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Sickle Cell Disease (sickle + cell_disease)
Terms modified by Sickle Cell Disease Selected AbstractsSICKLE CELL DISEASE: ROLE OF REACTIVE OXYGEN AND NITROGEN METABOLITESCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2007Katherine C Wood SUMMARY 1Sickle cell disease (SCD) is an inherited disorder of haemoglobin synthesis that is associated with significant morbidity and mortality due to sequelae of episodic vaso-occlusive events: pain crises and multiorgan damage. The microvascular responses to the initiation, progression and resolution of vaso-occlusive events are consistent with an inflammatory phenotype as suggested by activation of multiple cell types, an oxidatively stressed environment and endothelial cell dysfunction. 2Decreased anti-oxidant defences in SCD patients and mice are accompanied by activation of enzymatic (NADPH oxidase, xanthine oxidase) and non-enzymatic (sickle haemoglobin auto-oxidation) sources of reactive oxygen species. The resultant oxidative stress leads to dysfunction/activation of arteriolar and venular endothelial cells, resulting in impaired vasomotor function and blood cell,endothelial cell adhesion. 3Changes in substrate and cofactor availability for endothelial cell nitric oxide synthase may underlie reactive oxygen- and nitrogen-induced events that contribute to SCD-induced vasculopathy. 4The emerging role of reactive oxygen and nitrogen species in the pathogenesis of SCD provides a platform for the development of novel agents to treat this painful and lethal disease. [source] Hospital admissions for acute painful crisis in Trinidad and Tobago.INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2006Are the British Committee for Standards in Haematology (BCSH) guidelines applicable? Summary We observed consecutive hospital admissions for acute painful crisis (APC) among adults with Sickle Cell Disease (SCD) over a 6-month period in Trinidad and Tobago. Episodes (111) of APC resulted in 82 admissions of 59 patients. The most common site for pain was the trunk. Patients ranged in age from 17 to 53 years (median: 25). Median length of hospital stay was 4 days. Total dose of Pethidine given per admission ranged from 100 to 1650 mg (median: 525). The mean dose of morphine was 70 mg. Six (7%) of patients were readmitted within 10 days of discharge. Twenty-five (30%) of patients had chest pain at presentation of whom 10 (12%) had consolidation on chest X-ray, defining the acute chest syndrome (ACS). There was one death caused by biliary sepsis. The study revealed seemingly low opiate usage for in-hospital treatment of APC with acceptable rates of readmission. The BCSH 2003 guidelines seemed applicable apart for the choice and route of fluid for rehydration and opiate analgesia. [source] Stroke Prevention in Sickle Cell Disease (STOP) Study Guidelines for Transcranial Doppler TestingJOURNAL OF NEUROIMAGING, Issue 4 2001Fenwick T. Nichols MD ABSTRACT The Stroke Prevention in Sickle Cell Disease (STOP) trial used transcranial Doppler (TCD) to screen children with sickle cell disease with no history of stroke. Children (who consented) who had time-averaged mean of the maximum (TAMM) velocities in the middle cerebral artery and/or distal internal carotid artery were randomized to transfusion or standard. Over a slightly more than 20-month average follow-up, there were 11 strokes in the standard care arm and 1 stroke in the transfusion arm. This study has caused a great deal of interest in using TCD to screen children with sickle cell disease. For the STOP TCD data to be applied appropriately, it is necessary for users of TCD to understand how the STOP TCD examinations were performed, how the TCD velocities were measured, and which velocities were used. This article will review the STOP TCD scanning protocol and the reading protocol and review the TAMM velocity and how it differs from other velocity measurements. [source] Sickle Cell Disease: Health Promotion and Maintenance and the Role of Primary Care Nurse PractitionersJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 9 2003APRN-BC, FNP-C, Ruth A. Tanyi BSJ Purpose To discuss the role of nurse practitioners (NPs) with regard to early identification of affected individuals, effective monitoring and screening, effective pain management and prophylaxis, and health education for patients with sickle cell disease (SCD). Data Sources Electronic database searches were performed using Medline, Cinahl, and PsycINFO. Data were obtained from medical textbooks, research, and review articles. Conclusions SCD is a chronic inherited disease belonging to a group of conditions called hemo-globinopathies. Individuals with SCD often require close medical care from specialists. Nonetheless, NPs are in ideal positions to facilitate the health promotion and health maintenance necessary to decrease the high rate of morbidity and mortality associated with this disease. Implications for Practice NPs must understand the importance of early identification of affected individuals, effective monitoring and screening, effective pain treatment, and prophylaxis. The unpredictable trajectory of SCD can lead to frustration, fear, helplessness, hopelessness, and emotional distress. Ineffective pain management is a major problem for people with SCD. NPs can overcome this problem by initiating effective and prompt pain management in a nonjudgmental manner. [source] Polymerization and Sickle Cell Disease: A Molecular ViewMICROCIRCULATION, Issue 2 2004FRANK A. FERRONE ABSTRACT The present molecular-level understanding of polymerization and sickling is reviewed for 2 central questions in sickle hemoglobin pathophysiology, viz., what determines when cells sickle, and what determines when cells get stuck. The description of sickling includes the central aspects of the double nucleation mechanism, as well as recent results on the effects of crowding, with an emphasis on the physiological applicability of this fundamental knowledge. In considering when cells get stuck, new measurements of individual fiber stiffness and the processes of depolymerization are also considered. Finally, a fundamental connection is shown between thermodynamics and rheology. [source] Managing Genetic Information in Families of Children with Sickle Cell DiseaseNURSING & HEALTH SCIENCES, Issue 3 2007Agatha Gallo [source] Third Annual Sickle Cell Disease Research and Educational Symposium and Grant Writing Institute and Annual National Sickle Cell Disease Scientific MeetingAMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Article first published online: 17 JUN 200 First page of article [source] UGT1A1 promoter polymorphisms and the development of hyperbilirubinemia and gallbladder disease in children with sickle cell anemiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2008Shannon L. Carpenter Genetic modifiers contribute to phenotypic variability in patients with sickle cell anemia (SCA). The influence of the bilirubin UDP-glucuronosyltransferase (UGT) 1A1 (TA)nTAA promoter polymorphism on bilirubin levels and gallbladder disease in SCA was examined using prospectively collected data from the Cooperative Study of Sickle Cell Disease. A total of 324 children with HbSS (median age 6.9 years) had UGT1A1 genotyping; 243 (75%) had common (TA)6 or (TA)7 alleles, whereas 81 (25.0%) had variant (TA)5 or (TA)8 alleles. The UGT1A1 genotype significantly influenced average bilirubin levels for the common alleles: 6/6 genotype = 2.36 ± 1.13 mg/dL, 6/7 genotype = 2.90 ± 1.54 mg/dL, and 7/7 genotype = 4.24 ± 2.11 mg/dL (P < 0.0001). Thirty-nine percent of children with the 7/7 genotype had documented gallbladder disease, compared with 18.2% with the 6/7 genotype and only 9.9% with the wildtype 6/6 UGT1A1 genotype (P = 0.001). To analyze the (TA)5 and (TA)8 variant alleles, three groups were generated, showing increasing bilirubin levels with increasing TA repeats and age. Group 3 (genotypes 6/8, 7/7, and 7/8) had a significantly greater rate of bilirubin change than Groups 1 (genotypes 5/6, 5/7, and 6/6) or 2 (genotype 6/7). These results validate previous smaller studies and confirm that the UGT1A1 promoter polymorphism exerts a powerful influence on bilirubin levels and the development of gallbladder disease in children with SCA. UGT1A1 genotyping should be considered as a screening tool for predicting children most likely to develop gallbladder disease at a young age. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] Emergency Department Management of Acute Pain Episodes in Sickle Cell DiseaseACADEMIC EMERGENCY MEDICINE, Issue 5 2007Paula Tanabe PhD ObjectivesTo characterize the initial management of patients with sickle cell disease and an acute pain episode, to compare these practices with the American Pain Society Guideline for the Management of Acute and Chronic Pain in Sickle-Cell Disease in the emergency department, and to identify factors associated with a delay in receiving an initial analgesic. MethodsThis was a multicenter retrospective design. Consecutive patients with an emergency department visit in 2004 for an acute pain episode related to sickle cell disease were included. Exclusion criteria included age younger than 18 years. A structured medical record review was used to abstract data, including the following outcome variables: analgesic agent and dose, route, and time to administration of initial analgesic. Additional variables included demographics, triage level, intravenous access, and study site. Mann,Whitney U test or Kruskal,Wallis test and multivariate regression were used to identify differences in time to receiving an initial analgesic between groups. ResultsThere were 612 patient visits, with 159 unique patients. Median time to administration of an initial analgesic was 90 minutes (25th to 75th interquartile range, 54,159 minutes). During 87% of visits, patients received the recommended agent (morphine or hydromorphone); 92% received the recommended dose, and 55% received the drug by the recommended route (intravenously or subcutaneously). Longer times to administration occurred in female patients (mean difference, 21 minutes; 95% confidence interval = 7 to 36 minutes; p = 0.003) and patients assigned triage level 3, 4, or 5 versus 1 or 2 (mean difference, 45 minutes; 95% confidence interval = 29 to 61 minutes; p = 0.00). Patients from study sites 1 and 2 also experienced longer delays. ConclusionsPatients with an acute painful episode related to sickle cell disease experienced significant delays to administration of an initial analgesic. [source] ,-Globin gene cluster haplotypes and HbF levels are not the only modulators of sickle cell disease in LebanonEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2003A. Inati Abstract: Sickle cell disease (SCD) is an inherited autosomal recessive disorder of the , -globin chain. Despite the fact that all subjects with SCD have the same single base pair mutation, the severity of the clinical and hematological manifestations is extremely variable. This study examined for the first time in Lebanon the correlation between the clinical manifestation of SCD and the , -globin gene haplotypes. The haplotypes of 50 patients diagnosed with SCD were determined using polymerase chain reaction amplification of fragments containing nine polymorphic restriction sites around and within the ,,G,,A,,,,,,,, -globin gene complex. Most reported haplotypes were found in our population with the Benin haplotype as the most prevalent one. When the patients were divided according to their HbF levels into three groups (Group A: HbF < 5%, Group B: HbF between 5 and 15%, and Group C: HbF > 15%), surprisingly, the highest levels of HbF were associated with the most severe clinical cases. Our findings suggest that fetal hemoglobin levels are important but not the only parameters that affect the severity of the disease. In addition, the high levels of HbF in patients with CAR haplotypes did not seem to ameliorate the severity of symptoms, suggesting that genetic factors other than haplotypes are the major determinants of increased HbF levels in Lebanon. [source] Sickle Cell Trait Mimicking Multiple Inflicted Injuries in a 5-Year-Old BoyJOURNAL OF FORENSIC SCIENCES, Issue 5 2009Charis Kepron M.D. Abstract:, Sickle cell disease (SCD) and sickle cell trait (SCT) can be associated with sudden unexpected death in the pediatric population, usually due to pulmonary complications occurring within the acute chest syndrome (ACS). Musculoskeletal complications can occur and are classically limited to bone infarcts. The occurrence of bone pathology centered upon the epiphyseal growth plate in SCD/SCT is extremely rare, and multiple such injuries in a single patient have not been previously reported. Herein, we describe a case of sudden unexpected death in a 5-year-old child with undiagnosed SCT due to the ACS, with widespread epiphyseal and periosteal bone lesions mimicking multiple inflicted injuries at autopsy. This case highlights the importance of clinicopathological correlation and is the first to describe SCT pathology as a mimic of nonaccidental injury. [source] Sickle cell disease in the United States: Looking back and forward at 100 years of progress in management and survival,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Hari Prabhakar The past 100 years since James Herrick's first description of sickle cell disease in the United States have been characterized by the gradual development of management strategies. We review the progress in sickle cell disease management in the United States over the past 100 years, with emphasis on the diverse forces surrounding advances in disease management. Mortality and survival data are presented chronologically, with an attempt to highlight improvements in survival associated with specific advancements for pediatric and adult care. Finally, the future course for sickle cell disease management is explored, given the continued work in advancing the field. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] Definitions of the phenotypic manifestations of sickle cell disease,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Samir K. Ballas Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD (,100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This article provides an overview of the process and describes 12 body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype,phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood, and new diagnostic options are developed. Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc. [source] Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell diseaseAMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Courtney D. Fitzhugh Sickle cell disease (SCD) is associated with early mortality. We sought to determine the incidence, cause, and risk factors for death in an adult population of patients with SCD. All patients aged ,18 years seen at the Adult Sickle Cell Center at Duke University Medical Center between January 2000 and April 2005 were enrolled. Forty-three patients (21 males and 22 females) died during the study period. The median age of survival was 39 years for females (95% CI: 34,56), 40 years for males (95% CI: 34,48), and 40 years overall (95% CI: 35,48). Cardiac causes of death accounted for 25.6% (11/43 patients); pulmonary, 14.0% (six patients); other SCD related, 32.6% (14 patients); unknown, 14.0% (six patients); and others, 14.0% (six patients). Pulseless electrical activity arrest, pulmonary emboli, multiorgan failure, and stroke were the most frequent causes of death. Among the deceased patients, the most common premorbid conditions were cardiopulmonary: acute chest syndrome/pneumonia (58.1%), Pulmonary hypertension (pHTN; 41.9%), systemic HTN (25.6%), congestive heart failure (25.6%), myocardial infarction (20.9%), and arrhythmias (14.0%). Tricuspid regurgitant jet velocity was significantly higher (3.1 m/sec vs. 2.6 m/sec, P < 0.001) and hemoglobin significantly lower (8.3 g/dL vs. 9.2 g/dL, P < 0.05) in deceased patients when compared with patients who lived, respectively. With improved preventive and therapeutic advances, including hydroxyurea therapy, acute complications such as infection are no longer the leading cause of death; instead, causes of death and premorbid conditions are shifting to chronic cardiopulmonary complications. Further, arrhythmia leading to premature death is under-recognized in SCD and warrants further investigation. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Anaesthetic management of the child with sickle cell diseasePEDIATRIC ANESTHESIA, Issue 6 2003FRCA, Warwick A. Marchant BSc Summary Sickle cell disease (SCD) is a relatively common inherited disorder of haemoglobin with significant morbidity and mortality. This review describes the epidemiology and pathophysiology of the disease, and discusses the clinical manifestations found in children with SCD. A discussion of the evidence concerning the perioperative management of such children is presented. [source] Sickle cell disease caused by heterozygosity for Hb S and novel LCR deletion: Report of two patients,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2009Sara C. Koenig First page of article [source] Sickle liver disease,An unusual presentation in a compound heterozygote for HbS and a novel ,-thalassemia mutationAMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2007Timothy J.S. Cross A 38-year-old Ghanaian man presented with a 6-month history of worsening pruritus, jaundice, and ascites. He was previously fit and well and rarely drank alcohol. Screening tests for chronic liver disease including viral, autoimmune, and other metabolic causes including iron overload were unremarkable. A liver biopsy performed at the referring hospital demonstrated intralobular cholestasis and cirrhosis. He was listed for liver transplantation but subsequently developed sepsis with multiple organ failure and died. The sickle solubility test was positive. Blood smear showed cells consistent with liver failure and no sickle cells. Hemoglobin electrophoresis revealed HbA2 2.8%, HbF 0.5%, and HbS greater than HbA (49.6% vs. 41.3%) in the absence of blood transfusion. Sequence analysis of the ,IVS2-844 C , A). A diagnosis of sickle hepatopathy causing decompensated cirrhosis was made. This case is unusual insomuch as this patient was asymptomatic for over 35 years and represents a novel presentation of sickle cell disease. Sickle cell disease should be considered in appropriate patients when unusual presentations of liver disease arise. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Sickle cell disease and electroencephalogram hyperventilationANNALS OF NEUROLOGY, Issue 1 2006Mara Prengler MD No abstract is available for this article. [source] Inhibition of caspase-dependent spontaneous apoptosis via a cAMP-protein kinase A dependent pathway in neutrophils from sickle cell disease patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2007Nicola Conran Summary Sickle cell disease (SCD) is a chronic inflammatory condition characterized by high leucocyte counts, altered cytokine levels and endothelial cell injury. As the removal of inflammatory cells by apoptosis is fundamental for the resolution of inflammation, we aimed to determine whether the leucocyte apoptotic process is altered in SCD. Neutrophils from SCD individuals showed an inhibition of spontaneous apoptosis when cultured in vitro, in the presence of autologous serum for 20 h. Intracellular cyclic adenosine monophosphate (cAMP) levels were approximately twofold increased in SCD neutrophils; possible cAMP-upregulating factors present in SCD serum include interleukin-8, granulocyte-macrophage colony-stimulating factor and prostaglandin. Accordingly, co-incubation of SCD neutrophils with KT5720, a cAMP-dependent protein kinase (PKA) inhibitor, abrogated increased SCD neutrophil survival. Caspase-3 activity was also significantly diminished in SCD neutrophils cultured for 16 h and this activity was restored when cells were co-incubated with KT5720. BIRC2 (encoding cellular inhibitor of apoptosis protein 1, cIAP1), MCL1 and BAX expression were unaltered in SCD neutrophils; however, BIRC3 (encoding the caspase inhibitor, cIAP2), was expressed at significantly higher levels. Thus, we report an inhibition of spontaneous SCD neutrophil apoptosis that appears to be mediated by upregulated cAMP-PKA signalling and decreased caspase activity. Increased neutrophil survival may have significant consequences in SCD; contributing to leucocytosis, tissue damage and exacerbation of the chronic inflammatory state. [source] Childhood stroke in Eastern Province, KSA: pattern, risk factors, diagnosis and outcomeACTA PAEDIATRICA, Issue 10 2009Abdelhady Taha Emam Abstract Background and purpose:, Stroke has been increasingly recognized in children in recent years, but diagnosis and management can be difficult because of the diversity of underlying risk factors, atypical presentation and the absence of a uniform treatment approach. The aim of this study was to examine risk factors, clinical presentation, imaging findings and outcomes of paediatric stroke in Eastern Province, Kingdom of Saudi Arabia (KSA). Subjects and methods:, We evaluated 25 patients (11 boys and 14 girls) using computerized tomography scan of the brain, magnetic resonance (MR) imaging and MR angiography. Cardiac assessment, haematological tests, immunological tests, infection and metabolic screening were also performed in the patients. After discharge, the patients were monitored regularly in the neurology clinic to detect their outcomes. Results:, A total of 76% of the patients presented with ischaemic stroke, while the remaining 24% had haemorrhagic stroke. Sickle cell disease (SCD) was the commonest risk factor for stroke (36%) followed by non determinate causes (20%). Seizure was the commonest clinical presentation (54%) followed by haemiplegia (31%) and decreased level of consciousness (30%). Recurrence occurred in SCD patients (80%) and patients with moyamoya disease (20%). Regarding the outcome, long-term deficit was the commonest (44%), while short-term deficit and death were equal (28% each). Conclusion:, Our study in Eastern Province, KSA, showed agreement with other studies regarding risk factors, clinical presentation, imaging features and outcomes of stroke in children, yet with some points of differences, which are as follows: (1) SCD is the commonest risk factor in our study population, while in Chinese study it was not, (2) The percentage of cardiac disorders as a risk factor in this study was less than that in the European and American studies, and (3) there was relative discrepancy regarding predictors of outcome. [source] Universal newborn screening and adverse medical outcomes: A historical noteDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2006Jeffrey P. Brosco Abstract Universal newborn screening programs for metabolic disorders are typically described as a triumph of medicine and public policy in the US over the last 50 years. Advances in science and technology, including the Human Genome Project, offer the opportunity to expand universal newborn screening programs to include many additional metabolic and genetic conditions. Although the benefits of such screening programs appear to outweigh their costs, some critics have claimed that historical examples of inadvertent harm ensuing from false-positive screening results and subsequent inappropriate medical treatment should make us wary of expanding universal newborn screening. In this essay, we report the results of a review of the published literature to assess whether the extension of screening from at risk populations to all newborns led to substantial morbidity and mortality from misguided medical treatment. We provide a historical overview of universal newborn screening programs in the United States, and then focus on six early NBS programs: congenital hypothyroidism, phenylketonuria, congenital adrenal hyperplasia, galactosemia, sickle cell disease, and maple syrup urine disease. Our comprehensive search of published sources did not reveal a widespread problem of harm ensuing from medical treatment of children with false positive screening test results. © 2006 Wiley-Liss, Inc. MRDD Research Reviews 2006;12:262,269. [source] Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease: potential role of soluble fms-like tyrosine kinase-1EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Kenneth I. Ataga Abstract Background:, Pulmonary hypertension (PHT) is reported to be associated with measures of renal function in patients with sickle cell disease (SCD). The purpose of this exploratory study was to determine the relationship between albuminuria and both clinical and laboratory variables in SCD. Design and methods:, This cross-sectional study was performed using a cohort of adult patients with SCD and control subjects without SCD. Spot urine for microalbumin/creatinine ratio, measures of hemolysis, inflammation and other laboratory studies were obtained. Pulmonary artery systolic pressure was determined by Doppler echocardiography, and the diagnosis of PHT was defined using age-, sex- and body mass index-adjusted reference ranges. Results:, Seventy-three patients with SCD and 21 healthy, race-matched control subjects were evaluated. In patients with SCD, normoalbuminuria was observed in 34 patients (46.6%), microalbuminuria in 24 patients (32.9%) and macroalbuminuria in 15 patients (20.5%). There was a significant correlation between urine albumin excretion and age. In patients with HbSS and S,0 thalassemia, the levels of sFLT-1, soluble VCAM and NT pro-BNP were significantly higher in those with macroalbuminuria, compared to patients with microalbuminuria and normoalbuminura, but no significant differences were observed in the levels of laboratory measures of hemolysis. Urine albumin excretion was associated with PHT and a history of stroke. Conclusions:, Our study confirms the high prevalence of albuminuria in SCD. The association of urine albumin excretion with sFLT-1 suggests that this vascular endothelial growth factor receptor family member may contribute to the development of albuminuria in SCD. By inducing endothelial activation and endothelial dysfunction, sFLT-1 appears to be a link between glomerulopathy and PHT in SCD. [source] Role for cAMP-protein kinase A signalling in augmented neutrophil adhesion and chemotaxis in sickle cell diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2007Andreia A. Canalli Abstract The significance of the leukocyte in sickle cell disease (SCD) pathophysiology is becoming increasingly recognised; we sought to examine whether the chemotactic properties of neutrophils of SCD individuals may be altered and, further, to better understand the signalling events that mediate altered SCD neutrophil function. Adhesion to immobilised fibronectin (FN) and chemotaxis of control and SCD neutrophils were assessed using in vitro static adhesion assays and 96-well chemotaxis chamber assays. Adhesion assays confirmed a significantly higher basal adhesion of SCD neutrophils to FN, compared with control neutrophils. Chemotaxis assays established, for the first time, that SCD neutrophils demonstrate greater spontaneous migration and, also, augmented migration in response to IL-8, when compared with control neutrophils. Co-incubation of SCD neutrophils with KT5720 (an inhibitor of PKA) abrogated increased basal SCD neutrophil adhesion, spontaneous chemotaxis and IL-8-stimulated chemotaxis. Stimulation of SCD neutrophils with IL-8 also significantly augmented SCD neutrophil adhesion to FN with a concomitant increase in cAMP levels and this increase in adhesion was abolished by KT5720. Interestingly, the adhesive properties of neutrophils from SCD individuals on hydroxyurea therapy were not significantly altered and results indicate that a reduction in intracellular cAMP may contribute to lower the adhesive properties of these cells. Data indicate that up-regulated cAMP signalling plays a significant role in the altered adhesive and migratory properties in SCD neutrophils. Such alterations may have important implications for the pathophysiology of the disease and the cAMP-PKA pathway may represent a therapeutic target for the abrogation of altered leukocyte function. [source] Optical tweezers for measuring red blood cell elasticity: application to the study of drug response in sickle cell diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2003M. M. Brandão Abstract: The deformability of erythrocytes is a critical determinant of blood flow in microcirculation. By capturing red blood cells (RBC) with optical tweezers and dragging them through a viscous fluid we were able to measure their overall elasticity. We measured, and compared, the RBC deformability of 15 homozygous patients (HbSS) including five patients taking hydroxyurea (HU) for at least 6 months (HbSS/HU), 10 subjects with sickle cell trait (HbAS) and 35 normal controls. Our results showed that the RBC deformability was significantly lower in haemoglobin S (HbS) subjects (HbSS and HbAS), except for HbSS/HU cells, whose deformability was similar to the normal controls. Our data showed that the laser optical tweezers technique is able to detect differences in HbS RBC from subjects taking HU, and to differentiate RBC from normal controls and HbAS, indicating that this is a very sensitive method and can be applied for detection of drug-response in sickle cell disease. [source] ,-Globin gene cluster haplotypes and HbF levels are not the only modulators of sickle cell disease in LebanonEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2003A. Inati Abstract: Sickle cell disease (SCD) is an inherited autosomal recessive disorder of the , -globin chain. Despite the fact that all subjects with SCD have the same single base pair mutation, the severity of the clinical and hematological manifestations is extremely variable. This study examined for the first time in Lebanon the correlation between the clinical manifestation of SCD and the , -globin gene haplotypes. The haplotypes of 50 patients diagnosed with SCD were determined using polymerase chain reaction amplification of fragments containing nine polymorphic restriction sites around and within the ,,G,,A,,,,,,,, -globin gene complex. Most reported haplotypes were found in our population with the Benin haplotype as the most prevalent one. When the patients were divided according to their HbF levels into three groups (Group A: HbF < 5%, Group B: HbF between 5 and 15%, and Group C: HbF > 15%), surprisingly, the highest levels of HbF were associated with the most severe clinical cases. Our findings suggest that fetal hemoglobin levels are important but not the only parameters that affect the severity of the disease. In addition, the high levels of HbF in patients with CAR haplotypes did not seem to ameliorate the severity of symptoms, suggesting that genetic factors other than haplotypes are the major determinants of increased HbF levels in Lebanon. [source] A brief haemophilia pain coping questionnaireHAEMOPHILIA, Issue 5 2008J. ELANDER Summary., Pain coping strategies are important influences on outcomes among people with painful chronic conditions. The pain coping strategies questionnaire (CSQ) was previously adapted for sickle cell disease and haemophilia, but those versions have 80 items, and a briefer version with similar psychometric properties would facilitate research on pain coping. The full-length haemophilia-adapted CSQ, plus measures of pain frequency and intensity, pain acceptance, pain readiness to change, and health-related quality of life were completed by 190 men with haemophilia. Items were selected for a 27-item short form, which was completed 6 months later by 129 (68%) participants. Factor structure, reliability and concurrent validity were the same in the long and short forms. For the short form, internal reliabilities of the three composite scales were 0.86 for negative thoughts, 0.80 for active coping and 0.76 for passive adherence. Test,retest reliabilities were 0.73 for negative thoughts, 0.70 for active coping and 0.64 for passive adherence. Negative thoughts were associated with less readiness to change, less acceptance of pain and more impaired health-related quality of life, whereas active coping was associated with greater readiness to change and more acceptance of pain. The short form is a convenient brief measure of pain coping with good psychometric properties, and could be used to extend research on pain coping in haemophilia. [source] Adult Emergency Department Patients with Sickle Cell Pain Crisis: A Learning Collaborative Model to Improve Analgesic ManagementACADEMIC EMERGENCY MEDICINE, Issue 4 2010Paula Tanabe PhD Abstract Objectives:, The objectives were to report the baseline (prior to quality improvement interventions) patient and visit characteristics and analgesic management practices for each site participating in an emergency department (ED) sickle cell learning collaborative. Methods:, A prospective, multisite longitudinal cohort study in the context of a learning-collaborative model was performed in three midwestern EDs. Each site formed a multidisciplinary team charged with improving analgesic management for patients with sickle cell disease (SCD). Each team developed a nurse-initiated analgesic protocol for SCD patients (implemented after a baseline data collection period of 3.5 months at one site and 10 months at the other two sites). All sites prospectively enrolled adults with an acute pain crisis and SCD. All medical records for patients meeting study criteria were reviewed. Demographic, health services, and analgesic management data were abstracted, including ED visit frequency data, ED disposition, arrival and discharge pain score, and name and route of initial analgesic administered. Ten interviews per quarter per site were conducted with patients within 14 days of their ED discharge, and subjects were queried about the highest level of pain acceptable at discharge. The primary outcome variable was the time to initial analgesic administration. Variable data were described as means and standard deviations (SDs) or medians and interquartile ranges (IQR) for nonnormal data. Results:, A total of 155 patients met study criteria (median age = 32 years, IQR = 24,40 years) with a total of 701 ED visits. Eighty-six interviews were conducted. Most patients (71.6%) had between one and three visits to the ED during the study period. However, after removing Site 3 from the analysis because of the short data enrollment period (3.5 months), which influenced the mean number of visits for the entire cohort, 52% of patients had between one and three ED visits over 10 months, 21% had four to nine visits, and 27% had between 10 and 67 visits. Fifty-nine percent of patients were discharged home. The median time to initial analgesic for the cohort was 74 minutes (IQR = 48,135 minutes). Differences between choice of analgesic agent and route selected were evident between sites. For the cohort, 680 initial analgesic doses were given (morphine sulfate, 42%; hydromorphone, 46%; meperidine, 4%; morphine sulfate and ibuprofen or ketorolac, 7%) using the following routes: oral (2%), intravenous (67%), subcutaneous (3%), and intramuscular (28%). Patients reported a significantly lower targeted discharge pain score (mean ± SD = 4.19 ± 1.18) compared to the actual documented discharge pain score within 45 minutes of discharge (mean ± SD = 5.77 ± 2.45; mean difference = 1.58, 95% confidence interval = .723 to 2.44, n = 43). Conclusions:, While half of the patients had one to three ED visits during the study period, many patients had more frequent visits. Delays to receiving an initial analgesic were common, and post-ED interviews reveal that sickle cell pain patients are discharged from the ED with higher pain scores than what they perceive as desirable. ACADEMIC EMERGENCY MEDICINE 2010; 17:399,407 © 2010 by the Society for Academic Emergency Medicine [source] Management of acute painful crises in sickle cell diseaseINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2005T. R. KOTILA Summary Pain is a common mode of manifestation of sickle cell disease (SCD) but there is limited information on pain management in this disorder. This study examines the use of opioids and non-opioid analgesia in the management of painful crisis in adult SCD patients; the routine use of antimalarials and antibiotics as adjunct therapy was also examined. A total of 87% of the patients had had a form of analgesics before presentation, 20% of which had parenteral analgesia. Ten per cent had not used any form of medication while another 10% used non-steroidal anti-inflammatory drugs. When asked, 59% of the patients desired oral non-opioid analgesics while 31% were not concerned about the type of analgesic given. Only 8% requested opioids. Hospital admission was not necessary in 65% of the patients; they were observed in the day-care unit and allowed home within 24 h. Sixty per cent did not have a test for malaria; 66% of those who had the test performed were negative, 35% of those whose thick film for malaria was negative had antimalarials prescribed. Only five patients (7%) were febrile at presentation. Thirty-four per cent had antibiotics prescribed, a third of these parenterally. Thirty-nine per cent had no fever but received antibiotics. [source] Activated monocytes and platelet-monocyte aggregates in patients with sickle cell disease*INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2002TED WUN Tumour necrosis factor-, (TNF-,) and interleukin-1, (IL-1,) increase endothelial surface receptors that mediate the adherence of sickle erythrocytes to the endothelium. Increased circulating levels of these cytokines have been found in patients with sickle cell disease (SCD). Monocytes are a source of both of these inflammatory mediators; we therefore determined whether circulating monocytes were activated in SCD, as defined by intracellular expression of these cytokines. Blood was also assayed for the presence of platelet,monocyte aggregates (PMAs), as platelet adherence is one possible mechanism for monocyte activation. The median percentages of monocytes expressing intracellular TNF-, and IL-1, in SCD patients were 6.8 (2.8,17.3) [median (range)] and 14.1 (1.3,44.8), respectively. In African-American controls the corresponding percentages were 0.3 (0.1,0.5) and 0.4 (0.1,3.0), and in Caucasians 0.2 (0.1,0.5) and 0.8 (0.8,1.9) (P < 0.001, Kruskal,Wallis). The mean percentage (± SD) of PMA was 14.0 ± 8.3 for Caucasian controls, 25.7 ± 7.3 for African-American controls, and 45.7 ± 21.6 for patients with SCD (P < 0.001, RM ANOVA; P < 0.05, Newman,Keuls posthoc test). We conclude that there are increased circulating PMAs and monocyte activation in patients with SCD. [source] Foetal haemoglobin in homozygous sickle cell disease: a study of patients with low HBF levels*INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2001A. Donaldson High foetal haemoglobin (HbF) levels are believed to ameliorate the manifestations of homozygous sickle cell (SS) disease. The corollary implies that patients with low HbF levels should have more severe clinical courses. We investigated this in a retrospective study of 50 Jamaican patients with steady-state HbF levels below 1% compared with a control group (A) of 54 subjects with steady-state HbF levels between 2.5 and 3.4% (around the 25th centile for our population), and a second control group (B) of 60 patients with steady-state HbF levels between 4.6 and 5.2% (around the 50th centile). Comparisons across the groups indicated significantly fewer females in the study group (16, 50 and 57%, respectively). Examination for haematological trends across the groups showed positive linear trends for haemoglobin (Hb) (P=0.004), packed cell volume (PCV) (P=0.01), mean cell volume (MCV) (P=< 0.001), mean cell haemoglobin (MCH) (P=< 0.001) and a negative trend for haemoglobin A2 (P=0.03). Clinically, there were no differences in the incidence of painful crises, abdominal crises and the acute chest syndrome, but leg ulcers were significantly less frequent in the study group (P=0.04). Therefore low HbF levels do not appear to increase the clinical severity of SS disease and may be protective against leg ulceration. [source] | |||||||||||||||||||||||||||||||