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Assessment of Atherosclerosis in Peripheral and Central Circulation in Adult β Thalassemia Intermedia Patients by Color Doppler Ultrasound: Egyptian Experience
Abstract
Background:
Atherosclerosis has been extensively studied in thalassemia major (TM) and sickle cell disease but not yet in β thalassemia intermedia (TI). Previous studies concerned with TM were performed in children. TI patients usually live longer and, thus, are more prone to complications of atherosclerosis.
Aim:
In our study, we applied color Doppler for the determination of arterial conduit and flow velocities in β TI patients.
Methods:
For central circulation, we measured right and left middle cerebral arteries (MCAs) and basilar artery (BA) mean flow velocity (MFV), pulsatility index (PI), and peak systolic velocity (PSV) as well as carotid intimal media thickness, and to assess peripheral circulation, we studied ankle/brachial index and posterior and anterior tibial arteries' (ATA, PTA) pressure and PSV. This was applied for 30 adult TI patients and 20 age-, sex-, and ethnic group-matched controls.
Results:
Transcranial Doppler findings among cases and controls showed that the MFV, PSV of MCAs, and PSV, PI, and MFV of the BA were statistically higher in cases than controls. A comparison between splenectomized and nonsplenectomized patients showed that total leukocyte count, platelet count, lactate dehydrogenase, ferritin, PSV and MFV of the left MCA were all statistically higher in splenectomized cases. Differences between males and females with TI with respect to laboratory and Doppler findings were all statistically insignificant except for intima media thickness, PTA pressure, ATA pressure, and PSV.
Conclusion:
More than one parameter should be applied to assess atherosclerosis in TI. There is evidence of an increased risk of central ischemia rather than peripheral ischemia in these patients.
... In this study, no significant correlation between Thalass. Rep. 2023, 13 43 Intima-media Thickness (IMT), a marker for subclinical atherosclerosis, and ferritin or cholesterol level was found in such patients [53]. ...
... Despite the use of iron chelation, patients with TDT still suffered from high iron levels which led to alterations in arterial structures, damage of elastic tissue, and calcification deposits in the vascular structures. Many studies have confirmed the early changes of atherosclerosis in both TDT and NTDT patients [53]. On the one hand, the mechanism of atherosclerosis in NTDT is not fully clear in the absence of a correlation between IMT and ferritin/cholesterol. On the other hand, a study in TDT patients showed a positive correlation between carotid atherosclerosis and serum ferritin levels [54]. ...
Beta thalassemia is an inherited disorder resulting in abnormal or decreased production of hemoglobin, leading to hemolysis and chronic anemia. The long-term complications can affect multiple organ systems, namely the liver, heart, and endocrine. Myocardial iron overload is a common finding in β-thalassemia. As a result, different cardiovascular complications in the form of cardiomyopathy, pulmonary hypertension, arrhythmias, and vasculopathies can occur, and in extreme cases, sudden cardiac death. Each of these complications pertains to underlying etiologies and risk factors, which highlights the importance of early diagnosis and prevention. In this review, we will discuss different types of cardiovascular complications that can manifest in patients with β-thalassemia, in addition to the current diagnostic modalities, preventive and treatment modalities for these complications.
... In recent years, substantial scientific evidence has highlighted the detrimental impact of premature atherosclerosis, which is one of the major causes of morbidity and mortality in β-TM patients [6,25]. Our study revealed that in patients with β-TM, an increment in FOXO1 and HSP72 signaling with low levels of SIRT1 is linked to accelerated atherosclerosis, which is crucial as a novel biomarker for the prediction of atherosclerosis. ...
Background: Atherosclerosis represents one of the major causes of morbidity in children with β-thalassemia major (β-TM). Aim: This study was designed to investigate SIRT1-FOXO1 signaling in β-TM children and their role in early detection of premature atherosclerosis. Methods: We equally subdivided 100 Egyptian children aged 6–14 years with β-TM according to carotid intima media thickness (CIMT) into 50 with CIMT < 0.5 mm and 50 with CIMT ≥ 0.5 mm, and 50 healthy children of matched age were included. They were subjected to evaluation of SIRT1, heat shock protein 72 (HSP72), and hepcidin levels via ELISA and forkhead box protein 1 (FOXO1) mRNA expression using real-time PCR in PBMCs; meanwhile, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase activities were evaluated spectrophotometrically. Results: Our results show significantly high values for CIMT, β-stiffness, atherogenic index of plasma (AIP), MDA, HSP72 and FOXO1, ferritin with significantly low hepcidin, SOD, catalase, and SIRT1 in β-TM as compared to controls with a more significant difference in β-TM with CIMT ≥ 0.5 mm than those with CIMT < 0.5 mm. A significant positive correlation between CIMT and MDA, HSP72, and FOXO1 gene expression was found, while a significant negative correlation with hepcidin, SOD, catalase, and SIRT1 was found. FOXO1 gene expression and HSP72 levels were the strongest independent determinants of CIMT. Conclusion: In β-TM, FOXO1 signaling is activated with low levels of SIRT1, and this is attributed to accelerated atherosclerosis in β-TM, which would be crucial in prediction of atherosclerosis.
... e early onset of neonatal pneumonia is mostly accompanied by nonspecific symptoms. However, as the disease progresses, patients may experience symptoms such as cyanosis, dyspnea, and shortness of breath and become vulnerable to complications such as atelectasis and emphysema if timely and effective treatment is absent, which takes a toll on their life and health [5][6][7]. e current treatment mainly relies on comprehensive treatment methods to control inflammation, improve the lung ventilation function of patients, and mitigate clinical symptoms. Related studies have revealed that early diagnosis and treatment are of great significance to the prognosis of patients. ...
Objective:
To evaluate the diagnostic value of combined detection of color Doppler flow imaging (CDFI) and serum C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels for neonatal pneumonia.
Methods:
In this prospective study, 30 newborns with pneumonia and 30 healthy newborns in our hospital from January 2019 to January 2020 were recruited. The healthy newborns were assigned to the control group, and the newborns with pneumonia were assigned to the experimental group. All subjects underwent CDFI and measurement of the levels of serum CRP, PCT, and IL-6. The serum indices and imaging results of the two groups were analyzed, and the specificity and sensitivity of different detection methods in the diagnosis of neonatal pneumonia were calculated and analyzed.
Results:
The levels of serum CRP, PCT, and IL-6 in the experimental group were significantly higher than those in the control group (P < 0.001). Combined detection had a larger detection area, higher sensitivity, and a superior overall detection outcome than single detection (P < 0.05). The diagnostic results of combined detection and clinical diagnosis in 30 newborns with pneumonia were similar (P > 0.05).
Conclusion:
The combined detection of CDFI and serum CRP, PCT, and IL-6 levels in the diagnosis of neonatal pneumonia shows a promising diagnostic outcome, so it is worthy of clinical application.
... This method of assessing the amount of iron in the heart tissue is cheaper and more accessible than T2*CMR. [15] There are a few studies in the existing literature on the relationship between T2*CMR and advanced echocardiographic arterial elasticity criteria. If such relationship is found, it may be used as a prognostic tool for myocardial iron overload. ...
Background:
Despite the availability of iron chelators, toxicity due to increased iron load is the leading cause of death in thalassemia major patients, especially in Iran. This study was performed to determine the association between cardiovascular magnetic resonance using T2-weighted sequences (CMR T2*) and diagnostic value of echocardiographic arterial elasticity in major beta-thalassemia patients without cardiac symptoms in Isfahan, Iran, in 2019 and 2021.
Materials and methods:
This cross-sectional study assessed the association between CMR T2*, advanced echocardiographic arterial elasticity criteria, and serum ferritin in 67 patients with major beta-thalassemia patients without cardiac symptoms at Chamran Cardiovascular, Medical, and Research Center in Isfahan, Iran, in 2019-2021. Data analysis was performed among the 67 patients using SPSS, version 24.0 (Statistical Procedures for Social Sciences, Chicago, Illinois, USA). Spearman's rank test was used to assess the correlation between T2*CMR, echocardiographic arterial elasticity criteria, and ferritin. All parameters are presented as mean ± standard deviation. The results were considered statistically significant at P < 0.05.
Results:
There was a positive correlation between CMR T2* and arterial elastance index (P = 0.035, r = 0.258), according to the Spearman test. In addition, CMR T2* was not correlated with the serum ferritin (P = 0.158, r = 0.201).
Conclusion:
Totally, according to the obtained results, it may be concluded that the arterial elastance index from echocardiography and the CMR T2* may be indicators of myocardial iron overload in patients with major beta-thalassemia patients without cardiac symptoms.
... Thalassemia intermedia patients usually live longer and, thus, are more prone to complications of atherosclerosis. There is evidence of an increased risk of central ischemia rather than peripheral ischemia in these patients [8]. The growth differentiation factor-15 (GDF-15) is a multifactorial cytokine and a member of the transforming growth factor superfamily. ...
Objectives:
To study serum growth differentiation factor-15 (GDF-15) serum level in β-thalassemia patients and its relation to carotid intima-media thickness.
Background:
Thalassemia is a common genetic disease resulting in decreased beta-chains, leading to manifested anemia. It may be subsequently complicated by iron overload, which induces numerous morbidities and even death. Growth differentiation factor-15 (GDF-15) is a strong and independent predictor of mortality and disease progression in patients with atherosclerosis alongside with carotid-intimal media thickness (CIMT).
Patients and methods:
This monocentric case-control study was done on 90 subjects in the period from January 2020 to March 2021. Sixty transfusion-dependent beta-thalassemia (TDβT) cases (≥18 years) were selected from the thalassemia clinic of Hematology division at Menoufia University hospitals. We included also 30 sex and age matched healthy as the controls. Routine investigations were done beside. Serum GDF-15 was measured by ELISA. CIMT was measured by Doppler Ultrasonography.
Results:
CIMT on both sides was statistically significant higher in cases (median of 0.08 cm) than in the controls (median of 0.04). GDF-15 was also significantly higher in cases (median of 1839.89 pg/dl) than in controls (median of 256.14 pg/dl). So, we found that GDF-15 is a predictor of and associated with atherosclerosis in thalassemic adults (OR = 39.198, p value 0.008, 95% CI: 2.576-596.5).
Conclusion:
GDF- 15 is increased in TDβT. CIMT (as a marker of subclinical atherosclerosis) is increased in these patients alongside with GDF-15, is a predictor, and associated with atherosclerosis in thalassemic adults.
... However, no association was found between large-vessel stenosis and subcortical white matter lesions, leaving small arteriolar pathology as the most likely explanation [28]. In fact, transcranial Doppler (TCD) studies in NTDT patients showed higher intracranial arterial blood flow velocities and higher increase in vascular resistance than in normal subjects [29,30]. ...
Purpose of the Review
Anemia has been called the fifth cardiovascular risk factor. It is one of the most prevalent pathologies worldwide. In this article, we aimed to perform a narrative review of the main cerebrovascular complications of anemia and its influence on stroke prognosis.
Recent Findings
Both hypoproliferative anemia (thalassemia, iron deficiency anemia, etc.) and hyperproliferative anemia (sickle cell disease, paroxysmal nocturnal hemoglobinuria, hereditary spherocytosis, etc.) are associated to cerebrovascular disease ranging from transient ischemic attack to ischemic stroke and hemorrhagic stroke with both intraparenchymal hemorrhage and subarachnoid hemorrhage or cerebral venous thrombosis. Anemia is associated to a worse prognosis in patients with cerebrovascular disease
Summary
In some cases, like sickle cell disease, pathophysiological mechanisms and therapeutic guidelines are well established, while in others, due to their rarity, there are still lack of robust data. More studies are needed to clarify how the prognosis of stroke patients with anemia could be improved.
... Thus, comparative studies with large sample size are needed to illustrate the vascular reactivity of thalassemic patients with patients of known cardiovascular risk factors reinforced with gene sequencing to discover the alteration in the genomic platform causing a normal VRI in β-TI patients. Finally, the higher risk of TEEs and atherosclerosis in β-TI patients shown by previous studies [5,[18][19][20] might be explained by other factors unrelated to reactive hyperemia and the VRI detected by the DTM. When interpreting this study for external validity, the reader should keep in mind that this is a study of small sample size; however there is a scarcity of data in the literature on the topic. ...
Beta-thalassemia intermedia (β-TI) is associated with vascular dysfunction. We used digital thermal monitoring (DTM), a non-invasive tool that evaluates vascular function based on changes in fingertip temperature during and after cuff occlusion on β-TI patients. Thirty-three patients (18 years and older) were recruited in this study and divided into 3 groups: thalassemia, anemic controls, and healthy controls. Exclusion criteria included factors that are known to be associated with vascular damage. Patients underwent DTM and results were extracted as vascular reactivity index (VRI), a measure of how well the circulatory system responds to stimuli that require adjustments of blood flow. One-way analysis of variance (ANOVA) was used to test the mean difference in VRI between the 3 groups. A multiple linear regression was also carried out with VRI as the outcome of interest and a function of covariates that were thought to be of clinical relevance to VRI. The frequency, mean VRI ± standard error (SE) for the thalassemic group were (N = 16), mean = 2.243 ± 0.111; for anemic controls (N = 9), mean = 2.374 ± 0.162; and for the controls (N = 8), mean = 2.338 ± 0.092. ANOVA test indicated a non-significant difference in mean VRI between the three groups (P value = 0.731). Multiple linear regression couldn’t detect any significant association between VRI and any of the predictors including the groups. Our study did not show a significant difference in VRI between the 3 study groups. Prospective studies of larger sample size are warranted to establish DTM as a possible non-invasive tool used to evaluate vascular function in β-TI patients.
Background
A high incidence of thromboembolic events is observed in thalassemia patients. This study investigated the relationship between carotid intima-media thickness (CIMT) and lipid profile, iron metabolic indices (IMI), and inflammatory markers in β-thalassemia intermedia (β- TI) patients.
Research design and methods
Forty-five β-TI patients at Assiut University Hospital and thirty-four healthy individuals were enrolled in the study. We measured Lipid profile, IMI, high sensitive CRP (Hs-CRP), and interleukin-6 (IL-6) and compared the results between both groups. We used CIMT measurement as a marker for subclinical atherosclerosis. We used both univariate and multivariate analyses to test relations and independent predictors of CIMT.
Results
β- TI patients had higher CIMT (P = 0.000). CIMT was positively correlated with absolute neutrophil count (ANC) (r = 0.320, p = 0.032), ferritin (r = 0.544, p = 0.000), Hs-CRP (r = 0.603, p = 0.000), and IL-6 (r = 0.520, p = 0.000). Hs-CRP was an independent predictor of CIMT (p = 0.000). Hs-CRP cut off value of 60.4 ug/dl has sensitivity of 63.3% and specificity of 93.3% in predicting premature atherosclerosis.
Conclusion
β- TI patients had higher CIMT despite the protective lipid profile. Hs-CRP was an independent predictor of CIMT.
Background: β-thalassemia, a severe form of anemia, is an inherited blood disorder characterized by growth retardation, splenomegaly, and bone abnormalities. Complications related to treatment-induced iron overload also affect the quality of life of patients with major β-thalassemia. Some recent studies indicated cerebral hemodynamic disorders and increased risk of stroke in these patients. The aim of this study was to evaluate mean flow velocity (MFV) in some cerebral arteries of patients with major thalassemia using transcranial Doppler ultrasonography. Materials and Methods: In this cross-sectional study, 26 patients with major thalassemia were investigated. The definitive diagnosis was based on serum hemoglobin electrophoresis. Transcranial Doppler ultrasonography was performed in patients and MFV of internal carotid, anterior cerebral, and middle cerebral. Posterior cerebral arteries were measured. Demographic characteristics, duration of treatment, number of blood transfusions per month, the interval between the last blood transfusion, and the ultrasonography were recorded and analyzed statistically. Results: Ten female and 16 male patients participated in this study. Results showed that 57.7% of patients had a hemodynamic abnormality in at least one vessel. The abnormality was significantly higher in the anterior and middle cerebral arteries (p<0.001 and p=0.005, respectively). Among the variables evaluated, age was significantly associated with hemodynamic dysfunction. This relationship remained significant after using the logistic regression analysis (p=0.0267). Conclusions: Some patients with major thalassemia have a cerebral hemodynamic abnormality. Aging is associated with the higher frequency of this abnormality.
The threshold velocity ≥200 cm/s at transcranial Doppler (TCD) evaluation is a useful cut-off for preventing the stroke (STOP trial) in pediatric patients with sickle cell disease (SCD), term including different types of sickle genotypes. Scanty data are available for adult SCD patients. We compared intracranial blood flow velocities between adult SCD patients and controls using transcranial color Doppler (TCCD), measuring the peak of systolic velocity (PSV) with the insonation angle correction and the pulsatility index (PI), an indicator of endothelial elasticity. Fifty-three adult SCD patients (aged >18 years) were enrolled (15 sickle cell anemia, 26 sickle cell thalassemia, and 12 HbS/HbC). None of the patients presented neurological signs. PSVs in middle cerebral artery (MCA) were higher in SCD patients than in controls (p = 0.001). In sickle cell anemia patients, PSVs were higher when compared to HbS/βThal (p < 0.0060) and HbS/HbC patients (p < 0.0139). PI was within the lower range of normality in SCD patients compared to controls. Moreover, MCA-PSV was higher with lower Hb levels and higher HbS%; PI did not change with variation of Hb levels and HbS%.
PSV and PI in SCD adult patients could be a relevant index to indicate the abnormal cerebral blood flow and to detect the sickle endothelial damage, in order to prevent cerebrovascular accidents.
OBJECTIVES: Previous studies have demonstrated that both low and high hemoglobin concentrations are predictive of adverse cardiovascular outcomes in various populations. However, an association of hemoglobin with the ankle-brachial index, which is widely used as a screening test for peripheral arterial disease, has not yet been identified. METHODS: We examined 786 subjects (236 women and 550 men) who received routine physical check-ups. The ankle-brachial index and several hematological parameters, including the hemoglobin level, hematocrit and red blood cell count and other demographic and biochemical characteristics were collected. Univariate and multivariate linear regression analyses were performed to assess the relationships between the ankle-brachial index and the independent determinants. Receiver operating characteristic curve analysis was conducted to calculate the cut-off level of hemoglobin for detecting a relatively low ankle-brachial index (less than 20% of all subjects, which was 1.02). RESULTS: The hemoglobin level, hematocrit and red blood cell count were correlated with the ankle-brachial index in the males (r=-0.274, r=-0.224 and r=-0.273, respectively, p
Background & objectives:
Early atherosclerosis and vascular complication have been described in thalassaemia patients. There is lack of data or guidelines regarding monitoring of vascular health in thalassaemia. This study was conducted to compare carotid artery structural and functional indices such as carotid artery intima-media thickness (CIMT), stiffness index (SI) and Young's elastic modulus (YEM) in β-thalassemia patients with age and sex matched controls, and to correlate these parameters with serum ferritin, cardiac iron, and hepatic iron.
Methods:
This cross-sectional study included 53 β-thalassaemia patients receiving regular blood transfusions. Carotid artery indices such as CIMT, SI, and YEM were calculated by duplex ultrasound and colour Doppler. Serum ferritin levels were measured by chemiluminescence. Cardiac and hepatic iron estimation were done using MRI T2* sequences analyzed by a special thalassaemia software.
Results:
Mean CIMT of cases and controls were 0.48 ± 0.04 and 0.44±0.02 mm, respectively and these were significantly different (P<0.001). Similarly significant differences were noted in SI and YEM of cases (2.45±0.79 and 96.12±34.85, respectively) as compared to controls (1.98±0.54 and 68.60±24.29, respectively) (p<0.001). There was significant inverse correlation between stiffness index and cardiac iron overload assessed by MRI cardiac T2* (p=0.03). Mean SI and YEM of cases were (2.1736 ± 0.2986 and 107.3± 41.6, respectively) significantly higher among non-splenectomized patients compared to splenectomized patients (2.0136 ± 0.263 and 86.9 ± 25.2, respectively) (p<0.05).
Interpretation & conclusions:
CIMT and arterial stiffness indices were significantly increased in β-thalassaemia patients compared to controls which was indicative of early atherogenic changes. This study supports the hypothesis that iron overload is a risk factor for early atherosclerosis and cardiovascular disease.
Iron overload in patients with beta-thalassemia major (BTM) lead to alterations in the arterial structures and the thickness of the carotid arteries. Doppler ultrasound scanning of extra-cranial internal carotid arteries is non-invasive and relatively quick to perform and may identify children at increased risk of stroke that would otherwise be missed. Increased carotid artery intima media thickness (CIMT) is a structural marker for early atherosclerosis and correlates with the vascular risk factors and to the severity and extent of coronary artery disease.
To evaluate the role of carotid Doppler examination and CIMT measurement as a predictor of atherosclerotic changes in BTM children with iron overload.
Sixty two children with BTM and, thirty age and sex matched normal controls were included. Complete blood count, ferritin, serum cholesterol were done, as well as carotid Doppler ultrasonography to measure the CIMT in both patients and controls.
CIMT of thalassemic patients was significantly increased compared to controls (p=0.001). There was a significant positive correlation between CIMT and patient's age, the duration from first blood transfusion, serum cholesterol and, iron overload parameters as serum ferritin, frequency of blood transfusion, iron chelation. The length of the transfusion period was the highest risk factor, and an inadequate iron chelation was a further risk factor. Significant negative correlation was found between CIMT and hematocrit value while no significant correlation was found between CIMT and weight, height, BMI centiles and Hb level.
Carotid Doppler is very useful in measurement of CIMT that increased in thalassemic patients that shows a strong relationship with features of iron overload. Routine Doppler measurement of CIMT in these patients is recommended to predict early atherosclerotic changes as well as in follow-up.
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.
We aimed to study the endothelial dysfunction among children and adolescents with transfusion-dependent β-thalassemia using von Willebrand factor antigen (VWF:Ag) and flow cytometric analysis of circulating CD144(+) endothelial microparticles (EMPs) and endothelial progenitor cells (CD34(+)VEGFR2(+)) and assess their relation to iron overload, erythropoietin and chelation therapy as well as echocardiographic parameters and carotid intima-media thickness. The VWF:Ag, EMPs, and CD34(+)VEGFR2(+) cells were significantly higher among patients with β-thalassemia than controls (P < .001). The type of chelation and patients' compliance did not influence the results. No significant correlations were found between the studied vascular markers. Patients with evident heart disease had higher VWF: Ag, EMPs, and CD34(+)VEGFR2(+) cells than those without. Carotid intima-media thickness was increased among patients but not correlated with vascular markers. We suggest that procoagulant EMPs and VWF: Ag are involved in cardiovascular complications in patients with young β-thalassemia. CD34(+)VEGFR2(+) cells were further increased in response to tissue injury contributing to reendothelialization and neovascularization.
Transcranial Doppler ultrasonography (US) is a noninvasive, portable technique for evaluating the intracranial vasculature. It has found its most useful clinical application in the detection of vasospasm involving the cerebral vessels after subarachnoid hemorrhage due to aneurysm rupture. The technique has become an integral part of monitoring and managing patients with subarachnoid hemorrhage in the neurologic intensive care unit. In addition, it has proved useful for evaluating the intracranial vasculature in patients with sickle cell disease, stroke, or brain death. Transcranial US originated as a "blind" nonimaging study in which pulsed Doppler technology was used. Identification of the major intracranial vessels and evaluation of those vessels for vasospasm relied on spectral waveforms obtained in each vessel and was based on the depth of the vessel from the skull, the direction of blood flow, and the orientation of the transducer. Recent advances in US technology allow the use of gray-scale, spectral Doppler, and color Doppler flow imaging to directly visualize intracranial vessels, thereby simplifying flow velocity measurements and enhancing their accuracy for vasospasm detection. In particular, measurements of peak systolic velocity and mean flow velocity and calculation of the Lindegaard ratio facilitate the identification of vessels that may be in vasospasm and help differentiate vasospasm from physiologic conditions such as hyperemia and autoregulation. Thus, gray-scale and color Doppler flow imaging offer many advantages over the original pulsed Doppler technique for evaluating the intracranial vasculature.
Introduction. Patients with β-thalassemia intermedia have a higher incidence of thromboembolic events compared to the general population. Previous studies have shown that patients with sickle cell disease, who are also prone to ischemic events, have higher intracranial arterial blood flow velocities measured by transcranial Doppler sonography (TCD). The aim of this study is to evaluate intracranial arterial flow velocities in patients with β-thalassemia intermedia and compare the results with those found in healthy subjects. Methods. Sixty-four patients with β-thalassemia intermedia and 30 healthy subjects underwent transcranial Doppler sonography. Results. Significantly higher flow velocities were found in intracranial arteries of patients compared to controls (P = 0.001). Previously splenectomized patients with thrombocytosis showed higher flow velocities than nonsplenectomized patients without thrombosis. Conclusion. The increased flow velocities in patients with β-thalassemia intermedia may point to a higher risk of ischemic events. Preventive measures such as blood transfusion or antiplatelet treatment may be beneficial in these patients.
Although the life expectancy of thalassemia patients has markedly improved over the last few decades, patients still suffer from many complications of this congenital disease. The presence of a high incidence of thromboembolic events, mainly in thalassemia intermedia, has led to the identification of a hypercoagulable state in these patients. In this review, the molecular and cellular mechanisms leading to hypercoagulability in thalassemia are highlighted, with a special focus on thalassemia intermedia being the group with the highest incidence of thrombotic events as compared to other types of thalassemia. Clinical experience and available clues on optimal management are also discussed.
As the life expectancy of β-thalassemia patients has markedly improved over the last decade, several new complications are being recognized. The presence of a high incidence of thromboembolic events, mainly in thalassemia intermedia patients, has led to the identification of a hypercoagulable state in thalassemia. In this review, the molecular and cellular mechanisms leading to hypercoagulability in thalassemia are highlighted, and the current clinical experience is summarized. Recommendations for thrombosis prophylaxis are also discussed.
Thalassaemia is considered the most common genetic disorder worldwide. An association between the heterozygous beta-thalassaemia trait and myocardial infarction has previously been observed. However, the relationship between heterozygous beta-thalassaemia and atherosclerosis, considering other coronary artery disease (CAD) risk factors, has remained unclear.
A case-control study was conducted to evaluate the hypothesis that thalassaemia minor affects the likelihood of atherosclerotic plaque formation. Blood counts and blood chemistry data as well as traditional risk factors from 1,363 patients referred to heart centres for coronary angiography were recorded. Heterozygous beta-thalassaemia was diagnosed by the presence of hypochoromic-microcytic anaemia, ferritin levels > 12 ng/ml and haemoglobin-A2 levels > 3.5.
Chi-squared analysis showed that the prevalence of heterozygous beta-thalassaemia was not significantly different between patients with and without CAD (p > 0.05). Multivariate logistic regression analysis using CAD as the dependent variable and traditional risk factors, haematocrit, ferritin levels and heterozygous beta-thalassaemia as independent variables, did not show any significant difference either. Independent two-tailed student's t-tests showed that haematocrit levels were statistically different (p = 0.000) between CAD(+) and CAD(-) groups, but low-density lipids (LDL), high-density lipids (HDL), triglycerides (TG), total cholesterol and serum ferritin levels were not statistically different (p > 0.05).
The prevalence of heterozygous beta-thalassaemia in the case group was not significantly different from the control group. This case-control study did not support the hypothesis that thalassaemia minor affects the likelihood of atherosclerotic plaque formation.
Transcranial Doppler (TCD) ultrasonography is a noninvasive ultrasound study, which has been extensively applied on both outpatient and inpatient settings. It involves the use of a low-frequency (≤2 MHz) transducer, placed on the scalp, to insonate the basal cerebral arteries through relatively thin bone windows and to measure the cerebral blood flow velocity and its alteration in many different conditions. In neurointensive care setting, TCD is useful for both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, and brain stem death. It also allows to investigate the cerebrovascular autoregulation in setting of carotid disease and syncope. In this review, we will describe physical principles underlying TCD, flow indices most frequently used in clinical practice and critical care applications in Neurocritical Unit care. © 2016 Journal of Cardiovascular Echography Published by Wolters Kluwer - Medknow 27.
The aim of the present study was to evaluate left ventricular myocardial deformation and carotid arterial stiffness using 2-dimensional strain and echo-tracking in patients with asymptomatic β-thalassemia major (β-TM) without significant myocardial iron overload to determine whether early subclinical cardiovascular abnormalities would be detectable. We enrolled 32 patients with β-TM (23 women, mean age 35 ± 8 years) and 33 healthy volunteers (20 women, mean age 35 ± 6 years). All subjects underwent echocardiography with 2-dimensional strain analysis (XStrain) and ultrasonography of the carotid arteries with measurement of the stiffness parameters (ProSound Alpha 10). Cardiac magnetic resonance imaging using a T2* algorithm (37.7 ± 5.6 ms) for the assessment of myocardial iron overload was performed in each patient. The clinical and standard echocardiographic parameters were comparable between the patients and healthy subjects. The global left ventricular longitudinal strain was significantly impaired in the patients compared with the controls (-17.9 ± 3.5% vs -24.3 ± 3.4%, p = 0.002), although the radial and circumferential strain values were similar between the 2 groups (p = NS for both). The carotid intima-media thickness was comparable between the patients and healthy subjects (0.67 ± 0.20 mm vs 0.66 ± 0.15 mm, p = NS). In contrast, the arterial stiffness was significantly increased in the patients compared with the controls (stiffness index 6.16 ± 1.31 vs 4.65 ± 0.82, p <0.001; arterial compliance 1.10 ± 0.26 vs 1.28 ± 0.30 cm(2)/mm Hg, p = 0.027; elastic modulus 74.1 ± 19.5 vs 59.1 ± 12.1 mm Hg, p = 0.001). In conclusion, cardiovascular abnormalities, although often subclinical, occur at an early stage of β-TM and also in the absence of significant iron overload. Thus, 2-dimensional strain and echo-tracking might be more accurate than standard echocardiography and vascular parameters in the early identification of cardiovascular involvement.
Unlabelled:
Higher prevalence of cardiovascular disease in Thalassemia patients have been known. Potential mechanisms are enhanced platelet activation, LDL oxidation, macrophage activation, and increased nitric oxide destruction. We have investigated coronary flow reserve (CFR), brachial artery flow mediated dilation (FMD) and Carotid intima-media thickness (IMT) in patients with Beta thalessemia minor (BTM).
Methods:
Forty patients with BTM and 35 healthy control subjects were included. In all subjects CFR, brachial artery FMD, carotid artery IMT were measured.
Results:
CFR measurements: Coronary baseline diastolic peak flow velocity (DPFV) of left anterior descending coronary artery (LAD) was significantly higher in the BTM group (23.8 ± 3.9 vs. 22.1 ± 3.0, P = 0.04). However, hyperemic DPFV was significantly lower (61.1 ± 13.0 vs. 68.2 ± 14.2, P = 0.02), and CFR was significantly lower (2.57 ± 0.46 vs. 3.07 ± 0.48, P < 0.0001) in the BTM group than that in the control group. Brachial artery FMD and carotid IMT measurements: Percent FMD measurements were significantly lower in the BTM group than that in the controls (6.22 ± 4.29 vs. 8.10 ± 4.00, P = 0.01). Carotid IMT measurements were significantly but slightly higher in the BTM group than that in the controls (0.57 ± 0.07 vs. 0.54 ± 0.04, P = 0.04).
Conclusion:
CFR reflecting coronary microvascular function and brachial artery FMD are decreased, and carotid IMT is increased in patients with BTM.
Hypercoagulability and venous thromboembolism are common in patients with β-thalassemia intermedia (TI), especially in the splenectomized adult. Although arterial involvement is not commonly reported, we have recently observed a high prevalence (60%) of silent brain infarction on brain MRI in 30 splenectomized adults with TI. The pathophysiology of these white matter lesions remains unknown.
In this prospective work, we evaluated magnetic resonance angiography (MRA) scans of the same cohort of 30 patients. Data collected were the presence or absence of vascular lesions, their locations, and severity. Correlations between MRA abnormality and patients/disease characteristics were evaluated. Comparisons between MRA and previous MRI findings were made.
Of 29 evaluable patients, 8 (27.6%) had evidence of arterial stenosis on MRA. The majority of lesions had mild narrowing and mostly involved the internal carotid artery. Five patients (17.2%) had evidence of aneurysms. Low total hemoglobin and high non-transferrin-bound iron levels independently characterized patients with evidence of stenosis on MRA. Among the 18 patients with silent brain infarction on MRI, three had evidence of stenosis on MRA with only one patient having lesions that could explain the silent infarcts.
Cerebral vasculopathy is common in splenectomized adults with TI. However, large-vessel disease does not explain the occurrence of silent brain infarction. The combined use of MRA and MRI better identifies splenectomized TI adults with neuroimaging abnormalities.
β-Thalassemias are inherited hemolytic anemias with a broad phenotype and an increased rate of vascular complications despite a near absence of coronary artery disease.
We investigated the presence of endothelial dysfunction and subclinical atherosclerosis in non-transfusion-dependent patients with β-thalassemia intermedia (β-TI) by means of flow-mediated (FMD) and flow-independent (FID) brachial artery dilatation and carotid artery intima-media thickness.
In 20 nondiabetic young adults with β-TI, FMD (6.6 ± 3.7 vs. 10.3 ± 3.1%; p = 0.002) and FID (14.0 ± 4.7 vs. 18.0 ± 5.6%; p = 0.02) were both lower relative to the values in 20 matched control subjects, whereas the intima-media thickness was increased (0.51 ± 0.09 vs. 0.46 ± 0.07 mm; p = 0.049). Fibrin generation, soluble endothelial activation markers, and proinflammatory proteins were higher in the patient group, while the plasma cholesterol level was lower.
These findings indicate premature atherosclerosis among patients with β-TI; this is in accord with the high incidence of noncoronary vascular episodes in β-TI.
Subclinical atherosclerosis in young beta-thalassemia major (beta-TM) patients and its risk factors including dyslipidemia compared to type 1 diabetic patients were assessed. Ninety subjects were included and divided into three groups: group I comprised 30 beta-TM patients with a mean age of 18.4 +/- 6.18 years; group II comprised of 30 type 1 diabetic patients with a mean age of 19.23 +/- 4.25 years, and 30 healthy subjects served as controls in group III. Fasting lipid profiles, hemoglobin (Hb) electrophoresis, serum ferritin and high resolution ultrasound for the measurement of carotid artery intima media thickness (CIMT) were done. Serum triglycerides, total cholesterol, apoprotein A (ApoA), and CIMT were significantly elevated, while high density lipoproteins (HDL) were significantly lowered in thalassemic and diabetic patients compared to controls. In thalassemic patients, CIMT was positively correlated with age, Hb F, ferritin and cholesterol levels. Atherogenic lipid profiles in young thalassemic patients with increased CIMT highlights their importance as prognostic factors for vascular risk stratification.
Insulin-dependent diabetes mellitus (IDDM) is a frequent complication in patients with beta-thalassaemia major. It is believed to be a consequence of the damage inflicted by iron overload to the pancreatic beta-cell. Liver disorders and genetic influences seem to be additional predisposing factors to diabetes mellitus in patients with beta-thalassaemia. Ethnic variations are frequently reported on prevalence and complications of diabetes mellitus in the beta-thalassaemia patients. We investigated 50 Saudi children (< 15 years) with beta-thalassaemia major and 50 beta-thalassaemia minor, and age- and sex-matched controls for the prevalence of diabetes mellitus, and its relation to hitherto claimed predisposing factors. Fasting blood glucose, plasma insulin level, liver function tests, plasma ferritin, iron, and transferrin were assessed in each patient and glucose tolerance was evaluated. Results in patients with beta-thalassaemia major were compared with those obtained for beta-thalassaemia minor and the controls. The results showed moderate elevation of ferritin level in the majority of the beta-thalassaemia major despite desferroxamine therapy. Either hyperinsulinaemia or hypoinsulinaemia was encountered in the majority of these patients. The prevalence of diabetes mellitus was 6 per cent compared to 2 per cent in the beta-thalassaemia minor and normal children. Impaired glucose tolerance (IGT) occurred at a significantly higher (24 per cent) frequency in the beta-thalassaemia major compared to 2 and 0 per cent in the beta-thalassaemia minor patients and normal controls, respectively. The prevalence of diabetes mellitus was significantly lower in the Saudi thalassaemic patients compared to the results obtained from patients of other ethnic groups reported in literature.(ABSTRACT TRUNCATED AT 250 WORDS)
Platelet factor 3 (PF3) is a platelet membrane component that plays an important role in the activation of the coagulation mechanism. Whenever platelet activation occurred, PF3 is released and participates in thrombin formation. Erythrocyte membrane fraction has also some PF3 like activity, and in abnormal erythrocyte membrane disorders, eg thalassemia, some of the membrane fraction accelerates platelet activation by increasing the PF3 activity. Formerly it was difficult to measure the PF3 activity in plasma. Recently a sensitive chromogenic test to determine the PF3 activity, which could detect the changes in PF3 activity with time, was introduced. This study was done to observe the effect of abnormal erythrocyte on platelet activation. The results obtained using the chromogenic method are the following: whole blood taken from normal subjects showed OD 0.11 +/- 0.06 at 0 minutes after blood collection and then increased significantly (p < 0.01) to 0.21 +/- 0.10 after 90 minutes, while the platelet count did not differ significantly (p > 0.05). Those results showed that there were some platelet activation after 90 minutes as seen by the increased PF3 activity, with no significant change in platelet counts. In beta-thalassemic trait subjects the PF3 activity in whole blood at 0 minutes did not differ significantly compared to the normal subjects, but after 90 minutes it was significantly higher (p < 0.01), OD 0.52 +/- 0.35. However the PF3 in platelet rich plasma at 90 minutes did not increase. The platelet count after 90 minutes was significantly decreased (p < 0.01) This result suggest that the increase in PF3 activity was caused by the role of the abnormal erythrocytes.
Iron is a vital element in life. However, it may participate in diverse pathological processes by catalyzing the formation of reactive oxygen free radicals. During the past decade, considerable evidence has supported the role of oxidative stress in the development of atherosclerosis and related cardiovascular diseases. The oxidation of low-density lipoprotein (LDL) and lipid is believed to be one of the crucial events leading to plaque formation in vasculature. It has been hypothesized that iron-mediated oxidation is involved in this process. In favor of this idea, several epidemiological studies have shown that the level of body iron stores is positively correlated with the incidence of coronary heart disease in human populations. However, some studies have yielded conflicting results. Recently, studies conducted in our laboratory and others have demonstrated that iron deposition is prominent in human atherosclerotic lesions. The iron deposits appear to colocalize with ceroid, which is an end product of extensively oxidized lipid and protein complex, in lesions, providing histological evidence to support the iron hypothesis. Additional experiments in animals have further revealed that the severity of atherosclerosis can be markedly influenced by iron overload or deficiency. Collectively, these data provide a strong pathological basis to support the detrimental role of iron in vascular damage and progression of the disease.
Some epidemiological studies have shown that increased iron stores are associated with increased cardiovascular events. Redox-active iron may contribute to lipid peroxidation, endothelial cell activation, and generation of reactive oxygen species (especially hydroxyl radical, via Fenton chemistry). Increased oxidative stress is associated with impaired action of endothelium-derived nitric oxide in patients with atherosclerosis.
To test the hypothesis that reducing vascular iron stores would reverse endothelial dysfunction, we examined the effects of the iron chelator deferoxamine (500 mg intra-arterially over 1 hour) on vasomotor function in forearm resistance vessels of patients with coronary artery disease by venous occlusion plethysmography. Patients with coronary artery disease had impaired endothelium-dependent vasodilation in response to methacholine compared with healthy control subjects (P<0.001). Deferoxamine infusion decreased serum iron levels (P<0.001). Deferoxamine improved the blood flow response to methacholine in patients with coronary artery disease (P<0.01 by 2-way repeated-measures ANOVA) but had no effect on the response to sodium nitroprusside. In normal volunteers, deferoxamine had no effect on the response to methacholine. The nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine abolished augmentation of the methacholine response associated with deferoxamine. The hydroxyl radical scavenger mannitol had no effect on the methacholine response.
Deferoxamine improved nitric oxide-mediated, endothelium-dependent vasodilation in patients with coronary artery disease. These results suggest that iron availability contributes to impaired nitric oxide action in atherosclerosis.
Hypertension, hypercholesterolemia, and coronary artery disease are among the risk factors of cerebrovascular accidents. After age, hypertension is the most powerful stroke risk factor. Abnormalities of serum lipids are regarded as risk factors for cerebrovascular accidents. A significant reduction in stroke risk among persons treated with cholesterol-reducing medicines known as statins are reported. Stroke risk nearly doubles in those with antecedent coronary artery disease. Moreover, polycythemia and high hematocrit levels are considered to be potential stroke risk factors. Minor thalassemia is associated with decreased prevalence of arterial hypertension and myocardial infarction (the second effect observed only in males.) Total cholesterol and LDL levels are lower in minor thalassemics, as is the blood viscosity. Therefore, it could be hypothesized that minor thalassemia could afford some protection against cerebrovascular accidents.
The ankle-brachial index is the ratio of the ankle and the brachial systolic blood pressure and is used to assess individuals with peripheral arterial disease. An ankle-brachial index <0.90 suggests the presence of peripheral arterial disease and is a marker of cardiovascular risk. The objective of this review is to determine the sensitivity and specificity of an ankle-brachial index <0.90 to predict future cardiovascular events, including coronary heart disease, stroke, and death.
We conducted a systematic review of the literature and included studies that used an ankle-brachial index cutoff between 0.80 and 0.90 to classify patients with or without peripheral arterial disease, followed patients prospectively, and recorded cardiovascular outcomes (ie, myocardial infarction, stroke, or mortality). Data were combined using a random-effects model meta-analysis to determine the sensitivity, specificity, relative risks, and likelihood ratios of a low ankle-brachial index to predict future cardiovascular disease. A total of 22 studies were identified, 13 were excluded, and 9 studies were included in the meta-analysis. The sensitivity and specificity of a low ankle-brachial index to predict incident coronary heart diseases were 16.5% and 92.7%, for incident stroke were 16.0% and 92.2%, and for cardiovascular mortality were 41.0% and 87.9%, respectively. The corresponding positive likelihood ratios were 2.53 (95% CI, 1.45 to 4.40) for coronary heart disease, 2.45 (95% CI, 1.76 to 3.41) for stroke, and 5.61 (95% CI, 3.45 to 9.13) for cardiovascular death.
The specificity of a low ankle-brachial index to predict future cardiovascular outcomes is high, but its sensitivity is low. The ankle-brachial index should become part of the vascular risk assessment among selected individuals.
Levels of circulating red blood cell (RBC)-derived vesicles are increased in sickle cell anaemia (SCA) and thalassaemia intermedia (TI) but the mechanisms, effects and controlling factors may differ. This study found that levels of vesicles and intravascular haemolysis were linked as shown by the correlation between levels of vesicles and plasma Hb. Vesicle levels were 6-fold greater in SCA and 4-fold greater in TI than in controls. The proportion of plasma Hb within vesicles was increased in SCA and TI with a significantly higher proportion in TI. We examined whether subpopulations of RBC expressing phosphatidylserine (PS) were a source of PS(+) vesicles and observed a significant association. Thrombin generation was promoted by the vesicles in which 40-50% expressed PS. In TI, markers of thrombin generation were significantly related to PS(+) RBC. Splenectomy in TI had significant effects including greater increases in vesicle levels, plasma Hb, PS(+) RBCs and thrombin generation markers than in unsplenectomised patients. In hydroxycarbamide (HC)-treated SCA patients these measures were decreased compared with untreated controls. The relationship between vesicle levels and plasma Hb suggests a mechanism linking vesiculation to haemolysis and consequently nitric oxide (NO) bioavailability and suggests a means by which HC treatment improves NO bioavailability.
Southeast Asian J Trop Med Public Health. ; 24 Suppl 1():216-8.)
- IS Timan
- Y Funahara
- R Setiabudy
- J Latu
- E Silman
Kirsch, Mahan Mathur, Michele H. Johnson, Gunabushanam Gowthaman, Advances in Transcranial Doppler US: Imaging Ahead Radiographics: January-February .antiplatelet drug administration, could be beneficial.
- D. Jonathan
Tianlun Yang* Association of hemoglobin with ankle-brachial index in general populationClinics (Sao Paulo). Jul; 71(7): 375–380.
- Chenglong Zhang
- Lei Jing
- Ke Xia
ISBN: 978-9963-717-06-4.
- MD Cappellini
- A Cohen
- J Porter
- A Taher
- V Viprakasit
Intima-media thickness: Appropriate evaluation and proper measurement, described. An article from the e-journal of the ESC Council for Cardiology Practice. Vol. 13, N° 21 - 05 May
- Iana Simova