Compound Heterozygosity of β-Thalassemia and the Sickle Cell Hemoglobin in Various Populations of Chhattisgarh State,India

Hemoglobinopathies evolved as a protective mechanism against malaria, which exhibit selective advantage in the heterozygous state. However, in a homozygous recessive condition, it poses a serious socioeconomic burden. Sickle cell anemia is an autosomal recessive hemoglobinopathy associated with erythrocytes sickling, vaso-occlusive crisis (VOC), as well as multi-organ failure and death. The coinheritance of other hemoglobinopathies is known to substantially modulate the clinical manifestation of sickle cell anemia. In the present study, we aimed to analyze the coinheritance of β-thalassemia (β-thal) in Hb S (HBB: c.20A>T) patients. The study includes 918 sickle cell anemia patients from 10 ethnic populations of Chhattisgarh State, India. Complete blood counts (CBCs) and hemoglobin (Hb) high performance liquid chromatography (HPLC) fractionation data were collected from patient record books. We observed Hb S-β-thal in all the analyzed populations. Interestingly, high frequencies of Hb S-β-thal have been observed in Satnami (53.8%), Rawat (47.1%), Gond (35.1%) and Panika (30.6%) populations. Inter-population comparison of hematological parameters [Hb F (p?2 (p?p?=?0.03) and red blood cell distribution width (RDW) (p?相似文献   

Use of Direct Oral Anticoagulants in Patients with Sickle Cell Disease and Venous Thromboembolism: A Prospective Cohort Study of 12 Patients

Abstract

Patients with sickle cell disease have an increased risk of venous thromboembolism (VTE) and with a mortality 2-fold higher. The anticoagulation of VTE in a young population is an important question. Indeed, hemorrhagic complications of anticoagulation may occur more frequently than in the general population. The use of a direct oral anticoagulant (DOAC) is not recommended for VTE in patients with sickle cell disease because those patients were not included in the clinical studies. We aimed to study the safety of using DOACs in a prospective cohort of patients with sickle cell disease and VTE. We prospectively followed the cohort of all sickle cell disease patients undergoing recent DOAC treatment for VTE at a sickle cell disease reference center. Twelve patients received rivaroxaban for VTE (eight women and four men). The median age was 27?years (20–45). The sickle cell disease variants included homozygous Hb SS (HBB: c.20A>T) in eight patients, Hb S-β⁺-thalassemia (Hb S-β⁺-thal) in two, Hb S-β⁰-thal in one and Hb S-Hb C (HBB: c.19G>A) in one. The cumulative duration of follow-up was 3134?days under rivaroxaban treatment. There were two thrombotic events, including a patient with a double positivity of antiphospholipid antibodies. No major bleeding was observed, and 6/12 patients presented minor bleeding (epistaxis: n?=?4; anal fissure bleeding: n?=?1; menorrhagia n?=?4). Of these, 3/6 required their treatment to be switched to apixaban, which stopped the bleeding. Direct oral anticoagulants may be an alternative treatment for VTE in patients with sickle cell disease, except for an associated antiphospholipid syndrome.     

GBT440 increases haemoglobin oxygen affinity,reduces sickling and prolongs RBC half‐life in a murine model of sickle cell disease

A major driver of the pathophysiology of sickle cell disease (SCD) is polymerization of deoxygenated haemoglobin S (HbS), which leads to sickling and destruction of red blood cells (RBCs) and end‐organ damage. Pharmacologically increasing the proportion of oxygenated HbS in RBCs may inhibit polymerization, prevent sickling and provide long term disease modification. We report that GBT440, a small molecule which binds to the N‐terminal α chain of Hb, increases HbS affinity for oxygen, delays in vitro HbS polymerization and prevents sickling of RBCs. Moreover, in a murine model of SCD, GBT440 extends the half‐life of RBCs, reduces reticulocyte counts and prevents ex vivo RBC sickling. Importantly, oral dosing of GBT440 in animals demonstrates suitability for once daily dosing in humans and a highly selective partitioning into RBCs, which is a key therapeutic safety attribute. Thus, GBT440 has the potential for clinical use as a disease‐modifying agent in sickle cell patients.     

Prevalence of Sickle Cell Disease in a Pediatric Population Suffering From Severe Infections: A Congolese Experience

Neonatal screening for sickle cell anemia is not a common practice in the Democratic Republic of Congo (DRC). Children with sickle cell disease are known to have an increased risk of infections. We conducted a pilot study to determine the prevalence of sickle cell anemia during episodes of severe infection. A prospective study was conducted from July 2009 to July 2011. The study sites included four public hospitals at Kinshasa, DRC. The study population was selected from the source population using three-stage sampling. A total of 247 children with severe infection were consecutively recruited and screened for sickle cell disease. There were 124 boys (50.2%) and 123 girls (49.8%) with a sex-ratio of 1:1. More than two-thirds of patients (66.0%) were children between 1 and 24 months of age. Among these 247 children, 19 (7.7%) were homozygous sickle cell anemia patients (Hb SS). No patient had received Hemophilus influenzae, streptococcus pneumoniae and salmonella sp vaccines. Sepsis was the most common form of severe infection observed in 44.5% of patients. A total of 19 (7.7%) positive blood cultures were recorded. Most cases were reported in sickle cell patients (15.8%) compared to 6.1% in children who were negative for Hb S [β6(A3)Glu→Val; HBB: c.20A>T] (p?>?0.05). Of 247 children with severe infection, approximately 8.0% carried unknown sickle cell anemia mutations. Based on the findings in this study, opportunistic testing for sickle cell anemia is possible and worthwhile in children who present with severe infection in DRC until neonatal screening is universal.     

Enhancing Effect of Hydroxyurea on Hb F in Sickle Cell Disease: Ten-Year Egyptian Experience

Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted. We studied the laboratory changes, frequency of VOCs per year, frequency of hospital admisions per year and number of transfusions per year, both before and after HU therapy. The follow-up period was 4 to 120 months. Hb F levels after HU therapy positively correlated with the duration of HU therapy, baseline Hb F levels and baseline total hemoglobin (Hb) (r?=?0.4, p?=?0.04; r?=?0.45, p?=?0.001; r?=?0.5, p?=?0.019, respectively) and inversely correlated with baseline total leucocyte count (r?=?–0.33, p?=?0.034). Hydroxyurea therapy was associated with an increase in the total Hb and mean corpuscular volume (MCV) (p?=?0.009, p?=?0.000; respectively) and with a decrease in total leucocyte count, platelet count and reticulocyte count (p?=?0.00, p?=?0.03, p?=?0.02, respectively). Moreover, a significant reduction in the frequency of VOCs, transfusion frequency and hospital admissions per year after HU therapy was shown in the studied subjects. Hydroxyurea induced an increase in Hb F level, which was maintained over time and was associated with clinical efficacy and acceptable safety.     

Phenotypic Diversity of Sickle Cell Disease in Patients with a Double Heterozygosity for Hb S and Hb D-Punjab

Phenotypic heterogeneity for sickle cell disease is associated to several genetic factors such as genotype for sickle cell disease, β-globin gene cluster haplotypes and Hb F levels. The coinheritance of Hb S (HBB: c.20A?>?T) and Hb D-Punjab (HBB: c.364G?>?C) results in a double heterozygosity, which constitutes one of the genotypic causes of sickle cell disease. This study aimed to assess the phenotypic diversity of sickle cell disease presented by carriers of the Hb S/Hb D-Punjab genotype and the Bantu [–?+?– – – –] haplotype. We evaluated medical records from 12 patients with sickle cell disease whose Hb S/Hb D-Punjab genotype and Bantu haplotype were confirmed by molecular analysis. Hb S and Hb D-Punjab levels were quantified by chromatographic analysis. Mean concentrations of Hb S and Hb D-Punjab were 44.8?±?2.3% and 43.3?±?1.8%, respectively. Painful crises were present in eight (66.7%) patients evaluated, representing the most common clinical event. Acute chest syndrome (ACS) was the second most prevalent manifestation, occurring in two individuals (16.7%). Three patients were asymptomatic, while another two exhibited greater diversity of severe clinical manifestations. Medical records here analyzed reported a significant clinical diversity in sickle cell disease ranging from the absence of symptoms to wide phenotypic variety. The sickle cell disease genotype, Bantu haplotype and hemoglobin (Hb) levels did not influence the clinical diversity. Thus, we concluded that the phenotypic variation in sickle cell disease was present within a specific genotype for disease regardless of the β-globin gene cluster haplotypes.     

Hb F Levels in Indian Sickle Cell Patients and Association with the HBB Locus Variant rs10128556 (C>T), and the HBG XmnI (Arab-Indian) Variant

The prevalence of sickle cell disease in India is very high. Hb F is one of the most powerful modulators of disease severity in sickle cell disease patients. It was traditionally thought that the disease is milder in Indian sickle cell disease patients predominantly due to the Arab-Indian haplotype characterized by the HBG XmnI [rs7482144 (G>A)] variant, which is associated with increased Hb F levels. In the current study, we investigated the Hb F levels in individuals with the rs10128556 (C>T) variant and also determined its linkage with the HBG XmnI variant. The present study was conducted on a cohort of 275 individuals, which consisted of 221 patients with sickle cell disease and 54 patients with sickle cell trait. Analysis of hemoglobin (Hb) fractions and variants was done on the high performance liquid chromatography (HPLC) system. Genotyping for rs10128556 was done by direct sequencing of the products. Mean Hb F levels in the sickle cell disease patients was 19.36?±?6.79. The genotypic frequencies for rs10128556 were 82.0% (TT), 16.7% (CT) and 1.3% (CC) for sickle cell disease patients. The minor C allele resulted in 52.0% decrease in Hb F levels when homozygous and 7.0% decrease when heterozygous. The rs10128556 single nucleotide polymorphism (SNP) was in strong but not complete linkage with the HBG XmnI variant. In conclusion, the study determined for the first time the frequency and association of rs10128556 in Indian sickle cell disease patients with Hb F. It also established that it was not in complete linkage with the HBG XmnI variant in this high risk population.     

The Risk of Potential Thromboembolic,Renal and Cardiac Complications of Sickle Cell Trait

Many complications of sickle cell trait have been well-established, but associations with additional disease states remain controversial. We conducted a retrospective cohort study to examine the frequency of receiving a diagnosis of thromboembolism, pulmonary embolism (PE), ischemic stroke, renal disease (acute, chronic), coronary artery disease (CAD) and congestive heart failure (CHF) in patients with sickle cell trait. A total of 13?964 adult African Americans registered in the Kaiser Permanente Northern California (KPNC) health system (Oakland, CA, USA), were included based on laboratory and diagnostic code data for the years 1995–2008: 2642 with sickle cell trait, 11?183 with normal hemoglobin (Hb) and 139 with sickle cell disease. Disease outcomes were obtained from coded diagnoses. The adjusted relative risk of PE and chronic kidney disease in sickle cell trait patients compared to patients with normal Hb were 1.37 [95% confidence interval (CI) 1.07–1.75] and 1.13 (95% CI 1.03–1.23), respectively. There were no other significant differences in the outcomes for sickle cell trait patients compared to patients with normal Hb.     

Insulin Secretion and Resistance in Normoglycemic Patients with Sickle Cell Disease

Diabetes mellitus has been described in chronic hemolytic anemias, but data are scarce regarding glucose metabolism in normoglycemic patients. To address this issue, we evaluated insulin sensitivity and secretion in patients with sickle cell disease (SCD) and normal oral glucose tolerance test (OGTT). Forty-five adult patients with homozygous sickle cell disease and Hb S/β-thalassemia (β-thal) (mean age 42.5?±?9.5?years) and 45 healthy individuals matched for age and body mass index (BMI) were included in the study. All participants underwent an oral glucose tolerance test (OGTT) after an overnight fast. All patients had normal OGTT. Fasting glucose values did not differ significantly between groups, however, fasting insulin levels were significantly lower in the patient group compared to the control group (5.1?±?2.7 μUI/mL vs. 11.3?±?6.6 μUI/mL, p?<0.005, respectively). Pancreatic β-cell insulin secretion index in the fasting state was significantly lower in patients with sickle cell disease compared with controls as assessed by calculations of the homeostatic model assessment for β-cell function (HOMA β%) (77.0 vs. 106.0%, respectively, p?<0.001), while HOMA insulin resistance (HOMA IR), was lower in the sickle cell disease patients, albeit not statistically significant (0.8 vs. 1.1, respectively, p?=?0.054). The HOMA β% was significantly correlated with ferritin levels (r?=?–526, p?<0.001) (negative correlation) and with 25-hydroxy (OH)-vitamin D levels (r?=?0.479, p?<0.001) (positive correlation), even when adjusted for serum ferritin levels. Normoglycemic patients with sickle cell disease demonstrated impaired β-cell function with reduced insulin secretion even before OGTT was impaired.     

Distinctive Mutation Spectrum of the HBB Gene in an Urban Eastern Indian Population

Hemoglobinopathies such as β-thalassemia (β-thal) and sickle cell anemia (or Hb S [β6(A3)Glu→Val]) impose a major health burden in the Indian population. To determine the frequencies of the HBB gene mutations in eastern Indian populations and to compare with the available data, a comprehensive molecular analysis of the HBB gene was done in the normal Odisha State population. Using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), amplification refractory mutation system (ARMS) and DNA sequencing techniques, β-thal and sickle cell anemia mutations were characterized in 267 healthy individuals. Entire HBB gene sequencing showed 63 different mutations including 11 new ones. The predominant mutation HBB: c.9T?>?C was observed at a high frequency (19.57%) in the normal population. In the urban population of Odisha State, India, carrier frequency of hemoglobinopathies was found to be 18.48%, and for β-thal, the carrier rate was 14.13%, which is very high indeed. In the absence of a complete cure by any expensive treatment and drug administration, this information would be helpful for planning a population screening program and establishing prenatal diagnosis of β-thal in order to reduce the burden of such a genetic disease.     

A new sickle cell disease phenotype associating Hb S trait,severe pyruvate kinase deficiency (PK Conakry), and an α2 globin gene variant (Hb Conakry)

A Guinean woman, hetererozygous for haemoglobin (Hb) S, was studied because of episodes of marked anaemia, repeated typical metaphyseal painful crises and haemosiderosis. Her sickling syndrome resulted from the association of Hb S trait with a severe pyruvate kinase deficiency leading to a 2,3-DPG concentration of twice normal levels. Sequence of the PK-R gene revealed an undescribed mutation in the homozygous or hemizygous state within exon 5 (nucleotide 2670 C → A), leading to the interchange of Ser 130 into Tyr (PK Conakry). In addition, the patient carried a new haemoglobin variant, Hb Conakry [α80(F1) Leu → Val], which seemed to have a mild effect. The high intraerythrocytic 2,3-DPG concentration induced by the PK deficiency resulted in a decreased oxygen affinity which favoured sickling to a level almost similar to that of Hb S/C compound heterozygous patients. This was confirmed by oxygen binding measurements of Hb A/Hb S erythrocytes in which 2,3-DPG content was modified in vitro. Hysteresis between deoxy- and reoxygenation curves, as well as increase in the n_max value, demonstrated that the extent of HbS polymerization in the propositus was almost the same as that of RBCs from a homozygous sickle cell patient or those of an A/S heterozygous patient with an artificial in vitro increase of 2,3-DPG concentration.     

Hemoglobin S Antilles: a variant with lower solubility than hemoglobin S and producing sickle cell disease in heterozygotes.

We have found a sickling variant, Hb S Antilles, alpha 2 beta 2(6 Glu----Val, 23 Val----Ile), that has the same electrophoretic mobility as Hb S but a distinct isoelectric focus and produces sickling in the carriers of the Hb A/S Antilles trait. The carriers' erythrocytes tend to sickle at O2 partial pressures similar to those that induce sickling in Hb S/C disease. Pure deoxy-Hb S Antilles is 50% as soluble as deoxy-Hb S (saturating concentration = 11 g X dl-1 compared to 18.4 for Hb S). Dilute solutions of pure Hb S Antilles have a lower oxygen affinity than those of Hb A or Hb S (partial pressure for 50% binding is 9 mm Hg compared to 5.5 mm Hg for Hb A or S at pH 7.00). A/S Antilles erythrocytes have a much lower oxygen affinity than A/S cells; this is further decreased in dense cells fractionated on a Percoll density gradient. Their oxygen equilibrium curves had anomalous shapes like those of S/S cells. Fiber formation in the erythrocytes of Hb S Antilles carriers is clearly due to its low solubility and oxygen affinity, showing that heterozygosity for this hemoglobin presents another sickle cell syndrome and suggesting that Hb S heterozygotes who exhibit symptoms of sickle cell disease should be carefully screened for double mutations.     

Distance from an Urban Sickle Cell Center and its Effects on Routine Healthcare Management and Rates of Hospitalization

The St. Jude Children’s Research Hospital (St. Jude) comprehensive sickle cell center serves a 150 mile catchment radius around Memphis, TN, USA. Full travel expenses are provided for routine and acute care visits for sickle cell disease patients living ≥35 miles from St. Jude. We compared hospitalization rates to national estimates and assessed if driving distance was a barrier to sickle cell healthcare despite the travel reimbursement policy. We evaluated the associations between hospitalizations and routine clinic visits and distance from St. Jude using negative binomial models and we conducted bias analyses by Monte Carlo simulation. We followed 545 patients (2550 patient-years) aged ≤18 years with sickle cell disease (Hb SS only) from 2007 to 2012. The hospitalization rate per patient-year was 0.65 [95% CI (confidence interval): 0.62, 0.68), significantly lower than the national rate of 1.16 (95% CI: 1.14, 1.18). Children living <35 miles from St. Jude had 1.75 (95% CI: 1.41, 2.17) times the rate of hospitalization and 1.22 (95% CI: 1.07, 1.39) times the rate of clinic visits compared to those ≥35 miles. Bias analysis suggested that under-reporting could explain the observed difference in hospitalization rates if 30.0% of patients who lived ≥35 miles from the hospital under-reported six hospitalizations over 6 years. The hospitalization rate at St. Jude in children with sickle cell disease was lower than expected from national rates. Greater distance from the sickle cell center (>35 miles) was associated with decreased hospitalization rates, despite the travel allowances that are provided for those who live ≥35 miles from the hospital.     

Prevalence of the βS Gene Among Scheduled Castes,Scheduled Tribes and Other Backward Class Groups in Central India

Sickle cell disease is an inherited disorder of the blood, and characterized by vasoocclusive crises (VOC), risks for pneumococcal infections and organ toxicities, is associated with morbidity and premature mortality. India, with a population of 1.2 billion individuals, is estimated to be home to over 50.0% of the world’s patients with sickle cell disease. The β^S gene [β6(A3)Glu→Val; HBB: c.20A>T] has the highest prevalence in three socio-economically disadvantaged ethnic categories: the Scheduled Castes (SC), the Scheduled Tribes (ST), and Other Backward Class (OBC) groups in India. The tradition of endogamy practiced by the ethnic groups in India provides the rationale for the screening of individual populations to better understand the distribution of the β^S gene, guide counseling and awareness programs and aid development of public policy. We undertook a study to describe the prevalence of the β^S gene in these ethnic groups in the district of Nagpur, Maharashtra in Central India. Through community screening and subsequent targeted screening of high risk individuals, 35,636 individuals were screened, of whom 5466 were found to have sickle cell trait and 1010 were identified with sickle cell disease. Community screening revealed a sickle cell trait prevalence of 13.0% in the SC, 12.0% in the ST and 3.4% in the OBC population. This study describes the prevalence of the β^S gene within these groups in Central India determined by large scale community screening. This program has uncovered previously undiagnosed cases, provided detailed information to guide population-based disease counseling, prevention and comprehensive care programs.     

Prevalence and Characteristics of Priapism in Sickle Cell Disease

Priapism is a pathological condition of persistent penile erection in the absence of sexual arousal or desire. It is an urological emergency and its identification is important as lack of prompt treatment can result in erectile dysfunction. The aim of this study was to estimate and describe the characteristics (number of episodes, duration, time of occurrence and evolution) of priapism in patients with sickle cell disease. A bibliographical research was carried out in PubMed, searching for papers published in the last 5 years. Thirteen scientific articles were included in this review. The main results were: 1) the highest prevalence of priapism in males reported was 48.0% and the lowest 0.67%; 2) six studies were carried out on the African Continent (46.1%), three in America (23.1%), two in Europe (15.4%) and two in Asia (15.4%); 3) the main goal of ～50.0% of the studies was to determine the rate of priapism in patients with sickle cell disease; 4) there was predominance of sickle cell anemia patients [homozygous Hb S (HBB: c.20A>T) genotype]; 5) the minimum age of patients with priapism was 7 years old and the maximum 30 years. In general, the episodes of priapism occurred during sleep, were recurrent and had variable duration. The prevalence of priapism are not real and the explanations include underreporting by patients, lack of awareness by physicians and lack of proper prospective studies. Priapism is a complication that deserves close attention due to its significant impact on the life of the patient with sickle cell disease and, therefore, should be further clarified.     

Genetic Modifiers of Sickle Cell Disease: A Genotype-Phenotype Relationship Study in a Cohort of 82 Children on Mayotte Island

Abstract

Sickle cell disease presents a great clinical variability that remains largely misunderstood. New disease protective genetic modifiers acting mainly through an increased Hb F level have recently been described. We studied relations between clinical and hematological phenotypes and known sickle cell disease genetic modifiers in patients from Mayotte Island, a remote French territory located in the Indian Ocean. Eighty-two children with sickle cell disease were enrolled; their median age was 5.9 years (range 1-18). Clinical and hematological features of sickle cell disease were retrospectively collected. Genetic studies included determination of β-globin genotypes [Hb SS, Hb S-β⁰-thalassemia (Hb S-β⁰-thal), Hb S-β⁺-thal], β^S-globin locus haplotype, α-thalassemia (α-thal), and single nucleotide polymorphisms (SNPs) located in quantitative trait loci for Hb F expression (XmnI polymorphism, BCL11A rs4671393 and rs11886868, intergenic region of HBS1L-MYB rs28384513, rs4895441 and rs9399137). Univariate and multivariate analyses were conducted. Twenty-eight percent of the patients had Hb S-β-thal (eight different mutations in 21 patients), 55.0% had the ?α^3.7 (rightward) deletion and 88.0% of the homozygous Hb SS patients were carrying a homozygous Bantu haplotype. In the multivariate model, the prognosis role of the SNP BCL11A rs4671393 was confirmed in the studied population showing a significant association with an elevated Hb F level and with a low hospitalization rate. The ?α^3.7 deletion, XmnI polymorphism and intergenic region HBS1L-MYB SNPs were not significantly linked to any clinical criteria of severity. This report, the first to describe the main features of children with sickle cell disease on Mayotte Island, highlights the protective effect of the BCL11A polymorphism in this population.     

The super sickling haemoglobin HbS‐Oman: a study of red cell sickling,K+ permeability and associations with disease severity in patients heterozygous for HbA and HbS‐Oman (HbA/S‐Oman genotype)

Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K⁺ permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S‐Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K⁺ was markedly abnormal with elevated activities of P_sickle, Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca²⁺ entry and Mg²⁺ loss via P_sickle stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K⁺ transporters also correlated with the level of HbS‐Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS‐Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S‐Oman genotype.     

Coil embolization of cerebral aneurysms in patients with sickling disorders

In patients with sickle cell disease cerebral aneurysm formation is thought to be a complication of recurrent red cell sickling, and multiple aneurysms have been reported in these patients. Management of patients with suspected cerebral aneurysm has traditionally involved cerebral vessel angiography followed by craniotomy and aneurysmal clipping. In patients without sickle cell disease, non-operative intervention in the form of endovascular coil embolization is increasingly being used to ablate aneurysms, but has not thus far been reported in patients with sickle cell disease. We report two patients with sickling disorders who have undergone coil embolization of cerebral aneurysms with good functional and radiological outcomes. These patients illustrate that endovascular coiling is useful in the treatment of cerebral aneurysms associated with sickling disorders, although, as with surgical intervention, preparation with exchange transfusion is appropriate.     

Preliminary Evaluation of a Point-of-Care Testing Device (SickleSCAN™) in Screening for Sickle Cell Disease

Sickle cell disease affects about 150,000 births annually in Nigeria. Early diagnosis is hampered by factors such as centralized and urban localization of laboratories, high cost of diagnostic equipment and inadequate skilled manpower to operate them. The need for a low-cost, portable, easy-to-use diagnostic test for sickle cell disease is critical, especially in resource-poor countries. In this study, we evaluated the performance characteristics of a novel point-of-care testing device (SickleSCAN?), and its acceptability and feasibility, as a possible screening tool for sickle cell disease. In the first phase, we assessed the performance characteristics of SickleSCAN? by evaluating 57 subjects comprising both children and adults attending a primary health center, for Hb SS (β^S/β^S; HBB: c.20A>T), Hb SC (β^S/β^C; HBB: c.19G>A) and Hb AS (β^A/β^S) using SickleSCAN?, cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC). Performance characteristics such as diagnostic sensitivity and specificity were compared to HPLC as a standard method. We subsequently undertook a second phase wherein the acceptability and feasibility of the device for sickle cell disease screening, was evaluated using semi-structured and structured questionnaires among 197 healthcare personnel and 221 subjects, respectively. Sickle cell disease was carried by 3.4% of the subjects. The diagnostic sensitivity, specificity and test efficiency of SickleSCAN? for sickle cell disease (Hb SS and Hb SC), were 100.0, 98.2 and 98.2%, respectively. Findings from this study showed SickleSCAN? to be a viable screening tool that can easily be applied in community-based screening for early diagnosis of sickle cell disease with little expertise and low cost.     

Clinical correlates of steady-state oxyhaemoglobin desaturation in children who have sickle cell disease

Individuals with sickle cell disease (SCD) may have oxyhaemoglobin desaturation during the steady-state, the causes of which are incompletely known. We studied a cohort of 585 children who have sickle cell anaemia (SS), sickle beta0-thalassaemia (Sbeta0), sickle-haemoglobin C disease (SC), or sickle beta+-thalassaemia (Sbeta+) to determine the relationships between steady-state oxyhaemoglobin saturation (SpO2) and SCD genotype, age, gender, steady-state haemoglobin (Hb) and reticulocyte count, and rate of acute chest syndrome (ACS). The SS/Sbeta0 group (n = 390) had lower mean SpO2 than the SC/Sbeta+ group (n = 195) (96.3% vs. 98.7%, P < 0.001). Among SS/Sbeta0 subjects, a decrease in steady-state SpO2 correlated with a decrease in Hb, an increase in reticulocytes, older age and male gender. These correlations were not found in the SC/Sbeta+ group. Prior ACS did not correlate with steady-state SpO2. A multivariate model explained 45% of the variability in SpO2, but only 5% of the variation in SpO2 was explained by Hb. We conclude that steady-state desaturation is common in individuals with SCD, but it appears to be unrelated to prior episodes of ACS and largely unexplained by chronic anaemia.