Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Restriction endonuclease analysis was used to detect alpha-gene deletions and to determine the haplotypes in the DNA of the beta S-gene-cluster [Benin, Central African Republic (CAR), and Senegal] in 221 patients with sickle cell anemia (SS). The clinical expression of SS was modified by the beta S-gene-cluster polymorphisms and the alpha-gene status (alpha-thalassemia-2). The overall risk of soft tissue organ failure caused by the obliterative sickle vasculopathy (including stroke, renal failure, chronic lung disease with cor pulmonale, leg ulcers, and young adult death) was increased threefold in those with a CAR haplotype and was decreased in those with a Senegalese chromosome (p = 0.003). In the presence of a Senegalese haplotype, the patient's health is better, and with the CAR haplotype it is always worse. With the Benin, it is intermediate. Acute recurrent clinical events including hospitalized sickle cell crisis, bone infarction, and infection are decreased in frequency in those with a Senegalese haplotype. The risk of most acute events including acute chest syndrome is equivalent in those with Benin or CAR haplotypes. In the United States, alpha-thalassemia-2 is co-inherited randomly among the beta S-gene-cluster haplotypes. Acute events occurring during childhood are minimally effected by this co-inheritance. The risk of soft tissue organ failure is decreased. After the age of 20 years, painful episodes of the lumbar dorsal area are increased in patients who had alpha-thalassemia-2 in association with degenerative bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta S-gene-cluster haplotypes in sickle cell anemia: clinical implications. 170 Jun 39

Identification of the beta s-gene-cluster haplotype and alpha-gene status provide a useful tool to improve the possibility for early detection in high-risk SS patients. The DNA polymorphisms of the beta s-gene-cluster modify the clinical course in sickle cell anemia especially as it involves the risk of end-stage organ failure of the kidney, lung, and brain. In both Africa and America, the CAR beta s haplotype increases the risk of developing irreversible complications at an early age. The degree of anemia, the Hb F concentration, and the preservation (or lack thereof) of G gamma Hb F is haplotype dependent and correlates with the overall clinical course of the patient. Further modulation of the clinical course by the coinheritance of alpha-thalassemia-2 tends to decrease the risk of soft tissue organ failure but increases the risk of osteonecrosis. A single individual can be expected to fit into the overall pattern. Some sickle related illness will eventually occur in all patients. In the presence of a Senegal haplotype, the patient's health is better, with the CAR haplotype it is always worse; severity is intermediate in the Benin. These genetic markers can be used to identify the endangered patient before the onset of irreversible major organ failure. The high risk SS patient with a CAR chromosome or one who is homozygous Ben without alpha-thalassemia-2 should be monitored closely for evidence of vasculopathy-induced microinfarction of the brain, kidneys, or lungs. Such a patient needs preventive therapy before suffering a major hemisphere stroke, losing kidney function, or developing cor pulmonale secondary to restrictive lung disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sickle cell anemia: beta s-gene-cluster haplotypes as prognostic indicators of vital organ failure. 188 45

Sickle cell chronic lung disease (SCLD) is a prime contributor to mortality in young adult patients with sickle cell disease, especially those with sickle cell anemia (SS). Both perfusion and diffusion defects have been demonstrated, with generalized pulmonary fibrosis and disabling restrictive lung failure. We report 28 cases (25 SS, 1 S beta(0) thalassemia, 1 S beta(+) thalassemia and 1 SO-Arab) which began during the second decade of life and which ended in death by the fourth decade, after an ordered progression to pulmonary failure and cor pulmonale. Myocardial hypoxia with multifocal fibrosis and segmental infarction occurred in more than one-third of the cases and sudden death was a frequent final event. We define 4 stages of SCLD, based on pulmonary function tests, chest roentgenograms, blood gases, and noninvasive cardiac studies; each stage is 2 or 3 years in length, until death ensues in Stage 4. Case-control analysis showed that the significant risk factors associated with SCLD are 1) the total number of acute chest syndrome events in an individual before the onset of SCLD, (p = 0.0001), 2) sickle cell crisis marked by chest pain (p = 0.03) and 3) aseptic necrosis (p = 0.005). Temporal clustering of acute chest syndrome episodes frequently heralds the onset of SCLD. The pulmonary arterial bed, which has low oxygen tension and low pressure in a slow-flow system, is ideally suited to facilitate the polymerization of sickle hemoglobin, causing endothelial damage and culminating in an obstructive arteriolar vasculopathy. Identification of the significant risk factors predictive of SCLD can lead to early diagnosis of the disease; this is the only hope for effective intervention therapy.
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PMID:Sickle cell chronic lung disease: prior morbidity and the risk of pulmonary failure. 333 82

Pulmonary function tests were evaluated in 28 Chinese patients with beta-thalassemia major receiving regular transfusions and desferoxamine, and in 34 height-matched normal Chinese children. Comparison of lung function using analysis of covariance with reference to standing height showed that patients with thalassemia had a proportional decrease in forced vital capacity and forced expiratory flow volume in 1 second, whereas their expiratory flow rates, residual volume, and total lung capacity were comparable to those in normal children. The single-breath carbon monoxide diffusion capacity was normal. Our findings suggest that children with thalassemia major have mild restrictive lung disease. The previous controversy regarding the presence of restrictive or obstructive lung disease in patients with thalassemia may be related to the use of inappropriate control values.
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PMID:Pulmonary function in thalassemia major. 365 83

The acute chest syndrome (ACS), a pneumonia-like illness in sickle cell patients, is one of the most frequent causes of their morbidity and hospitalizations. Repeated ACS events may predict the development of chronic lung disease. ACS is reported as a frequent cause of death in these patients. We examine here the incidence and risk factors of ACS in 3,751 patients with sickle cell disease who were observed prospectively for at least 2 years (19,867 patient-years [pt-yrs]) as part of a multicenter national study group. The ACS, defined by a new pulmonary infiltrate on x-ray, occurred at least once in 1,085 patients (2,100 events). ACS incidence was higher in patients with homozygous sickle cell disease (SS; 12.8/100 pt-yrs) and in patients with sickle cell-beta(0) -thalassemic (9.4/100 pt-yrs), and lower in patients with hemoglobin (Hb) SC disease (5.2/100 pt-yrs) and patients with sickle cell-beta(+) thalassemia (3.9/100 pt-yrs). alpha-Thalassemia did not affect the rate of ACS incidence in SS patients. Within each Hb type the incidence was strongly but inversely related to age, being highest in children 2 to 4 years of age (25.3/100 pt-yrs in SS) and decreasing gradually to its lowest value in adults (8.8/100 pt-yrs in SS). In SS children (< 10 years of age), we documented an age-related within-person reduction in ACS attack rates. Adults with a higher ACS rate had a higher rate of mortality (from all causes) than those with low ACS rates. This increased rate of mortality might also have contributed to the decline in ACS rate with age. In multivariate analysis, other factors affecting incidence in SS patients were degree of anemia (lower ACS rates in patients with lower steady-state Hb levels) and fetal Hb (lower rates in patients with high fetal Hb). There was also a positive association between ACS rate and steady-state leukocyte count. The relationship of ACS rate to higher steady-state Hb levels in SS patients is unexplained but might be caused by increased blood viscosity.
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PMID:The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease. 751 23

Pulmonary function abnormality, arterial hypoxemia and platelet hyperaggregation were commonly seen in severe or moderately severe thalassemic patients. In previous studies, these abnormalities were found in beta-thalassemia, beta-thalassemia/Hb E disease and Hb H disease in 62, 40 and 52%, respectively. However these functional abnormalities in mild form of Hb H disease have not yet been reported. Pulmonary function test by using standard spirometry, platelet aggregation and arterial blood gases were performed in 23 children with mild form of Hb H disease, whose age ranged from 6-18 years (average 11 years), and hematocrit status was 30-40%. Mild to moderate degree of restrictive lung disorder was found in 48% of these patients, 5% had mild platelet hyperaggregation and none of these had arterial hypoxemia. This study showed that a pulmonary function defect was noted as one significant finding in thalassemic patients, being noted even in the very mild form and early age of life. This information will lead to further exploration of the pathogenesis of pulmonary function defects as well as their role is the patients' future health and prognosis.
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PMID:Pulmonary and platelet function in mild form of Hb H disease. 788 77

To study pulmonary function tests (PFT) in multiple transfusion recipient thalassemics, PFTs were done for 30 thalassemics and 20 matched controls. Confirmed cases of thalassemia on regular transfusion therapy were the subject of study. Apart from history and physical examination of the thalassemics, serum ferritin estimation and spirometry were done. Parameters studied included lung volumes--functional residual capacity (FRC), forced vital capacity (FVC), residual volume (RV) and total lung capacity (TLC); and flow rates--forced expiratory volume in one second (FEV1), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), peak expiratory flow 25-75 (PEF 25-75%) and peak expiratory flow rate (PEFR). Single breath carbon monoxide diffusing capacity (DLco) and arterial blood gas (ABG) were also analysed. The mean height and weight of thalassemics were below that of age matched controls. A restrictive abnormality in PFT was found in 86.6% cases. These patients were found to have a decrease in all the lung volumes namely FVC, FRC, RV and TLC with a proportional decrease in the flow rates, FEV1, PEF 25-75% and PEF with a normal (> 0.75) FEV1/FVC ratio. DLco was decreased in all the patients with restrictive lung disease and fall in DLco showed a good correlation (r = 0.7, P < .001) with the severity of restrictive disease suggesting that some intrapulmonary pathology is likely to be responsible for the restrictive pattern. None of the cases had an obstructive or mixed pattern of pulmonary dysfunction. No correlation was found between severity of restrictive disease and the serum ferritin levels. A negative correlation with degree of hepatosplenomegaly was found. No correlation was found between severity of the defect and age, number of blood transfusions received and hemoglobin at the time of doing the test. To conclude, restrictive lung disease is the predominant abnormality in multi-transfused thalassemics, which is probably due to pulmonary parenchymal pathology. The abnormality of PFTs is not directly related to iron overload.
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PMID:Pulmonary function tests in beta thalassemia. 1133 20

Although restrictive lung disease is the predominant abnormality of pulmonary function in patients with thalassaemia major (TM), its aetiology and its association with pulmonary hypertension (PH) detected in some patients with TM remains unknown. We report a patient with TM, iron overload, frequent pulmonary infections, and progressive severe precapillary PH over the previous 5 years. A severe restrictive pattern and interstitial lung fibrosis were revealed by pulmonary function tests and high resolution computed tomography, respectively. This presentation suggests that interstitial fibrosis may complicate lung involvement in TM and can significantly contribute to the development of PH.
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PMID:Pulmonary hypertension, interstitial lung fibrosis, and lung iron deposition in thalassaemia major. 1151 97

Pulmonary hypertension (PHT) occurs in approximately 30% of adults with sickle cell disease (SCD) and is an independent risk factor for early death. In this study, we aimed to determine the value of general laboratory testing, plain chest radiography, electrocardiography (ECG), high-resolution computer tomography (HRCT) of the thorax, pulmonary function testing, and plasma N-terminal brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in patients with SCD-related PHT. A cohort of 85 ambulatory sickle cell patients were prospectively screened for PHT with echocardiography (defined as a tricuspid regurgitation flow velocity of > or =2.5 m/sec). All patients were systematically evaluated by the aforementioned diagnostic tests comparing patients with and without PHT. The prevalence of PHT was 41% in HbSS/HbSbeta(0)-thalassemia patients and 13% in HbSC/HbSbeta(+)-thalassemia patients. No statistically significant differences were detected in ECG, chest radiography, HRCT, and pulmonary function testing between patients with and without PHT. The degree of anemia and renal dysfunction, but not the presence of PHT, were the most important determinants of plasma (NT-pro)BNP levels. The performed imaging and functional studies do not seem to be of value in identifying etiological conditions (such as airflow obstruction or parenchymal lung disease) nor do they offer clues to the presence of mild PHT in SCD.
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PMID:Cardiopulmonary imaging, functional and laboratory studies in sickle cell disease associated pulmonary hypertension. 1926 Jan 23

Thalassemia major is characterized by chronic ineffective erythropoiesis and anemia as its primary problems. These, in turn, produce physiologic adaptations in the cardiovascular system as well as pathologic/iatrogenic processes such as iron overload, splenectomy, nutritional deficiencies, chronic oxidative stress, and lung disease. This article discusses the pathophysiology of thalassemia as it relates to the cardiovascular system, the mechanisms and monitoring of iron cardiomyopathy, pulmonary hypertension, and vascular aging in thalassemia patients.
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PMID:Cardiac complications in thalassemia major. 2000 37


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