Showing papers on "Sickle cell anemia published in 1993"
TL;DR: Intravenous recombinant erythropoietin with iron supplementation alternating with hydroxyurea elevates fetal-hemoglobin and F-cell levels more than hydroxyuresa alone, and may also increase levels of fetal hemoglobin in patients with sickle cell disease who have not been helped by hydroxyUREa alone.
Abstract: Background Hydroxyurea increases the production of fetal hemoglobin in patients with sickle cell anemia, inhibiting the polymerization of hemoglobin S and potentially improving vaso-occlusive manifestations and hemolysis. Recombinant erythropoietin increases the number of reticulocytes containing fetal hemoglobin in laboratory animals and in humans. We studied whether hydroxyurea and erythropoietin might have a potentiating effect on the production of fetal hemoglobin in patients with sickle cell disease. Methods We treated four patients who were receiving hydroxyurea for sickle cell disease (three who were homozygous for sickle cell anemia and one with sickle β0-thalassemia) with escalating doses of intravenous erythropoietin for seven weeks, along with oral iron sulfate. Doses of hydroxyurea on four consecutive days were alternated with doses of erythropoietin on three consecutive days. Results There was a 28 percent increase in the number of reticulocytes containing fetal hemoglobin and a 48 percent in...
234 citations
TL;DR: ' Although there is significant variability in clinical severity, recent data suggest that most African-Americans with SCD have crises",'8 and require hospitalization at some point."
187 citations
TL;DR: Following B19 infection, serial specific IgG concentrations remained high after 5 years in only 45% of SS patients, although the rarity of recurrent aplasia suggests lifelong immunity, and an effective vaccine against B19 might make an important contribution to the management of sickle cell disease.
133 citations
TL;DR: Cultures of cells derived from five patients with sickle cell anemia have shown a twofold to fivefold increase in the percentage of Hb F following addition of HU while four patients with beta-thalassemia showed a 1.3- to 6.2-fold increase.
119 citations
TL;DR: With the use of conservative eligibility criteria, at least half the febrile episodes in children with sickle cell disease can be treated safely on an outpatient basis, with substantial reductions in cost.
Abstract: Background Because of their susceptibility to pneumococcal sepsis, children with sickle cell disease and fever are usually hospitalized for antibiotic therapy. Outpatient treatment may be a safe and less expensive alternative for selected patients. Methods After evaluation in the emergency room, children ranging from 6 months to 12 years of age who had sickle hemoglobinopathies and temperatures exceeding 38.5 °C were randomly assigned to treatment as either inpatients or outpatients. We excluded from randomization children at higher risk of sepsis (as defined by specific criteria, including temperature above 40 °C, white-cell count below 5000 per cubic millimeter or above 30,000 per cubic millimeter, and the presence of pulmonary infiltrates) or with complications of sickle cell disease (such as a hemoglobin level below 5 g per deciliter, dehydration, or severe pain); these children were treated as inpatients. All patients received an initial intravenous dose of ceftriaxone (50 mg per kilogram of body wei...
86 citations
TL;DR: The resting metabolic rate in 20 patients with homozygous sickle cell (SS) disease was 19% higher than in 20 age- and sex-matched control subjects with a normal hemoglobin genotype (AA).
84 citations
TL;DR: This constellation of events is termed the ASPEN syndrome, an eponym for association of sickle cell disease, priapism, exchange transfusion and neurological events, and the proposed pathophysiology is related to cerebral ischemia after an acute increase in per cent total hemoglobin.
74 citations
TL;DR: Analysis of the relationship of the long-term clinical course of patients with the beta s gene cluster haplotype and alpha-gene status has revealed that those with the haplotype designated Senegal have decreased severity, Those with the Benin haplotype have intermediate severity, andThose with the Central African Republic (CAR) haplotypes have the most severe clinical expression.
Abstract: • Identification of the βsgene cluster haplotype and α-gene status provides a useful tool for the detection of high-risk patients with sickle cell anemia. Analysis of the relationship of the long-term clinical course to the above parameters has revealed that those with the haplotype designated Senegal have decreased severity, those with the Benin haplotype have intermediate severity, and those with the Central African Republic (CAR) haplotype have the most severe clinical expression. Further modulation of the clinical course occurs with the coinheritance of α-thalassemia-2. In both Africa and the United States, the CAR βshaplotype increased the risk (relative risk, 2.25; 95% confidence interval, 1.41 to 3.87) of developing a complication and death at an early age. Detection of the CAR haplotype identifies the child with sickle cell anemia at risk for a rapid rate of progression of sickle-induced microvasculopathy, ultimately leading to irreversible organ damage during the first three decades of life. In patients with the CAR haplotype, potential curative therapy, such as bone marrow transplantation or gene insertion, should be seriously considered during childhood, before organ failure is clinically evident. (AJDC. 1993;147:1197-1202)
74 citations
TL;DR: It is suggested that subclinical vaso-occlusion may generate a covert inflammatory response and that the cytokine mediators of this response may contribute to the metabolic abnormalities and growth failure in sickle cell disease.
73 citations
TL;DR: A patient with sickle cell disease and recurrent priapism who was treated successfully for more than a year with monthly gonadotropin-releasing hormone analogue therapy after failure of standard medical management is reported on.
73 citations
TL;DR: The causes of early mortality in sickle cell disease in Jamaica are described and the major complications such as acute splenic sequestration, pneumococcal septicaemia, aplastic crisis, hypersplenism, and acute chest syndrome have been addressed with varying success.
TL;DR: The authors have found an association between cerebrovascular accident and elevated blood pressure in men, even in a range of systolic and diastolic pressures that would be considered normal by conventional standards.
TL;DR: The acute chest syndrome (ACS), characterized by fever, chest pain, leukocytosis and a new infiltrate on chest roentgenogram, is a common complication of sickle hemoglobinopathies.
TL;DR: The prevalence and incidence of osteonecrosis of the humeral head in sickle cell disease was determined by a study of 2524 patients who were entered into a prospective study and followed for an average of 5.6 years.
Abstract: The prevalence and incidence of osteonecrosis (ON) of the humeral head in sickle cell disease was determined by a study of 2524 patients who were entered into a prospective study and followed for an average of 5.6 years. At entry, 5.6% had roentgenographic evidence of ON in one or both shoulders. There was little difference in age-adjusted prevalence among genotypes, but there were striking differences in age-specific rates. Observed at ages ranging from five to 24 years, 3.25% of sickle cell anemia (S/S) patients, but only 1.1% of sickle cell disease (S/C) patients, had ON. No S/beta+ thalassemia patients younger than 25 years of age had ON on entry. The highest age-adjusted incidence rate was found in S/S patients with concomitant alpha-thalassemia (4.85 per hundred patient-years), followed by S/beta zero-thalassemia (4.84 per hundred patient-years), S/beta+ thalassemia (2.61 per hundred patient-years), S/S without alpha-thalassemia (2.54 per hundred patient-years), and S/C (1.66 per hundred patient-years). Only 20.9% of patients reported pain or had limited range of movement at the time of diagnosis. Sickle cell disease is a frequent cause of ON of the humeral head, especially in children and young adults.
TL;DR: Intracellular HbS polymerization leads to a marked decrease in the flexibility or rheological properties of the sickle erythrocytes and obstruction in various microcirculatory beds, as well as chronic anaemia, so the effects of α-thalassaemia can be explained with reference to changes in MCHC and syndromes with high HbF are understandable.
Abstract: The primary pathophysiological event in the erythrocytes of individuals with the various sickle syndromes is the intracellular aggregation or polymerization of sickle haemoglobin (HbS). The extent of polymerization is determined by the intracellular haemoglobin composition (% HbS and % HbS A, A2 and F), concentration (MCHC and % of dense cells) and oxygen saturation, as well as minor factors such as intracellular pH and DPG concentration. Intracellular HbS polymerization leads to a marked decrease in the flexibility or rheological properties of the sickle erythrocytes and obstruction in various microcirculatory beds, as well as chronic anaemia. Other abnormalities in the properties of the sickle erythrocytes, including membrane abnormalities, changes in ion fluxes and volume and endothelial adhesion, result from acute and chronic oxygen-linked polymerization events and may, in turn, modify polymerization. However, within a good approximation, many aspects of sickle cell disease pathophysiology--for example variations in anaemia among the different sickle syndromes--can be explained in terms of differences in polymerization tendency. Thus, the effects of alpha-thalassaemia can be explained with reference to changes in MCHC and syndromes with high HbF are understandable in terms of the sparing effect of HbF on polymerization. Recent therapeutic approaches to sickle cell disease focus on attempts to reduce intracellular HbS polymerization by altering the haemoglobin molecules, erythrocyte properties, or the distribution of intracellular haemoglobin species. The last, through pharmacological elevation of HbF, has become the central focus of much laboratory and clinical research in recent years. Agents such as hydroxyurea (with or without recombinant erythropoietin) and butyrate compounds elevate HbF (and reduce HbS) in a majority of sickle erythrocytes, thus decreasing intracellular polymerization. Current prospective protocols are designed to see if these changes cause clinical improvement at acceptable doses. Other treatment strategies, including bone marrow transplantation and possible gene replacement therapies, are also under active clinical or laboratory investigation.
TL;DR: It is concluded that children with sickle cell disease, particularly those with HbSS, may have abnormally small lungs that function normally relative to their size; clustering of ACS episodes is not specifically associated with the observed abnormality.
TL;DR: It is document that free iron is nonrandomly associated with the membranes of sickle and beta-thalassemic RBCs and whether this plays a causative role in the premature removal of such cells from the circulation remains to be seen.
TL;DR: The results reported have shown a relationship between the presence of the beta s gene product and partial resistance to malaria in an experimental model in vivo and shows that the spleen plays an important role in this protection.
TL;DR: Preliminary data indicate that among the Omani population with sickle cell disease, homozygosity of the alpha+ gene markedly modifies the clinical picture, and this gene is pandemic in this population.
Abstract: The frequencies of four malaria associated erythrocyte genetic abnormalities have been established in 1000 Omani subjects. They are: homozygous alpha+ thalassaemia (-alpha/-alpha) 0.45; high Hb A2 beta thalassaemia trait 0.015; sickle trait (Hb A/S) 0.061; and glucose 6 phosphate dehydrogenase deficiency (Gd-): males 0.27, females 0.11. From our data the alpha+ (-alpha/) thal gene (confirmed by Southern blotting) is pandemic in this population. Moreover, in spite of the very high frequency of Gd-, oxidative haemolytic syndromes are very uncommon. Also preliminary data indicate that among the Omani population with sickle cell disease, homozygosity of the alpha+ gene markedly modifies the clinical picture.
TL;DR: It was concluded that the lower protein C and S levels in SCD is either due to decreased production or increased consumption though this reduction does not seem to play a role in producing thrombo-embolic disorders.
Abstract: Proteins C and S are vitamin K-dependent proteins with an essential anti-coagulant function. Protein C exists in an inactive form and is activated by a thrombin-thrombomodulin complex. Protein S combines with protein C and forms a stoichiometric complex which regulates coagulation in the presence of calcium. As patients with sickle cell disease (SCD) bear a high risk of developing thrombo-embolic disorders, we studied the coagulation derangement in 100 patients and 40 normal age- and sex-matched controls. The patients were clinically assessed and classified into sickle cell homozygotes (Hb SS), Hb S heterozygotes (Hb AS) and double heterozygotes for Hb S/beta 0-thalassaemia based on haematological parameters, red cell indices, Hb A2 and F levels and genetic studies. The proteins C and S were estimated and related to the type of the gene defect. The results showed significantly reduced levels of proteins C and S in SCD patients with the highest prevalence of deficiency in patients with a severe disease and frequent episodes of crisis. However, no significant differences were encountered in the level of proteins C and S in the same patients during the steady state and during episodes of crisis. It was concluded that the lower protein C and S levels in SCD is either due to decreased production or increased consumption though this reduction does not seem to play a role in producing thrombo-embolic disorders.
TL;DR: The data indicate that BMT can correct "permanent asplenia" in SCA patients, however, it remains to be determined if such treatment can also correct other SCA-related organ dysfunctions.
TL;DR: Twenty-two children with major sickle hemoglobinopathy underwent cholecystectomy for symptomatic cholelithiasis and were transfused to achieve a hemoglobin level greater than 9 g/dL and hemoglobin S less than 37%.
TL;DR: Sickle cell disease involves many organs but musculo-skeletal problems present most often with bone pain, the most common reason for admission to hospital, and two separate pathological abnormalities cause these lesions.
Abstract: Sickle cell disease involves many organs but musculo-skeletal problems present most often with bone pain, the most common reason for admission to hospital Two separate pathological abnormalities cause these lesions Sickling of the red cells produces thromboembolic infarcts in bone leading to pain, crises and sometimes osteomyelitis; increased destruction of sickle red cells produces haemolysis, an increase in erythroblastic activity and expansion of the bone marrow cavity Dactylitis, avascular necrosis of the head of the femur particularly, osteomyelitis, retardation of growth and leg ulcers are commonly encountered Management is by standard orthopaedic principals At operation care must be taken in the use of a tourniquet, adequate oxygenation is required and the possibility of acute renal failure must be recognised
TL;DR: The results indicate that Sickle cell patients have hypocalcaemic tendency associated with supranormal PTH, and imply impaired intestinal absorption of calcium and vitamin D leading to a disturbed calcium metabolism which might contribute to the skeletal changes seen in sickle cell disease.
Abstract: The concentrations of serum calcium, parathyroid hormone (PTH), 25 Hydroxyvitamin D (25OHD), and 1,25 Dihydroxyvitamin D (1,25(OH)2D) were determined in 99 Saudi patients with sickle cell disease a...
TL;DR: The finding of increased antiphospholipid antibodies in patients with sickle cell disease is compatible with the concept that antiph phosphate antibody formation is associated with structural changes in the red cell membrane and that such structural changes occur in thered cells of patients with Sickle Cell disease.
Abstract: Antiphospholipid antibody formation can be induced in mice by phospholipid in a hexagonal II phase but not by phospholipid in a bilayer phase. Since sickle red cell membranes have increased hexagonal II phase content, we have measured serum antiphospholipid antibody levels in 25 patients with sickle cell disease to determine whether anti-phospholipid antibody may similarly be induced in these patients. Seventeen of the 25 patients (68%) had increased levels of antiphospholipid antibodies. Eleven patients (65%) had IgG and six each (35%) had IgM and IgA isotypes. Antiphosphatidylethanolamine, antiphosphatidylserine, antiphosphatidylinositol, and antiphosphatidic acid were the most frequently increased antibodies. The finding of increased antiphospholipid antibodies in these patients is compatible with the concept that antiphospholipid antibody formation is associated with structural changes in the red cell membrane and that such structural changes occur in the red cells of patients with sickle cell disease.
TL;DR: Alloimmunization can be reduced prospectively in patients with SCD by meeting their transfusion requirements with blood selected from random black blood donors.
Abstract: Patients with sickle cell disease (SCD) form immune alloantibodies more frequently than other transfused populations because red cells (RBCs) from white donors (with a higher incidence of certain Rh, Duffy, Kell, and Kidd blood group antigens) are transfused to black patients often lacking these antigens. We propose a model to reduce alloimmunization in patients with SCD by providing them with blood from only black random donors. Rationale is shown by examining calculations based on the phenotype E–, C–, Fy(a–), K–, and Jk(b–). There is a 7% probability that this phenotype belongs to a white donor, while there is a 93% probability that this phenotype belongs to a black donor. The probability of selecting blood from a black donor identical with the above phenotype for black recipients from an all black population and from a typical urban blood inventory population (90% white, 10% black) is 1/4 and 1/33, respectively. Therefore, an 8-fold greater chance of selecting antigen non-identical blood occurs if blood is obtained from a typical urban donor population as compared to a black population. Based on these calculations, alloimmunization can be reduced prospectively in patients with SCD by meeting their transfusion requirements with blood selected from random black blood donors.
TL;DR: A sex‐related difference in the somatic growth of adolescent and adult patients with sickle cell anemia is suggested and it is suggested that, although an inadequate food intake may be partly responsible for the impaired somatic Growth in sicklecell anemia, other factors are also probably important.
Abstract: To evaluate the possible role of inadequate food intake in the pathogenesis of the growth retardation of patients with sickle cell anemia, we determined the daily intake of calories and macronutrients and measured several anthropometric indices in 20 patients with sickle cell anemia aged 17-35 years and in 15 of their normal siblings of similar age. Compared to the control groups, the male patients, but not the females, had a significantly lower mean weight, body mass index, midarm circumference, and triceps and subscapular skinfold thicknesses. Also, while the male patients consumed significantly less total calories, proteins, carbohydrates, and fats per day than their control group, no difference was noted between the daily intake of calories or macronutrients in the female patients and their control group. However, when the intake of calories and macronutrients was corrected for body weight, there was no statistically significant difference between the intake of nutrients in the male patients and their control subjects or between the female patients and their control group. These results suggest a sex-related difference in the somatic growth of adolescent and adult patients with sickle cell anemia and also suggest that, although an inadequate food intake may be partly responsible for the impaired somatic growth in sickle cell anemia, other factors are also probably important.
TL;DR: Three children with homozygous sickle cell disease had clinical and hematologic manifestations of aplastic and splenic sequestration crisis simultaneously and evidence of recent parvovirus infection was demonstrated.
TL;DR: The study shows the incidence of sensorineural hearing loss in the UK to be similar to that reported in the USA and much lower than that found in malaria endemic areas of the tropics.
Abstract: Sensorineural hearing loss (SNHL) has been a well-documented complication of sickle cell disease in the literature from West Africa, West Indies, United States of America and the Middle East. We present a study of 52 patients with homozygous sickle cell disease and 36 control patients with haemoglobin genotype AA, matched for age and sex. Seven patients with sickle cell disease (13.5 per cent) were found to have sensorineural hearing loss i.e. > 20 dB at two or more frequencies, while all the patients in the control group had normal hearing (p < 0.05). Our study shows the incidence of SNHL in the UK to be similar to that reported in the USA and much lower than that found in malaria endemic areas of the tropics. We highlight the factors which we consider responsible for these differences and suggest that the crucial period in the development of SNHL in sickle cell disease may be intra-uterine or during the first few years of life. All sickle cell patients should be encouraged to have regular hearing assessment.
TL;DR: Evidence is provided that malaria plays a significant role in the persistence of splenomegaly in African patients and age‐ and sex‐matched Nigerian and U.S. steady‐state SS patients were compared.
Abstract: Anecdotal reports have attributed persistent splenomegaly in African sickle cell anemia (SS) patients to the effects of malaria. However, no comparative studies of patients in malarial and nonmalarial regions have been conducted, and few studies of malaria antibody titers have been reported. In the present study, age- and sex-matched Nigerian and U.S. steady-state SS patients were compared. Splenomegaly was found in 22.3% of Nigerian patients (n = 310), while it was found only in 8% of U.S. patients (n = 100) from Georgia. There was significant linear correlation between spleen size and Hb levels and with serum immunoglobulins in the Nigerian group. However, serum complement levels (C3 and C4) were not affected by spleen size. In both groups, patients with splenomegaly had fewer circulating pitted red cells than their counterparts without splenomegaly. The mean ± SE of IgG-specific malaria antibody titer among the Nigerian patients without palpable spleens was 9,386 ± 2,036; 9,334 ± 2,980 in those with spleens between 1 and 5 cm, 16,201 ± 4,502 in those with spleens between 6 and 10 cm, and 22,445 ± 8,456 in those with spleens above 10 cm. Coexistent α-thalassemia did not influence the prevalence of splenomegaly among the Nigerian SS patients. This study provides additional evidence that malaria plays a significant role in the persistence of splenomegaly in African patients. © 1993 Wiley-Liss, Inc.