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)

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

The clinical and haematological features of 77 patients of Bini and 107 patients of Yoruba origin with homozygous sickle cell (SS) disease have been compared. The Bini population were generally younger and had a slightly lower incidence of alpha thalassaemia but even after correction for age and alpha thalassaemia status, this group had significantly lower HbA2 and higher HbF and MCV values. Clinically the Bini group had significantly less dactylitis and more acute chest syndrome. The decreased frequency of dactylitis is consistent with the higher HbF level in the Bini population and the mechanism of the other effects are discussed.
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PMID:Sickle cell anaemia in Nigeria: a comparison between Benin and Lagos. 754 30

High total haemoglobin levels in homozygous sickle cell (SS) disease are a risk factor for painful crises, avascular necrosis of the femoral head, proliferative sickle retinopathy, and the acute chest syndrome. Since lowering the haemoglobin level may ameliorate these features, understanding the determinants of total haemoglobin may be of practical importance. A range of possible determinants including red cell characteristics, reticulocytes, serum iron, transferrin saturation, serum ferritin, alpha thalassaemia status, red cell mass and plasma volume, oxygen affinity, red cell survival, transferrin receptor and erythropoietin levels have been measured in 62 patients selected to provide a range of total haemoglobin and fetal haemoglobin levels. There were weak negative associations of haemoglobin with mean cell volume and mean cell haemoglobin concentration, strong negative associations with proportional reticulocyte counts, oxygen affinity, plasma volume, serum transferrin receptors, and erythropoietin levels and strong positive associations with red cell mass. Weighted analysis suggested that the statistically independent determinants of haemoglobin level were alpha thalassaemia, sex, red cell mass/body weight, plasma volume/body weight, fetal haemoglobin, and red cell count. The apparent contributions of red cell survival, P50, reticulocyte count, serum transferrin receptor and erythropoietin levels were explained by the effects of these other variables. The independent determinants as a group explained 91% of the variation in haemoglobin level.
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PMID:Determinants of haemoglobin level in steady-state homozygous sickle cell disease. 856 87

Oxygen saturation was determined by pulse oximetry in a representative sample of Jamaican patients with steady-state sickle cell disease in a cohort study from birth. There were 220 with homozygous sickle cell (SS) disease and 142 with sickle cell-haemoglobin C (SC) disease aged 9-18 years, and 122 with a normal haemoglobin (AA) genotype aged 15-18 years. Pulse oximetry (SpO2) values were lower in SS disease (mean [95% confidence interval], 92.5 [92.0-93.0]) than in SC disease (96.7[96.5-96.9]) or AA controls (97.1 [96.8-97.3]). Inhalation of 100% oxygen in SS patients with O2 saturations below 90% consistently increased saturation to 99-100%. In SS disease, SpO2 correlated positively with haemoglobin and fetal haemoglobin and negatively with reticulocyte counts but not with MCHC, MCV or bilirubin level. Mean SpO2 in SS subjects with a normal alpha globin gene complement (mean [SD], 91.7 [3.9]%) was lower than in heterozygotes (93.4 [4.0]%) or homozygotes (96.1 [3.0]%) for alpha+ thalassaemia, the effects of alpha-thalassaemia not being explained by differences in haemoglobin or MCHC. In SS disease, SpO2 levels were not associated with age (within this age range), sex, number of sick clinic visits or number of hospital admissions. Higher SpO2 levels were associated with greater height and weight, more frequent painful crises and less frequent acute chest syndrome, but these associations were not significant after adjustment for haemoglobin level. Desaturation is common in steady-state SS disease and knowledge of the individual's steady-state value may be important in the interpreting low values during acute complications.
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PMID:Pulse oximetry in a cohort study of sickle cell disease. 914 42

Hydroxyurea (HU) is the first widely used treatment to have an impact on the severity of disease in adult patients with sickle cell anemia, but limited data are available for younger patients or those with variant genotypes. We reviewed 324 months of experience with HU in 16 patients from 5.3 to 18.4 years of age treated for 6 to 50 months. The major toxicity was reversible neutropenia. Linear growth continued unchanged, and all patients gained weight. Hematologic results were similar to those reported in adults with increases in mean corpuscular volume (MCV) and total and fetal hemoglobin (HbF). We noted that the maximal hematologic effects occurred at less than the maximum dose. Clinically, patients experienced an 80% reduction in episodes of acute chest syndrome and a reduced need for blood transfusion, as well as a 30% decrease in the number of hospitalizations for painful events during HU therapy compared with an equivalent number of months before HU. These highly statistically significant results confirmed the value of HU in ameliorating the severe clinical course of pediatric patients. Similar effects were observed in three patients with sickle beta degrees-thalassemia, sickle beta+-thalassemia, and S-O Arab. Recurrent acute splenic sequestration and progressive symptomatic osteonecrosis were observed during HU. Thus, HU may not prevent the development of complications once organ damage is present. The challenge remains to determine when and to which pediatric patients with sickle cell disease HU should be offered.
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PMID:Hydroxyurea therapy for diverse pediatric populations with sickle cell disease. 931

This study evaluated the efficacy of hydroxyurea treatment in the prevention of vaso-occlusive crises among children and teenagers with severe sickle cell anemia and sickle cell beta-thalassemia. Nineteen children and young adults with severe sickle cell disease were enrolled to the hydroxyurea treatment trial. The incidence of vaso-occlusive crises, acute chest syndrome, hemolytic crises, splenic sequestration episodes, blood transfusions, and hospital days in the 2 years before hydroxyurea (HU) treatment were compared with the same parameters in the first 2 years of treatment. The patients received a mean dose of 21.3 mg/kg/day daily and were treated during a mean period of 40.3 +/- 14 months (range 20 to 68 months). Significant increases were observed after 1 month in the Hgb, MCV, MCH, and MCHC levels and were more notable after 3 months. The increase in the Hgb F level became important after 3 months of HU therapy and was highly significant (p < .001) beyond 6 months. No differences were observed in the RDW, reticulocyte count, Hgb S, and Hgb A2. Severe neutropenia was observed in one case. A decrease in the frequency of vaso-occlusive crises, acute chest syndrome, hemolytic crises, blood transfusions, and days spent in the hospital was demonstrated during the HU treatment period compared to the same period before. The clinical and laboratory response to HU was dramatic in severely affected sickle cell anemia (SCA) patients. The response to HU in children and teenagers with severe sickle cell anemia is similar to the response in adults, and no severe adverse effects were observed.
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PMID:Effect of hydroxyurea in sickle cell anemia: a clinical trial in children and teenagers with severe sickle cell anemia and sickle cell beta-thalassemia. 1032 20

A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr). Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia strongly reduced the risk of stroke (p <0.001) and increased that of painful crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas-chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03). Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27 patients (p < 0.02). The patients come from a population of unmixed immigrants in whom the beta-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the beta-globin gene locus.
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PMID:Acute clinical events in 299 homozygous sickle cell patients living in France. French Study Group on Sickle Cell Disease. 1100 50

Cerebral infarction is a frequent, severe complication of sickle cell anaemia. During childhood, most strokes are due to infarction with the majority resulting from occlusion of the large cerebral arteries. Risk factors include transient ischaemic attacks, acute chest syndrome, severe anaemia and elevated blood pressure. Less certain is the association with leucocytosis, or protection provided by alpha-thalassaemia or fetal haemoglobin. Children who have one stroke are at significant risk for having subsequent events that can be substantially reduced by maintaining haemoglobin S below 30%. It has not yet been possible to identify individuals for whom transfusion can be safely stopped. Haemosiderosis is a consequence of intensive and long term transfusion therapy, which requires chelation with deferoxamine. Iron accumulation can be minimised using erythrocytapheresis but this is technically difficult in children, expensive and results in increased donor exposure. In addition to lesions associated with strokes, an additional 17% of patients can be shown to have clinically silent cerebral infarcts. Although these are termed 'silent', those affected have mild neuropsychological deficits. Their relationship to stroke or risk for recurrence is unknown. Transfusion therapy has been shown to provide primary stroke prevention for children who have elevated cerebral artery velocity. Finally, intracranial haemorrhages, more commonly found in adults, also affect children. Subarachnoid haemorrhage is frequently found to result from cerebral artery aneurysms. A condition that mimics the moyamoya syndrome radiographically, as well as for its risk of haemorrhage, can be found in children with partly occluded cerebral arteries either as a result of stroke or silent infarct.
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PMID:Stroke in children with sickle cell anaemia: aetiology and treatment. 1143 87

In order to define the morbidity profile of sickle cell disease in Omani children, we analysed data on 97 children (53 boys, 44 girls) aged < or = 12 years admitted under our care in a regional referral hospital between July 1999 and June 2000. Ninety of them had sickle cell anaemia (HbSS disease) and seven had sickle cell thalassaemia (beta zero). Their mean (SD) steady-state Hb was 7.9 (1.2), range 6-10 g/dl. They were admitted on 316 occasions during the 12-month period. The number of admissions per child ranged from one to 12 (mean 3.3). Vaso-occlusive crises were the main reason for admission (83%), followed by severe anaemia (12%) and infections (4%). During the study period, 31% received blood transfusions. Weight faltering was very common, 68% falling below the 5th percentile of the National Center for Health Statistics reference curves compared with 28% of age- and sex-matched non-sicklers (p < 0.001). Other complications included hypersplenism (four), ischaemic necrosis of the femoral head (two), and one case each of acute chest syndrome, acute splenic sequestration, cholelithiasis and pathological fracture of a lumbar vertebra. Overall, 71% of the children had moderately severe or severe disease. This pattern seems to be attributable, at least in part, to meteorological and genetic factors. The severe morbidity profile reported in this study underscores the need to continue the search for optimal management modalities, including the often emotion-laden issue of prevention.
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PMID:Sickle cell morbidity profile in Omani children. 1192 49

Hematopoietic cell transplantation (HCT) has been used for more 30 years for the treatment of selected malignant and nonmalignant diseases. Traditionally, HCT for hematological disorders has relied on myeloablative conditioning before HLA-identical sibling bone marrow transplantation to correct the underlying hematological defect. Most children with hematological diseases who are referred to HCT have features that portend significant morbidity and early mortality. Among SAA patients who have HLA-identical sibling donors, younger patients with profound pancytopenia might be considered early for HCT. For others who lack sibling donors, patients who receive HCT from alternate sources have generally failed one or more courses of intensive immunosuppressive therapy and remain transfusion-dependent, some with hemosiderosis, red cell alloimmunization, and platelet transfusion refractoriness [44,46,48]. Currently, HCT for SCD is generally restricted to those who have experienced a significant sickle-related complication such as stroke, recurrent acute chest syndrome, or recurrent painful episodes [7,13]. In contrast, most reserve HCT in thalassemia for younger, Lucarelli class I, good-risk patients who have HLA-identical sibling donors, and veer away from older, high-risk thalassemics for whom transplantation is a riskier clinical intervention. For groups such as young adults with thalassemia major, HCT might become more widely applicable if its toxicity was reduced. Several approaches undergoing development include reduced-intensity conditioning and attempts to prevent GVHD. New methods to reduce the intensity and toxicity of conditioning as well as to use highly purified stem cells with the reduction in graft versus host disease may allow for the use of matched unrelated donors or haploidentical donors. This would serve to provide potentially more children who could benefit from stem cell transplantation with donors. These advances will hopefully lead to benefits for the majority of children who lack HLA-identical donors.
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PMID:New approaches to hematopoietic cell transplantation for hematological diseases in children. 1243 Jun 22


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