Showing papers on "Sickle cell anemia published in 1995"
TL;DR: Hydroxyurea therapy can ameliorate the clinical course of sickle cell anemia in some adults with three or more painful crises per year and Maximal tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic effect.
Abstract: Background In a previous open-label study of hydroxyurea therapy, the synthesis of fetal hemoglobin increased in most patients with sickle cell anemia, with only mild myelotoxicity. By inhibiting sickling, increased levels of fetal hemoglobin might decrease the frequency of painful crises. Methods In a double-blind, randomized clinical trial, we tested the efficacy of hydroxyurea in reducing the frequency of painful crises in adults with a history of three or more such crises per year. The trial was stopped after a mean follow-up of 21 months. Results Among 148 men and 151 women studied at 21 clinics, the 152 patients assigned to hydroxyurea treatment had lower annual rates of crises than the 147 patients given placebo (median, 2.5 vs. 4.5 crises per year, P<0.001). The median times to the first crisis (3.0 vs. 1.5 months, P = 0.01) and the second crisis (8.8 vs. 4.6 months, P<0.001) were longer with hydroxyurea treatment. Fewer patients assigned to hydroxyurea had chest syndrome (25 vs. 51, P<0.001), and...
2,062 citations
TL;DR: Within the Cooperative Study of Sickle Cell Disease, 694 infants with confirmed sickle cell disease were enrolled at less than 6 months of age and information about the nature and frequency of complications was collected prospectively over a 10-year period.
479 citations
TL;DR: It is concluded that maintenance of hemoglobin S at a level less than 30% appears to be effective in reducing the rate of recurrent infarction but does not prevent transient neurologic events.
340 citations
TL;DR: Incentive spirometry can prevent the pulmonary complications associated with the acute chest syndrome in patients with sickle cell diseases who are hospitalized with chest or back pain above the diaphragm.
Abstract: Background This study was designed to determine the incidence of thoracic bone infarction in patients with sickle cell diseases who were hospitalized with acute chest or back pain above the diaphragm and to test the hypothesis that incentive spirometry can decrease the incidence of atelectasis and pulmonary infiltrates. Methods We conducted a prospective, randomized trial in 29 patients between 8 and 21 years of age with sickle cell diseases who had 38 episodes of acute chest or back pain above the diaphragm and were hospitalized. Each episode of pain was considered to be an independent event. At each hospitalization, patients with normal or unchanged chest radiographs on admission were randomly assigned to treatment with spirometry or to a control nonspirometry group. Each patient in the spirometry group took 10 maximal inspirations using an incentive spirometer every two hours between 8 a.m. and 10 p.m. and while awake during the night until the chest pain subsided. A second radiograph was obtained thre...
257 citations
TL;DR: In this article, the plug and socket targeting technique was used to generate a mouse model of beta 0-thalassemia in which both the b1 and b2 adult globin genes have been deleted.
Abstract: We have used a "plug and socket" targeting technique to generate a mouse model of beta 0-thalassemia in which both the b1 and b2 adult globin genes have been deleted. Mice homozygous for this deletion (Hbbth-3/Hbbth-3) die perinatally, similar to the most severe form of Cooley anemia in humans. Mice heterozygous for the deletion appear normal, but their hematologic indices show characteristics typical of severe thalassemia, including dramatically decreased hematocrit, hemoglobin, red blood cell counts, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration, as well as dramatically increased reticulocyte counts, serum bilirubin concentrations, and red cell distribution widths. Tissue and organ damage typical of beta-thalassemia, such as bone deformities and splenic enlargement due to increased hematopoiesis, are also seen in the heterozygous animals, as is spontaneous iron overload in the spleen, liver, and kidneys. The mice homozygous for the b1 and b2 deletions should be of great value in developing therapies for the treatment of thalassemias in utero. The heterozygous animals will be useful for studying the pathophysiology of thalassemias and have the potential of generating a model of sickle cell anemia when mated with appropriate transgenic animals.
251 citations
TL;DR: In SC patients, preoperative transfusion was beneficial for all surgical risk levels (P = .009), Thus, surgical procedures can be performed safely in patients with SCD.
219 citations
TL;DR: Early diagnosis and simple prophylactic measures significantly reduce deaths associated with homozygous sickle cell disease.
Abstract: Objective:To examine whether simple interventions in a sickle cell clinic improve survival in sickle cell disease Design:Survival curve analysis and hazard ratios in a cohort study followed from birth. Setting: MRC Laboratories (Jamaica) at the University of the West Indies, and Victoria Jubilee Hospital, Kingston, Jamaica Subjects:315 patients with homozygous sickle cell disease detected during the screening of 100000 consecutive non-operative deliveries between June 1973 and December 1981 at the main government maternity hospital, Kingston, Jamaica. Interventions:Prophylactic penicillin to prevent pneumococcal septicaemia, parental education in early diagnosis of acute splenic sequestration, close monitoring in sickle cell clinic Main outcome measures:Survival. Results: Survival appeared to improve, the log rank test for trend comparing the first, second, and last third of the study reaching borderline significance (P=0.05). Combined deaths from acute splenic sequestration and pneumococcal septicaemia-meningitis declined significantly (test for trend, P=0.02). Conclusion:Early diagnosis and simple prophylactic measures significantly reduce deaths associated with homozygous sickle cell disease.
183 citations
TL;DR: Ten weeks of intravenous arginine butyrate did not produce a hematologic response in 10 patients with either severe beta-thalassemia or sickle cell disease.
Abstract: Background Enhanced production of fetal hemoglobin lessens the severity of β-thalassemia and sickle cell disease. Intravenous infusion of arginine butyrate can increase the number of reticulocytes containing fetal hemoglobin in patients with these disorders, and it has induced a substantial increase in hemoglobin in one patient with thalassemia. We therefore tested the efficacy of this agent in patients with β-hemoglobinopathies. Methods We treated 10 patients with severe β-thalassemia or sickle cell disease with arginine butyrate at an initial dose of 500 mg per kilogram of body weight per day (final dose, 2000 mg per kilogram per day), 6 days per week, for a mean (±SD) of 10±1.2 weeks (range, 9 to 13). A hematologic response was defined as an increase in the hemoglobin concentration of at least 2 g per deciliter in patients with thalassemia and as a twofold increase in fetal hemoglobin in patients with sickle cell disease. Results There were increases in γ-globin messenger RNA and in reticulocytes conta...
167 citations
TL;DR: Though left ventricular dilatation was inversely related to hemoglobin, age (duration of illness) was an important factor in that relationship and no specific cardiomyopathy was associated with sickle cell anemia.
147 citations
TL;DR: Blood transfusion, even simple transfusion of packed erythrocytes, significantly improves oxygenation in children with acute chest syndrome and is a valuable adjunct to therapy.
141 citations
TL;DR: Patients with sickle cell anemia are at increased risk for neurologic complications after marrow ablative therapy and patients with prior stroke are at increase risk for intracranial hemorrhage, and transplantation of patients before the onset of overt stroke may reduce this risk.
TL;DR: The aim is to determine the outcome of pregnancies complicated by sickle cell disease in the UK during 1991‐1993 and the effect of prophylactic blood transfusion programmes on maternal and fetal outcome.
TL;DR: It is concluded that exchange transfusion and supportive care aimed at correction of coagulopathy, stabilization of the acute liver disease, and perhaps most important, avoidance of surgical intervention are the keys to a successful outcome of sickle cell intrahepatic cholestasis.
TL;DR: A case of life‐threatening posttransfusion hyperhaemolysis is described in an adult patient with SCD in whom severe anaemia necessitated further RBC transfusion, which was successfully performed in conjunction with intravenous immunoglobulin.
Abstract: Delayed haemolytic transfusion reactions (DHTRs) are seen more frequently in patients with sickle cell disease (SCD) than in other groups of patients, and are characterised by a positive direct antiglobulin test and the appearance of previously undetected red blood cell (RBC) alloantibodies in the patient's serum. Recently a syndrome of post-transfusion hyperhaemolysis has been described in children with SCD, characterised by destruction of both autologous and transfused RBCs with negative serological findings: continuation of RBC transfusion exacerbated haemolysis further. We describe a case of life-threatening post-transfusion hyperhaemolysis in an adult patient with SCD in whom severe anaemia necessitated further RBC transfusion, which was successfully performed in conjunction with intravenous immunoglobulin. This approach may be useful in the management of post-transfusion hyperhaemolysis in SCD as well as in the management of severe DHTRs.
TL;DR: Transfusion therapy should be reserved for those patients with previous perinatal mortality, pre-eclampsia, acute chest syndrome, new onset neurological event, severe anemia and in preparation for surgical intervention.
TL;DR: The effect of HU in HbS/β‐thalassaemia may be better than that reported for homozygous HBS disease because the synthesized λ‐chains not only inhibit the sickling process but they also neutralize the noxious effects of the excess α‐chains and cut down the ineffective erythropoiesis of the patients.
Abstract: Hydroxyurea (HU), a widely used cytostatic, has been given over a long period of time to 14 adult Caucasian compound heterozygotes for beta s and various beta-thalassaemia genes. All patients had severe pain crises and other complications prior to receiving the drug. After 4-8 weeks on high 'sub-toxic' doses of HU all patients responded with a multifold increase of fetal haemoglobin (HbF) and a marked increase of MCV and MCH; they also felt significantly better and ceased having pains or other complaints. Haematological toxicity was minimal and rapidly reversible. Follow-up of the patients has now exceeded 100 weeks and goes up to 180 weeks in two of them. Pain crises have never recurred. Maintenance of high levels of HBF requires continuous administration of high doses of HU; whenever the latter were decrease in various attempts to avoid potential long-term toxicity, the observed changes gradually faded. The effect of HU in HbS/beta-thalassaemia may be better than that reported for homozygous HbS disease because the synthesized gamma-chains not only inhibit the sickling process but they also neutralize the noxious effects of the excess alpha-chains and cut down the ineffective erythropoiesis of the patients.
TL;DR: A child with homozygous sickle cell anaemia who developed acute liver disease of abrupt onset during an episode of limb pain with sudden onset of persistent vomiting, headache, lethargy, epistaxis, and painful liver enlargement is described.
Abstract: Acute liver failure is unusual unusual in sickle cell anaemia We describe a child with homozygous sickle cell anaemia who developed acute liver disease of abrupt onset during an episode of limb pain She presented with sudden onset of persistent vomiting, headache, lethargy, epistaxis, and painful liver enlargement Laboratory investigations were indicative of cholestasis and severe liver failure with profound prolonged clotting times, hypofibrinogenaemia, elevated serum ammonia and lactic acidosis The symptoms were promptly and completely reversed by two partial exchange transfusions No evidence of viral infection was found Cholelithiasis was ruled out by ultrasonography The child recovered from what appeared to be massive hepatic sickling with no apparent sequelae
TL;DR: In this article, the authors evaluated the effects of enalapril, an angiotensin-converting enzyme inhibitor, on albuminuria associated with sickle cell anemia.
TL;DR: Elevated C3a and C4d levels were observed in patients with continuous pain regardless of hospitalization status, suggesting a continuous underlying inflammatory process in these patients.
TL;DR: Sickle trait is traditionally considered a benign condition by ophthalmologists, but patients with sickle trait are at risk of retinopathy if coincident ocular or systemic disease is present.
Abstract: Sickle trait is traditionally considered a benign condition by ophthalmologists. Three cases of sickle retinopathy in subjects with sickle trait are reported. In all cases the onset of retinopathy was related to other contributing factors: in one case a traumatic hyphaema and raised intraocular pressure, in two others diabetes mellitus. Patients with sickle trait are at risk of retinopathy if coincident ocular or systemic disease is present.
TL;DR: Blood transfusion is used as a life‐saving and prophylactic treatment in sickle cell disease but few randomised controlled trials and careful research studies have been performed to fully define its role.
Abstract: Blood transfusion is used as a life-saving and prophylactic treatment in sickle cell disease. Despite the many complications associated with its use, few randomised controlled trials and careful research studies have been performed to fully define its role. This subjects is, therefore, discussed in the context of the current literature and authors' experience.
TL;DR: It is concluded that fat embolism syndrome must be considered as a possible cause of acute neurologic deterioration in patients with sickle cell anemia.
TL;DR: The lack of difference in academic performance between the two groups suggests that there may be factors other than school absenteeism that affect academic achievement, which require further investigation.
Abstract: Painful episodes have been identified as one of the most frequent manifestations of sickle cell anemia (hemoglobin HbSS). This retrospective study compared the frequency of hospitalization and the ...
TL;DR: A 15 year old boy with sickle cell disease developed intrahepatic cholestasis and a course of exchange transfusion successfully corrected the extreme hyperbilirubinaemia over one year.
Abstract: A 15 year old boy with sickle cell disease developed intrahepatic cholestasis. A course of exchange transfusion successfully corrected the extreme hyperbilirubinaemia over one year. Upon stopping the exchange transfusion programme the hyperbilirubinaemia relapsed but transfusion was effective when reinstituted.
TL;DR: The hypothesis that viruses, through double-stranded RNA elements, can induce sickle erythrocyte adherence to endothelium through alpha 4 beta 1-VCAM-1--mediated adhesion is supported and a potential link between viral infection and microvascular occlusion precipitating sickle cell pain episodes is provided.
TL;DR: In this paper, the effect of age on testicular function and fertility profile of adult males with homozygous sickle cell disease was evaluated in a cross-sectional study at a university teaching hospital in Nigeria and the results showed that there is a significant amelioration of hypogonadism, abnormal sexual function, and poor semen profile with increasing age.
TL;DR: It is estimated that polymerization contributes twice as much to impaired filterability of sickle erythrocytes as the abnormal membranes in homozygous sickle cell disease, and at lower saturation values, the effects of polymer are even greater.
Abstract: Sickle cell anemia is a disease of abnormal rheology caused by acute and reversible, as well as chronic and irreversible, changes in the properties and deformability of sickle erythrocytes. Deformability is determined by several factors, including intracellular sickle hemoglobin polymerization, the abnormal membrane properties of sickle cells, and the abnormal rheological properties of the soluble concentrated hemoglobin solution within dense sickle red blood cells. In this study, we used a 5-microns pore nickel mesh filter to evaluate quantitatively the effects of these factors on the filterability of erythrocytes containing sickle hemoglobin. We used sickle trait and sickle/beta(+)-thalassemia cells, because they have minimal membrane abnormalities or density heterogeneity, to investigate the effects of polymer formation on rheological properties. We found that filterability of these cells is sensitive to small amounts of intracellular polymer and that impaired filtration is linearly related to oxygen-dependent polymer formation, up to a polymer fraction of 0.3. By increasing the proportion of dense cells in populations of normal cells or cells from individuals with sickle syndromes and equilibrating these cells with gas ligands, we estimate that polymerization, even at 95% saturation, contributes twice as much to impaired filterability of sickle erythrocytes as the abnormal membranes in homozygous sickle cell disease. At lower saturation values, the effects of polymer are even greater. The viscosity of the concentrated hemoglobin in dense cells had the smallest effect, over physiologically relevant saturation values. These results emphasize the importance of sickle hemoglobin polymerization in the pathogenesis of sickle cell disease and should help define its pathophysiology and responses to therapy in quantitative terms.
TL;DR: Bone marrow transplantation is the only curative therapy for sickle‐cell disease, but is not devoid of failure risk, and nine patients with severe SCD were grafted in this institution between 1988 and 1993.
Abstract: Summary. Bone marrow transplantation (BMT) is the only curative therapy for sickle-cell disease (SCD), but is not devoid of failure risk. Nine patients with severe SCD were grafted in our institution between 1988 and 1993. Six patients successfully engrafted, but three failed to engraft and had delayed autologous recovery.
All patients had, prior to BMT, low levels of fetal haemoglobin (HbF ≤3.5%). No change in HbF occurred in successfully grafted patients. In the three patients with graft failure HbF increased and remained persistently present at a high level (≥22%) 14 months, 16 months and 39 months post BMT, although two of the three patients were homozygous for either the Benin or the Central African Republic haplotype, a characteristic associated with low HbF level. Of interest, these three previously severely affected patients remain free of vaso-occlusive events.
The mechanism responsible for the expression of high levels of HbF in our three patients with graft failure is not understood, but it protects them from the recurrence of severe vaso-occlusive crises.
TL;DR: The data confirm the high prevalence of nocturnal enuresis in patients with sickle cell disease and support the role of desmopressin acetate in the treatment of these patients.