scholarly journals How to avoid the problem of erythrocyte alloimmunization in sickle cell disease

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 689-695
Author(s):  
France Pirenne ◽  
Aline Floch ◽  
Anoosha Habibi
Keyword(s):  
Sickle Cell Disease ◽  
Blood Group ◽  
Sickle Cell ◽  
African Ancestry ◽  
Preventive Measure ◽  
Blood Groups ◽  
Clinical State ◽  
Cell Disease ◽  
Major Barrier ◽  
American Society

Abstract Erythrocyte alloimmunization is a major barrier to transfusion in sickle cell disease (SCD) because it can lead to transfusion deadlock and the development of life-threatening hemolytic transfusion reactions (HTRs). Several risk factors have been identified, such as blood group polymorphism in these patients of African ancestry frequently exposed to antigens they do not carry and an inflammatory clinical state of the disease. The most important preventive measure is prophylactic red blood cell antigen matching, and there is a consensus that matching for Rh (D, C, E, c, e) and K antigens should be performed for all SCD patients. However, some patients are high responders and more at risk of developing antibodies and HTRs. For these patients, the extension of matching to other blood groups, including variant antigens of the RH blood group, the use of genotyping rather than serology to characterize significant blood groups, and the prophylactic administration of immunosuppressive treatments remain a matter of debate due to low levels of certainty concerning their effects and the difficulty of determining which patients, other than those already immunized, are at high risk. These issues were recently addressed by a panel of experts established by the American Society of Hematology. Here, we review and stratify the various interventions for preventing alloimmunization, based on the literature and our experience and taking into account the obstacles to their implementation and any future developments required.

scholarly journals RH genotyping in a sickle cell disease patient contributing to hematopoietic stem cell transplantation donor selection and management

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2836-2838 ◽  
Author(s):  
Ross M. Fasano ◽  
Alessandro Monaco ◽  
Emily Riehm Meier ◽  
Philippe Pary ◽  
A. Hallie Lee-Stroka ◽  
...  
Keyword(s):  
Stem Cell ◽  
Sickle Cell Disease ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Blood Group ◽  
Sickle Cell ◽  
Disease Patient ◽  
Nucleotide Sequencing ◽  
Cell Disease ◽  
Hematopoietic Stem

Abstract African individuals harbor molecular RH variants, which permit alloantibody formation to high-prevalence Rh antigens after transfusions. Genotyping identifies such RH variants, which are often missed by serologic blood group typing. Comprehensive molecular blood group analysis using 3 genotyping platforms, nucleotide sequencing, and serologic evaluation was performed on a 7-year-old African male with sickle cell disease who developed an “e-like” antibody shortly after initiating monthly red blood cell (RBC) transfusions for silent stroke. Genotyping of the RH variant predicted a severe shortage of compatible RBCs for long-term transfusion support, which contributed to the decision for hematopoetic stem cell transplantation. RH genotyping confirmed the RH variant in the human leukocyte antigen–matched sibling donor. The patient's (C)ces type 1 haplotype occurs in up to 11% of African American sickle cell disease patients; however, haplotype-matched RBCs were serologically incompatible. This case documents that blood unit selection should be based on genotype rather than one matching haplotype.

Abstract P726: Cytochrome B5 Reductase 3 Modifies The Brain-Blood Axis Response To Ischemic Stroke In Mice With Sickle Cell Disease

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Katherine C Wood ◽  
Heidi M Schmidt ◽  
Scott Hahn ◽  
Mehdi Nouraie ◽  
Mara Carreno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ischemic Stroke ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
African Ancestry ◽  
Cytochrome B5 ◽  
Heme Iron ◽  
Wild Type ◽  
Cell Disease ◽  
Cytochrome B5 Reductase

Introduction: Stroke and silent infarcts are serious complications of sickle cell disease (SCD), occurring frequently in children. Decreased nitric oxide bioavailability and responsiveness contribute to neurovascular disease. Cytochrome b5 reductase 3 (Cyb5R3) is a heme iron reductase that reduces oxidized soluble guanylate cyclase heme iron (Fe 3+ --> Fe 2+ ) to preserve nitric oxide signaling. A loss-of-function Cyb5R3 missense variant (T117S) occurs with high frequency (0.23 minor allele) in persons of African ancestry. Hypothesis: We hypothesized that impaired reductase function of T117S Cyb5R3 exacerbates brain damage after ischemic stroke in SCD. Methods: Bone marrow transplant was used to create male SCD mice with wild type (SS/WT) or T117S (SS/T117S) Cyb5R3. Blood was sampled before and after middle cerebral artery occlusion (55 minutes occlusion, 48 hours reperfusion). Infarct volume (IV) was determined by 2,3,5-triphenyltetrazolium chloride. Intravascular hemolysis and correlation (Pearson’s R) of hematology changes with IV were determined. Baseline Walk-PHaSST (NCT00492531) data were analyzed for stroke occurrence. Results: Brain IV (63 vs 27 cm 3 , P=0.003) and mortality (3/6 vs 0/8) were greater in SS/T117S vs SS/WT. Red blood cells, hemoglobin and hematocrit declined as IV increased. Plasma oxyhemoglobin increased in parallel with IV (r = 0.74, P=0.09). There were different signatures to hematologic changes that occurred with IV in SCD. Relative to wild type, T117S contracted the erythroid compartment (red blood cell: -13% vs 13%, P=0.003; hematocrit: -20% vs 1%, P=0.008; hemoglobin: -18% vs 2%, P=0.007). Mean platelet volume correlated with IV in SS/T117S (r = 0.87, P=0.06), while the inverse occurred in SS/WT (r = -0.63, P=0.09) Monocytes increased in parallel with IV in SS/T117S (r = 0.73, P=0.16), but followed the opposite trajectory in SS/WT (r = -0.77, P=0.04). WalkPHaSST participants with T117S Cyb5R3 self-reported more ischemic stroke (7.4% vs 5.1%) relative to wild type. Conclusion: Cyb5R3 is an important modifier of the evolution and outcome of ischemic brain injury in SCD and its hematologic consequences. Our findings indicate a bidirectional relationship between stroke and anemia in SCD that may axially turn on Cyb5R3 activity.

scholarly journals End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource settings

2019 ◽  
Vol 3 (23) ◽  
pp. 4002-4020 ◽  
Author(s):  
Ann T. Farrell ◽  
Julie Panepinto ◽  
Ankit A. Desai ◽  
Adetola A. Kassim ◽  
Jeffrey Lebensburger ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Patient Reported Outcome ◽  
Cell Disease ◽  
End Points ◽  
Low Resource Settings ◽  
Low Resource ◽  
Patient Reported ◽  
The Us ◽  
American Society

Abstract To address the global burden of sickle cell disease and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to patient-reported outcome, pain (non–patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.

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 2019 sickle cell disease guidelines by the American Society of Hematology: methodology, challenges, and innovations

2019 ◽  
Vol 3 (23) ◽  
pp. 3945-3950 ◽  
Author(s):  
M. Hassan Murad ◽  
Robert I. Liem ◽  
Eddy S. Lang ◽  
Elie A. Akl ◽  
Joerg J. Meerpohl ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Guideline Development ◽  
A Priori ◽  
Cell Transplant ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Assessment Development ◽  
Cerebrovascular Complications ◽  
American Society

Abstract The American Society of Hematology (ASH) convened 5 guideline panels to develop clinical practice recommendations addressing 5 management areas of highest importance to individuals living with sickle cell disease: pain, cerebrovascular complications, pulmonary and kidney complications, transfusion, and hematopoietic stem cell transplant. Panels were multidisciplinary and consisted of patient representatives, content experts, and methodologists. The Mayo Clinic Evidence-Based Practice Center conducted systematic reviews based on a priori selected questions. In this exposition, we describe the process used by ASH, including the GRADE approach (Grades of Recommendations, Assessment, Development and Evaluation) for rating certainty of the evidence and the GRADE Evidence to Decision Framework. We also describe several unique challenges faced by the guideline panels and the specific innovations and solutions used to address them, including a curriculum to train patients to engage in guideline development, dealing with the opioid crisis, and working with indirect and noncomparative evidence.

scholarly journals American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain

2020 ◽  
Vol 4 (12) ◽  
pp. 2656-2701 ◽  
Author(s):  
Amanda M. Brandow ◽  
C. Patrick Carroll ◽  
Susan Creary ◽  
Ronisha Edwards-Elliott ◽  
Jeffrey Glassberg ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pain Management ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Practice Research ◽  
Management Approach ◽  
Evidence Based ◽  
Cell Disease ◽  
Targeted Interventions ◽  
American Society

Background: The management of acute and chronic pain for individuals living with sickle cell disease (SCD) is a clinical challenge. This reflects the paucity of clinical SCD pain research and limited understanding of the complex biological differences between acute and chronic pain. These issues collectively create barriers to effective, targeted interventions. Optimal pain management requires interdisciplinary care. Objective: These evidence-based guidelines developed by the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in pain management decisions for children and adults with SCD. Methods: ASH formed a multidisciplinary panel, including 2 patient representatives, that was thoroughly vetted to minimize bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic reviews. Clinical questions and outcomes were prioritized according to importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel reached consensus on 18 recommendations specific to acute and chronic pain. The recommendations reflect a broad pain management approach, encompassing pharmacological and nonpharmacological interventions and analgesic delivery. Conclusions: Because of low-certainty evidence and closely balanced benefits and harms, most recommendations are conditional. Patient preferences should drive clinical decisions. Policymaking, including that by payers, will require substantial debate and input from stakeholders. Randomized controlled trials and comparative-effectiveness studies are needed for chronic opioid therapy, nonopioid therapies, and nonpharmacological interventions.

scholarly journals INCREASED VASOOCCLUSIVE CRISIS IN “O” BLOOD GROUP SICKLE CELL DISEASE PATIENTS: ASSOCIATION WITH UNDERLYING THROMBOSPONDIN LEVELS.

2017 ◽  
Vol 9 (1) ◽  
pp. e2017028 ◽  
Author(s):  
M. Al Huneini ◽  
Anil Pathare
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Blood Group ◽  
Sickle Cell ◽  
Inverse Relation ◽  
Cell Disease ◽  
Protein Variant ◽  
Whitney Test ◽  
Mann Whitney Test ◽  
Function Tests

Abstract:Objectives: To explore the incidence of vaso-occlusive crisis (VOC) in Blood Group “O” sickle cell disease (SCD) patients, and correlate it with the blood group and thrombospondin (TSP) levels.Methods: In 89 consecutive SCD patients, blood samples were obtained for vWF antigen, collagen binding activity, blood group typing, C-reactive protein, variant hemoglobin analysis (HPLC), Serum TSP 1 and TSP 2 levels, complete blood counts, liver function tests, LDH and renal function tests during VOC episodes and in steady state conditions.Results: In the steady state SCD patients (n=72), “O” blood group patients (n=37) showed significantly higher median serum TSP 1 and TSP 2 levels than the non “O” blood group patients [n=35] [p <0.05, Mann-Whitney test], with an inverse relation between VWF:Ag, Factor VIII:C and TSP levels. Furthermore, the serum TSP 1 and TSP 2 levels were significantly higher in patients presenting with acute VOC [n=17], and in those with repeated VOC’s (group 1, n=16) especially amongst those patients with blood group “O” [p, <0.05, Mann-Whitney test].Conclusions: The study shows that there was an inverse relation between TSP and vWF levels, in blood group “O” SCD patients with an upregulation of the TSP levels. Expectedly, during active VOC crisis, the TSP 1 and TSP 2 levels were significantly elevated.  Key Words: VOC; SCD; TSP; vWD; Blood groups

scholarly journals A Cross Sectional Study of Association of HLA typing with Haemoglobin Level in Sickle Cell Anaemia

2021 ◽  
pp. 523-531
Author(s):  
Raed Alserihi ◽  
Saeed Kabrah ◽  
Hadeel Alsadoun
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Blood Cell ◽  
Sickle Cell ◽  
Blood Groups ◽  
Hemoglobin Level ◽  
Hla Typing ◽  
Control Group ◽  
Allelic Association ◽  
Cell Disease

Background: Sickle-cell Disease (SCD) is the most common blood cell disorder affecting millions of people. In severe cases, regular blood transfusion is an essential practice to relieve clinical symptoms. However, since regular blood transfusion can lead to alloimmunization to foreign human leukocyte antigens (HLA), this may result in severe anemia due to red blood cell destruction. Therefore, this study aimed to determine the association between the hemoglobin level and the presence of HLA genotypes among Sickle Cell Anemia patients.  Methodology: A total of 64 SCD patients and 21 healthy donors seen at King Abdulaziz hospital between November 2019 and February 2021 were recruited for this study. Demographic data including ABO/Rhesus blood groups, hemoglobin concentration, were among the clinical information obtained. HLA genotyping was performed using Polymerase Chain Reaction-Sequence Specific Oligonucleotide (PCR-SSO). The data were cleaned using the Microsoft Excel and analysed using the statistical packages for Social Sciences (SPSS) version 24. Results: The incidence of SCD is not strictly gender-related because of its transmission as an autosomal recessive disorder. Sixty-four individuals (33 females; 31 males) having SCD were analyzed. O blood group recorded the highest prevalence compared to other ABO blood groups in SCD patients. After analysing allelic association, HLA-A*02 was more frequent in SCD patients compared to control. After further allelic combination analysis of patients and compared with the control group, HLA-DQB1*02 was majorly involved in overexpression and decreasing hemoglobin level and significantly different among control and experimental groups. Conclusion: Rhesus-positive blood types were more associated with the SCA. HLA- type II alleles could influence the clinical course of sickle cell disease and HLA-DQB1*02 was significantly different among SCD group and control individuals, which signifies the concept that the allele was overexpressed among patients resulting in low Hb level.

scholarly journals Copper-To-Zinc Ratio as an Inflammatory Marker in Patients with Sickle Cell Disease

Sci ◽  
2020 ◽  
Vol 2 (4) ◽  
pp. 89
Author(s):  
Mathias Abiodun Emokpae ◽  
Emmanuel Bamidele Fatimehin
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Levels ◽  
Serum Copper ◽  
The Body ◽  
Zinc Homeostasis ◽  
Clinical State ◽  
Cell Disease ◽  
Copper And Zinc ◽  
Copper Zinc

Sickle cell disease (SCD) is an inherited disorder and a major health challenge in Nigeria. Micronutrient deficiencies often associated with the disorder may cause inflammation and abnormal metabolism in the body. The copper-to-zinc ratio is a more relevant diagnostic measure than the concentration of either metal alone in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and the copper-to-zinc ratio, and to correlate the latter with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age- and sex-matched subjects with normal hemoglobin. Serum copper and zinc were assayed by the colorimetric method using reagents supplied by Centronic, Germany, while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper-to-zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using the Students t-test, and the Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and the copper-to-zinc ratio were significantly higher (p < 0.001), while zinc level was lower in SCD patients than in controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and the copper-to-zinc ratio (r = 0.312; p < 0.002), but the correlation between CRP and fibrinogen was not significant. Inflammation may modulate copper and zinc homeostasis, and the copper-to-zinc ratio may be used as a marker of nutritional deficiency and inflammation in SCD patients.

scholarly journals Keys to Recruiting and Retaining Seriously Ill African Americans With Sickle Cell Disease in Longitudinal Studies: Respectful Engagement and Persistence

2019 ◽  
Vol 37 (2) ◽  
pp. 123-128
Author(s):  
Marie L. Suarez ◽  
Judith M. Schlaeger ◽  
Veronica Angulo ◽  
David A. Shuey ◽  
Jesus Carrasco ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Repeated Measures ◽  
African Ancestry ◽  
Healthy Controls ◽  
Cell Disease ◽  
And Gender ◽  
Seriously Ill ◽  
Participation In Research

Objectives: Sickle cell disease (SCD) is a serious illness with disabling acute and chronic pain that needs better therapies, but insufficient patient participation in research is a major impediment to advancing SCD pain management. The purpose of this article is to discuss the challenges of conducting an SCD study and approaches to successfully overcoming those challenges. Design: In a repeated-measures, longitudinal study designed to characterize SCD pain phenotypes, we recruited 311 adults of African ancestry. Adults with SCD completed 4 study visits 6 months apart, and age- and gender-matched healthy controls completed 1 visit. Results: We recruited and completed measures on 186 patients with SCD and 125 healthy controls. We retained 151 patients with SCD with data at 4 time points over 18 months and 125 healthy controls (1 time point) but encountered many challenges in recruitment and study visit completion. Enrollment delays often arose from patients’ difficulty in taking time from their complicated lives and frequent pain episodes. Once scheduled, participants with SCD cancelled 49% of visits often because of pain; controls canceled 30% of their scheduled visits. To facilitate recruitment and retention, we implemented a number of strategies that were invaluable in our success. Conclusion: Patients’ struggles with illness, chronic pain, and their life situations resulted in many challenges to recruitment and completion of study visits. Important to overcoming challenges was gaining the trust of patients with SCD and a participant-centered approach. Early identification of potential problems allowed strategies to be instituted proactively, leading to success.

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