scholarly journals Five-Year Outcomes of Chronic Red Blood Cell Exchange Transfusion Program for Patients with Sickle Cell Disease, the Experience of University of Nebraska Medical Center

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4988-4988
Author(s):  
Omar Abughanimeh ◽  
Steven Ebers ◽  
Mahammed Khan Suheb ◽  
Julie Eclov ◽  
Robin High ◽  
...  

Abstract Background: Red blood cell exchange (RBCX) is an effective therapy in treatment of acute and chronic complications of sickle cell disease (SCD). It involves exchanging patient's red blood cells (RBCs) with donor RBCs to significantly lower hemoglobin S concentration without subjecting the patient to the risk of iron overload. The University of Nebraska Medical Center (UNMC) established a chronic RBCX program in November 2015, which cared for patients with multiple hemoglobinopathies. In this study, we aim to evaluate some of the outcomes of patients with SCD who joined the program. Methods: This is a retrospective study based on review of medical records of patients with sickle cell disease. We reviewed the health records of patients with SCD who were enrolled in the chronic RBCX program between 11/2015-8/2020 at UNMC. We included patients with SCD, regardless of age, who underwent RBCX in the outpatient setting during the study period. Data were collected to assess if RBCX influenced the frequency of SCD crisis, emergency room visits, hospitalizations, and other sickle cell-related complications. Results: A total of 404 sessions of exchange transfusions were performed between November 2015 and August 2020 for 21 patients with SCD. The study included 9 adults (age ≥ 18 years) and 12 children with a median age of 12 years (2-31 years). During the study period, 3 adults left the program due to relocation out of state, patient's preference, or physician's decision. Table 1 summarizes the population demographic. The most common indication for enrollment in the RBCX program was recurrent sickle cell crisis (Figure 1). The mean number of emergency room visits before enrollment in the RBCX program was 22.5 visits (2-62 visits), which reduced after enrollment to 10.4 visits (0-65 visits), with a difference in mean of 12.1 visits (P=0.0021). The mean number of hospital admissions before enrollment in the RBCX program was 13.2 admissions(0-54 admissions), which also reduced to 6.7 admissions (0-50 admissions), with a significant difference in the means equal to 6. 6 admissions (P=0.0013) (Figure 2). Thirteen patients had a baseline ferritin > 500 ng/ml at enrollment; all of them had a decrease in their baseline ferritin during the study, with 4 of them achieving a new baseline < 500 ng/ml. Six patients had pre-existing antibodies at enrollment due to prior alloimmunization; however, no new alloantibodies were noticed after enrollment. The patients without preexisting antibodies were transfused with Rh and Kell matched blood. The patients with pre-existing antibodies were transfused with phenotypically matched blood. Three patients became pregnant during the study period, and their pregnancies were uncomplicated except for one patient with preeclampsia resulting in early delivery. There was no reportable death, acute chest syndrome, or stroke among the patients during the study period. Conclusion Outpatient chronic RBCX demonstrated safety and feasibility in both adults and children. It also showed promising outcomes in terms of reduction of sickle cell complications, number of emergency room visits and hospitalizations. These results can provide the basis for evaluating RBCX in a prospective study to better understand changes in quality of life and clinical outcomes of patients with SCD and limited therapeutic options. Figure 1 Figure 1. Disclosures Gundabolu: Pfizer: Research Funding; Samus Therapeutics: Research Funding; BioMarin Pharmaceuticals: Consultancy; Bristol-Myers Squibb Company: Consultancy; Blueprint Medicines: Consultancy.

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Mahammed Khan Suheb ◽  
Omar Abughanimeh ◽  
Steven Ebers ◽  
Julie Eclov ◽  
Aleh Bobr ◽  
...  

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.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2386-2386
Author(s):  
Alexandra Boye-Doe ◽  
Jane Little

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.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Richard Curtis Godby ◽  
Ashton Kornbrust ◽  
Denis Noubouossie ◽  
Jose Lima ◽  
Marisa B. Marques ◽  
...  

Introduction: The World Health Organization declared COVID-19 a global pandemic on 03/11/20. Subsequent concerns around caring for patients with sickle cell disease who require automated red blood cell (RBC) exchange transfusions emerged, especially in the setting of physical distancing and national shortages in blood product supplies. In this vulnerable population at high risk of allo-immunization, ideal transfusion parameters (e.g., antigen optimization) will likely grow increasingly difficult to satisfy and require careful evaluation and strategic planning. Methods: Automated RBC exchange transfusions were performed at the University of Alabama at Birmingham (UAB) in patients with sickle cell disease for a variety of clinical indications with the primary objective of lowering the amount of Hemoglobin S (goal 15%) and replacing it with Hemoglobin A. We collected the number of weekly RBC exchange transfusions performed and then compared the frequencies between 01/05/20 and 03/14/20 (pre-pandemic) to those between 03/15/20 and 08/01/20 (intra-pandemic) using a one-tailed t-test. We also examined the number of RBC units ordered per week at UAB, in both the inpatient and outpatient settings, shortly before and after the declaration of a global pandemic using a one-tailed t-test. Results: The mean frequency of RBC exchange transfusions performed per week was 8.1 [standard deviation 2.3] pre-pandemic and 8.6 [2.3] intra-pandemic (Figure 1a). There was no statistically significant difference (p=0.27) in the frequency between these two periods. Shortly prior to the start of the pandemic (02/23/20-03/14/20), a mean of 77.3 [17.9] units/week were ordered for outpatient RBC exchange transfusions. Shortly after the start of the pandemic (03/15/20-04/26/20), a mean of 55.3 [22.8] units/week were ordered for outpatient RBC exchange transfusions, which was also not significantly different (p=0.09). During this time period, the mean number of RBC units per week ordered in the inpatient surgical setting significantly declined from 719.3 [43.1] to 390.0 [46.8] as elective procedures were delayed (p&lt;0.005) (Figure 1b). Conclusions/Future Directions: The frequency of automated RBC exchange transfusions performed at UAB did not decrease after the onset of the pandemic. UAB was able to continue caring for patients with sickle cell disease receiving RBC exchange transfusions as the pandemic emerged and national blood product supplies declined despite a similar overall demand. Interestingly, there was also a concomitant decrease in the demand for RBCs from inpatient surgical settings as elective procedures were delayed, possibly contributing to the blood bank's ability to maintain ideal transfusion parameters and perform antigen optimization of transfused RBCs. As the COVID-19 pandemic continues, the national shortage of blood product supplies will likely worsen and necessitate multidisciplinary efforts, including intra-institutional and inter-institutional collaborations, to continue caring for patients with sickle cell disease receiving RBC exchange transfusions. Furthermore, community education, safely structured blood drives, and other efforts to encourage donations are essential to maintain the national blood product supply. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2170-2170
Author(s):  
John Chinawaeze Aneke ◽  
Aliraza Rajabali ◽  
Nafanta Fadiga ◽  
Stéphanie Forté ◽  
George A. Tomlinson ◽  
...  

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.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Bindu K Sathi ◽  
Kelsey Busken ◽  
Emily Coberly ◽  
Barbara Gruner

Introduction Red blood Cell (RBC) transfusion therapy is an important disease modifying treatment in sickle cell disease (SCD). RBC alloimmunization is one of the more serious complications associated with transfusion therapy and limits its wider clinical application. This complication can result in both acute and delayed hemolytic reaction in the recipients. It is unknown at this time if alloimmunization can lead to broader downstream end-organ complications in sickle cell disease. In this retrospective study, we analyzed the complications associated with RBC alloimmunization in the Central Missouri SCD cohort following development of allo- antibodies (Allo-Ab). Methods We performed a retrospective chart review of all SCD individuals treated at the University of Missouri Medical Center from December 2000 to 2017. Only SCD patients that received RBC transfusions at the Center were included in the study. A two-tailed student's t-test was used to analyze all continuous variables. Fischer's exact test was used to analyze all categorical variables. Apvalue of &lt;0.05 was considered statistically significant. Results Of the 130 SCD patients, 80 patients were eligible to be included in the study based on available laboratory and clinical data. There were 51 HbSS, 25 HbSC, and 4 HbSβ0/+ patients, and overall, 28% of the patients had alloantibodies following transfusion therapy. The mean hemoglobin and hematocrit were lower in alloimmunized versus non-alloimmunized (8.65 gm/dl vs 9.48 gm/dl, p = 0.016) SCD individuals. Reticulocyte count, total bilirubin (2.9 mg/dl versus 1.8 mg/d, p = 0.02), and urine urobilinogen were elevated in allo-immunized individuals. Overall, alloimmunized patients received more packed red blood cell (PRBC) units/life year (9.18 versus 3.60 units, p = 0.021). Demographic factors like age of first transfusion, systolic, diastolic, and mean blood pressures were not significantly different between the groups. Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP) were not significantly different in alloimmunized and non-alloimmunized individuals. Absolute neutrophil count, platelet count, and lymphocyte counts were not significantly altered in patients with and without allo-AB. Hemoglobin F concentration or hydroxyurea usage were not significantly different between the groups. Distinct gender differences in hematological profile and end-organ complications were observed in allo-immunized individuals (Table 1). Indirect markers of hemolysis were persistently elevated in alloimmunized men (Table1) compared to women. Seizures were an associated complication in alloimmunized compared to non-alloimmunized (66.6% versus 33.3%, p = 0.0058) men. Decreased glomerular filtration rate (GFR) was observed in women with alloimmunization compared to men. Conclusions Alloimmunization in men is associated with distinct downstream complications compared to women. Persistence of elevated indirect markers of hemolysis were observed more in men with allo-Ab. Men with allo- Ab had more central nervous system complications compared to women. These findings have important clinical and therapeutic significance and needs to be tested in larger clinical trials. Figure 1 Disclosures Busken: ASH:Other: 2018 HONORS Award Recipient.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 811
Author(s):  
Camille Boisson ◽  
Minke A. E. Rab ◽  
Elie Nader ◽  
Céline Renoux ◽  
Celeste Kanne ◽  
...  

(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC, and S/β+) or under different treatments (hydroxyurea or chronic red blood cell exchange). (2) Methods: Oxygen gradient ektacytometry was performed in 167 adults and children at steady state. In addition, five SS patients had oxygenscan measurements at steady state and during an acute complication requiring hospitalization. (3) Results: Red blood cell (RBC) deformability upon deoxygenation (EImin) and in normoxia (EImax) was increased, and the susceptibility of RBC to sickle upon deoxygenation was decreased in SC patients when compared to untreated SS patients older than 5 years old. SS patients under chronic red blood cell exchange had higher EImin and EImax and lower susceptibility of RBC to sickle upon deoxygenation compared to untreated SS patients, SS patients younger than 5 years old, and hydroxyurea-treated SS and SC patients. The susceptibility of RBC to sickle upon deoxygenation was increased in the five SS patients during acute complication compared to steady state, although the difference between steady state and acute complication was variable from one patient to another. (4) Conclusions: The present study demonstrates that oxygen gradient ektacytometry parameters are affected by sickle cell disease (SCD) genotype and treatment.


Lab on a Chip ◽  
2021 ◽  
Author(s):  
Yuncheng Man ◽  
Debnath Maji ◽  
Ran An ◽  
Sanjay Ahuja ◽  
Jane A Little ◽  
...  

Alterations in the deformability of red blood cells (RBCs), occurring in hemolytic blood disorders such as sickle cell disease (SCD), contributes to vaso-occlusion and disease pathophysiology. However, there are few...


2001 ◽  
Vol 23 (3) ◽  
pp. 165-169 ◽  
Author(s):  
Tay S. Kennedy ◽  
Ellen B. Fung ◽  
Deborah A. Kawchak ◽  
Babette S. Zemel ◽  
Kwaku Ohene-Frempong ◽  
...  

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