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)

Fifty-two patients with sickle-cell (SC) disease (48 with SC-beta-thalassaemia and 4 with homozygous SC-anaemia) were studied as regards blood coagulation and fibrinolysis. It was found that the thrombin and the reptilase times of the patients' plasma were significantly shorter than normal. The mean values of platelet count, fibrinogen level and factor VIII activity of patients with SC disease were higher than normal; however, in the group of patients transfused, with less than 50% haemoglobin S (HbS), the fibrinogen level and the factor VIII activity were significantly lower compared to the other patients. Antithrombin-III (At-III) activity was normal in all. The fibrinolytic activity was normal in patients with asymptomatic SC disease, but reduced in patients on painful crises. Plasminogen and fibrinogen/fibrin degradation product (FDP) levels were normal in all patients. Two patients on painful crises with complications had additional abnormal findings, namely prolonged prothrombin time, reduced At-III level and elevated FDP.
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PMID:Hypercoagulability and hypofibrinolysis in sickle-cell disease. 120 41

We studied 66 Israeli hemophiliacs for antibodies to HIV in blood samples collected between 1978 and 1985. By May 1985, 2 had AIDS, 2 had ARC, 4 had lymphadenopathy with some immunologic dysfunction, and 58 were asymptomatic. Antibodies to HIV were detected in 40 (60.6%) patients, including all 8 with disease. Presence of HIV antibodies was significantly associated with receipt of non-heat-treated commercial factor VIII concentrates (NHT fac VIII) between 1980 and 1983. Thirty-eight of 45 (84.44%) patients treated with NHT fac VIII developed antibodies to HIV, compared to 1 of 16 (6.25%) treated with cryoprecipitates and fresh plasma only. Of 40 seropositive patients, 1 (2.5%) had antibodies by 1980, 4 (10%) by 1982, 14 (35%) by 1983, 10 (25.0%) by 1984, and 11 (27.5%) by May 1985. The decline in the rate of seroconversion can be attributed to the replacement of NHT fac VIII concentrate with heat-inactivated factor VIII (HT fac VIII) concentrate by November 1983. As of January 1984 only HT fac VIII was administered. Twenty-nine multitransfused thalassemia patients as well as 20 healthy Israeli blood donors were seronegative to HIV. All 40 (100%) seropositive hemophiliacs had antibodies to viral env gene encoded gp120/gp160 antigens. Twenty-four (60.05%) also had antibodies to viral gag gene encoded p24 and/or p55 antigens. While antibodies to gp120/160 persisted during the follow-up time, a loss of antibodies to p24/55 was observed in 5 of 16 (31.25%) seropositive patients from whom multiple samples were available. gp120/160 positive, p24/55 negative hemophiliacs had significantly lower absolute T-helper cell counts and reversed Th/Ts ratios when compared to gp120/160 p24/55 seropositive patients. Four of the 16 (25.0%) asymptomatic gp120/160 positive, p24/55 negative patients developed overt disease within 15 months of the last blood collection. The data suggest that exposure to HIV antigens is widespread among hemophiliacs in Israel, and can be attributed to receipt of NHT fac VIII concentrates prior to 1984. Antibodies to gp120/160 are of the most important diagnostic value while loss of antibodies to p24/p55 may be of prognostic value.
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PMID:Antibodies to HIV in Israeli hemophiliacs: relationship between serological profile and disease development. 312 74

We report the development of a rapid nonradioactive technique for the genetic prediction of human disease and its diagnostic application to hemophilia A. This method is based on enzymatic amplification of short segments of human genes associated with inherited disorders. A novel feature of the procedure is the use of a heat-stable DNA polymerase, which allows the repeated rounds of DNA synthesis to proceed at 63 degrees C. The high sequence specificity of the amplification reaction at this elevated temperature permits restriction-site polymorphisms, contained in the amplified samples, to be analyzed by visual inspection of their digestion products on polyacrylamide gels. By means of this method, we have performed carrier detection and prenatal diagnosis of hemophilia in two families with use of the factor VIII intragenic polymorphisms identified by the restriction enzymes BclI and XbaI. Predictions can be made directly from chorionic villi, without previous DNA extraction, and fetal sex can be determined by amplification of sequences specific for the Y chromosome. Specific amplification of genomic sequences with heat-stable DNA polymerase is applicable to the diagnosis of a wide variety of inherited disorders. These include diseases diagnosed by restriction-site variation, such as Duchenne's muscular dystrophy and sickle cell anemia, those due to a collection of known mutations, such as beta-thalassemia, and those due to gene deletion, such as alpha-thalassemia.
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PMID:An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences. Application to hemophilia A. 365 65

Persons with hemophilia are at risk of the acquired immunodeficiency syndrome (AIDS), and clinically asymptomatic hemophiliacs have shown a high incidence of AIDS-like immune abnormalities, facts leading to speculation that many hemophiliacs have been exposed to the AIDS agent through their blood products. We therefore evaluated the immune status of three groups of blood product recipients without AIDS in New York City, including 47 persons with hemophilia A receiving factor VIII concentrate, 50 persons with homozygous beta-thalassemia, and 27 persons with sickle cell anemia receiving frozen-packed RBCs and 20 healthy persons who had not received a transfusion. Hemophiliac participants had significantly lower lymphocyte counts (median, 1,826/cu mm) than did the thalassemic (6,110/cu mm) or anemic (4,443/cu mm) participants, had lower numbers of T-helper lymphocytes (median, 533 cells/cu mm v 1,733 cells/cu mm and 1,554 cells/cu mm), and had a lower T-helper/suppressor ratio (median, 0.8 v 1.8 and 2.1). These differences remained after adjustment for age and sex. Thus, AIDS-like immune abnormalities were found in patients receiving factor concentrate, but not in those receiving RBCs. These defects could be due to both an immunosuppressive effect of the lyophilized factor itself and to contact with the AIDS agent.
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PMID:Immune status of blood product recipients. 391 87

A mail survey sent to 25 hemophilia centers in France enquiring on the occurrence of AIDS or AIDS-related disorders was done in May 1983. Of 2 388 hemophiliacs representing approximately 60% of the total expected population, no case of AIDS was found. Four patients had lymphodenopathies. A relatively high frequency of lymphopenia (8%) and hyper gammaglobulinemia (21%) was found. Only 37 patients were tested for T-lymphocyte populations, 14 of whom had a T4/T8 ratio below 1. A state funded multicenter prospective study has been designed in order to evaluate the relationship between the type (domestic or imported factor VIII or IX concentrate), the dose of blood product and various clinical, immunological and virological parameters related to AIDS. Approximately 400 hemophiliacs will enter the study together with a small population of patients with thalassemia receiving packed red cells.
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PMID:[AIDS, related syndromes and hemophilia: the situation in France and studies in progress]. 633 48

Two of four sisters have multiple sclerosis (MS), lamellar ichthyosis, beta thalassaemia minor and a quantitative deficit of factor VIII-von Willebrand complex. The mother and the other sisters have only beta thalassaemia minor. The association of MS and a cluster of genetically determined diseases is rare. Such families could offer a new approach to the investigation of the polygenetic background of MS.
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PMID:Two sisters with multiple sclerosis, lamellar ichthyosis, beta thalassaemia minor and a deficiency of factor VIII. 833 72

The genotype of hepatitis C virus (HCV) of 172 HCV-RNA positive serum specimens taken from patients with chronic liver diseases, thalassaemia major, chronic renal failure (CRF), haemophilia and intravenous drug abusers (IVDA) was determined by analysis of the amplified 5'UTR region by genotype-specific oligonucleotide probes and restriction fragment length polymorphism (RFLP). Six different genotypes and subtypes (1a, lb, 2, 3, 4 and 6) were found. Genotype lb was the predominant genotype among patients with chronic liver diseases (69.6%), followed by genotype 6 (18.8%), which was similar to that reported for blood donors in earlier studies. Pronounced differences in the distribution of genotypes were seen between the four risk groups. Patients with CRF had a similar distribution to those with chronic liver diseases, whilst the greatest diversity of genotypes was seen in patients with haemophilia, which was expected since they were given factor VIII manufactured overseas. Genotype 6 was particularly prominent in patients with thalassaemia major (50%) and IVDA (62.5%). It is possible that clonal spread of HCV genotype 6 has taken place among a closed subset of the population in Hong Kong through intravenous drug abuse.
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PMID:High prevalence of hepatitis C virus genotype 6 among certain risk groups in Hong Kong. 974 72

Hydroxyurea (HU) has been shown to reduce the frequency of vaso-occlusive manifestations in both adults and children with sickle cell disease (SCD), and the induction of hemoglobin F (HbF) is thought to be the underlying mechanism responsible for clinical improvement in some patients. However, there exists no good correlation between the amount of HbF increase and clinical response. Recent studies suggest that increased activity of the coagulation system may be important in the pathogenesis of vascular occlusion in sickle cell disease. To analyze the effect of HU on the coagulation system in children, the authors studied the levels of some coagulation factors and natural inhibitors. Eleven children who had been treated with HU because of SCD (5 patients), sickle-beta-thalassemia (3 patients), and beta-thalassemia intermedia (3 patients) were enrolled in the study. Levels of the coagulation factors II, V, VII, VIII, IX, X, XI, and XII, and of protein C and protein S, prothrombin times, activated partial thromboplastine times, thrombin times, and reptilase times were measured before the treatment and at the 5th or 6th months of HU therapy when the patients were in a steady-state condition. There was a decrease in all of the coagulation factors except for FIX and FXII and in inhibitors such as protein C and protein S. However, statistically significant decreases were observed only in factor VIII and protein C levels. The rates of decrease were 54.8 and 12.5% (p = .015 and p = .018) in FVIII and protein C, respectively. This result shows that HC has significant effects on the coagulation and natural inhibitory systems.
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PMID:The effect of hydroxyurea on the coagulation system in sickle cell anemia and beta-thalassemia intermedia patients: a preliminary study. 1463 15

Haemoglobinopathies represent a significant national health burden in India. The distribution of specific disorders varies geographically and by community. Heterozygote frequencies of beta-thalassaemia range from 1 to 15%, resulting in an estimated 20 million carriers. HbS is mainly present in tribal and non-caste communities, with carrier prevalences of up to 40%. By comparison, alpha-thalassaemia carriers are found in both the caste and tribal communities, and can reach a frequency of >90% in the latter case. Community control of haemoglobinopathies relies mainly on out-reach education programmes and genetic counselling, with antenatal diagnosis offered in specific major centres. Only partial data are available on the prevalence of haemophilia, but it has been estimated that there are some 50,000 affected individuals nationwide, with an additional 1,500 new cases born each year. RFLP-based techniques have been established to detect mutations in the factor VIII and IX genes, enabling the limited introduction of carrier detection and antenatal diagnosis.
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PMID:Genetic disorders in haematological practice in India. 1496 Aug 92

Neuroimaging and management advances require review of indications for excluding cerebral venous sinus (sinovenous) thrombosis (CSVT) in children. Our goals were to examine (i) clinical presentations of CSVT, (ii) prothrombotic risk factors and other predisposing events, (iii) clinical and radiological features of brain lesions in CSVT compared with arterial stroke, and (iv) predictors of outcome. We studied 42 children with CSVT from five European paediatric neurology stroke registries. Patients aged from 3 weeks to 13 (median 5.75) years (27 boys; 64%) presented with lethargy, anorexia, headache, vomiting, seizures, focal signs or coma and with CSVT on neuroimaging. Seventeen had prior chronic conditions; of the 25 previously well patients, 23 had recent infections, eight became dehydrated and six had both. Two children had a history compatible with prior CSVT. Anaemia and/or microcytosis (21 probable iron deficiency, five haemolytic, including two with sickle cell disease and one with beta-thalassaemia) was as common (62%) as prothrombotic disorder (13/21 screened). High factor VIII and homozygosity for the thermolabile methylene tetrahydrofolate reductase polymorphism were the commonest prothrombotic disorders. The superficial venous system was involved in 32 patients, the deep in six, and both in four. Data on the 13 children with bland infarction and the 12 with haemorrhage in the context of CSVT were compared with those from 88 children with ischaemic (AIS) and 24 with haemorrhagic (AHS) arterial stroke. In multiple logistic regression, iron deficiency, parietal infarction and lack of caudate involvement independently predicted CSVT rather than arterial disease. Five patients died, three acutely, one after recurrence and one after 6 months being quadriparetic and blind. Follow-up ranged from 0.5 to 10 (median 1) years. Twenty-six patients (62%) had sequelae: pseudotumour cerebri in 12 and cognitive and/or behavioural disabilities in 14, associated with epilepsy in three, hemiparesis in two and visual problems in two. Eighteen patients, including six with haemorrhage, were anticoagulated. Older age [odds ratio (OR) 1.54, 95% confidence limits (CI) 1.12, 2.13, P = 0.008], lack of parenchymal abnormality (OR 0.17, 95% CI 0.02, 1.56, P = 0.1), anticoagulation (OR 24.2, 95% CI 1.96, 299) and lateral and/or sigmoid sinus involvement (OR 16.2, 95% CI 1.62, 161, P = 0.02) were independent predictors of good cognitive outcome, although the last predicted pseudotumour cerebri. Death was associated with coma at presentation. Of 19 patients with follow-up magnetic resonance (MR) venography, three had persistent occlusion, associated with anaemia and longer prodrome. A low threshold for CT or MR venography in children with acute neurological symptoms is essential. Nutritional deficiencies may be modifiable risk factors. A paediatric anticoagulation trial may be required, after the natural history has been further established from registries of cases with and without treatment.
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PMID:Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. 1569 61


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