Are There True Non-Responders to Hydroxyurea in Sickle Cell Disease? a Multiparameter Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4073-4073 ◽  
Author(s):  
Arati Rani Chand ◽  
Hongyan Xu ◽  
Leigh G Wells ◽  
Betsy Clair ◽  
Cindy Neunert ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Response Rate ◽  
Treatment Time ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Average Dose ◽  
Cell Disease ◽  
Laboratory Parameters

Abstract Hydroxyurea (HU) is the only FDA approved anti-switching agent for the management of sickle cell disease (SCD). The non-response rate to HU (inadequate increase in fetal hemoglobin (HbF)) has been reported to be as high as 30%. However, the role of patient non-compliance as a cause of sub-optimal response to HU has not been studied. Establishing the rate of non-response to HU despite adequate dose and compliance would help in ascertaining patients who might benefit from alternate treatment strategies in SCD. The primary objective of this study was to differentiate between non-compliance and lack of response in patients using laboratory parameters other than HbF. We conducted a retrospective review of 137 adult SCD patients from GRU's Sickle Cell Center that were reportedly taking HU for ≥ 6 months. Data included weight, dose, HbF, Hb, RBC, RDW, retic, MCV, MCH, WBC, ANC, platelets, bilirubin, prior to initiation of HU therapy and at the time of maximal HbF response. Dose of HU/Kg required to achieve that response and time to response was calculated. We defined response as an absolute HbF value of ≥20% or a ≥5% increase in HbF from baseline. The anticipated direction of change in laboratory parameters indicative of compliance was an increase in MCV, MCH, Hb, PCV, and a decrease in RDW, retic count, WBC, neutrophils, platelets, and bilirubin. Patients without a change in HbF but with response from the additional parameters were classified as inadequate-responders. Patients without response in HbF as well as additional parameters were classified as non-compliant. We performed a regression analysis to study the effect of dose and patient age on the response (change in HbF). To model dosage, a new variable called HU exposure was calculated as the product of dose (mg/kg/day) and treatment time (days). The HU exposure and age was used as the predictors for change in HBF. Our results showed that of the 137 patients, 82(59.9%) were responders to HU (mean dose of 18.8mg/kg) with an expected increase in HbF and 36(26.3%) were non-compliant (mean dose of 18.48mg/kg) based on the fact that the aforementioned laboratory values did not change significantly. Only 19(13.9%) were non-responders (mean dose of 16.84 mg/kg) based on a lack of HbF response despite other laboratory parameters being indicative of compliance with HU. Out of the 19 patients who were non-responders only 2 patients were on HU doses more than 20mg/kg. In the overall sample, we found that both age and HU exposure were positively associated with HbF change, which was highly statistically significant (p=2.55E-08 and 7.03E-10, respectively). When we performed regression analysis in the responders, non-responders and non-compliant groups separately we found that in the responder group both age and HU exposure were positively associated with HbF change, with high statistical significance. In the non-responder group however, age and HU exposure were not statistically significant. Patients with SCD on HU who fail to show an adequate increase in HbF are more likely to be non-compliant with medication than actually being truly resistant to it. We have shown that laboratory measurements beside HbF help make the distinction between true HU non-responders and non-compliant patients. We believe a non-response rate of 13.9% may still be too high based on the fact that the average dose of HU was 16.97mg/kg, barely over the recommended starting dose of 15 mg/kg/day. These data suggest that among adult patients on HU, the rates of the non-responders are very low when given adequate doses of HU for sufficient periods of time. Disclosures No relevant conflicts of interest to declare.

scholarly journals Utility of Procalcitonin in Differentiating Acute Chest Syndrome from Vaso-Occlusive Crisis in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Satish Maharaj ◽  
Simone Chang ◽  
Karan Seegobin ◽  
Marwan Shaikh ◽  
Kamila I. Cisak
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Acute Chest Syndrome ◽  
Adult Males ◽  
Cell Disease ◽  
Unequal Variances ◽  
Recorded Data

Background: Acute chest syndrome (ACS) frequently complicates sickle cell disease (SCD) and is a leading cause of hospitalization and mortality. Many factors have been implicated in ACS, including infections, thrombosis, fat and pulmonary emboli. However, a clear etiology is not defined in 50% of the cases and ACS is considered a clinical endpoint for different pathogenic processes (Vichinsky et al 2000). The non-specific nature of ACS makes diagnostic tests challenging, and there are no serum tests clinical used to aid diagnosis. Procalcitonin (PCT) is a prohormone of calcitonin and serum PCT rises within hours of an inflammatory stimulus. PCT has clinical utility as a marker of severe systemic inflammation, infection, and sepsis (Becker et al. 2008). Few studies have evaluated PCT as a biomarker for ACS in patients presenting with vaso-occlusive crises (VOC). Two studies have reported no difference in PCT (Biemond et al. 2018 and Stankovic et al 2011), while one study reported higher PCT between ACS and VOC (Patel et al 2014). Methods: We retrospectively reviewed 106 patients with SCD who presented to the emergency department with fever and painful crises during 2015-2019. The patients were divided into two categories based on discharge diagnoses - patients with VOC only (n=88) and patients with ACS (n=18). Inclusion criteria for both groups were patients with SCD, 17 years and older and PCT measurement on presentation. Exclusion criteria were defined as patients who had received empiric antibiotics prior to PCT testing. Data collected on presentation included genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin and hydroxyurea use. Length of stay was recorded. Data was analyzed between the two groups using descriptive statistics and accounting for unequal variances, withp-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The sample included primarily adult males (77%), with about two-thirds on hydroxyurea. Genotype HbSS (73.6%) was most prevalent followed by HbSC (22.6%) and HbSβ (3.8%). The ACS group had a higher percentage of HbSS, lower use of hydroxyurea and higher mean bilirubin. Mean PCT for the ACS group was 0.52 ng/mL (range, 0.05-2.04), compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group; withp=0.084. ROC analysis showed a PCT>0.5ng/mL had 39% sensitivity and 85% specificity for ACS in this sample. Conclusion: In this sample, PCT on presentation was higher in those with ACS compared to VOC, but this difference did not achieve statistical significance. Further study in a larger population would be useful to evaluate this finding. Disclosures No relevant conflicts of interest to declare.

Daytime and Nocturnal Hypoxemia Are Related With Hemolysis In Adults With Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2229-2229
Author(s):  
Ana Carolina Cabanas-Pedro ◽  
Sandra Satiko Matsuda, ◽  
Suely Roizenblatt ◽  
Joao Roberto Reinfelderon ◽  
Sergio Tufik ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Cell Disease ◽  
Clinical Complications ◽  
Nocturnal Hypoxemia ◽  
Previous Stroke ◽  
The Mean ◽  
De Medicina

Abstract Introduction Different studies had shown that nocturnal hypoxemia is associated with clinical complications in children with sickle cell disease (SCD), and, more recently, iron availability was related with nocturnal oxymetry in these children. However, there are few studies about this subject in adults with SCD, despite the fact that nocturnal hypoxemia occurred in 60% of the patients. We aimed to evaluate daytime and overnight hypoxia and its influence on clinical and laboratorial parameters in adults with SCD. Patients and Methods 82 steady state patients with SCD followed at Anemia Out-Patient Clinic from Escola Paulista de Medicina/UNIFESP were invited to this study. This study was approved by Ethical Committee, and all patients agreed in participate. The daytime oximetry (SpO2) utilized was the mean of at least 3 measurements by pulse oximeter during regular appointments at the out-patient clinic. The nocturnal oximetry data (basal SpO2 and mean nocturnal SpO2) were obtained during polysomnography (PSG). Besides clinical evaluation, routine laboratory tests performed near the realization of the PSG were analyzed. The data was analyzed by parametric and non-parametric tests, with α=5%. Results The median (range) age was 28 (18-69) years, and 44 (54%) were female. Moderate sleep apnea was diagnosed in 11% of the patients. The mean of SpO2 obtained for each measurement was: daytime SpO2: 95.1±4.3, basal SpO2: 94.3±3.5, and mean nocturnal SpO2: 93.3±3.6; with statistical significance between daytime and basal SpO2 (X2=17.0; p<0.001) and between daytime and mean nocturnal SpO2 (X2=10.3; p=0.001). The percentage of patients with hypoxemia (SpO2 ≤ 90%) varied according with the measurement: 14.1% at daytime SpO2, 13.7% at basal SpO2, and 20.0% at mean nocturnal SpO2. However, 55% of the patients achieved hypoxemia level during PSG. Association between daytime SpO2 and previous stroke was observed (X2=4.0; p=0.04). Patients with daytime and basal SpO2 ≤ 90% had higher lactate dehydrogenase (LDH) (634.3±114.9 and 538.0±198.3) compared to the ones with SpO2>90% (384.0±171.6 and 375.7±171.9; p<0.001 and p=0.02, respectively). Reticulocyte count was more elevated in patients with SpO2 ≤ 90% (daytime SpO2: 277,639.2±96,108.4; basal SpO2: 290,722.9±87,791.2 and mean nocturnal SpO2: 260,582.1±83,532.8) when compared to the ones with SpO2 >90% (185,537.3±90,445.7; 188,432.2±101,277.1 and 189,194.1±104,478.8; p=0.01; p=0.01 and p=0.03, respectively). No correlation was found within iron and SpO2. Conclusion Daytime and nocturnal hypoxemia showed effect on hemolytic markers in adults with SCD. Daytime SpO2 presented an association with previous stroke and considering that it was also observed an association between daytime and nocturnal SpO2, we suggest that daytime SpO2determination should be monitored in each appointment and can be used as a predictor of SCD severity Supported by CAPES/SUS and AFIP. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Identification of Patient-Specific Factors Associated with Alloimmunization in Sickle Cell Disease

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 989-989
Author(s):  
Ryan A Virden ◽  
Kelsey Busken ◽  
Richard Madsen ◽  
Emily Coberly ◽  
Bindu Kanathezhath Sathi
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Laboratory ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Laboratory Data ◽  
Patient Specific ◽  
Continuous Variables ◽  
Cell Disease ◽  
Specific Factors

Abstract Background: Alloimmunization is a frequent complication of red blood cell (RBC) transfusion in sickle cell disease (SCD), arising from disparities between the recipient and donor RBC antigens. This potentially life-threatening complication impacts the utilization of chronic transfusion, a disease-modifying treatment in SCD. Many centers across the country use dedicated donor programs that match SCD recipients to a small group of racially and phenotypically-matched RBC donors in order to minimize exposure to foreign RBC antigens. The pathogenesis of alloimmunization remains an area of active research. Emerging data suggests that a pro-inflammatory state in the recipient plays a role in alloantibody (alloAb) generation. Some SCD patients develop an alloAb after minimal exposure to donor RBC units, whereas others do not. In a subset of these latter patients, multiple exposures to disparate RBC units will not lead to alloAb formation. To further understand this phenomenon, we sought to identify patient-specific factors in SCD that are associated with a higher risk of alloimmunization. Methods: We retrospectively analyzed clinical, laboratory, and transfusion-related data for all pediatric and adult SCD patients treated at the University of Missouri between 2000-2017. Descriptive statistics were expressed for continuous variables. Two-tailed Student's t-tests and Chi-squared analyses were used to determine statistical significance. Results: Of a total of 130 SCD patients identified, 89 patients (58 HbSS, 25 HbSC, and 6 HbSβ0/+ patients) had adequate transfusion, clinical, and laboratory data for inclusion in this study. The overall alloimmunization rate was 28%, with genotype-specific alloimmunization rates of 36% (HbSS), 4% (HbSC), and 50% (HbSβ0/+). Neither age nor gender significantly differed between the alloimmunized and non-alloimmunized groups. Alloimmunized SCD patients received, on average, 4 times more lifetime RBC units as compared to the non-alloimmunized group (264 units vs. 65 units, respectively, p = 0.002). Among all SCD patients, individuals who received more than 5 units per year of life were more likely to become alloimmunized (61% vs. 16%, p = 0.02, Figure 1). The most common alloantibodies identified in our patients were C, E, and Kell (Figure 2). Warm autoantibodies were identified in 36% of all alloimmunized patients versus only 5% of non-alloimmunized patients (p = 0.0001). Lastly, alloimmunization was associated with lower hemoglobin (8.66 ± 1.17 vs. 9.52 ± 1.54, p = 0.01) and higher creatinine (0.71 ± 0.36 vs. 0.56 ± 0.22, p = 0.02) among all SCD patients. In addition, higher LDH (549 ± 180 vs. 386 ± 127, p = 0.01) was observed in pediatric SCD patients who were alloimmunized. Both pediatric and adult SCD patients with the HbSS genotype demonstrated higher creatinine in the alloimmunized group (p = 0.03). An increased incidence of leg ulcers was found to be associated with alloimmunization (12% vs. 0%, p = 0.005, Table 1) amongst all of the clinical variables analyzed. Hydroxyurea therapy was not associated with a decreased prevalence of alloimmunization (Table 2). Conclusions: We identified an association between alloimmunization and higher LDH, lower hemoglobin, and higher creatinine in our SCD patient population. In addition, increased alloimmunization was seen in patients with a higher exposure to RBC units, both cumulatively and on a per life year basis. These data suggest that SCD patients with increased hemolysis or recipients of more than 5 RBC units per life year are associated with a higher risk of developing an alloAb. Larger studies will be required to define a causative relationship between this clinical SCD phenotype and a higher risk of alloimmunization. Disclosures No relevant conflicts of interest to declare.

Adequacy of Vaccine Documentation Against Encapsulated Bacteria in a Population of Children with Sickle Cell Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4853-4853
Author(s):  
Andrew S. Freiberg ◽  
Antea C Singleton
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Primary Care Physicians ◽  
Conflicts Of Interest ◽  
Pediatric Population ◽  
Statistical Significance ◽  
Retrospective Chart Review ◽  
Cell Disease ◽  
Encapsulated Bacteria

Abstract Abstract 4853 Immunization status is often used as an indicator of improved quality of health care and access in pediatric populations. The increased life expectancy in the general pediatric population has largely been attributed to the prevention of infectious disease through immunizations, and this fact is even truer for individuals with sickle cell disease. Adherence to recommended vaccination schedules against encapsulated bacteria in patients with sickle-cell anemia has not been well studied in any population. In order to determine documented compliance rates based on the current recommendations of the Department of Health and Human Services Center for Disease Control Immunization Schedules, a retrospective chart review was performed on 117 patients diagnosed with sickle cell anemia (HbSS) followed at the Penn State Hershey Children's Hospital Regional Pediatric Sickle Cell Center, through the year 2009. Since the vaccinations were given by each patient's primary provider(s), we attempted to obtain documentation of immunizations given by these providers, particularly against encapsulated bacteria. For 35 of the 117 patients, we were unable to obtain any forwarded documentation of any vaccinations. The vaccination schedules of the remaining 82 patients were audited for coverage against encapsulated bacteria. Only 16 of the 82 patients (19.5%) with forwarded documents demonstrated complete documented compliance, defined as having complete coverage against H. influenzae, N. meningitides, and S. pneumococcus. Of the remaining forwarded charts, 63 patients (76.8%) demonstrated some form of partial documented compliance, but four patients (4.9%) did not have documentation of vaccinations against any encapsulated bacteria despite documentation of receiving other vaccinations. Full documented compliance as indicated by forwarded records was most noted in children between the ages of 0–11.9 years (14/16 of patients with complete compliance). The proportion of adolescents without any forwarded documentation was larger than the younger age group; however, this difference did not reach statistical significance (p=0.36). Of the 82 patients whose primary care physicians forwarded documents, significantly more (14 of 34) adolescents (≥12 years of age) than children aged 0–11.9 years (8 of 48) were missing documentation of more than half of their vaccines (p=.014). These results indicate deficient documentation of vaccination coverage against encapsulated organisms, particularly in the adolescent population. To determine the clinical implications of these results, further studies detailing the demographics, socioeconomic status and correlations of such characteristics to morbidity and mortality should be completed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hemoglobinopathy Education in Canadian Hematology Training Programs: How Much Are Residents Learning?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2168-2168
Author(s):  
Madeleine M Verhovsek ◽  
Vicky R Breakey ◽  
Richard Ward ◽  
Shannon M Bates ◽  
Parveen Wasi ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
North America ◽  
Sickle Cell ◽  
Outpatient Care ◽  
Inpatient Care ◽  
Response Rate ◽  
Training Programs ◽  
Conflicts Of Interest ◽  
Cell Disease ◽  
Learning Modules

Abstract The number of hemoglobinopathy patients in North America continues to increase, due to high rates of immigration from countries with high prevalence and improved survival. Recent research has led to evidence-based improvements in acute and chronic care of patients with sickle cell disease and thalassemia. Studies have noted gaps in clinicians’ knowledge about management of hemoglobinopathies, with the result that common presentations, such as sickle vaso-occlusive episodes, are often mismanaged. Hematologists completing training in North America require the knowledge and expertise to manage these medically complex patients. To ascertain the extent of hemoglobinopathy teaching and exposure in Canadian Adult and Pediatric Hematology Training Programs, and to assess the perceived importance of hemoglobinopathy knowledge, we administered an online survey to all Training Program Directors (TPDs), and to all residents who were currently enrolled or who had completed training in the previous year. Surveys were available in English and French. The response rate for TPDs was 92% (22/24). Ninety five percent of PDs felt that hemoglobinopathy learning is “important” or “very important” for hematology trainees in their region. Four programs have a mandatory hemoglobinopathy rotation, 14 programs have mandatory hemoglobinopathy clinic participation, and 17 programs have mandatory hemoglobinopathy lab exposure. Laboratory time ranges widely, from “0-2 hours” to “greater than 20 hours”. All programs covered laboratory aspects of hemoglobinopathy, outpatient care of sickle cell disease and inpatient care of sickle cell disease, and all but one program covered outpatient care of thalassemias. In 1/2 to 2/3 of adult training programs, these topics were covered at only a basic level. All pediatric programs covered outpatient and inpatient care of sickle cell disease “in-depth”, with 90% and 40% of programs covering outpatient thalassemia care and laboratory diagnostics “in-depth”, respectively. All 22 programs had academic half-days with teaching devoted to hemoglobinopathy. Seventy-seven percent of programs had faculty member(s) with an interest in hemoglobinopathy. The response rate for residents was 45% (70/156). The majority of respondents were senior residents, with 88% currently in post-graduate year five, or above. Among residents in adult hematology programs, 61% had completed a rotation or elective with a focus on hemoglobinopathy versus 25% in the pediatric programs. Total numbers of hemoglobinopathy patients seen ranged from “0” to “more than 50”, and laboratory exposure varied from “none” to “in-depth”. Most residents with clinical hemoglobinopathy experience had seen patients with both sickle cell disease and thalassemia major or intermedia. Of residents who responded, 83% felt that hemoglobinopathy knowledge was “important” or “very important” to their future practice. All TPDs and 90% of residents felt that online hemoglobinopathy learning modules could be beneficial for resident learning. There appears to be wide variability in depth and breadth of clinical and laboratory hemoglobinopathy learning in Hematology training programs across Canada. TPDs and residents place high importance on hemoglobinopathy learning, but some centres have small patient numbers, or lack faculty with interest in hemoglobinoapthies. Online learning modules could provide added learning opportunities for residents. Disclosures No relevant conflicts of interest to declare.

scholarly journals Case Report: Acute Stroke in Young Adult Patient with Moyamoya Syndrome Secondary to Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Oladipo Cole ◽  
Asia Filatov ◽  
Javed Khanni ◽  
Patricio Espinosa
Keyword(s):  
Case Report ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Moyamoya Disease ◽  
Conflicts Of Interest ◽  
Acute Chest Syndrome ◽  
African American Female ◽  
Moyamoya Syndrome ◽  
Cell Disease ◽  
Radiographic Findings

Moyamoya disease, well described in literature, is a chronic cerebrovascular occlusive disorder. It is characterized by progressive stenosis/occlusion of the terminal portions of the internal carotid arteries (ICA) and the proximal portions of the middle cerebral arteries (MCA). Less frequently described is Moyamoya syndrome, the name given to radiographic findings consistent with Moyamoya disease, but with an identifiable cause. The diseases associated with Moyamoya Syndrome include Sickle Cell Disease (SCD), Thalassemias, and Down's Syndrome to name a few. Common complications of Moyamoya include both ischemic and hemorrhagic strokes. Upon literature review, Moyamoya syndrome caused by SCD is not well described. When it is, the discussion is centered around the pediatric patient population and surgical management. Our case report describes a 22-year-old African American female with SCD who initially presented with Acute Chest Syndrome. Her hospital course was complicated by development of overt debilitating neurologic deficits. Subsequently, she was found to have Moyamoya Syndrome on neuroimaging. She was successfully treated with medical management without any surgical intervention. This case highlights the necessity of thorough examination, differential diagnosis, imaging findings, and consideration of predisposing syndromes in the work-up for Moyamoya syndrome; especially individuals with Sickle Cell Disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Interferon Induction By HbS, SERINC5 Upregulation and Reduction of HIV-1 Nef and AP2 Contribute to HIV-1 Restriction in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Namita Kumari ◽  
Marina Jerebtsova ◽  
Songping Wang ◽  
Sharmin Diaz ◽  
Sergei Nekhai
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Interferon Response ◽  
Cell Disease ◽  
Restriction Factors ◽  
Peripheral Blood Mononuclear ◽  
Hiv 1

Concerted action of numerous positively acting cellular factors is essential for Human immunodeficiency virus type 1 (HIV-1) replication but in turn is challenged by anti-viral restriction factors. Previously we showed that ex vivo one round HIV-1 replication and replication of fully competent T-tropic HIV-1(IIIB) is significantly reduced in peripheral blood mononuclear cells (PBMCs) obtained from patients with Sickle Cell Disease (SCD). Further, we identified and confirmed CDKN1A (p21) and CH25H as host restriction factors expressed in SCD PBMCs that may contribute to the HIV-1 inhibition, in addition to the previously reported SAMHD1 and IKBα. Since CH25H is an interferon stimulated gene (ISG), we analyzed IRFs and interferon expression in SCD PBMCs. Higher levels of IRF7 and IFNβ mRNA were observed in SCD PBMCs compared to controls. We probed further to ascertain if hemin or sickle Hb was responsible for interferon response. We found upregulation of IFNβ in THP-1 - derived macrophages treated with lysates of HbSS RBCs or purified HbS as compared to untreated or HbA treated controls. HbSS RBCs lysates and purified HbS inhibited HIV-1 gag mRNA expression in monocyte-derived macrophages infected with HIV-1(Ba-L). Recent clinical study showed increased levels of CD4 in HIV-1 infected SCD patients in Africa. Thus we analyzed CD4 levels in HIV-1 IIIB infected SCD PBMCs, and found them to be higher compared to controls. Levels of HIV-1 nef mRNA, that controls CD4 expression was lower in HIV-1 IIIB infected SCD PBMCs. As Nef counteracts SERINC3/5 restriction factor, we analyzed its expression as well as the expression of AP2 clathrin adaptor that is required for Nef mediated internalization of CD4. AP2 expression was lower and SERINC5 expression was higher in SCD PBMCs. CONCLUSIONS: SCD PBMCs could resist HIV-1 infection because of the increased IFNβ production by macrophages exposed to HbSS or sickle cell RBCs. SCD PBMC have increased levels of SERNIC5 and lower levels of HIV-1 Nef and host AP2 expression that, culumlatively, can increased CD4 levels and lead to the overall improved immunological health of SCD patients. ACKNOWLEDGMENTS: This work was supported by NIH Research Grants (1P50HL118006, 1R01HL125005, 1SC1HL150685, 5U54MD007597, 1UM1AI26617 and P30AI087714). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Disclosures No relevant conflicts of interest to declare.

scholarly journals American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support

2020 ◽  
Vol 4 (2) ◽  
pp. 327-355 ◽  
Author(s):  
Stella T. Chou ◽  
Mouaz Alsawas ◽  
Ross M. Fasano ◽  
Joshua J. Field ◽  
Jeanne E. Hendrickson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Guideline Development ◽  
Practice Research ◽  
Evidence Based ◽  
Red Cell ◽  
Cell Disease ◽  
American Society

Background: Red cell transfusions remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. Guidance for specific indications and administration of transfusion, as well as screening, prevention, and management of alloimmunization, delayed hemolytic transfusion reactions (DHTRs), and iron overload may improve outcomes. Objective: Our objective was to develop evidence-based guidelines to support patients, clinicians, and other healthcare professionals in their decisions about transfusion support for SCD and the management of transfusion-related complications. Methods: The American Society of Hematology formed a multidisciplinary panel that was balanced to minimize bias from conflicts of interest and that included a patient representative. The panel prioritized clinical questions and outcomes. The Mayo Clinic Evidence-Based Practice Research Program supported the guideline development process. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to form recommendations, which were subject to public comment. Results: The panel developed 10 recommendations focused on red cell antigen typing and matching, indications, and mode of administration (simple vs red cell exchange), as well as screening, prevention, and management of alloimmunization, DHTRs, and iron overload. Conclusions: The majority of panel recommendations were conditional due to the paucity of direct, high-certainty evidence for outcomes of interest. Research priorities were identified, including prospective studies to understand the role of serologic vs genotypic red cell matching, the mechanism of HTRs resulting from specific alloantigens to inform therapy, the role and timing of regular transfusions during pregnancy for women, and the optimal treatment of transfusional iron overload in SCD.

scholarly journals Identification of Clinical and Laboratory Parameters Associated with the Development of Acute Chest Syndrome during Vaso-Occlusive Episodes in Children with Sickle Cell Disease: A Preliminary Step before Assessing Specific and Early Treatment Strategies

2019 ◽  
Vol 8 (11) ◽  
pp. 1839
Author(s):  
Madhi ◽  
Kamdem ◽  
Jung ◽  
Carlier-Gonod ◽  
Biscardi ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Pain Score ◽  
Sickle Cell ◽  
Multivariate Model ◽  
Red Blood Cell Transfusion ◽  
Predictive Score ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Laboratory Parameters ◽  
Increased Risk

This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days, p < 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (p < 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 109/L) and neutrophil (>10 × 109/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74–0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS.

scholarly journals TheCCR5Δ32Polymorphism in Brazilian Patients with Sickle Cell Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Mariana Pezzute Lopes ◽  
Magnun Nueldo Nunes Santos ◽  
Eliel Wagner Faber ◽  
Marcos André Cavalcanti Bezerra ◽  
Betânia Lucena Domingues Hatzlhofer ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Statistical Significance ◽  
Population Sample ◽  
Selective Advantage ◽  
Northeastern Brazil ◽  
Control Group ◽  
Cell Disease ◽  
Specific Pcr

Background. Previous studies on the role of inflammation in the pathophysiology of sickle cell disease (SCD) suggested that theCCR5Δ32allele, which is responsible for the production of truncated C-C chemokine receptor type 5 (CCR5), could confer a selective advantage on patients with SCD because it leads to a less efficient Th1 response. We determined the frequency of theCCR5Δ32polymorphism in 795 Afro-Brazilian SCD patients followed up at the Pernambuco Hematology and Hemotherapy Center, in Northeastern Brazil, divided into a pediatric group (3 months–17 years,n=483) and an adult group (18–70 years,n=312). The adult patients were also compared to a healthy control group (blood donors, 18–61 years,n=247).Methods. TheCCR5/CCR5Δ32polymorphism was determined by allele-specific PCR.Results. No homozygous patient for theCCR5Δ32allele was detected. The frequency of heterozygotes in the study population (patients and controls) was 5.8%, in the total SCD patients 5.1%, in the children 5.4%, in the adults with SCD 4.8%, and in the adult controls 8.1%. These differences did not reach statistical significance.Conclusions. Our findings failed to demonstrate an important role of theCCR5Δ32allele in the population sample studied here.

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