Symptoms Of Sickle Cell Disease Research Articles

Insights into elevated distortion product otoacoustic emissions in sickle cell disease: Comparisons of hydroxyurea-treated and non-treated young children

Distortion product otoacoustic emissions (DPOAEs) were examined in 15 normal-hearing African-American children between the ages of 6 and 14 years with homozygous sickle cell disease (SCD), who were on a regimen of hydroxyurea (HDU), a drug that reduces inflammatory processes and symptoms of SCD; a matched group of 15 African-American children with homozygous SCD not on HDU; and 15 African-American children with normal hemoglobin. DPOAEs were evoked by 13 primary tone pairs with f 2 frequencies ranging from 1000 to 4500 Hz. Increased DPOAE amplitudes, believed to be a precursor of eventual hearing loss, were evident in children with SCD who were not receiving HDU. Those taking HDU had DPOAE amplitudes similar to normal controls. These findings suggest that HDU, in addition to reducing symptoms of SCD, may play a role in inhibiting or preventing cochlear pathology and hearing loss in individuals with SCD.

Mean Platelet Volume in Children with Sickle Cell Disease on Chronic Transfusion Therapy.

The symptoms in sickle cell disease are related to ischemic/vaso-occlusive episodes involving the bones, spleen, brain and lungs. One of the possible mechanisms for vaso-occlusion is platelet activation and increased platelet reactivity which is demonstrated by increased platelet volume resulting in an elevated platelet distribution width. We hypothesized that chronic transfusion therapy given to patients with recurrent severe ischemic episodes and/or stroke may lower mean platelet volume (MPV) in addition to decreasing hemoglobin S. We performed a retrospective chart analysis of all patients with sickle cell disease who were on a chronic transfusion regimen at Schneider Children's Hospital between January 1995 and March 2005. Out of 60 eligible patients, only 42 were eligible for this study. The remaining patients were excluded for less than 3 transfusions in total or incomplete records. The data retrieved included age and sex of the patient, type of sickle cell disease, indication for chronic transfusion therapy, duration of transfusions and blood count variables during the three phases, i.e. prior to, during and after transfusion therapy. The variables included hemoglobin, mean cellular volume, platelet count, reticulocyte count and MPV for each patient with a minimum of one value in each phase. As many values were recorded based on the availability in the records, with at least an interval of 3 months between each blood count and at least 3 months apart from a transfusion.Results: Sixty-four percent were males and 95% had HbSS genotype. The major indication for transfusion therapy (85%) was stroke. Mean values of each variable and their ranges were compared across the 3 periods using the Kruskal Wallis test. Although the platelet count decreased significantly during transfusions compared to pre-transfusion period, the mean value of MPV did not differ across the 3 periods with a range between 5.9 and 11.3 in all the 3 periods. Furthermore, using the Anacova method proposed by Bland and Altman, there was an overall significant negative correlation between MPV and platelet count, while no correlation at all was present between MPV, reticulocyte count and hemoglobin in any of the 3 periods. Our findings suggest that multiple transfusions do not alter platelet size or volume, which indirectly may indicate that there is no change in platelet function or activity in these patients on chronic transfusion therapy. The changes in MPV values seen in this study are real, as they follow the natural thrombokinetics by maintaining a negative correlation with the platelet count during all 3 periods.

Psychological Outcome after Hematopoietic Cell Transplantation for Sickle Cell Disease.

Hematopoietic cell transplantation (HCT) is the only potentially curative treatment for sickle cell disease (SCD). The probability of event-free survival is currently between 85 and 90% after matched sibling-donor HCT. This intensive treatment conducts to a major change for patients and families. The purpose of the present study was to determine the psychological impact on individuals and their families of this recovery process after HCT. The hypothesis was that the recovery is a process with different aspects (medical, psychological, individual, familial and cultural) which could be discordant. This study was supported by the Etablissement Français des Greffes (EFG) and conducted by child and adolescent psychiatrists, psychologists and a medical anthropologist. The assessment consisted in two semi-structured interviews adressed to the patients and their families for studying their illness narratives and questionnaires for quality of life, post-traumatic stress disorder (PTSD), depression and anxiety. 28 patients (17 males, 11 females) with SCD treated in France by HCT (22 by bone marrow and 6 by cord blood transplantation) and their families were evaluated at least one year (median 5 years, range, 1–14 years) after HCT at the median age of 14 years (range, 4–24 years). Among these 28 patients, 7 had prior history of severe vasculopathy and 6 of stroke before the HCT. At evaluation, 27 patients were free from SCD symptoms (but 3 had moderate chronic GVHD), 1 had graft rejection. 9 patients (4 males, 5 females) (median age 16 years, range 7–23 years) presented psychiatric symptoms as inhibition, depression, hypomaniac symptoms, anxiety, stutter. A psychiatric care was indicated for these 9 subjects. No diagnosis of current PTSD was found. Psychological distress was reported by parents. 21 patients considered themselves as cured, 4 of them in an incomplete way (none with stroke before the HCT, 3 with moderate chronic GVHD), and 3 not cured at all (none with stroke before the HCT, 1 with graft rejection). The study of the narratives illustrated the major individual, familial and cultural changes after the HCT. The recovery needed complex adjustments. Patients had to cope with new potentialities and requirements: school and relationships with peers, identity issues (disease transmission, infertility) and family changes. This study underlies the importance of psychological interventions for improving the outcome of patients with SCD treated by HCT and their families.

Hypodontia in an adolescent with the HbSC genotype: a case report

The haemoglobin SC (HbSC) genotype is a variant form of haemoglobin disorder that often presents less frequent clinical symptoms of sickle cell disease (SCD) than the homozygous state (HbSS). Various dental abnormalities, such as enamel hypoplasia, hypomineralization, midline diastema and delayed eruption of the teeth, have been associated with SCD. This report presents the case of an adolescent patient with HbSC who had hypodontia, transposition of a permanent canine, retained primary teeth, multiple carious lesions and poor oral hygiene complicated by sickle cell crisis. This report focuses on the need for preventive care in such patients to reduce functional and aesthetic complications.

Extracellular Regulating Kinase (ERK) Inhibition by U0126: A Novel Mechanism for γ-Globin Gene Activation.

Fetal hemoglobin (HbF) effectively inhibits hemoglobin S polymerization in red blood cells and improves symptoms in sickle cell disease. Studies in K562 cells induced with sodium butyrate (NaB), apicidin and hydroxyurea suggest that ERK inhibition is required for induction of cell differentiation and HbF synthesis. Multiple K562 stable lines were established with the pcmvMEK1/2 expression vector which mediates constitutively active ERK signaling. We observed a 75% decrease in γ-globin expression at baseline which was completely reversed by the ERK pathway inhibitor, U0126. This data confirmed the ability of ERK to silence γ-gene expression. Western blot analysis was performed to determine whether ERK inhibition is a common mechanism for γ-globin activation by other HbF inducers as well. We tested the histone deacetylase inhibitors: trichostatin A (TSA), SAHA, and MS275, decitabine and hemin, and the ERK inhibitors U0126 and PD98059. ERK phosphorylation was decreased from 45% to 99% at 24 and 48 hrs in K562 cells treated with TSA, decitabine, U0126 and PD98059 supporting a common mechanism for HbF induction. Concomitantly, γ-globin mRNA synthesis increased 2 to 8-fold, measured by real-time PCR analysis. When U0126 was combined with NaB or TSA, γ-gene expression increased 9-fold and 13-fold respectively. To evaluate the therapeutic potential of U0126 in sickle cell disease, we tested its effects on cell viability at 5 to 40μg concentrations. K562 cell viability remained >60% at the highest concentration for 72 hrs. Another positive effect of U0126 is its ability to inhibit cell proliferation mediated by ERK thus promoting differentiation and hemoglobin induction. Subsequent studies were completed in ES10 stable lines established with an HS2γβ mini-construct in MEL cells to test γ-gene activation in the presence of the β-globin gene. We also determined whether ERK signaling is inhibited by HbF inducers in an adult intracellular environment. ERK phosphorylation was blocked by U0126, TSA and NaB in parallel with a 5 to 34-fold increase in γ-globin expression. Additional studies are in progress to test the ability of U0126 to induce HbF in primary erythroid progenitors. Investigations are underway to ascertain mechanisms for γ-globin regulation by U0126 using DNA microarray analysis. K562 cells were induced with 20μM U0126 for 48 hrs and total RNA with 5-fold γ-globin induction was analyzed using ArrayIt DNA microarray chips (TeleChem International, Inc., Sunnyvale, CA) containing 380 genes from several functional groups. Hierarchical cluster analysis confirmed a >2-fold increase in gene expression for heat shock 70 kD protein 6, insulin receptor substrate 2 and transcription factor Dp-1. Genes inhibited >2-fold by U0126 included the proto-oncogene fms-tyrosine kinase and glutathione-S-transferase. When NaB was combined with U0126 a synergistic 13-fold increase in Dp-1 was observed. The role of these and other transcription factors identified by microarray analysis in γ-globin regulation will be investigated. The ability of U0126 to act as a potent HbF inducer and the limited number of genes altered by this agent makes it an ideal lead compound for clinical development.

Assessment of cerebral tissue oxygenation in patients with sickle cell disease: effect of transfusion therapy.

This study used spatially resolved transcranial near-infrared spectroscopy (NIRS) to compare brain tissue oxygenation in sickle cell disease (SCD) patients with that of healthy children. In addition, NIRS was used to measure the dynamic response of cerebral oxygen balance to erythrocytapheresis. Transcranial NIRS measurements were obtained from 25 children with SCD who were not receiving transfusion or hydroxyurea therapy (NT-SCD). These patients were divided into two subgroups, those with mild (n = 10) or severe (n = 15) SCD symptoms. In addition, NIRS measurements were performed in 16 SCD patients with severe disease maintained on long-term erythrocytapheresis (T-SCD) and in 35 control children. The lowest mean brain tissue oxygen saturation occurred in the NT-SCD subgroup with severe symptoms (48 +/- 9%; P < 0.001 vs. control). NT-SCD patients with mild symptoms had higher saturation (62 +/- 8%; P < 0.001 vs. control), while the highest appeared in the control group (72 +/- 7%). In T-SCD patients, however, brain tissue oxygen saturations were higher than severely symptomatic NT-SCD children and similar to mildly symptomatic NT-SCD children (65 +/- 7%). Non-invasive measurements of brain tissue oxygenation with NIRS revealed that abnormal oxygen saturation levels in SCD patients correlated with the severity of their clinical manifestations. Additionally, cerebral oxygen balance seems to be favorably affected by erythro-cytapheresis.

Sickle Cell Disease: History And Origin

The symptoms related to sickle cell crises were known by various names in Africa, long before they were recognized in the western hemisphere1. Symptoms of sickle cell anemia could be tracked back to year 1670 in one Ghanian family2. It was in 1910 when James Herrick3 observed, “peculiar elongated sickle shaped RBCs” in the blood of an anemic black medical student, and then the scientific community came to know about it.

Enhancement of hemoglobin and F-cell production by targeting growth inhibition and differentiation of K562 cells with ribonucleotide reductase inhibitors (didox and trimidox) in combination with streptozotocin.

Upon appropriate drug treatment, the human erythroleukemic K562 cells have been shown to produce hemoglobin and F-cells. Fetal hemoglobin (Hb F) inhibits the polymerization events of sickle hemoglobin (Hb S), thereby ameliorating the clinical symptoms of sickle cell disease. Ribonucleotide reductase inhibitors (RRIs) have been shown to inhibit the growth of myeloid leukemia cells leading to the production of Hb F upon differentiation. Of the RRIs currently in use, hydroxyurea is the most effective agent for Hb F induction. We have examined the capacity of two novel RRIs, didox (DI) and trimidox (TRI), in combination with streptozotocin (STZ), to induce hemoglobin and F-cell production. The K562 cells were cultured with different concentrations of didox-STZ or trimidox-STZ at a fixed molar ratio of 3:1 and 1:5 for 96 hr, respectively. At pre-determined time intervals, aliquots of cells were obtained and total hemoglobin (benzidine positive) levels, number of F-cells, and Hb F were determined by the differential staining technique, fetal hemoglobin assay kit, and fluorescence cytometry respectively. The effect of combined drug treatment on the growth of K562 cells was examined by isobologram analysis. Our results indicate that a synergistic growth-inhibitory differentiation effect occurred when didox or trimidox was used in combination with STZ on K562 cells. There was an increase in the number of both benzidine-positive normoblasts and F-cells, accompanied by morphologic appearances typical of erythroid maturation. On day 4, the number of benzidine-positive cells showed a 6-9-fold increase and the number of F-cells was between 2.5- and 5.7-fold higher than the respective controls. Based upon these results, treatment with a ribonucleotide reductase inhibitor, such as didox or trimidox, in combination with STZ, might offer an additional promising option in sickle cell disease therapy.

The feasibility of nursing patients with sickle cell crisis at home

The most common symptom of sickle cell disease is the vaso-occlusive crisis, which studies have shown is generally poorly managed. This study aimed to assess whether nursing intervention in crisis management could facilitate movement of the pain care environment from hospital to the home. Studies have highlighted that patients want this type of service provision, and 90% of cases currently try to remain within the home when in crisis (Elander and Midence, 1997), despite the poor support of primary care services. Thirty-six subjects were part of the experimental arm of this study. The results demonstrated that it was feasible to manage the majority of non-complicated crises within the home, but suggest that to do this would necessitate an increase in current primary care input into this patient group, especially of community and specialist haemoglobinopathy nurses.

Effects of S-Nitrosation on Oxygen Binding by Normal and Sickle Cell Hemoglobin

S-Nitrosated hemoglobin (SNO-Hb) is of interest because of the allosteric control of NO delivery from SNO-Hb made possible by the conformational differences between the R- and T-states of Hb. To better understand SNO-Hb, the oxygen binding properties of S-nitrosated forms of normal and sickle cell Hb were investigated. Spectral assays and electrospray ionization mass spectrometry were used to quantify the degree of S-nitrosation. Hb A(0) and unpolymerized Hb S exhibit similar shifts toward their R-state conformations in response to S-nitrosation, with increased oxygen affinity and decreased cooperativity. Responses to 2, 3-diphosphoglycerate were unaltered, indicating regional changes in the deoxy structure of SNO-Hb that accommodate NO adduction. A cycle of deoxygenation/reoxygenation does not cause loss of NO or appreciable heme oxidation. There is, however, appreciable loss of NO and heme oxidation when oxygen-binding experiments are carried out in the presence of glutathione. These results indicate that the in vivo stability of SNO-Hb and its associated vasoactivity depend on the abundance of thiols and other factors that influence transnitrosation reactions. The increased oxygen affinity and R-state character that result from S-nitrosation of Hb S would be expected to decrease its polymerization and thereby lessen the associated symptoms of sickle cell disease.

Mild clinical expression of S-&lt;FONT FACE=Symbol&gt;b&lt;/font&gt; thalassemia in a Brazilian patient with the &lt;FONT FACE=Symbol&gt;b&lt;/font&gt;+ IVS-I-6 (T&lt;FONT FACE=Symbol&gt;®&lt;/font&gt;C) mutation

We report on an eight-year-old Brazilian girl with S-b+ thalassemia. The patient had a steady 10.1 g/dl hemoglobin with 57% HbS. Direct sequence analysis of b-globin gene showed her to be heterozygous for the IVS-I-6 (T®C) mutation. This b+ thalassemia mutation, sometimes referred to as the Portuguese type, was found to be associated with the C®T polymorphism at codon 2. In combination with the bS gene, this mutation results in very mild sickle cell disease symptoms.

Shifts in affinity and enthalpy of oxygen binding to human hemoglobin A induced by pyridoxal and pyridoxal 5′-phosphate

A therapeutic agent capable of inhibiting the polymerization of hemoglobin S would relieve the symptoms of sickle cell disease. The P 50 of oxygen binding to hemoglobin A (HbA) in the presence of an effector has been used for the initial screening of potential antisickling agents. We evaluated the thermodynamic parameters, P 50, ΔG, ΔH, and ΔS and Hill coefficient for oxygen binding to human HbA o (HbA stripped of all endogenous effectors) in the presence of two antisickling agents, pyridoxal (PL) and pyridoxal 5′-phosphate (PLP), and two sickling-enhancing agents, 2,3-diphosphoglycerate (DPG) and inositol hexaphosphate (IHP). The P 50 of oxygen binding to HbA o in phosphate/EDTA buffer, pH 7.6, was found to be 560 Pa. The P 50 was increased to 653 Pa and 1746 Pa by DPG and IHP, respectively. The antisickling agents, PLP, and PL, had opposite effects on the P 50, shifting it to 840 Pa and 187 Pa, respectively, indicating that a decrease in P 50 may not be the best predictor of an antisickling agent. The Hill coefficient was 2.9 for both HbA o and HbA o + DPG and 2.6 for HbA o + IHP. The Hill coefficient was reduced by both PLP to 2.3 and by PL to 2.1. The enthalpies for oxygen binding to HbA o, HbA o + DPG, and HbA o + IHP were −48.1 kcal/mol Hb, −48.0 kcal/mol Hb, and −42.2 kcal/mol Hb, respectively. In contrast, the enthalpies for HbA o + PLP and HbA o + PL were −57.0 kcal/mol Hb and −51.1 kcal/mol Hb. Our study suggests that decreases in cooperativity and enthalpy, alone or in combination, may be useful indices of potential antisickling agents.

Factitious sickle cell acute painful episodes: A secondary type of Munchausen syndrome

Three adult patients with factitious acute sickle cell painful episodes are presented and the literature is reviewed. The prevalence of this disorder among patients with sickle cell disease in our program was found to be about 0.9%. The patients described to date were all young adults who demonstrated pathological lying (pseudologico fantastico) and most of them had an underlying authentic medical illness to which the feigned signs and symptoms of sickle cell disease were added, thus making the diagnosis more plausible. It is recommended that all patients who present themselves with the signs and symptoms of sickle cell painful episodes be carefully studied in order to confirm the diagnosis. © 1996 Wiley-Liss, Inc.

Hydroxyurea therapy in children severely affected with sickle cell disease

HYPOTHESIS: The major clinical manifestations of sickle cell disease (SCD) are hemolytic anemia, predisposition to infection, and recurrent vaso-occlusive episodes resulting in pain, organ dysfunction, or both. There has been no satisfactory treatment for children with recurrent severe painful episodes caused by SCD. Hydroxyurea is an antimetabolite drug shown in adults with SCD to increase fetal hemoglobin levels and reduce the symptoms of SCD. We hypothesized that hydroxyurea therapy in children with severe (defined as ≥3 vaso-occlusive events per year) SCD could improve hematologic parameters and reduce vaso-occlusive events. OBJECTIVE: To assess the safety and efficacy of hydroxyurea for the treatment of severe SCD in children. STUDY DESIGN: After obtaining informed consent, we initiated hydroxyurea therapy at a dosage of 10 to 20 mg/kg per day in 15 patients with severe SCD (hemoglobin SS, hemoglobin SS-α thalassemia, or hemoglobin S-β 0-thalassemia). Doses were escalated as tolerated. Patients were monitored with bimonthly physical examinations and monthly laboratory measures. To assess the impact of hydroxyurea on clinical symptoms, we recorded the number of inpatient days for each patient during the period of treatment and compared it with the number of inpatient days for the 12- to 24-month period before institution of hydroxyurea therapy, using the subject as his or her own control subject. RESULTS: Thirteen patients received hydroxyurea for a median of 24 months (range, 6 to 39 months). The mean dose of hydroxyurea was 21.4 ± 5.2 mg/kg. Treatment with hydroxyurea induced statistically significant increases in the total hemoglobin concentration, mean corpuscular volume, and percentage of hemoglobin F, and a decrease in the serum concentration of bilirubin. Toxic effects included three episodes of a reversible myelotoxic reaction, two of which required transfusion of packed erythrocytes. For the entire group, hospitalization decreased from a prehydroxyurea median of 3.9 ± 2.0 days per month to 1.1 ± 2.1 days per month of therapy ( p = 0.09). For those subjects (n = 10) completing at least 1 year of treatment, the decrease in hospitalization from 4.1 ± 2.2 to 1.0 ± 1.7 days per month was significant ( p = 0.03). CONCLUSIONS: In this pilot trial, hydroxyurea treatment of severe SCD in children was associated with improved hematologic parameters, acceptable toxic effects, and a trend to reduced hospitalization. Hydroxyurea appears to be a safe and potentially effective agent for the treatment of severe SCD in children. A prospective, controlled trial to investigate the efficacy of hydroxyurea in children is therefore warranted. (J P EDIATR 1996;128:820-8 )

Amino Acid and Peptide Approaches to Anti-sickling Agents

Sickle cell anemia is a genetic disease that affects a large number of people throughout the world. This disease is very well understood at the molecular level, but for which there is still no effective treatment or cure. Phenylalanine, a natural amino acid, has long been known to inhibit the aggregation of sickle hemoglobin (HbS) that leads to the symptoms of sickle cell anemia. However, phenylalanine is weakly potent and thus limited as a potential treatment. Various investigators have developed approaches that seek to improve the effectiveness of amino acid and peptide analogues as anti-sickling agents. These are discussed here in some detail, in addition to a summary of some recent approaches utilizing computer assisted drug design (CADD). CADDis used to understand the potential binding pockets on hemoglobin and to design effective ligands that are more potent as anti-sickling agents. Recently synthesized peptides are considerably more potent than phenylalanine and offer hope that an effective treatment can be developed soon.

Cation transport and volume regulation in sickle red blood cells.

Cellular dehydration is one of several pathological features of the sickle cell. Cation depletion is quite severe in certain populations of sickle cells and contributes to the rheological dysfunction that is the root cause of vascular occlusion in this disease. The mechanism of dehydration of sickle cells in vivo has not been ascertained, but three transport pathways may play important roles in this process. These include the deoxygenation-induced pathway that permits passive K+ loss and entry of Na+ and Ca2+; the K(+)-Cl- cotransport pathway, activated by acidification or cell swelling; and the Ca(2+)-activated K+ channel, or Gardos pathway, presumably activated by deoxygenation-induced Ca2+ influx. Recent evidence suggests that these pathways may interact in vivo. Heterogeneity exists among sickle cells as to the rate at which they become dense, suggesting that other factors may affect the activity or interactions of these pathways. Understanding the mechanism of dehydration of sickle cells may provide opportunities for pharmacological manipulation of cell volume to mitigate some of the symptoms of sickle cell disease.

Pain in Sickle Cell Disease

Acute episodes of pain are the principal symptom of sickle cell disease, but little is known about the epidemiologic features of these episodes or risk factors for them, nor is it known whether patients with high rates of such episodes die prematurely. We prospectively studied the natural history of sickle cell disease in 3578 patients ranging from newborns to persons up to 66 years old who were followed at clinical centers across the United States. There were 12,290 episodes of pain in 18,356 patient-years. The average rate was 0.8 episode per patient-year in sickle cell anemia, 1.0 episode per patient-year in sickle beta 0-thalassemia, and 0.4 episode per patient-year in hemoglobin SC disease and sickle beta(+)-thalassemia. The rate varied widely within each of these four groups--e.g., 39 percent of patients with sickle cell anemia had no episodes of pain, and 1 percent had more than six episodes per year. The 5.2 percent of patients with 3 to 10 episodes per year had 32.9 percent of all episodes. Among patients with sickle cell anemia who were more than 20 years old, those with high rates of pain episodes tended to die earlier than those with low rates. High rates were associated with a high hematocrit and low fetal hemoglobin levels. alpha-Thalassemia had no effect on pain apart from its association with an increased hematocrit. The "pain rate" (episodes per year) is a measure of clinical severity and correlates with early death in patients with sickle cell anemia over the age of 20. Even when the fetal hemoglobin level is low, one can predict that small increments in the level may have an ameliorating effect on the pain rate and may ultimately improve survival. This outcome is particularly encouraging to investigators studying hydroxyurea and other treatments designed to increase the fetal hemoglobin level.

Neonatal screening for sickle cell disease: A cost-effectiveness analysis

To determine the cost-effectiveness of screening newborn infants for sickle cell disease. We developed a decision model that examined two strategies: (1) screening neonates and administering penicillin to infants found to have sickle cell disease in the hope of preventing pneumococcal sepsis, and (2) not screening but administering penicillin to infants after symptoms of sickle cell disease develop. The model calculates the cost-effectiveness of these strategies during the first 3 years of life. We applied the model to three prototypic populations of neonates--black, nonblack with a relatively high prevalence of hemoglobin S genes, and nonblack with a low prevalence of hemoglobin S genes. We obtained from the published literature the effectiveness and risk of penicillin prophylaxis, the risk of pneumococcal sepsis, and the probability that in infants not screened the development of symptoms would lead to the discovery of sickle cell disease within the first 3 years of life; we used the published literature and the Hardy-Weinberg law to determine the prevalence of sickle cell disease. We used actual variable costs of screening, antibiotic prophylaxis, and hospitalization for pneumococcal sepsis or anaphylaxis. Screening and then treating affected black infants costs only $3100 more per life saved than not screening. Screening nonblack populations with a high prevalence of hemoglobin S genes would cost $1.4 million per life saved, and screening low prevalence populations would cost $450 billion per life saved. Screening black infants is very worthwhile, but screening populations in which the hemoglobin S gene is rare is unjustified.

A Benign Sickle-Cell Disease in a Saudi Subject with &amp;beta;&amp;deg;-Thalassemia and Glucose-6-Phosphate Dehydrogenase Deficiency

Sickle-cell disease with raised fetal hemoglobin is found relatively frequently in the eastern part of the Arabian Peninsula. In contrast to the severe and sometimes life-threatening complications of sickle-cell disease in the black population, Saudi Arabs homozygotes for HbS gene exhibit a mild course for this disease. Here we present a Saudi sickle-cell patient with an unusually low fetal hemoglobin level. Moreover, this individual has beta 0-thalassemia and a deficiency in the enzyme glucose-6-phosphate dehydrogenase. Clinical and hematological examinations revealed a remarkably benign condition. This observation is potentially important since most of the mild clinical symptoms of sickle-cell disease have been attributed to high fetal hemoglobin. Clearly in this case, other factors are operating and may be also operating in those patients with high fetal hemoglobin.

Regional Variations in Sickle Cell Anemia in Saudi Arabia

ABSTRACT We examined mean corpuscular volume (MCV), fetal hemoglobin (HbF) levels, and severity of clinical disease in 81 patients with sickle cell anemia from various regions of Saudi Arabia. We f...