End-Alveolar Carbon Monoxide As a Measure of Erythrocyte Survival and Hemolytic Severity in Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2696-2696
Author(s):  
Caterina P. Minniti ◽  
John H. Baird ◽  
Dihua Xu ◽  
Laurel Mendelsohn ◽  
Rehan Saiyed ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Life Span ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Adult Patients ◽  
Red Cell ◽  
Cell Disease ◽  
Indirect Bilirubin ◽  
Cell Lifespan

Abstract Introduction: In sickle cell disease, polymerization of sickle hemoglobin gives rise to changes in the integrity and viability of the erythrocyte, leading to both extravascular and intravascular hemolysis and shortened life-span. Current gold standard techniques to estimate RBC survival require that a label be placed on the cells that can be followed while the RBCs age in the circulation. These studies are infrequently employed in practice, due to the need for multiple blood draws and an extended period of observation (6 weeks) in order to obtain the necessary time points. Endogenous CO is a technique that has been used in multiple studies to assess RBC survival, based upon the principal that virtually all CO produced in human beings results from cleavage of the α-methene bond of heme and is completely excreted via the lungs. Because RBC destruction accounts for approximately 80% of heme turnover in the body, endogenous CO production can be used as a quantitative indicator of RBC life span. Furne has reported on the development of a simple, rapid, and noninvasive method for determining RBC life span based on gas chromatography measurement of exhaled alveolar CO (EACO) concentration immediately upon awakening corrected for atmospheric CO, as determined with a device that simulates the body's equilibration with CO. We set up to investigate the use of early morning end-alveolar CO (EACO) concentration as a quantitative measure of RBC life span and correlate it to indirect measurements of hemolytic rate in subjects with sickle cell disease. Material and methods: EACO was measured within 24 hours of breath collection in 67 SCD adult patients (67 HbSS, 4 HbSC and 1 HbSb-Thalassemia) and 14 HbAA race matched controls on an Ametrek TA 7000 Gas Purity Monitor. Subjects were at steady state, at least 30 days from transfusion or acute exacerbations. Breath samples were collected immediately upon awakening the same day as blood sampling for additional tests. EACO groups were compared using the Mann-Whitney test. EACO values were used to calculate the red blood cell lifespan by the method of Furne (PMID 12878986), using the calculation: RBC survival (days) = 1,380 · [Hb]/EACO. Correlation analyses are reported using Pearson's correlation coefficient. The statistical significance was set at a two-side p < .05. Analyses were performed with R version 2.13.1 (2011-07-08). Results: EACO was nearly four-fold higher in patients than controls (median 2.25 vs. 0.58 ppm, p<.0001, figure). In patients with SCD, unadjusted EACO values were correlated with %HbS (p<.01), indirect markers of hemolysis: absolute reticulocyte count (p<.02), and percentage of reticulocytes (p<.01), indirect bilirubin (p<.001), and negatively with plasma nitrite (p<.02). EACO-derived red blood cell lifespan correlated negatively with LDH (p<.04), hematocrit (p<.01), hemoglobin (p<.06) indirect bilirubin (p<.01), absolute and percent reticulocyte counts (p<.01), AST (p<.01), and %HbS (p<.01). Conclusions: Our results confirm the usefulness of exhaled CO measurement as a marker of hemolysis and red cell survival and in substantial, prospective cohort of adult patients with SCD, confirming and considerably extending results of other investigators. EACO-derived RBC survival can be used to update estimates from Crosby in 1955 regarding the proportion of overall hemolysis falling into the extravascular and intravascular categories, the latter related to oxidative stress and scavenging of nitric oxide. This assay may be a useful biomarker in clinical trials of therapeutic interventions aimed at improving red cell life-span in SCD and other hemolytic anemias. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Non-crisis related pain occurs in adult patients with sickle cell disease despite chronic red blood cell exchange transfusion therapy

2021 ◽  
pp. 103304
Author(s):  
Susanna A. Curtis ◽  
Balbuena-Merle Raisa ◽  
John D. Roberts ◽  
Jeanne E. Hendrickson ◽  
Joanna Starrels ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Exchange Transfusion ◽  
Adult Patients ◽  
Cell Disease ◽  
Transfusion Therapy

Clinical Effects of Chronic Red Blood Cell Exchange and Different Types of Red Cell Concentrates in Patients with Sickle Cell Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4823-4823
Author(s):  
Sergio Cabibbo ◽  
Agostino Antolino ◽  
Giovanni Garozzo ◽  
Carmelo Fidone ◽  
Pietro Bonomo
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Iron Overload ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Whole Blood ◽  
Clinical Effects ◽  
Red Cell ◽  
Blood Components ◽  
Cell Disease

Abstract For patients with severe SCD not eligible for hydroxyurea, two major therapeutic options are currently available: blood transfusion, and bone marrow transplantation. Either urgent or chronic red blood cell transfusion therapy, is widely used in the management of SCD but determines a progressive increase of ferritin level and is also limited by the development of antibodies to red cell antigens. The introduction of chronic red blood cell exchange and prestorage filtration to remove leucocytes and the use of techniques for multicomponent donation could be a good solutions. Thus, the aims of our studies were to evaluate the clinical effects of the different blood components in terms of annual transfusion needs and the intervals between transfusion, moreover we evaluated the efficacy of chronic red blood cell exchange (manual or automatic with cell separator) in preventing SCD complications and limiting iron overload. In our center we follow 78 patients affected by Sickle Cell Disease. We selected 36 patients occasionally treated with urgent red blood cell exchange because they had less than 2 complications/Year, and 42 patients regularly treated with chronic red blood cell exchange because they had more than 2 complications/Year with Hospital Admission. Moreover among these we selected 10 patients for fulfilling the criteria of continuous treatment at the Centre for at least 48 months with no interruptions, even sporadic and absolute transfusion dependency. All 10 patients were evaluated for a period of 4 years, during which two different systems of producing RCC were used. In the second two the patients were transfused with RCC obtained from filtering whole blood prestorage or with RCC from apheresis filtered prestorage. These products differed from those used in the preceding two years, during which the leucodepletion was obtained by bed-side filtration For all the patients we performed 782 automatic red blood cell exchanges and 4421 units of RCC were transfused. The exchange procedures were extremely well-tolerated by the patients and adverse effects were limited to symptoms of hypocalcaemia during automatic red blood cell exchange with cell separator. After every red blood cell exchange we obtained HbS level &lt; 30%. The10 patients selected received respectively a mean of 6.9 and 6.1 units of RBCs exchanged per automatic procedure, in the first two years and in the second two years. Alloantibody developed in 14 patients but only 2 clinically significant and about the observed frequency of transfusion reactions it was very low. All patients treated with chronic red blood cell exchange had an improvement of the quality of life with a reduced number of complications/year (&lt;2/year) and good compliance and moreover patients had limited iron overload making chelating therapy easier. In conclusion this study was focused on the most suitable characteristics of blood components for use in sickle cell disease patients and the choice of systematically adopting prestorage filtration of whole blood, enabled us to have RCC with a higher Hb concentration than standard. Moreover chronic manual or automatic red blood cell exchange as an alternative approach to simple long-term RBC transfusions give many advantages by being more rapid and tolerable as well as clinically safe and effective and minimize the development of iron overload especially when procedure was carried out with an automatic apparatus. To note that the clinical advantages for patients derived from good selection of the donor and good practices in the production of the blood components

scholarly journals Outcomes of Red Cell Exchange in Pregnant Patients with Sickle Cell Disease: A Case Series

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Mahammed Khan Suheb ◽  
Omar Abughanimeh ◽  
Steven Ebers ◽  
Julie Eclov ◽  
Aleh Bobr ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Emergency Room ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Red Cell ◽  
Cell Disease ◽  
Modest Improvement ◽  
Exchange Program ◽  
The Third

Background: Pregnant patients with sickle cell disease (SCD) have higher morbidity compared to patients without SCD. SCD during pregnancy can increase the risk of fetal and obstetrical complications including preterm birth, preeclampsia, and others. Moreover, during pregnancy SCD can become more severe resulting in more sickle cell vasoocclusive crisis. Prophylactic transfusion during pregnancy has been used in practice to reduce sickle cell pain crisis since hydroxyurea is contraindicated during pregnancy. However, using prophylactic red blood cell exchange (RBCX) has been a controversial topic. In this study, we aim to evaluate the outcomes of red blood cell exchange in pregnant patients with SCD Methods: This is a retrospective study. We evaluated the charts of three pregnant patients who were enrolled in the chronic RBCX program at the University of Nebraska Medical Center at the time of their pregnancy. Data was collected to assess the sickle cell disease related complications during pregnancy, outcomes of pregnancy, and safety of the red blood cell exchange. Results: A total of 19 exchange procedures were performed for three pregnant patients while being enrolled in the chronic red blood cell exchange program. Patients demographic is summarized in table 1. The indication for enrollment in the red cell exchange program were recurrent vasooclussive crisis in patient 1 and 3, avascular necrosis in patient 2. The pregnancies were uncomplicated except for preeclampsia in the third patient resulting on early delivery. Overall, the three patients had less frequent visits to the emergency room for sickle cell related complications after starting apheresis and during pregnancy (Figure 1). We believe that the modest improvement that was noticed for the third patient was due to late enrollment in the exchange transfusion program and her older age compared to the two other patients Conclusion: Our study shows that red blood cell exchange for SCD patients during pregnancy can be safe, feasible, and can reduce the visits to the emergency room due to SCD related complication. Further larger studies are warranted to confirm this. Disclosures Gundabolu: BioMarin:Consultancy;Bristol Myers Squibb pharmaceuticals:Consultancy.

scholarly journals Assessment of Average Hematocrit of Red Cell Units for Erythrocytapheresis Procedure in Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4285-4285
Author(s):  
Veronica Cook ◽  
Teresa Munson ◽  
Elpidio Pena ◽  
Ashok Raj
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Small Sample ◽  
Red Cells ◽  
Red Cell ◽  
Limited Data ◽  
Cell Disease ◽  
Consensus Report

Abstract Background: Erythrocytapheresis, or red blood cell exchange (RCE) is a non-invasive procedure in which a patient's erythrocytes are removed from the bloodstream while being replaced with erythrocytes from blood donors. RCE is commonly used as a transfusion technique in patients with sickle cell disease (SCD) to help treat and prevent complications associated with sickling of erythrocytes and iron overload. The AABB consensus report (1) outlines the procedural guidelines for RCE including appropriate indications and ideal forms of vascular access. However, the guidelines make no recommendation for determining the hematocrit (Hct) of the red cell bags for the procedure. Institutions take several different approaches to determine how many red cell units to exchange. The number of units needed depends on the volume and Hct of the individual units as well as the patient's pre-procedure Hct and HbS levels, height, weight, and the desired HbS and Hct targets. Red cell units are routinely labeled with volume, but are not generally labeled with Hct. The AABB consensus report (1) states that some institutions use an estimated Hct of 56% to 57% for each unit. The report rationalizes the use of an estimated Hct for input for the RCE, by citing the approximated Hct of bags of red cells (55% to 60%) with additive solution produced from whole blood donation, based on limited data. The goal of our study was to determine the average Hct on the red cell units used for RCE. Methods: This study used a retrospective chart review to investigate the Hct of red cell units during a RCE in a calendar year. Our institution uses pre-storage leuko-reduced red blood cells units in citrate phosphate dextrose adenine (CPDA-1) and adsol preservative (AS-1), which are 21 days old or less for RCE. The average Hct of the bags of red cells infused during the procedure was determined by accessing each bag for a small sample of blood to determine the Hct. Data was excluded if the patient did not meet standard weight requirements (&gt; 30 kg) or required additional treatment protocols including the use of washed cells or machine priming. Results: A total of 297 encounters were recorded for 30 different patients. A total of 1953 bags (approximately 517 liters of red cell units in volume) were administered. Data from the encounters were used to calculate measures of central tendency. The average calculated Hct for each encounter was 63.3%, with a median and mode Hct being 63% and 62%. The range of Hct from the bags was 54.6% to 72.9%. The average Hct of the bags ranged from 60.6% (in March) to 64.8 % (in July). Conclusions: Our study suggests a higher average Hct of transfused red cell units than stated in the AABB consensus report (1), which was based on limited data. Our findings indicate that a standardized average of 63.3%, would be appropriate for our institution. Conversely, our findings also signify that the standardized average Hct must be determined in each institution prior to their application for RCE. However, our data also reveals that it is possible to subject patients to estimates as far as 9.7% above and 9.6 % below the true average Hct of the red cell bags used. The process of determination of Hct for each of the red cell units increases the time of pre-service activities, laboratory costs, and the overall infusion center time for the patients leading to higher costs per infusion. Consequently, using a standardized average of the Hct would result in cost savings. We have therefore adopted the practice of using the standardized average of Hct of 63.3% for RCE in our patients. Reference: 1. Biller E, Zhao Y, Berg M, Boggio L, Capocelli KE, Fang DC, Koepsell S, Music-Aplenc L, Pham HP, Treml A, Weiss J, Wool G, Baron BW. Red blood cell exchange in patients with sickle cell disease-indications and management: a review and consensus report by the therapeutic apheresis subsection of the AABB. 2018 Aug;58(8):1965-1972. doi: 10.1111/trf.14806 Disclosures Munson: Terumo Medical Corporation: Consultancy, Honoraria, Speakers Bureau. Raj: Terumo Medical Corporation: Honoraria, Speakers Bureau; Global biotherapeutics: Speakers Bureau; Forma therapeutics: Consultancy.

scholarly journals Red Blood Cell Adhesion in Adult Patients with Sickle Cell Disease, at Baseline and with Pain, Measured on SCD Biochip Microfluidic Assay

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2386-2386
Author(s):  
Alexandra Boye-Doe ◽  
Jane Little
Keyword(s):  
Cell Adhesion ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Research Funding ◽  
Adult Patients ◽  
Cell Disease ◽  
University Hospitals ◽  
Western Reserve

Abstract Red Blood Cell Adhesion in Adult Patients with Sickle Cell Disease, at Baseline and with Pain, Measured on SCD Biochip Microfluidic Assay Alexandra Boye-Doe1, Erina Quinn1, Charlotte Yuan1, Umut A. Gurkan, PhD1, and Jane A. Little, MD2 1Case Western Reserve University, Cleveland, OH; 2Division of Hematology/Oncology, Case Western Reserve University/ University Hospitals Seidman Cancer Center, Cleveland, OH Background: Despite being monogenic, sickle cell disease (SCD) has a variable phenotype, in which clinical complications and manifestations evolve as patients age. In children, pain generally resolves between crises, whereas adults may experience acute, chronic, or acute-on-chronic pain. We have taken a multifaceted approach to characterize adhesion and inflammation during self-identified pain episodes in adults with SCD in order to better understand pain syndromes in adults and the potential for more specifically targeted therapies. In this pilot study, we assessed changes in red blood cell (RBC) adhesion to the subendothelial protein laminin (LN) during crisis in adults with SCD self-reporting for pain crisis on whom we had baseline adhesion data from a routine clinic visit. Methods: Surplus blood from patients' routine bloodwork was used. Crisis samples were collected from patients at the Acute Care Clinic or Emergency Department at University Hospitals Cleveland Medical Center (UHCMC) when patients presented for management of pain. Baseline samples were collected during routine visits to the Sickle Cell Clinic. This study was approved by the IRB at UHCMC. Within a 24-hour period, RBC adhesion to LN was quantitated by microscopy after passage of unprocessed whole blood through a LN-coated microfluidic adhesion assay, the SCD biochip [1]. Samples were analyzed for hemoglobin (Hb) phenotype by high-performance liquid chromatography (HPLC) in the clinical lab. Correlative clinical data, including, baseline lab values, and medical history, were obtained from the patients' medical records and used to characterize our results. Data from people with multiple samples were used as median values. Results: Blood samples from 19 unselected patients with sickle cell hemoglobin SS (HbSS) were obtained at crisis, and compared with baseline samples obtained from 2014 to 2018 (n = 67 samples). 2 groups were identified: Group 1 with increased adhesion (>25% rise from baseline, n= 10) during crisis, and Group 2 with decreased adhesion (>25% fall from baseline, n=8) or no change (<25% change) (n=1) during crisis (Fig. 1). Time between a patient's initial crisis event and when they presented for pain management varied, possibly affecting observed adhesion. Nonetheless, patients showing an increased adhesion in crisis also showed a decrease in Hb (p = 0.039) between their baseline analyses and the crisis visit. A decrease in Hb may associate with increased adhesion, if the latter contributes to crisis-related hemolysis. However, other markers of hemolysis did not change. By contrast, patients with decreasing RBC adhesion showed a decrease in absolute reticulocyte count (ARC, p = 0.019) at their crisis visit. Statistical analysis of HbS, HbA, and HbF levels n = 64 showed no significant change between baseline or crises. Discussion: A decrease in adhesion during crisis may reflect the presence of sickled RBCs that adhere preferentially to other basement membrane proteins such as fibronectin or thrombospondin. In addition, inflammatory white blood cell adhesion, possibly central to vaso-occlusion, is not evaluated in this study. We are currently examining cytokine and monocyte profiles from people with SCD presenting for management of pain, so that we may better understand inflammatory mediators of pain. Our data are the first to try to understand RBC adhesion in people with SCD who present for management of pain, whether this as an isolated or common event for that person. We found that unselected adults with SCD who presented for management of pain had heterogeneous changes in RBC adhesion, which may reflect differences in underlying mechanism. The pathophysiologic heterogeneity of pain in adults with SCD will be important to understand as anti-adhesion therapies are being developed and adopted clinically. Disclosures Little: Doris Duke Charitable Foundations: Research Funding; NHLBI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; PCORI: Research Funding.

Barriers to using molecularly typed minority red blood cell donors in support of chronically transfused adult patients with sickle cell disease

Transfusion ◽  
2015 ◽  
Vol 55 (6pt2) ◽  
pp. 1399-1406 ◽  
Author(s):  
Matthew S. Karafin ◽  
Joshua J. Field ◽  
Jerome L. Gottschall ◽  
Gregory A. Denomme
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Adult Patients ◽  
Cell Disease

scholarly journals Rate of Sickle Hemoglobin Recovery in Sickle Cell Disease Patients Undergoing Red Blood Cell (RBC) Exchange Transfusion Is Associated with Age of Patients and Number of RBC Units Transfused

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2170-2170
Author(s):  
John Chinawaeze Aneke ◽  
Aliraza Rajabali ◽  
Nafanta Fadiga ◽  
Stéphanie Forté ◽  
George A. Tomlinson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Research Funding ◽  
Exchange Transfusion ◽  
Rate Of Change ◽  
Cell Disease ◽  
Sickle Hemoglobin ◽  
Indirect Bilirubin

Rate of Sickle Hemoglobin Recovery in Sickle Cell Disease Patients Undergoing Red Blood Cell (RBC) Exchange Transfusion is Associated with Age of Patients and Number of RBC Units Transfused Introduction: Automated and manual red blood cell exchange (RBCX) transfusions are useful in the primary and secondary prevention of sickle cell disease (SCD) complications (Ware et al., 2012). The ability to consistently maintain sickle hemoglobin (HbS) below target (30% or 50% depending on indication) is quite variable (Kuo et al., 2012). With emerging indications such as silent cerebral infarction, it is imperative that effective means of chronic transfusion to maintain appropriate hematological and clinical targets be identified. We hypothesize the rate of HbS recovery is dependent on the individual's hemolytic and erythropoietic rate. The purpose of this study is to evaluate the effect of the rate of erythropoiesis and hemolysis on HbS recovery in SCD patients undergoing RBCX. Methods: Fifteen (15) patients were prospectively recruited from the adult SCD transfusion program (9 automated, 6 partial manual), from December 2018 to July 2019, and followed through one exchange cycle (4 weeks). Automated and partial manual exchange transfusion protocols have been previously described elsewhere (Canadian Haemoglobinopathy Association Consensus Statement on the Care of Patients with Sickle Cell Disease in Canada, Version 2.0, Ottawa; 2015). Exclusion criteria included active hydroxyurea or erythropoietic stimulating agents use, reported ill health in the preceding 4 weeks, co-morbid hemolytic condition or non-HbSS genotype. Hemoglobin, hematocrit, HbS, lactate dehydrogenase (LDH), reticulocyte count, indirect bilirubin, and serum erythropoietin level were determined for each patient: pre- and post- first exchange, weekly for 3 weeks and pre- second exchange (the 4th week). Descriptive variables were either expressed as means ± SD or median (IQR), based on normality, while linear regression was performed for continuous variables. Co-variates were included in multivariable analysis if P < 0.10. Multivariable linear regression was conducted to examine the potential association between the change in HbS over one RBCX cycle and age of patients, pre-RBCX hematocrit, LDH, and number of RBC units transfused. Results: We identified 36 eligible patients from the Program database, after which 15 consented to participate in the study. Mean age was 32.9 ± 12.3 years, consisting of 7 males and 8 females. There was an association between the rate of change in HbS and age of patients (p=0.035), pre-RBCX hematocrit (p=0.030) and number of transfused RBC units (p=0.030). LDH showed a trend towards reduced rate of change in HbS (p=0.069). Rate of change in HbS was not associated with automated vs. partial RBCX (Figure), female vs. male patients, pre-RBCX HbS, erythropoietin, indirect bilirubin, reticulocyte and age of transfused RBCs. Age of patients (p<0.001) and number of units transfused (p=0.010) were independently associated with the rate of change of HbS, after adjusting for hematocrit and LDH. For every decade increase in age, the rate of HbS recovery was 3% lower in one RBCX cycle. For each additional unit of RBC exchanged, the rate of HbS recovery was 0.78% higher in one RBCX cycle. Conclusion: This is the first study to evaluate the determinants of variability in the rate of HbS recovery in SCD patients on RBCX. Age of patients and number of RBC units transfused may underlie the significant variability in achieving HbS targets in SCD patients on RBCX. We failed to show a significant difference in the rate of change in HbS between automated and partial manual exchange transfusion. Reduction in HbS recovery with advancing age may be related to erythropoietic reserve in the patients' marrow. However, the influence of units of RBC recovery appeared paradoxical, and the finding may be spurious due to small sample size. It may therefore be possible to appropriately titrate the number of RBC units with advancing age of SCD patients with a view to achieving desired HbS targets. Disclosures Patriquin: Ra Pharma: Consultancy, Research Funding; Apellis: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding. Kuo:Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy.

scholarly journals Red Blood Cell Alloimmunization in Sickle Cell Disease: Advantage of Ethnic Heritage between Donors and Patients in Jeddah, Saudi Arabia

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S157-S157
Author(s):  
F Anwar ◽  
M Almohammadi ◽  
A Garni ◽  
S Jamallail ◽  
W Alsamkari ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Eastern Region ◽  
Red Cell ◽  
Cell Disease ◽  
History Of ◽  
K Antigen

Abstract Introduction/Objective Red blood cell (RBC) transfusion is frequently required for patients with sickle cell disease (SCD). Development of alloantibodies in these patients complicates the blood bank process needed to identify these antibodies and to find compatible RBC units. The rate of alloimmunization has been reported as high as 47% in one study and 34.2% in another study from Eastern region of Saudi Arabia. The purpose of this study was to determine incidence and rate of RBC alloimmunization in the Saudi population in the Western region in SCD. Methods/Case Report A retrospective analysis of the immunohematological and transfusion history of a total of 161 SCD patients was reviewed, of which there 95 males and 66 females. All patients had erythrocytapheresis, ranging from one to 24 full red cell exchange sessions. A total of 490 red cell exchanges were performed and 4,914 units of blood were used. Extended compatibility to RhCcEe and K antigen was performed. Patient who developed alloimmunization to any of RhCcEe and K antigen were matched for Kidd, Duffy and MSN antigens for subsequent RBC requirements. Results (if a Case Study enter NA) The RBC alloimmunization incidence was 18% with a rate of 0.6 antibodies per 100 RBC transfusions. Alloimmunization in females was significantly higher than in the patients. Eighteen (11.2%) female patients demonstrated antibodies as compared to eleven (6.8%) male patients. Twelve patients (7.4%) had a history of at least one alloantibody and 17 (10.6%) had more than one. Antibodies found were directed against E (7.4%), K (5.6%), and D, C, c, S, M, Lea, Jk a, Chido/Rodgers, Fy a. Seven (4.3%) patients also had warm autoantibodies. Conclusion RBC alloimmunization incidence and rate in our study was lower to those reported in less heterogeneous population of donors and patients. Nonetheless, RBC alloimmunization still occurs in patients with SCD, often due to Rh variants or lack of consistency in the application of prophylactic antigen matching between institutions. Therefore, we believe that this rate can still be further reduced if all centers in the region establish transfusion programs to include at least RhCcEe and K phenotypic compatibility and communication mechanisms between major treating centers and transfusion centers in smaller cities to minimize the risks of exposing the patient to different RhCcEe and K phenotype and of developing RBC alloimmunization.

scholarly journals Blood Transfusion in Adult Patients with Sickle Cell Disease: Incidence of Alloimmunization

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4859-4859 ◽  
Author(s):  
Samip Master ◽  
Menchu Ong ◽  
Richard Preston Mansour
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Disease Incidence ◽  
Adult Patients ◽  
Red Blood Cell Transfusion ◽  
Acute Chest Syndrome ◽  
Cell Disease

Abstract Background: Chronic red blood cell transfusion has been proven to be effective in prevention of strokes, silent cerebral infarcts, acute chest syndrome, recurrent priapism and in pregnancy. The use of regular transfusions to mitigate other morbidities of sickle cell disease (SCD) is evolving. In the silent infarct transfusion (SIT) trial in children, chronic transfusion lead to a significant improvement in quality of life. Some of the common reasons patient with SCD do not get chronic transfusion is fear of alloimmunization, iron over load and risk of viral infections. We did a retrospective analysis of adult patients with SCD who need chronic blood transfusion to determine the incidence of alloimmunization. At our institute all pediatric sickle cell patients needing chronic transfusion are placed on protocol, receive C, E, and K matched blood, and remain on the protocol until they become adults. Methods: We electronically collected data from 180 adult SCD patients who need chronic transfusions and analyzed the data for the number of transfusions received, incidence of allo- immunization and most common antibodies identified. Results: A total of 3967 red blood cell transfusions were administered on 180 adult sickle cell disease patients. Twenty five patients developed antibodies (13.8 %). Fifteen out of the 25 had multiple antibodies (60%). The alloantibodies identified were : anti- K(11), anti- E(12), anti- Fya(5), anti-C (4), anti-V (4), anti- S (3), anti-D (2), anti- Jkb (1), anti-Jsa(1) , and anti- Lutherana (3). Two patients had cold and 5 patients had warm autoantibodies. Conclusion: The policy to place patients with SCD needing chronic transfusion on protocol to receive C, E, and K matched red blood cells has decreased the alloimmunization rate to 13.8 %. We conclude that, fear of alloimmunization should not preclude physicians from using chronic red cell transfusions to prevent complications in sickle cell disease. Disclosures No relevant conflicts of interest to declare.

Clinical and Genetic Variability of Red Blood Cell Hemolysis in Sickle Cell Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1077-1077
Author(s):  
Jacqueline N Milton ◽  
Paola Sebastiani ◽  
Yingze Zhang ◽  
Mehdi Nouraie ◽  
Janet Lee ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Globin Gene ◽  
Red Cell ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Plasma Hemoglobin ◽  
Cell Storage

Abstract Abstract 1077 Intravascular hemolysis is an important pathological mechanism underlying some complications of sickle cell disease and other hemolytic anemias. Hemolysis contributes to endothelial dysfunction, pulmonary and systemic vasculopathy, and platelet and hemostatic activation via nitric oxide catabolism by plasma hemoglobin and arginine catabolism by red blood cell arginase. Little is known about the molecular mechanisms of hemolysis and how the propensity of erythrocytes to hemolyze is modulated. Hemoglobin F concentration and the presence of ∝ thalassemia affect the level of hemolysis but it is likely that other genes and their products are also important. We hypothesize that genetic variation, much of which is outside the β-globin gene-like cluster, underlies the susceptibility of erythrocytes to hemolyze in response to diverse disease stressors. We first characterized hemolysis by creating a principal component analysis (PCA) of age-adjusted values for LDH, AST, reticulocyte count and total bilirubin, but not hemoglobin concentration, to develop a hemolytic component that reflects shared variability among markers. The development of such a component helps to resolve the problem of dealing with correlated predictors in multivariate analyses and confounding variables such as site, and it permits for adjustment for the degree of anemia. To validate the PCA, we measured the plasma hemoglobin levels and red cell microparticle levels in the first and fourth quartile of PCA intensity of hemolysis in 118 HbS-only patients without detectable HbA, from the Walk-PHASST cohort We observed a highly significant increase in plasma hemoglobin (p<0.0001) and red cell microparticles (p=0.0004) based on PCA quartile. Despite the small sample size of this validating cohort we reproduced significant associations between high hemolytic rate and the subphentypes of low arterial oxygen saturation, high pulse pressure, leg ulcers, TRV, high NT-proBNP levels, and low 6-minute walk test distance. More patients with ∝ thalassemia and more females were present in the lower hemolytic index quartile (p=0.006). The hemolytic index and its individual components were then used as phenotypes in genome-wide association studies (GWAS) in the CSSCD (Cooperative Study of Sickle Cell Disease) and walk-PHaSST cohorts to discover novel genes that might be associated with hemolysis. As further validation of our approach using PCA stratification, patients in the quartile with the lowest hemolytic index from the CSSCD also had a much higher prevalence of ∝ thalassemia than patients within the highest quartile of hemolytic index (p=2.2E-16). We first examined 1117 cases from the CSSCD and found 303 SNPs, 265 with a MAF >0.05, that reached a threshold of significance of p<5E-4. For replication, we examined these SNPs in the Walk-PHASST cohort. Eight SNPs replicated with the same effects in a GWAS in 449 subjects from Walk-PHAAST and p-value<0.01. Of the 8 SNPs that replicated, 4 SNPs were in olfactory receptor (OR) genes on chromosome (chr) 11p; OR51L2 (rs7948471, rs7938426. rs1391617), and OR51L1 (rs2445284). Several of these SNPs were also associated with HbF in previous GWAS analyses. Polymorphisms in the OR gene cluster upstream of HBG might modulate HbF levels by altering chromatin structure within the HBB globin gene-like cluster. One SNP in an intron of NPRL3 (rs7203566) on chr16p is ∼34 kb upstream from a SNP causing ∝ thalassemia. In CSSCD cases there was an association of SNPs in NPRL3 with reticulocytes (p=5.1E-0006) and LDH (p=0.0003). In silico analysis did not predict any function for this SNP. Genetic studies to discover new biologic modifiers of hemolysis will help to identify critical molecular determinants of hemolysis for functional studies, to develop new disease severity biomarkers, and to suggest candidate therapies for some common human diseases with intravascular hemolysis. We anticipate that our studies will identify genetic variants enriched in the African-American population primarily determined by the evolved human response to endemic malaria infection. These studies are expected to broadly impact many human diseases and blood banking by providing genomic markers of susceptibility to hemolytic anemia, red cell storage stability and transfusion risk, and insights into novel strategies to reduce anemia and to enhance red blood cell storage and post-transfusion erythrocyte recovery. Disclosures: Gladwin: Patents filed related to treating hemolysis.: Patents & Royalties.

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