scholarly journals Alloimmunization Is Associated with Increased Indirect Markers of Hemolysis and Distinct End-Organ Specific Complications in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Bindu K Sathi ◽  
Kelsey Busken ◽  
Emily Coberly ◽  
Barbara Gruner
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Medical Center ◽  
Categorical Variables ◽  
Cell Disease ◽  
Hemoglobin F ◽  
Transfusion Therapy ◽  
Organ Complications

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 <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.

scholarly journals Designated Donor Program Enrollment Does Not Affect Red Blood Cell Alloimmunization Rates in Children with Sickle Cell Disease on Chronic Transfusion Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4291-4291
Author(s):  
Ronald Jackups ◽  
Debbie Woods ◽  
Robert J. Hayashi ◽  
Monica L. Hulbert
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Categorical Variables ◽  
Patient Specific ◽  
Cell Transplant ◽  
Blood Group Antigens ◽  
Cell Disease ◽  
Transfusion Therapy

Abstract Background: Chronic red blood cell (RBC) transfusion therapy is the predominant treatment modality in children with sickle cell disease (SCD) at high risk of first or recurrent strokes. RBC alloimmunization develops in some patients receiving chronic transfusion therapy, due in part to genetic differences in the prevalence of blood group antigens between the patient population and the blood donor pool. Many children’s hospitals have developed designated donor or “buddy” programs to recruit African-American blood donors and assign them to specific SCD patients with matched phenotypes, particularly in the Rh and Kell antigen groups, to reduce the likelihood of RBC alloimmunization. However, the practical constraints of such programs may make it difficult to ensure that patients’ transfusions always come from designated donors. Moreover, it is unclear whether such programs result in a lower risk of RBC alloimmunization when compared to the use of non-designated-donor but phenotype-matched RBC units. We aimed to determine the proportion of transfusions from designated donors at our institution, hypothesizing that the development of new RBC alloantibodies is associated with a lower proportion of transfused units from designated donors. Methods: This is a single-institution retrospective cohort study of 38 patients with SCD who received chronic transfusion therapy (manual exchange or erythrocytapheresis) for primary or secondary stroke prevention from 1/1/2008 through 12/31/2012. Patients on transfusion therapy for 6 or more months were included. Subjects were censored at last date of follow-up or date of hematopoietic stem cell transplant. The local designated donor program was started in 1999. Designated donors are selected to be ABO/RhD compatible and phenotype-matched to patients for the C, E, and K antigens. When units from designated donors are not available, compatible units phenotype-matched for C, E, and K are issued from general inventory. The number and percentage of units transfused from either designated or non-designated donors, and the identification of new RBC alloantibodies during the study period, were evaluated. The rates of alloimmunization were compared between patients who received a “high” (above the median) or “low” (below the median) proportion of designated donor units. Categorical variables were compared with Fisher’s exact test and medians with the Mann-Whitney U-test in SPSS version 21 (IBM, Armonk, NY). A p-value below 0.05 was statistically significant. Results: During the study period, 38 subjects (42% male) met all inclusion criteria. A median of 120 units (IQR 60-186) was transfused to each subject, and each subject received a median of 63% (IQR 45%-77%) of units from designated donors. Of the 38 subjects, 18 (47%) produced at least one newly identified RBC alloantibody during the study period. Among these 18 antibody producers, a total of 29 new alloantibodies were detected, with a range of 1-3 per subject. Ten of the newly identified alloantibodies were directed against C, D, E, or K. No statistically significant difference between antibody producers and non-producers was identified for total number of RBC units transfused (median 161 vs. 96, p = 0.067), number of units transfused from designated donors (median 107 vs. 49, p = 0.099), number of non-designated-donor, phenotype-matched units transfused from general inventory (median 38 vs. 26, p = 0.059), or proportion of units transfused from designated donors (median 68% vs. 49%, p = 0.28). Although there was a trend toward a higher incidence of alloimmunization in patients who received a high proportion of designated donor units (OR 2.4, CI 0.6-8.7), it was not statistically significant (p= 0.33). Conclusions: Despite receiving phenotypically matched RBC units, almost half of the children with SCD on chronic transfusion therapy in this cohort developed new RBC alloantibodies during a five-year period. The number of units transfused from a designated donor did not significantly affect alloimmunization rate. One-third of the new alloantibodies were directed against antigens specifically matched for in the designated donor program. Patient-specific factors, such as genetic variation in the Rh locus, may be responsible for the risk of alloimmunization. Alternative matching strategies, such as genotypic matching of RBC donors and recipients, should be explored in prospective studies. Disclosures Jackups: Immucor: Consultancy.

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

Sickle crisis in the critically ill

2016 ◽  
Author(s):  
Shilpa Jain ◽  
Mark T. Gladwin
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Systemic Infection ◽  
Red Blood Cell Transfusion ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Ischaemia Reperfusion Injury ◽  
Transfusion Therapy

Sickle cell disease crises are precipitated by an acute occlusion of microvessels, which can lead to end organ ischaemia reperfusion injury and acute haemolysis. Acute fat emboli syndrome, acute lung injury (the acute chest syndrome), acute pulmonary hypertension, and cor pulmonale, haemorrhagic and occlusive stroke, and systemic infection represent the most common life-threatening complications observed in current ICU practice. General principles of management in all patients admitted to the critical care unit are hydration, antibiotics, pain control, and maintenance of oxygenation and ventilation. Red blood cell transfusion therapy is the treatment of choice for most complications of sickle cell disease requiring intensive care management. Transfusion of sickle negative, leukoreduced red blood cells, phenotypically matched for Rhesus and Kell antigens is the minimum standard of care in sickle cell disease patients as they have a high incidence of red blood cell alloimmunization.

Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 76-79 ◽  
Author(s):  
Paul Harmatz ◽  
Ellen Butensky ◽  
Keith Quirolo ◽  
Roger Williams ◽  
Linda Ferrell ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Liver Injury ◽  
Liver Biopsy ◽  
Blood Cell ◽  
Iron Overload ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Cell Disease ◽  
Liver Iron ◽  
Transfusion Therapy

Chronic transfusion therapy is being used more frequently to prevent and treat the complications of sickle cell disease. Previous studies have shown that the iron overload that results from such therapy in other patient populations is associated with significant morbidity and mortality. In this study we examined the extent of iron overload as well as the presence of liver injury and the predictive value of ferritin in estimating iron overload in children with sickle cell disease who receive chronic red blood cell transfusions. A poor correlation was observed between serum ferritin and the quantitative iron on liver biopsy (mean 13.68 ± 6.64 mg/g dry weight;R = 0.350, P = .142). Quantitative iron was highly correlated with the months of transfusion (R = 0.795, P < .001), but serum ferritin at biopsy did not correlate with months of transfusion (R = 0.308, P = .200). Sixteen patients had abnormal biopsies showing mild to moderate changes on evaluation of inflammation or fibrosis. Liver iron was correlated with fibrosis score (R = 0.50, P = .042). No complications were associated with the liver biopsy. Our data suggest that, in patients with sickle cell disease, ferritin is a poor marker for accurately assessing iron overload and should not be used to direct long-term chelation therapy. Despite high levels of liver iron, the associated liver injury was not severe.

scholarly journals Effects of Combination Hydroxyurea and Chronic Red Blood Cell Transfusion Therapy on the Immune Parameters of Patients with Sickle Cell Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4840-4840
Author(s):  
Mahogany Oldham ◽  
Gelina Sani ◽  
Stefanie Margulies ◽  
Jennifer Webb ◽  
Robert Sheppard Nickel ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Combination Therapy ◽  
Blood Cell ◽  
Nk Cells ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Nk Cell ◽  
Red Blood Cell Transfusion ◽  
Cell Disease ◽  
Transfusion Therapy

Background: Sickle cell disease (SCD) is typically characterized as a red blood cell disorder but our understanding of the effects on the immune system is limited. Patients with sickle cell disease have been shown to have unique inflammatory profiles, immune phenotypes and function. Others have shown that during vaso-occlusive crises patients with SCD have elevated counts of neutrophils, monocytes, and cytokines as well as increased activity of invariant natural killer T cells (iNKT).We have previously shown that hydroxyurea use is associated with a normalization of the increased NK cell number and function. While there are studies that describe on the effects of single therapy, there is little known about combination therapy. Therefore, our study investigated immunological changes in pediatric patients on combination therapy, which was defined as hydroxyurea added to chronic red blood cell transfusion treatment. Methods: Patient data and peripheral blood samples were collected from an ongoing pilot study of combination therapy hydroxyurea and simple chronic transfusion in patients with SCD previously on chronic transfusion for stroke prevention. A total of 11 patients with hemoglobin SS were studied at two time points; baseline (on chronic RBC transfusion only) and 3 months follow up after initiation of hydroxyurea 20 mg/kg/day. Comparisons were performed using paired t-tests with a p-value <0.05 being considered significant. Results: T, B and NK cell percentage was similar between baseline and after 3 months of combination therapy 62.5% (44.3-71.9) vs 67% (17.6-82.7), 16.29%(8.15-30.2) vs. 13.26% (1.07-32.8) and 7.79% (4.16-14.7) vs. 6.88 (1.54-21) (p>0.05). There were no significant differences between markers of NK cell activation between baseline and 3 months as follows: NKG2D 4.89% (0.47-28.4) vs. 24.38% (0.88-63), and NKp30 8.40% (0.81-58.7) vs. 32.42% (0.45-86.9). However there was a significant decrease in the percentage of mature (CD57+) NK cells 33.8% (10.7-67.6) vs. 23.07%(4.23-37), p =0.005. Similar results were also seen when using absolute values of the different lymphocyte subsets. Conclusion: Combination therapy appears to not affect overall percentages of B, T and NK cells but does appear to decrease the percentage of mature CD57+ NK cells that are known to have increased cytolytic activity. We plan to investigate the implications of these findings using NK functional studies such as cytotoxicity assays and cytotoxic granule release to further elucidate if combination therapy can lead to a decrease in NK cell function to normal levels. Additionally we plan to assess the effect on the immune parameters at 1 year as the hydroxyurea effect is likely time-dependent. These findings may have implications for patients on chronic transfusion therapy who plan to undergo bone marrow transplantation where a reduction in the potential for graft rejection by NK cells is desired. Disclosures No relevant conflicts of interest to declare.

Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 76-79 ◽  
Author(s):  
Paul Harmatz ◽  
Ellen Butensky ◽  
Keith Quirolo ◽  
Roger Williams ◽  
Linda Ferrell ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Liver Injury ◽  
Liver Biopsy ◽  
Blood Cell ◽  
Iron Overload ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Cell Disease ◽  
Liver Iron ◽  
Transfusion Therapy

Abstract Chronic transfusion therapy is being used more frequently to prevent and treat the complications of sickle cell disease. Previous studies have shown that the iron overload that results from such therapy in other patient populations is associated with significant morbidity and mortality. In this study we examined the extent of iron overload as well as the presence of liver injury and the predictive value of ferritin in estimating iron overload in children with sickle cell disease who receive chronic red blood cell transfusions. A poor correlation was observed between serum ferritin and the quantitative iron on liver biopsy (mean 13.68 ± 6.64 mg/g dry weight;R = 0.350, P = .142). Quantitative iron was highly correlated with the months of transfusion (R = 0.795, P &lt; .001), but serum ferritin at biopsy did not correlate with months of transfusion (R = 0.308, P = .200). Sixteen patients had abnormal biopsies showing mild to moderate changes on evaluation of inflammation or fibrosis. Liver iron was correlated with fibrosis score (R = 0.50, P = .042). No complications were associated with the liver biopsy. Our data suggest that, in patients with sickle cell disease, ferritin is a poor marker for accurately assessing iron overload and should not be used to direct long-term chelation therapy. Despite high levels of liver iron, the associated liver injury was not severe.

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 ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Emergency Room ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Research Funding ◽  
Medical Center ◽  
Emergency Room Visits ◽  
Cell Disease ◽  
The Mean

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 &gt; 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 &lt; 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.

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