operations. Conclusions: SHL can be used safely in the management of traumatic splenic injuries in rats.
... 16 Amendola et al in 2007 suggested that the brisk bone marrow activity with enhanced cholesterol consumption could be the basis of low cholesterol levels. 19 Although the serum TG did not demonstrate significance in some studies, it was established to be high in most studies, 16,20,21 concurring with our findings. Hypertriglyceridaemia was observed in 36.1% in our series of patients. ...
Objective: Serum fasting lipid profile has been studied in various clinical spectrum of Beta (β)- thalassaemia syndrome. Premature cardiac impairment in thalassaemia major appears primarily due to iron accumulation and oxidative injury; however it might be a sequel of abnormal lipoprotein concentrations. The rational of this study is to analyse the serum fasting lipid profile in cardiovascular disease free β-thalassaemia major (β-TM) patients. Relationships with age, gender, haematological parameters, liver enzymes and serum ferritin were observed. Method: Fasting serum lipid levels, liver function test (LFT), complete blood count (CBC) and serum ferritin were measured in 36 patients with homozygous β-TM from March 2012 to March 2014. Patients were stratified into two groups, age ≤15 and >15 years, to determine the possible lipid profile distinction in relation to age. Results: 17 were males and 19 were females, with median age of 12.0 years. The mean total cholesterol (TC) and triglyceride (TG) were 5.01±1.32 and 8.36±5.28 mmol/L respectively. High TG was detected in 36.1%, while high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) were markedly low, 0.98±0.51 and 2.35±1.22 mmol/L respectively. No statistically significant difference was noted between the two age groups. The median TC to HDL ratio (TC:HDL) was elevated, 5.7 (4.0). We established significant correlation of total bilirubin with TC (r=-0.4), HDL(r=-0.5) and LDL (r=-0.4) (P<0.05). Conclusion: Dyslipidaemia in β-TM patients is irrespective of age and gender including low HDL and high TC:HDL, whilst high TC:HDL may contribute as a significant risk marker for future cardiac events in these patients. © 2015, Malaysian Society of Pathologists. All rights Reserved.
... 3 Several studies have reported that splenectomy resulted in thrombocytosis, leukocytosis, concentrated hemoglobin, hyperlipidemia, and increased C-reactive protein levels. [18][19][20][21][22][23] All these alterations are independently associated with an increased risk of vascular complications in splenectomized patients. Cumulative incidences of stroke in the control cohort and splenic injury patients with and without splenectomy. ...
The spleen is a crucial organ in humans. Little is known about the association between stroke and splenic injury or splenectomy. The aim of this study was to determine the risk of stroke in patients with splenic injury and splenectomy.
A nationwide cohort study was conducted by analyzing the National Health Insurance Research Database in Taiwan. For comparison, control patients were selected and matched with splenic injury patients in a ratio of 4:1 according to age, sex, and the year of hospitalization. We analyzed the risks of stroke using a Cox proportional-hazards regression analysis.
A total of 11,273 splenic injury patients, including 5294 splenectomized and 5979 nonsplenectomized patients, and 45,092 control patients were included in this study. The incidence rates of stroke were 8.05, 6.53, and 4.25 per 1000 person-years in splenic injury patients with splenectomy, those without splenectomy, and the control cohort, respectively. Compared with the control cohort, splenic injury patients with splenectomy exhibited a 2.05-fold increased risk of stroke (95% confidence interval [CI] 1.8–2.34), whereas those without splenectomy exhibited a 1.74-fold increased risk (95% CI 1.51–2). Splenectomy entailed an additional 1.21-fold increased risk of stroke compared with nonsplenectomy in patients with splenic injury.
This study revealed that splenic injury and splenectomy were significantly associated with an increased risk of hemorrhagic and ischemic strokes. The results of this study may alert physicians and patients to the complications of splenic injury and splenectomy.
... Some theories have been raised to explain the possible mechanism of splenic regulation of lipid metabolism. [20,22,28] One theory has suggested that the spleen acts as a lipid reservoir, which would be exacerbated in the case of hypersplenism. [22] Due to an increase in phagocytic ability, spleen macrophages might accumulate large quantities of fat, resulting in hypolipidemia. ...
The spleen has been reported to participate in the development of nonalcoholic fatty liver disease (NAFLD), but the mechanism has not been fully characterized. This study aims to elucidate how the spleen affects the development of NAFLD in a rat model.
Following either splenectomy or sham operation, male Sprague-Dawley (SD) rats were fed a high-fat diet to drive the development of NAFLD; animals fed a normal diet were used as controls. Two months after surgery, livers and blood samples were collected. Serum lipids were measured; liver histology, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene expression, and the ratio of pAkt/Akt were determined.
Splenectomy increased serum lipids, except triglyceride (TG) and high-density lipoprotein (HDL), in animals fed either a high-fat or normal diet. Furthermore, splenectomy significantly accelerated hepatic steatosis. Western blot analysis and real-time polymerase chain reaction showed splenectomy induced significant downregulation of PTEN expression and a high ratio of pAkt/Akt in the livers.
The spleen appears to play a role in the development of NAFLD, via a mechanism involving downregulation of hepatic PTEN expression.
... A large body of evidence from prospective and retrospective studies has clearly shown that patients affected by thalassaemia have reduced levels of TC with respect to healthy age-and sex-matched controls. [3][4][5][6][7][8][9][10] Hypocholesterolaemia has been reported in all phenotypes of β-thalassaemia and has also been described in various haematological disorders associated with high erythropoietic activity. 11-14 Table 1 shows cholesterol levels found in different reports exploring lipid profiles in young and adult patients affected by all phenotypes of thalassaemia. ...
In this review, the role of hypocholesterolaemia as a potential source of several clinical features of patients affected by thalassaemia is assessed. The primary focus is on the extent of the phenomenon among different forms of thalassaemia in order to highlight the particularly reduced level in patients with thalassaemia intermedia. In addition, we explore how the reduced levels of cholesterol could influence the atherogenic process and many typical clinical features of patients affected by thalassaemia.
... Rev que aqueles observados na talassemia intermédia. 26 O tratamento transfusional regular, obrigatório nos doentes portadores de talassemia maior, mantém a hemoglobina em valores toleráveis para o paciente e bloqueia a eritropoiese ineficaz que acompanha essa condição, reduzindo, possivelmente, a demanda de colesterol pelo processo proliferativo medular. Na beta talassemia menor, as alterações dos perfis hematológico e lipídico são menos expressivas em relação àquelas observadas nas formas clínicas mais graves de beta talassemia. ...
Annually, innumerable studies approach varying aspects regarding the epidemiology, etiology, physiopathology, diagnosis and therapy of the various types of anemia. With variable objectives and results that promote a continuous process to better characterize the physiopathologic and therapeutic aspects related to red blood cell disorders, these studies are contributing to a better quality of life for the patients and to the elucidation of the impact that such hematological changes exert on the whole body metabolism. In this context, the aim of this article is to contemplate the lipid profile in anemic patients, which has not been well explored and reported in scientific literature. This article will focus on changes of the lipid profile in association with sickle cell anemia and thalassemia, as well as on the implication that the presenting chronic hemolytic state in these diseases exert on the cholesterol metabolism.
... The possible aggravation of cardiovascular risks with low circulating HDLC in anemia may be assumed. In a study involving 67 patients with homozygous beta-thalassemia, circulating HDLC was found low compared to that of healthy or heterozygous subjects of the same families [26]. In another study, levels of HDLC were found low with a mean of only 70% of the controls, where plasma and erythrocyte lipids were estimated in children with different types of anemia and healthy control and a positive correlation of Hct (hematocrit) with HDLC was reported [27]. ...
Circulating level of low HDLC (high-density lipoprotein cholesterol) represents a common critical risk factor for IHD (ischemic heart disease) and may further aggravate the condition in anemic subjects, as the presence of anemia itself is a threat to cardiovascular consequences. To investigate the relationship of circulating HDLC with anemia, first we determined the levels of total hemoglobin (Hb) in a total of 301 subjects (male, n = 158; female, n = 143) randomly, and then examined the circulating levels of HDLC in fasting condition. Age of the study subjects was 47.9 ± 16.6 (mean ± SD) years. Both the male and female subjects were divided into three groups according to their levels of Hb. The relationship of circulating levels of HDLC with the levels of total Hb was statistically analyzed. In case of the male subjects, we found that the levels of HDLC differed significantly among the three groups with different levels of Hb (P = 0.0233) and decrease in the levels of HDLC correlated significantly with the gradual decrease of total Hb level (r = 0.2504; P = 0.0015). In female subjects, we observed a similar trend of difference among the three groups (P = 0.0685). However, decrease in the levels of HDLC correlated significantly with the gradual decrease of Hb level (r = 0.2199; P = 0.0083). Altogether, this study demonstrates that decrease in the circulating HDLC is related to the gradual decrease of Hb level. This study also indicates that circulating level of HDLC may be influenced by the level of total Hb and reveals the cardiovascular risks in anemia as well.
... Rev que aqueles observados na talassemia intermédia. 26 O tratamento transfusional regular, obrigatório nos doentes portadores de talassemia maior, mantém a hemoglobina em valores toleráveis para o paciente e bloqueia a eritropoiese ineficaz que acompanha essa condição, reduzindo, possivelmente, a demanda de colesterol pelo processo proliferativo medular. Na beta talassemia menor, as alterações dos perfis hematológico e lipídico são menos expressivas em relação àquelas observadas nas formas clínicas mais graves de beta talassemia. ...
Inúmeros estudos abordam anualmente diversos aspectos relacionados à epidemiologia, etiologia, fisiopatologia, diagnóstico e tratamento dos diferentes tipos de anemias. Com objetivos variados e resultados que promovem um processo contínuo de melhor caracterização dos aspectos fisiopatológicos e terapêuticos relacionados às doenças da série vermelha, tais estudos têm contribuído para melhoria da qualidade de vida dos pacientes bem como para a elucidação do impacto que essas alterações hematológicas exercem sobre as outras faces do metabolismo corporal. Nesse contexto, o presente artigo tem por objetivo contemplar o perfil lipídico nas anemias, que ainda permanece pouco explorado e relatado na literatura científica. Será conferida maior ênfase às alterações do perfil lipídico associadas à anemia falciforme e talassemias, bem como às implicações que o estado hemolítico crônico inerente a essas condições exercem sobre o metabolismo do colesterol.
... Abnormal lipid profile has been repeatedly reported in all clinical phenotypes of β-thalassemia including thalassemia major, thalassemia intermedia and thalassemia minor [7] [8] [9] [10] [11]. Patients with β-thalassemia trait have been found to have lower plasma concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), but unmodified plasma levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) [12,13]. ...
The aim of present study was to evaluate the association of thalassemia minor with suicide, impulsivity and aggression. The study group consisted of 293 suicidal subjects, 300 violent criminals and 300 control subjects. Thalassemia trait was slightly more common in criminals (7.3%) than in controls (6.67%), this difference was not statistically significant (p = 0.75). Similarly, carrier trait was observed more in suicidal subjects (8.87%) though this difference was not statis-tically significant (p = 0.3). Despite a plausible biological hypothesis, our study results do not support that thalassemia minor could be a risk factor for suicidal, impulsivity and aggressive behaviors.
... In patients with BTM, total cholesterol, HDLcholesterol, LDL-cholesterol levels were low, 30 triglyceride level was high, 1 whereas another study reported that the levels were the same in both study group and the control group. 31 In the study group, total cholesterol, HDLcholesterol, LDL-cholesterol levels were lower and the triglyceride level was higher than that of the control group. However, the differences were not statistically significant. ...
The aim of this study was to study paraoxonase and arylesterase activities along with oxidative status parameters, and to find out whether there is any increased susceptibility to atherogenesis, which might be reflected with increased oxidative stress and decreased serum paraoxonase/arylesterase activity in beta-thalassemia major (BTM) patients.
Eighty-seven patients with BTM and 33 healthy individuals were enrolled in the study.
Paraoxonase and arylesterase activities were significantly lower in BTM patients than controls (for all P<0.0001), whereas total oxidant status, total peroxide concentration levels, and oxidative stress index were significantly higher (P<0.0001, <0.0001, and <0.001, respectively). Correlations were found between serum iron and ferritin and levels of total oxidant status in BTM patients. Significant correlation was found with serum total peroxide concentration levels and paraoxonase and arylesterase activities in patients with BTM.
It was seen that oxidative stress increases, while serum paraoxonase activity is decreased in BTM patients. Decrease in paraoxonase activity seems to be associated with both the degree of oxidative stress and anemia. BTM patients may be more prone to development of atherogenesis because of low serum paraoxonase/arylesterase activity.
Vascular occlusion is a complex process that has a central role in the pathophysiology of sickle cell disease (SCD) and it is known that thrombosis contributes to large vessel and possibly also to small vessel occlusion. In childhood the most serious complication of SCD is stroke secondary to cerebrovascular disease (CVD) which is symptomatic in 7-10% of children and a further 14% have asymptomatic disease on imaging. The role of haemostatic abnormalities in the development of vascular occlusion in children with SCD, in particular those with CVD, has not been comprehensively studied before. The principle objectives of this thesis were to perform a prothrombotic profile, including coagulation inhibitors and markers of thrombin generation, in children with SCD and to compare results between different groups; untransfused and transfused; those with CVD and those without; those with haemoglobin SS (HbSS) and those with haemoglobin SC (HbSC), thalassaemia major, other haemolytic red cell disorders and normal controls. I have found significant reductions in the majority of the natural anticoagulants in children with HbSS compared to sibling controls and also substantial elevation in markers of thrombin generation in the steady-state and evidence of acquired activated protein C resistance. These findings were only partially reversed by transfusion and were not as marked in the group with HbSC though thalassaemics also had reduced levels of most inhibitors. There was no evidence that antiphospholipid antibodies were involved in any group. In the groups with or without CVD there were no differences for any of the parameters measured except for lower haemoglobin levels and higher white cell counts in those with asymptomatic CVD so the abnormalities found in the HbSS children do not appear to play a primary role in the development of CVD.
Abstract
Introduction: Beta thalassemia is one of the most common inherited single gene disorders result from absent or reduced β - chain production. Regular blood transfusions are required to correct anemia for normal growth and development, this cause secondary iron overload which is responsible for peroxidative damage. Iron overload causes high concentrations of serum ferritin which is a protein that plays a key role in iron metabolism by binding and storing excess iron within cells. In β-thalassemia major, liver damage accounts for the changes in lipid profile including total-cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TGL). Trace elements including zinc (Zn), copper (Cu) and magnesium (Mg) play a vital role in the body to perform its functions properly and should present in the body in appropriate amounts and must be available for reacting with other elements to form critical molecules as well as to participate in various important chemical reactions. The aims: to evaluate serum ferritin and trace elements (Copper, zinc and magnesium) and lipid profile in beta thalassemia major patients. Patients, material and methods: Patients: sixty patients were diagnosed as beta thalassemia major, they were on blood transfusion program, and thirty healthy medication free volunteers matched for age and sex were studied as control .Blood samples were taken after an overnight fast (12-14-hours.) and serum was obtained for estimation of ferritin levels by ELISA and for TC and TG that were determined enzymatically. The HDL-C was measured after precipitation of other lipoproteins .Copper; zinc and magnesium were estimated by Atomic Absorption Spectrophotometer. Results: A high ferritin level (747.55 ± 158.62 mg/l) was observed. The serum cholesterol and high density lipoprotein levels were found to be lower than normal control (94.4±7.48 and 40.83±4.64 mg/dl respectively), while serum triglyceride level was significantly higher than normal control (177.83±15.91). There was no correlation between serum ferittin and any of the studied lipids. Serum Copper and magnesium levels were significantly higher than normal control (152±6.4 mg/dl and 2.28±0.17 mg/dl respectively), while Serum zincs levels were significantly lower than normal (67.55±2.7 mg/dl) In conclusion : assessment of serum ferittin , trace elements and lipid profile in patients with beta thalassemia major revealed different levels in different studies suggesting variation in the factors influencing their levels in each patients and could be useful in follow up patients with beta thalassemia major.
?-Thalassemia minor (?-?m) is associated with rheological and biochemical alterations that can affect cardiovascular function. We aimed to evaluate the elastic arterial properties and the pulse wave augmentation indices in a population of patients with ?-?m. Seventy-five individuals with ?-?m (age 55.5 [42.75-65.25], women 48%) and 127 controls (age 57 years [48-63], women 55.1%) underwent comprehensive echocardiographic evaluation and applanation tonometry of the radial and femoral artery. Pulse wave analysis revealed that augmentation pressure, augmentation index (AIx), and heart rate-corrected AIx were significantly lower (median [interquartile range]: 8.75 [4.625-13] vs 11 [6.5-14.5], P = .017; 26.5 [17.5-33.375] vs 30.5 [20.75-37.5], P = .014; and 22.25 [15.125-29.5] vs 27 [20.5-33], P = .008, respectively) in the ?-?m group compared to controls. The left atrial active emptying volume was significantly lower and the isovolumic relaxation time was shorter in the ?-?m group compared to the control group (10.2 [7.4-14.4] vs 12.0 [8.6-15.8], P = .040 and 78 [70-90] vs 90 [70-104], P = .034, respectively). ?-Thalassemia minor is associated with favorable pulse wave augmentation indices and left ventricular diastolic function profile in asymptomatic individuals with cardiovascular risk factors.
The spleen is a crucial organ in humans. However, little is known about the association of venous thromboembolism (VTE) with splenic injury and splenectomy in trauma patients. The aim of this study was to determine the subsequent risk of VTE following splenic injury and splenectomy. A nationwide retrospective cohort study was conducted by analysing data from the National Health Insurance Research Database in Taiwan. We included 6,162 splenic injury patients (3,033 splenectomised and 3,129 nonsplenectomised patients) and 24,648 comparison patients who were selected by frequency match based on sex, age, and the index year during 2000-2006. All patients were followed until the occurrence of VTE, 31 December, 2011, death, or withdrawal from the insurance program. The age of patients with splenic injury was 41.93 ± 16.44 years. The incidence rates of VTE were 11.81, 8.46, and 5.21 per 10,000 person-years in the splenic injury patients with splenectomy, splenic injury patients without splenectomy, and comparison patients, respectively. Compared with the comparison cohort, splenic injury patients with splenectomy exhibited a 2.21-fold risk of VTE (95 % confidence interval [CI], 1.43-3.43), whereas those without splenectomy exhibited a 1.71-fold risk of VTE (95 % CI, 1.05-2.80). The overall incidence rate of VTE was 1.97-fold higher in the splenic injury cohort than the comparison cohort (95 % CI, 1.38-2.81). Although splenectomy increased the risk of VTE 1.35-fold compared with no splenectomy, the difference was not statistically significant (95 % CI, 0.74-2.45). These results may alert physicians and patients to the complications of splenic injury and splenectomy.
β-Thalassemia (β-thal) is a genetic disorder, representing a major health problem in Algeria. It is associated with altered lipid levels and a state of oxidative stress that can lead to cardiac complications and premature death. We examined the plasma lipid profile and redox status of 46 patients with β-thal major (β-TM) and β-thal intermedia (β-TI) compared to 36 healthy subjects. Plasma lipids including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were investigated. Oxidative status was evaluated by measuring malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT) activity. The potential relationships between these parameters and the hemoglobin (Hb) blood concentrations, serum ferritin, duration and frequency of transfusion, splenectomy as well as age, were examined. Our data indicated that the study patients were under increased state of oxidative stress associated with hypertriglyceridemia, and hypocholesterolemia. The CAT activity was negatively correlated with Hb concentration and LDL-C/TG ratio and positively with years of transfusion. The elevated TC/HDL-C ratio particularly in β-TM patients who were younger, correlated positively with ferritinemia and triglyceride levels and suggested an increased coronary risk. This heightened risk state should lead to the inclusion of this index (TC/HDL-C) in clinical management, particularly in splenectomized patients.
Biochemical parameters in β-thalassemia.β-thalassemias, by their high frequency and gravity, represent a serious health problem in Tunisia. Clinical and biological disorders bred by β-thalassemia vary with the importance of globin synthesis deficiency. Thus hematological and biochemical parameters are perturbed. We report here the results of a biochemical exploration made on a 27 β-thalassemic patients (15 homozygotes and 12 heterozygotes) compared by those of a reference population of 30 subjects. Blood samples were collected for the analysis. Hemoglobin electrophoresis was used on alkaline pH for the identification of hemoglobin fractions. Specific techniques were used to complete the biochemical exploration (martial, hepatic and lipid balance-sheets). Results have confirmed perturbation of hemoglobinic fractions varying with genotype. Homozygotes have shown a persistence of HbF (fetal hemoglobin) while HbA1 (adult hemoglobin) is absent for β0 thalassemic and decreased for β+ thalassemic. HbA2 is increased in heterozygotes (>3.5 %). Serum iron and serum ferritin are highly increased in homozygote patients comparing to normal subjects. In heterozygotes, serum iron normally persists but serum ferritin is significantly increased. Hepatic balance-sheet shows a high transaminases level in homozygotes while lipid balance doesn't exhibit any modification compared by normal subjects.Our study confirmed the perturbation of some biochemical parameters in b-thalassemic patients. Their variations constitute an alarm signal of serious complications accompanying theses perturbations. The establishment of an adequate therapeutic program must limit these complications occuring particularly in homozygotes to improve their life quality.
Thromboembolic (TE) events have been frequently reported in beta-thalassemic patients in association with known risk factors such as diabetes, complex cardiopulmonary abnormalities, hypothyroidism, liver function anomalies, and postsplenectomy thrombocytosis. In a recent survey involving 9 Italian thalassemic centers, we identified 32 patients with TE episodes in a total of 735 subjects, of whom 683 had thalassemia major and 52 thalassemia intermedia, corresponding to 3.95 and 9.61%, respectively. There was a great variation in localization: the main one (16/32) was CNS, with a clinical picture of headache, seizures and hemiparesis. Other localizations were the pulmonary (3 patients), mesenteric (1 patient) and portal (2 patients) sites. There were 6 cases of deep venous thrombosis (2 in the upper limbs, 4 in the lower ones). Intracardiac thrombosis was found in 2 subjects and clinical and laboratory signs of DIC were observed in 2 others during pregnancy. Since our patients with TE events present a statistically significantly higher incidence of associated dysfunction (cardiomyopathy, diabetes, liver function anomalies, hypothyroidism) than those without TE events (50 vs. 13.8%), we suggest close monitoring of those patients who are at higher risk of developing TE events because of the presence of one or more of these predisposing factors.
Beta-thalassaemic patients who usually have a combination of; chronic hemolytic anemia, iron storage disease, myocarditis, and premature death especially due to heart failure may also have increased oxidation of lipids and abnormal lipoprotein concentrations.
To determine plasma lipids, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipid peroxidation product malondialdehyde (MDA) in children with β-thalassemia and unaffected control children. Relationships with age, gender, hemoglobin, serum iron, and serum ferritin were examined. Children with β-thalassemia (28 males and 15 females, aged 4 to 18 years) and 31 age- and gender-matched healthy controls were studied.
In children with β-thalassemia, there was an increase in TG, MDA, and the MDA/LDL-C ratio (P = .000) and a decrease in TC, LDL-C, HDL-C, and the LDL-C/ TG ratio (P < .001) compared to unaffected controls. The LDL-C/HDL-C ratio was not different. The MDA/LDL-C ratio was correlated negatively with blood hemoglobin and TC (P < .05 for each), whereas the LDL-C/HDL-C ratio was correlated with age, weight, body mass index, and TC (P < .05, < .05, < .05, and < .01 respectively).
Despite the derangement in plasma lipid profile in children with β-thalassemia accompanied by excess lipid peroxidation, the lipoprotein concentrations do not suggest increased risk. The MDA/LDL-C ratio may prove to be a valuable marker for lipid peroxidation.
To determine the plasma lipid and lipoprotein profiles and their possible association with the type of β-thalassemia mutation we studied 103 major β-thalassemia patients including 71 children and 32 young adults compared to 102 healthy subjects consisted of 90 children and 12 young healthy adults. The plasma lipid and lipoprotein levels were measured by conventional methods. Considering all of the patients the levels of total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C) were significantly lower compared to controls. However, the level of TG was significantly higher in cases than controls. Comparing thalassemic patients homozygous for a β0 type of mutation with those homozygous for a β+ type of mutation (IVSI.110 G:A) indicated that the levels of LDL-C, TC were significantly increased and TG concentration tended to be higher in the latter patients. In conclusion, our study indicates that hemolytic stress results in hypocholesterolemia in major β-thalassemia patients and the presence of more severe genotype in patients is correlated with more reduction in TG, TC, and LDL-C levels.
Oxidative modification of low-density lipoprotein (LDL) has been reported in thalassemia, which is a consequence of oxidative stress. However, the levels of oxidized high-density lipoprotein (HDL) in thalassemia have not been evaluated and it is unclear whether HDL oxidation may be linked to LDL oxidation. In this study, the levels of total cholesterol, iron, protein, conjugated diene (CD), lipid hydroperoxide (LOOH), and thiobarbituric acid reactive substances (TBARs) were determined in HDL from healthy volunteers and patients with beta-thalassemia intermedia with hemoglobin E (beta-thal/Hb E). The protective activity of thalassemic HDL on LDL oxidation was also investigated. The iron content of HDL(2) and HDL(3) from beta-thal/HbE patients was higher while the cholesterol content was lower than those in healthy volunteers. Thalassemic HDL(2) and HDL(3) had increased levels of lipid peroxidation markers i.e., conjugated diene, LOOH, and TBARs. Thalassemic HDL had lower peroxidase activity than control HDL and was unable to protect LDL from oxidation induced by CuSO(4). Our findings highlight the oxidative modification and poor protective activity of thalassemic HDL on LDL oxidation which may contribute to cardiovascular complications in thalassemia.
The most widely recognized long-term risk of splenectomy is overwhelming bacterial infection. More recently, thrombosis has become appreciated as another potential complication of the procedure. Because of these long-term risks, the indications for and timing of splenectomy are debated in the medical community. Accordingly, the adverse effects and benefits of splenectomy for hematologic disorders and other conditions demand further study. This comprehensive review summarizes the existing literature pertaining to vascular complications after splenectomy for hematologic conditions and attempts to define the potential pathophysiologic mechanisms involved. This complex topic encompasses diverse underlying conditions for which splenectomy is performed, diverse thrombotic complications, and multiple pathophysiologic mechanisms.
OBJETIVO: Apesar de serem bem estabelecidas as alterações esplênicas nas dislipidemias, como a doença de Gaucher, ainda não se estudou adequadamente a relação do baço com o metabolismo lipídico. Com vista a contribuir para preencher esse hiato, a presente investigação avaliou experimentalmente o lipidograma na presença do baço, em asplenia e após operações conservadoras desse órgão. MÉTODOS: Foram utilizadas 50 ratas Wistar de pesos e idades semelhantes distribuídas em quatro grupos: Grupo 1- controle, com baço íntegro; Grupo 2 - laparotomia e laparorrafia, Grupo 3 - esplenectomia total; Grupo 4 - esplenectomia subtotal e Grupo 5 - esplenectomia total complementada por implantes de tecido esplênico autógeno. Após quatro meses, foram dosados os níveis séricos de triglicérides, colesterol total e suas frações VLDL, LDL, HDL. Os resultados dos quatro grupos foram comparados entre si pela análise de variância, seguida pelo teste de Tukey-Kramer, com significância para p < 0,05. RESULTADOS: Não houve diferença entre os grupos 1, 2, 3 e 4. Nos animais submetidos a esplenectomia total, as concentrações de colesterol total (p = 0,0151) e de sua fração LDL (p < 0,0001) foram maiores, enquanto a fração HDL foi menor (p = 0,0026) do que as encontradas nos demais grupos. Não houve diferença entre os grupos com relação aos triglicérides (p = 0,1571) e VLDL (p = 0,2527). CONCLUSÕES: É provável que o baço desempenhe um papel de destaque no metabolismo lipídico de ratas e que a esplenectomia total se relacione com alterações no controle do colesterol. É possível que a preservação de tecido esplênico previna tais distúrbios metabólicos.
Vascular abnormalities such as endothelial dysfunction and arterial stiffness have been described in patients with beta-thalassemia major (beta-TM). Increased concentrations of oxidised low-density lipoprotein cholesterol (oxLDL) have been observed in those patients, but possible associations between oxLDL and arterial function in beta-TM have not been defined.
Twenty-six patients (11 males) with beta-TM (age 23 +/- 4 yr) and 30 age and gender-matched healthy subjects were studied. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWVc-f) using applanation tonometry; brachio-radial artery stiffness was assessed by carotid-radial PWV (PWVc-r). Flow-mediated dilatation (FMD) of the brachial artery and oxLDL (ELISA) were also measured.
Patients with beta-TM had higher oxLDL levels (68.6 +/- 13.7 mU/mg vs. 50.0 +/- 12.6 mU/mg, P = 0.005), decreased FMD (3.6 +/- 2.5% vs. 7.3 +/- 3.5%, P = 0.001) and higher PWVc-f compared with controls (8.4 +/- 1.7 vs. 7.2 +/- 1.1. P < 0.002). FMD of the brachial artery was negatively associated with OxLDL concentrations in simple linear (r(2) = -0.25, P = 0.001) and multiple linear regression analysis (beta = -0.242, P = 0.03, R(2) = 0.43, P = 0.0002). PWVc-r was positively associated with OxLDL (r(2) = 0.23, P = 0.003) and showed a tendency in multiple regression analysis (beta = 0.18, P = 0.05). PWVc-r and FMD were also significantly correlated (beta = -0.213, P = 0.04) in beta-TM patients. There was no association between oxLDL and PWVc-f.
An association between oxLDL, arterial elastic properties and endothelial dysfunction of muscular arteries was found. OxLDL may represent a contributing factor for the vascular manifestations described in beta-TM patients.
Atherosclerosis observations after splenectomy for trauma and hypersplenism suggests a possible role for the spleen in lipid metabolism. The authors examined the effects of splenectomy on serum lipids in rats and also cholesterol-fed rats with experimental atherosclerosis.
This study was designed on rats. The rats were divided into five groups: splenectomy, normal diet (SP-N, n: 8), splenectomy, cholesterol-fed groups (SP-C, n: 8), splenic autotransplantation after splenectomy, normal diet (SA-N, n: 8), splenic autotransplantation after splenectomy, cholesterol-fed groups (SA-C, n: 8) and sham groups (n: 8). Total triglyceride, total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), and VLDL (very low-density lipoprotein) levels were determined in 40 rats. The rats were classified into five groups based on the surgical procedures. The spleens were removed and then the rats were fed a normal diet in Group SP-N (n = 8). The spleens were removed and then the rats were fed a diet containing 1% cholesterol in Group SP-C (n = 8). Splenectomy and splenic autotransplantations were performed and then the rats were fed a normal diet in Group SA-N (n = 8). Splenectomy and splenic autotransplantations were performed and then the rats were fed a diet containing 1% cholesterol in Group SA-C (n = 8). The rats were sham-operated in the control group (Group S, n = 8). An active splenic function was shown in rats that underwent splenic autotransplantation in both groups by using Technicium 99 m sulphurcolloide sintiscan on day 30. Blood lipid levels were repeated 6 months later.
There was no difference between pre- and postoperative lipid levels in the sham group and SA-N group (p >.05). All lipid levels including HDL were increased significantly in SP-C group (p <.05). Also VLDL and total tryglyceride levels were increased significantly in SP-N and SA-C groups (p <.05).
This study showed that the spleen might have an important effect on lipid metabolism and splenic autotransplantation may be protective in conditions with increased lipid levels.
A model to examine the in vivo relationship of acute phase serum amyloid A (SAA) to spleen cholesterol mobilisation was devised. Reticuloendothelial cells in vivo were loaded with a known quantity of cholesterol (1.5 mg) by infusing fragmented red blood cell membranes, which consist of approximately 50% cholesterol by dry weight. Following infusion, 7% of the infused cholesterol was in the spleen and significantly increased (by 35%) spleen cholesterol concentration above the baseline. An acute inflammatory reaction was induced by the subcutaneous injection of AgNO(3) which also raised spleen cholesterol values, but not significantly. Both treatments were also administered together and the increase in spleen cholesterol concentration after 1 h was equivalent to the sum of the individual treatments. In all the treatment groups, the spleen cholesterol concentration and the plasma SAA values were then followed over a period of 24 h. In all treatment groups the spleen cholesterol values fell to baseline values primarily between 18 and 24 h which coincided with significantly raised levels of plasma SAA. In the case of the dual treatment, between 4 and 18 h, SAA increased from 92.1 +/- 12.3 to 478 +/- 58.3 microg/ml, respectively and depletion of spleen cholesterol occurred gradually reaching baseline values after 24 h. The significant flux of cholesterol though the spleen raises the distinct possibility that the spleen is much more involved in cholesterol metabolism than previously appreciated. Furthermore, the speed with which plasma SAA increases following the infusion of fragmented red blood cell membranes and the role that SAA plays in cholesterol mobilisation raise issues that may be relevant to alterations in plasma acute phase protein and lipid parameters in patients undergoing transfusions or suffering from hemolytic disorders.
Thromboembolic events, which are associated with significant morbidity and mortality, occur in betathalassaemia. We studied the expression of the platelet selectin PADGEM/GMP-140 on intact cells from thalassaemic patients, as a marker of in vivo platelet activation. The mean of positive cells (%) was 38 · 143 · 20 · 65 in the patients versus 5 · 048 | 1 · 8 in the controls. n= 21. P < 0<001.
No correlation was found between GMP-140 expression and splenectomy, platelet counts, plasma ferritin and natural coagulation inhibitors. Instead an indirect correlation was found between GMP-140 expression and HDL-cholesterol. Moreover platelet activation was directly correlated with prebeta lipoproteins. Our data indicate that thalassaemic patients present an in vivo platelet activation, which possibly depends on the dyslipidaemia, which is now regarded as a frequent feature of this disease.
We report a rare association of beta-thalassaemia major and hypertriglyceridaemia in a 4-month-old boy. The possible significance of this association is highlighted.
Recombinant human growth hormone (rhGH) is now available for treatment of short stature due to growth hormone (GH) deficiency. It's potential use in other causes of short stature raises concerns about adverse effects of long term treatment on carbohydrate and lipoprotein metabolism. We describe the serial changes in lipids, lipoproteins and apolipoproteins, including apo(a) in 12 children with beta-thalassaemia major undergoing rhGH treatment for 24-36 months. All showed satisfactory increases in height and weight. A significantly higher mean plasma apo(a) was observed at 3 months (102.6 U/l) versus baseline (71.4 U/l, P < 0.01, geometric means). Subsequently apo(a) levels gradually decreased returning to pretreatment levels after 36 months of rhGH treatment. There were parallel rises and falls in the apo(a) isoforms of different sizes during treatment. There were only minimal changes in the other lipid related parameters. All children had markedly reduced cholesterol levels (3.0 +/- 0.49 mmol/l, mean +/- S.D.) characteristic of their underlying disease. In conclusion the elevation of apo(a) by GH is only transient, there is no differential effect of rhGH on the large and small isoforms of apo(a) and there are no clinically significant adverse effects of rhGH treatment on lipoprotein metabolism.
We searched for a biochemical explanation to the modification of lipoproteins like low-density lipoproteins (LDL) observed in patients with the severe hemolytic anemia beta-thalassemia. Because a large fraction of the LDL surface is composed of phospholipids, we first explored the possible involvement of phospholipids in the oxidative interaction of LDL with hemoglobin (Hb), using brain extract phospholipid liposomes as a model. The relative binding affinity and oxidative interaction of three hemoglobin variants (intact Hb A and isolated beta- and alpha-chains) with LDL and liposome were compared. Studies carried out at low pH/ionic strength and under physiological conditions revealed that association of hemoglobin variants with the phospholipid liposomes is driven by electrostatic forces but their binding is not a prerequisite for oxidative interaction. Unlike phospholipid liposomes, LDL underwent only a negligible association with the Hb variants under all pH/ionic strength conditions. Nevertheless, LDL induced oxidation of Hb variants, mostly alpha-chains. The dissimilar behavior of the liposomes and LDL indicated that LDL protein apo B rather than phospholipids is the actual LDL surface component which interacts with the hemoglobin variants. This agrees with the finding that apo B protein underwent oxidative crosslinking by the hemoglobin variants among which alpha-chains were most active. We concluded from these results that the ability of hemoglobin to undergo autooxidation is the key to its oxidative reactivity toward LDL. The results of the present study indicate that the modified LDL particles observed in beta-thalassemia may reflect lipoprotein oxidation by alpha-chains in circulation.
Patients with sickle-cell anemia exhibit pro-oxidative metabolic perturbations. We hypothesize that because of chronic oxidative stress, plasma low-density lipoprotein (LDL) from patients with sickle-cell anemia is more susceptible to oxidation. To test this hypothesis, LDL susceptibility to copper-mediated oxidation was measured in 24 patients with sickle-cell anemia and 48 control subjects. Sickle-cell LDL was more susceptible to oxidation than control LDL, measured by a 22% shorter mean lag time between LDL exposure to CuSO4 and conjugated diene formation (97 vs 124 minutes; P = .023). LDL vitamin E, iron, heme, and cholesterol ester hydroperoxide (CEOOH) levels were also measured. LDL vitamin E levels were significantly lower in patients with sickle-cell anemia compared with control subjects (1.8 vs 2.9 mol/mol LDL; P = .025), but there was no correlation with lag time. Pro-oxidant heme and iron levels were the same in sickle-cell and control LDL. LDL CEOOHs were not significantly different in sickle and control LDL (3.1 vs 1.2 mmol/mol of LDL unesterified cholesterol, P = .15), but LDL CEOOH levels were inversely correlated with lag times in patients with sickle-cell anemia (r2 = 0.38; P = .018). The cytotoxicity of partially oxidized LDL to porcine aortic endothelial cells was inversely correlated with lag times (r2 = 0.48; P = .001). These preliminary data suggest that increased LDL susceptibility to oxidation could be a marker of oxidant stress and vasculopathy in patients with sickle-cell anemia.
One of the genetic features of the Sardinian population is the high prevalence of hemoglobin disorders. It has been estimated that 13% to 33% of Sardinians carry a mutant allele of the alpha-globin gene (alpha-thalassemia trait) and that 6% to 17% are beta-thalassemia carriers. In this population, a single mutation of beta-globin gene (Q39X, beta(0) 39) accounts for >95% of beta-thalassemia cases. Because previous studies have shown that Sardinian beta-thalassemia carriers have lower total and low density lipoprotein (LDL) cholesterol than noncarriers, we wondered whether this LDL-lowering effect of the beta-thalassemia trait was also present in subjects with familial hypercholesterolemia (FH). In a group of 63 Sardinian patients with the clinical diagnosis of FH, we identified 21 unrelated probands carrying 7 different mutations of the LDL receptor gene, 2 already known (313+1 g>a and C95R) and 5 not previously reported (D118N, C255W, A378T, T413R, and Fs572). The 313+1 g>a and Fs572 mutations were found in several families. In cluster Fs572, the plasma LDL cholesterol level was 5.76+/-1.08 mmol/L in subjects with beta(0)-thalassemia trait and 8.25+/-1.66 mmol/L in subjects without this trait (P<0.001). This LDL-lowering effect was confirmed in an FH heterozygote of the same cluster who had beta(0)-thalassemia major and whose LDL cholesterol level was below the 50th percentile of the distribution in the normal Sardinian population. The hypocholesterolemic effect of beta(0)-thalassemia trait emerged also when we pooled the data from all FH subjects with and without beta(0)-thalassemia trait, regardless of the type of mutation in the LDL receptor gene. The LDL-lowering effect of beta(0)-thalassemia may be related to (1) the mild erythroid hyperplasia, which would increase the LDL removal by the bone marrow, and (2) the chronic activation of the monocyte-macrophage system, causing an increased secretion of some cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) known to affect the hepatic secretion and the receptor-mediated removal of apolipoprotein B-containing lipoproteins. The observation that our FH subjects with beta(0)-thalassemia trait (compared with noncarriers) have an increase of blood reticulocytes (40%) and plasma levels of interleukin-6 (+60%) supports these hypotheses. The lifelong LDL-lowering effect of beta(0)-thalassemia trait might slow the development and progression of coronary atherosclerosis in FH.
Evidence for the existence of a plasma lecithin: cholesterol acyltransferase is reviewed with emphasis not only on the lipid reactants, but also on the lipoprotein “substrates” and “products.” The cholesteryl esters of all major lipoprotein classes become labeled when plasma is incubated with cholesterol-¹⁴C. However, the smaller, lecithin-rich high density lipoproteins appear to be preferred substrates. Most studies of factors that influence the acyltransferase reaction have not adequately distinguished between effects on the enzyme and effects on the lipoprotein substrates. However, the fact that cholesterol esterification is diminished in plasma from eviscerated animals or from patients with reduced liver function suggests that the liver may regulate both the level of the enzyme and that of the substrates. Several indications exist that the acyltransferase reaction is the major source of plasma esterified cholesterol in man. Furthermore, the reaction may have a broader, extracellular function. One possibility is that it plays a role in the transport of cholesterol from peripheral tissues to the liver.
Serum lipids, phospholipid fractions and the composition of serum lipid fatty acids were studied in 20 children presenting β-thalassaemia major, 20 heterozygous children and 20 normal controls. Total serum phospholipids, their fractions and cholesterol were significantly lower in patients with thalassaemia major. These changes were referred to hepatic damage and to severe anaemia, respectively. Some serum lipid polyunsaturated fatty acids were significantly decreased in patients with thalassaemia major as compared to heterozygotes and normal controls. Since these alterations are a sign of lipid oxidation, the causes of this phenomenon are discussed.Copyright © 1978 S. Karger AG, Basel
Serum lipids, phospholipid fractions and the composition of serum lipid fatty acids were studied in 20 children presenting beta-thalassaemia major, 20 heterozygous children and 20 normal controls. Total serum phospholipids, their fractions and cholesterol were significantly lower in patients with thalassaemia major. These changes were referred to hepatic damage and to severe anaemia, respectively. Some serum lipid polyunsaturated fatty acids were significantly decreased in patients with thalassaemia major as compared to heterozygotes and normal controls. Since these alterations are a sign of lipid oxidation, the causes of this phenomenon are discussed.
A method is described for the determination of the initial rate of cholesterol esterification in human plasma, based on the enzymatic determination of free cholesterol in the plasma before and after incubation at 37 degrees C. The cholesterol esterification rate was linear up to 40 minutes. In 18 normal male and 10 normal female subjects the cholesterol esterification rate was 91 +/- 15 (mean +/- SD) and 62 +/- 12 nmoles/hr/ml of plasma, respectively.
The major lipoprotein density classes (chylomicrons-VLDL, LDL, HDL(2) and HDL(3)) were isolated from human plasma in a two-step ultracentrifugal procedure using the Ti-14 zonal rotor. The isolation of the two major high density lipoprotein subclasses (HDL(2) and HDL(3)) was achieved in a 24-hr run using a nonlinear NaBr gradient in the density range of 1.00-1.40. The lipoproteins with a density < 1.063 found in the rotor's center were isolated in a second run of 140 min duration using a continuous linear NaBr gradient in the density range of 1.00-1.30. The isolated lipoproteins were analyzed for chemical composition and for electrophoretic mobility; purity of isolated fractions was checked by immunochemistry. The lipoproteins exhibited flotation rates, chemical compositions, and molecular weights similar to those found with the common sequential procedures in angle-head rotors. The amount of lipoprotein lipids in the bottom fraction of the zonal rotor was comparable to that of the angle-head rotor. The described method yields the main lipoprotein density classes free from albumin in a very short running time; compared with the rate-zonal techniques already in use, this method allows the quantitative separation of an additional lipoprotein density class (HDL(2)) without increasing the running time. Furthermore, this procedure proved to be suitable for isolation of plasma lipoproteins from subjects with various types and varying degrees of hyperlipoproteinemia.
The effects of triglyceridemia on plasma lipoproteins were investigated in 16 hypertriglyceridemic (HTG) subjects (222-2,500 mg/dl) before and after the initiation of bezafibrate therapy. Bezafibrate caused a mean reduction of 56% in plasma triglyceride and increased the levels of lipoprotein and hepatic triglyceride lipases by 260 and 213%, respectively. The natures of very low density lipoprotein (VLDL), isolated at plasma density and of low and high density lipoprotein (LDL and HDL), separated by zonal ultracentrifugation, were determined. HTG-LDL appears as multiple fractions whereas HTG-HDL is seen predominantly as HDL3. HTG-VLDL is relatively poor in apoproteins and triglycerides but enriched in free and esterified cholesterol. HTG-LDL (main fraction) is depleted of free and esterified cholesterol but enriched in apoprotein and triglyceride. It is also denser and smaller than normal. HTG-HDL3 is denser than N-HDL3 and demonstrates compositional abnormalities similar to those of HTG-LDL. With the reduction of the VLDL mass, all abnormalities revert towards normal. This is accompanied by an increase in LDL-apoprotein B and cholesterol levels, which indicates an increased conversion of VLDL to LDL. Significant correlations between plasma triglyceride and the degree of all abnormalities are shown. The data obtained during treatment corroborate these relationships. The observations support the concept that most abnormalities reflect the degree of triglyceridemia. We suggest that plasma core-lipid transfer protein(s) is an effector of the abnormal cholesteryl ester distribution. Its prolonged action on increasingly large and slowly metabolized VLDL populations would entail a correspondingly excessive transfer of cholesteryl ester to VLDL and of triglyceride to LDL and HDL. It is calculated that, in moderate HTG, LDL and HDL contain only 50% of the normal cholesterol load. It is suggested that cholesteryl ester redistribution in HTG might be important in regulating metabolic events.
Plasma and erythrocyte lipids were estimated in 9 children with different types of anaemia and in 9 healthy control children. The anaemic children had rather high plasma triglycerides, but low total cholesterol and phospholipids. The levels of high density lipoprotein (HDL) cholesterol were particularly low, with a mean of only 70% of the controls. A positive correlation was found for haematocrit with HDL cholesterol, but not with low density lipoprotein (LDL) cholesterol. Plasma albumin was at the same level in both groups of children, however, suggesting that the diluting effect of increase in plasma volume could only partly explain the lowering of HDL cholesterol.
A striking, inverse correlation between HDL cholesterol and very low density lipoprotein (VLDL) triglycerides was present in the anaemic children. Anaemia in children adds to previously recognized pathophysiological conditions which induce inversely interrelated changes in HDL and VLDL.
Serum cholesterol and triglyceride levels were determined in 17 children with various forms of anaemia and varying rates of red cell production. Anaemic patients had low serum cholesterol values, and a good correlation between Hb and serum cholesterol levels was found. The serum triglyceride levels were also low in most patients, but the results were less closely related to Hb. No relationship could be demonstrated between the rate of red cell production as judged by reticulocyte counts, and serum cholesterol or triglycerides. Apparently all lipoprotein classes are reduced in individuals with uncomplicated anaemias. This hypolipidaemia can only partly be explained by the diluting effect of the increase in plasma volume accompanying anaemia.
S ummary
The present study has examined the relationship and significance of hypocholesterolaemia to anaemia and to the red cell. The level of plasma cholesterol is closely related to haematocrit levels both initially and throughout the course of the anaemias associated with hypocholesterolaemia. The association is maintained, regardless of the cause of the haematocrit change, i.e. transfusion or response to treatment. Hypocholesterolaemia does not affect the red cell, i.e. its survival, cholesterol concentration or osmotic fragility and occurs in a diverse group of anaemias. As such, it is not causally related to anaemia. The changes in plasma cholesterol are most likely related to its ‘redistribution’ or to plasma ‘dilution’, with contributory factors occurring. The presence of anaemia, even to a modest degree, would be important to consider when comparing cholesterol levels between groups of individuals.
We believe that on the basis of all available data, severe oxidative damage occurs in alpha- and beta-thalassemic RBCs, as depicted schematically in Fig 6. The differences in the severity and pattern of the oxidative damage may be related to the type and, perhaps, quantity of precipitated globin chains. The detrimental effect of the excess chains is multifold. In the process of globin-chain precipitation, free radicals are generated. The end product of the precipitated hemoglobin chains is heme, from which eventually iron and globin are liberated. Globin chains have been found to interact and disrupt the RBC membrane, damaging the cytoskeleton. The role of heme has not yet been studied in detail in thalassemic RBCs. However, there is some evidence that it participates in damaging RBCs in other types of hemoglobinopathies. Excess of iron is known to be a catalyst of peroxidation via the Fenton reaction, causing damage to the various RBC membrane components (lipids, proteins, etc). The denatured hemaglobin, in the form of hemichromes, aggregates with protein 3, forming Actual proof of excessive free radical production in thalassemia is still warranted. It will not be easy to document since the amount of superoxide dismutase in RBCs is above and beyond that required for neutralizing excess amount of superoxide. The more active radicals, particularly hydroxyl free radical, are difficult to measure because they are so active an interact immediately with any given substrate in their vicinity. In addition, we have to better understand the finding of excess membrane lipids in thalassemic RBCs and whether there are changes in the formation and propagation of lipid peroxidation in these cells compared with normal RBCs. Regarding the proteins, further understanding is required concerning the exact type and sites of oxidation that occurs in the beta-thalassemia 4.1 protein, and whether the damage found in alpha-thalassemia is due to oxidation of ankyrin itself or its entrapment within the complex of the precipitated hemichromes of beta chains. What is the role of the different globin chain oxidation and precipitation in generating such different cytoskeletal protein alterations? Another point that needs to be elucidated is the role of different kinds of antibodies that are attached to the newly exposed antigenic sites on the thalassemic RBC membranes.(ABSTRACT TRUNCATED AT 400 WORDS)
There is no longer any doubt that high plasma levels of LDL are atherogenic and that lowering them can reduce the risk of coronary heart disease, but the specific events induced by high levels of LDL in the artery wall are only now being elucidated. Once these processes are understood, we may find that there are ways to intervene at the level. Recent advances have brought us closer to being able to do this with regard to the uptake of LDL by macrophages and the development of the fattty streak, the earliest lesion in atherogenesis. Studies both in vitro and in vivo support the hypothesis that LDL undergoes an oxidative modification that targets it for uptake by the macrophage through a specific receptor - the acetyl LDL or scavenger receptor. Intervention studies in the LDL receptor-deficient animal model for atherosclerosis (the WHHL rabbit), using probucol as an antioxidant, show that the progression of the fatty streak can be slowed under conditions that do not lower plasma cholesterol levels. Much more remains to be done to establish the clinical relevance of these findings. Nevertheless, the experimental data available to date encourage aggressive additional research on the oxidative modification of LDL. This review has emphasized the oxidative modification of LDL because the evidence for its occurrence in vivo and for its role in atherogenesis is already persuasive. However, we recognize that with further study additional modifications may prove to be equally important or even more important. For example, the glycation of LDL may help explain the increased susceptibility of diabetic subjects to atherosclerotic complications. If so, rigid control of hyperglycemia may reduce such complications. As we learn more about these and other postsecretory modifications of LDL, we can hope to find ways of preventing them. To the extent that modifications of these kinds play an important part in atherogenesis, we may be able to intervene and obtain protection beyond that obtained by lowering plasma LDL levels.
A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, de- pending on the patient population compared. Additional Keyph rases hyperlipoproteinemia classifi- cation #{149} determination of plasma total cholesterol, tri- glyceride, high-density lipoprotein cholesterol #{149} beta lipo proteins
Evidence for the existence of a plasma lecithin : cholesterol acyltransferase is reviewed with emphasis not only on the lipid reactants, but also on the lipoprotein "substrates" and "products." The cholesteryl esters of all major lipoprotein classes become labeled when plasma is incubated with cholesterol-(14)C. However, the smaller, lecithin-rich high density lipoproteins appear to be preferred substrates. Most studies of factors that influence the acyltransferase reaction have not adequately distinguished between effects on the enzyme and effects on the lipoprotein substrates. However, the fact that cholesterol esterification is diminished in plasma from eviscerated animals or from patients with reduced liver function suggests that the liver may regulate both the level of the enzyme and that of the substrates. Several indications exist that the acyltransferase reaction is the major source of plasma esterified cholesterol in man. Furthermore, the reaction may have a broader, extracellular function. One possibility is that it plays a role in the transport of cholesterol from peripheral tissues to the liver.
We studied serum lipids and lipoproteins in 20 patients with beta-thalassemia major, under high transfusion programme and regular chelation therapy, and in 20 control subjects. Total cholesterol, HDL-cholesterol, HDL2-and HDL3-cholesterol, apolipoprotein A and B levels were significantly lower in patients with Cooley's anemia, whereas free cholesterol, triglycerides and the HDL-/HDL3-cholesterol ratio did not differ in the two groups. We think that liver damage plays an important role in determining the altered lipoprotein pattern in beta-thalassemia major. However, other factors may contribute to cause such lipid changes.
A fluorescent enzyme-linked immunosorbent assay is described for the rapid measurement of serum ferritin. Increased sensitivity was achieved by using 4-methyl-umbelliferyl-beta-D-galactopyranoside as the substrate for beta-galactosidase coupled to the purified antiferritin antibody. Further enhancement of the specific antigen-antibody reaction was attained by the addition of 4% polyethylene glycol 6000 to the antiferritin-beta-galactosidase conjugate. The procedure is performed in microELISA plates. These modifications of the method permit the measurement of serum ferritin at concentrations ranging from 0.25 to 50 microgram/liter with a coefficient of variation of 8% or less. The entire procedure is performed at ambient temperature and is completed within one working day. The cost of the assay is less than 10% of the immunoradiometric assay for serum ferritin.
The distribution of plasma cholesterol, triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) was examined in 6,654 17-yr-old young men and women who attended an army medical examination. There were highly significant differences among the four main groups, classified according to their father's place of birth: Israel, the Asian Near East, North Africa and Europe (including the Americas, Oceania and Southern Africa). Mean levels of plasma cholesterol in each group varied in males from 126.9 to 137.4 mg/dl, TG from 72.1 to 77.8 mg/dl and HDL-C from 41.3 to 44.4 mg/dl. In females, the cholesterol levels ranged from 144.6 to 154.8 mg/dl, TG from 72.7 to 76.3 and HDL-C from 47.3 to 50.5 mg/dl. In the various groups, subjects of North African origin consistently had the lowest lipid values, and subjects whose fathers were born in Europe or Israel, the highest. When the subjects were classified according to their fathers' specific country of origin, mean cholesterol values ranged from a low of 126.2 mg/dl in Moroccan males to a high of 143.0 in Austrian and Swiss males, and from 137.6 mg/dl in Tunisian females to 161.6 in those whose fathers had emigrated from North American countries. HDL-C ranged in males from 40.0 mg/dl in the Egyptian group to 47.0 in the Austrian-Swiss-Lichtenstein group; in females, the values ranged from 46.0 mg/dl in the Algerian group to 53.4 in the Austrian-Swiss-Lichtenstein group. These findings are discussed in light of published reports of lipid and lipoprotein levels in individuals living in different countries.
In Cooley's anaemia the serum lipid fraction, determined by chemical analysis, was found to be decreased. The lipoprotein distribution by paper electrophoresis showed a characteristic pattern with abnormally low alpha(1) fraction and high concentrations of the beta fractions. There is no relationship between age and serum lipoprotein distribution. A correlation was found between the electrophoretic pattern, liver function tests, and the E/C index. Similar changes but of lesser degree were found in sickle cell anaemia. Liver damage is thought to be the probable cause of the reduced alpha(1) fraction.
Since 1922 when Wu proposed the use of the Folin phenol reagent for
the measurement of proteins (l), a number of modified analytical pro-
cedures ut.ilizing this reagent have been reported for the determination
of proteins in serum (2-G), in antigen-antibody precipitates (7-9), and
in insulin (10).
Although the reagent would seem to be recommended by its great sen-
sitivity and the simplicity of procedure possible with its use, it has not
found great favor for general biochemical purposes.
In the belief that this reagent, nevertheless, has considerable merit for
certain application, but that its peculiarities and limitations need to be
understood for its fullest exploitation, it has been studied with regard t.o
effects of variations in pH, time of reaction, and concentration of react-
ants, permissible levels of reagents commonly used in handling proteins,
and interfering subst.ances. Procedures are described for measuring pro-
tein in solution or after precipitation wit,h acids or other agents, and for
the determination of as little as 0.2 y of protein.
1 972) Hypertriglyceridernia in thalassaemia major Serum cholesterol and triglycerides in children with anaemia. Scandinavian Iournal of Haernatology
- A V Rao
- K L Bai
- D Ramanuniah
Rao, A.V.. Bai. K.L. & Ramanuniah. D. (1 972) Hypertriglyceridernia in thalassaemia major. Journal of Indian Medical Association. 59, Seip. M. & Shrede. S. (1977) Serum cholesterol and triglycerides in children with anaemia. Scandinavian Iournal of Haernatology. 1, 503-508.
I9891 Intravascular lipoprotein reniodelling: Neutral lipid transfer proteins Abnormalities in very low. low. and high density lipopro-teins in hypertriglyceridemia-reversal toward normal with beza-fibrate treatment
- Risenberg S K Ileckelbaum
Risenberg. S. L? Ileckelbaum. K. ( I9891 Intravascular lipoprotein reniodelling: Neutral lipid transfer proteins. Clirricd Biocliwtisfrg. Huriicrn Plasma Lipoproteiris (ed. by J. C. Frurhart and J. Shepherd). pp. 153-171. Walter de Gruyter. New York. Eisenberg. S.. Gavish. D.. Oschry. Y.. Fainaru. M. & Deckelbaum. R.L. ( 1 984) Abnormalities in very low. low. and high density lipopro-teins in hypertriglyceridemia-reversal toward normal with beza-fibrate treatment. lournal of Clinical Zrtvestigatiort, 74, 470-482.
Hypertri-glyceridemia in homozygous beta-thalassaemia. /ournal of Pedia-trics ( I 9 59) Phosphorus assay in column chromatography
- M R Ameri
- M Alebouyeh
- M Ziai
- R B Conn
Ameri. M.R.. Alebouyeh. M.. Ziai. M. & Conn. R.B. (1975) Hypertri-glyceridemia in homozygous beta-thalassaemia. /ournal of Pedia-trics. 87. 1002-1003. Bartlett. C.R. ( I 9 59) Phosphorus assay in column chromatography. /ourrrnl q / Riologicvl Clwrtiistrq, 2 34, 466-468.
Hypertriglyceridemia in thalassaemia major
- Rao A. V.
Serum lipoproteins in children with anaemia
- Shrede S.