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COVID-19 convalescent plasma boosts early antibody titer and does not influence the adaptive immune response
McDyer JF, Azimpouran M, Durkalski-Mauldin VL, Clevenger RG, Yeatts SD, Deng X, Barsan W, Silbergleit R, El Kassar N, Popescu I, et al
JCI insight. 2023
Abstract
Multiple randomized, controlled clinical trials have yielded discordant results regarding the efficacy of convalescent plasma in outpatients, with some showing an approximate two-fold reduction in risk and others showing no effect. We quantified binding and neutralizing antibody levels in 492 of the 511 participants from the C3PO trial of a single unit of COVID-19 convalescent plasma (CCP) vs. saline infusion. In a subset of 70 participants, peripheral blood mononuclear cells were obtained to define the evolution of B and T cell responses through day 30. Binding and neutralizing antibody responses were measurably higher one hour post-infusion in recipients of CCP compared to saline plus multivitamin, but levels achieved by the native immune system by day 15 were much higher than seen immediately after CCP administration. Infusion of CCP did not block generation of the host antibody response or skew B or T cell phenotype or maturation. Activated CD4+ and CD8+ T cells were associated with more severe disease outcome. These data show that CCP leads to a measurable boost in anti-SARS-CoV-2 antibodies, but that the boost is modest and may not be sufficient to alter disease course.
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2.
Additive solution-7 reduces the red blood cell cold storage lesion
Cancelas JA, Dumont LJ, Maes LA, Rugg N, Herschel L, WhitleyPH, Szczepiokowski ZM, Siegel AH, Hess JR, Zia M
Transfusion. 2015;55((3):):491-8.
Abstract
BACKGROUND Transfusion of long-stored red blood cells (RBCs) is associated with decreased in vivo RBC recovery, delivery of RBC breakdown products, and increased morbidity and mortality. Reducing the burden of this RBC "storage lesion" is a major challenge in transfusion medicine. Additive solution-7 (AS-7) is a new RBC storage solution designed to improve RBC metabolism by providing phosphate and increasing buffering capacity. STUDY DESIGN AND METHODS Storage quality in AS-7 was measured in a prospective, randomized, three-center trial using units of whole blood from healthy human subjects whose RBCs were stored for up to 56 days in AS-7 (n=120) or for 42 days in the control solution AS-1 (n=60). RESULTS Hemolysis and shedding of protein-containing microvesicles were significantly reduced in RBCs stored in AS-7 for 42 and 56 days compared with RBCs stored in AS-1. Autologous in vivo recoveries of RBCs stored in AS-7 was 88+/-5% at 42 days (n=27) and 82+/-3% at 56 days (n=27), exceeding recoveries of RBCs stored in currently used solutions. CONCLUSION Increasing the phosphate, pH range, and buffer capacity of a RBC storage system allowed RBCs to be stored better and longer than currently approved storage systems. AS-7 ameliorates the long-term storage lesion resulting in significantly increased viability in vitro and in vivo.Copyright 2014 AABB.
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3.
In vitro and in vivo quality of leukoreduced apheresis platelets stored in a new platelet additive solution
Dumont LJ, Cancelas JA, Graminske S, Friedman KD, Vassallo RR, Whitley PH, Rugg N, Dumont DF, Herschel L, Siegal AH, et al
Transfusion. 2013;53((5):):972-80.
Abstract
BACKGROUND Platelets (PLTs) stored in additive solutions (PASs) may reduce the risk of several plasma-associated adverse transfusion reactions such as allergic reactions and potentially transfusion-associated lung injury. The objective of this study was to determine the in vitro characteristics and the in vivo radiolabeled recovery and survival of apheresis PLTs (APs) stored in a new PAS and compare the latter to Food and Drug Administration (FDA) criteria. STUDY DESIGN AND METHODS Hyperconcentrated APs were collected from healthy subjects in a paired crossover study comparing PAS (35% plasma) and 100% plasma-stored APs (Part 1) up to 7 days and, in Part 2, to determine the in vivo recovery and survival of PAS stored AP at 5 days compared to fresh PLT controls. In vitro and in vivo assays were performed following standard methods. RESULTS Sixty-six and 25 evaluable subjects successfully completed Parts 1 and 2, respectively. pH for PAS AP was maintained above 6.6 for 5 days of storage. P-selectin values were consistent with published values for commonly transfused PLT products. The PAS in vivo PLT recovery (54.3+/-8.1%) was 86.7% of the fresh control, and survival (6.4+/-1.3 days) was 78.0% of the fresh control, both meeting the FDA performance criteria. CONCLUSION APs stored in PAS with 35% plasma carryover maintained pH over 5 days of storage and met current FDA criteria for radiolabeled recovery and survival. The use of PAS for storage of single-donor PLTs in clinical practice represents an acceptable transfusion product that reduces the volume of plasma associated with PLT transfusion. 2012 American Association of Blood Banks.
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4.
A randomized controlled trial comparing autologous radiolabeled in vivo platelet (PLT) recoveries and survivals of 7-day-stored PLT-rich plasma and buffy coat PLTs from the same subjects
Dumont LJ, Dumont DF, Unger ZM, Siegel A, Szczepiorkowski ZM, Corson JS, Jones MK, Christoffel T, Pellham E, Bailey SL, et al
Transfusion. 2011;51((6):):1241-8.
Abstract
BACKGROUND A recent review concluded that there was inadequate evidence to show a difference between buffy coat (BC) and platelet (PLT)-rich plasma (PRP) PLT concentrates prepared from whole blood. We hypothesized that 7-day-stored BC-PLTs would have superior autologous recoveries and survivals compared to PRP-PLTs and that both would meet the Food and Drug Administration (FDA) criteria for poststorage viability. STUDY DESIGN AND METHODS This was a randomized, crossover study design in healthy subjects who provided informed consent. Each participant donated a unit of whole blood on two occasions. In random order, either BC-PLTs or PC-PLTs were prepared after a 20 ± 2 °C overnight hold of the whole blood. PLTs were stored under standard conditions. On Day 7, fresh PLTs were prepared from 43 mL of autologous whole blood. The fresh PLTs paired with either BC-PLTs or PRP-PLTs were alternately labeled with (111) In or (51) Cr and simultaneously reinfused to determine recoveries and survivals. In vitro assays were performed on Days 1 and 7. RESULTS Fourteen subjects completed the study at two sites. No differences in poststorage PLT viabilities were observed between BC-PLTs and PRP-PLTs; recovery differences averaged 3.7 ± 2.4% (± SE, p = 0.15) and survival differences averaged 0.48 ± 0.56 days (p = 0.41). Neither type of PLTs met the current FDA criteria for either poststorage PLT recoveries or survivals. CONCLUSION We were unable to demonstrate that single-unit BC-PLTs stored for 7 days have superior poststorage viability compared to PRP-PLTs. Failure to meet the minimum FDA criteria for poststorage PLT viability raises questions regarding the acceptance thresholds of these metrics.
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5.
A randomized controlled trial comparing autologous radiolabeled in vivo platelet recoveries and survivals of 7-Day stored PRP and buffy coat platelets from the same donors
Dumont LJ, Dumont DF, Unger ZM, Siegel A, Szczepiorkowski ZM, Corson JS, Jones M, Christoffel T, Pellham E, Slichter SJ
Transfusion. 2010;50((Suppl 2):):1A-2A.. Abstract No. P3-020A.
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6.
Multi-institutional randomized control study of haemolysis in stored red cell units prepared manually or by an automated system
McAteer MJ, Dumont LJ, Cancelas J, Rugg N, Vassallo R, Whitley P, Graminske S, Friedman K
Vox Sanguinis. 2010;99((1):):34-43.
Abstract
BACKGROUND The haemolysis level at the end of storage is a performance parameter for RBC preparations. In the evaluation of new devices or new processes for processing blood, it is relevant to evaluate whether the haemolysis is linked to (1) specific characteristics of the blood donor, or (2) the nature of the blood-processing methodologies. MATERIALS AND METHODS As part of the validation of a new automated whole blood processing system compared to the current manual methods, randomized, paired crossover studies were conducted evaluating measures of blood component quality, including RBC haemolysis over 42 days of storage. RESULTS The association between haemolysis and the individual subject was evaluated by modelling haemolysis with independent predictors of treatment (control and test processing) and leucocyte reduction as fixed factors with donor and laboratory as random effects in a mixed-effects ANOVA model. It was found that the day 42 haemolysis values were strongly dependent on the donor subject, with an intraclass correlation coefficient of 0. 81. CONCLUSIONS The data reported in this study suggest a link between the specific whole blood donor and the haemolysis levels observed in red-blood-cell units stored refrigerated for 42 days. Additional research to identify possible donor characteristics associated with haemolysis during storage is warranted.
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7.
Comprehensive evaluation of a new process for S-303 pathogen-inactivation of red blood cells
Cancelas JA, Rugg N, Dumont LJ, Szczepiorkowski ZM, Siegel A, Erickson A, Propst M, North AK, Mufti N, Corash L
Transfusion. 2010;50((Suppl 2):):9A-10A.. Abstract No. S15-010C.
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8.
The effects of additive solution pH and metabolic rejuvenation on anaerobic storage of red cells
Yoshida T, AuBuchon JP, Dumont LJ, Gorham JD, Gifford SC, Foster KY, Bitensky MW
Transfusion. 2008;48((10):):2096-105.
Abstract
BACKGROUND Red cell (RBC) storage can be extended to 9 weeks under anaerobic or alkaline conditions. Simultaneous use of these approaches has not provided additive benefit. Our objective was to determine whether anaerobic storage with acidified additive solution (AS) coupled with metabolic rejuvenation might further improve the benefits of anaerobic storage. STUDY DESIGN AND METHODS RBC storage in AS with a pH value of 6. 5, 7. 4, or 8. 3 in aerobic or anaerobic conditions was examined using a panel of in vitro biochemical and RBC markers. RBC rejuvenation during cold storage was also evaluated. A randomized crossover radiolabeled recovery study (eight subjects) evaluated anaerobic RBC storage using AS65 with cold rejuvenation for up to 16 weeks of storage. RESULTS Adenosine triphosphate (ATP) and diphosphoglycerate acid (DPG) were better maintained in anaerobic storage than in aerobic storage. Acidic or neutral AS preserved ATP concentration better, while a neutral or basic pH AS favored maintenance of DPG levels at higher levels for a longer period. AS pH had less of an effect on exposure of phosphatidylserine (PS), vesicle protein release, and hemolysis. Rejuvenation of RBCs during cold, anaerobic storage resulted in increases in ATP and DPG levels and a reversal of PS exposure. Anaerobic storage of RBCs in pH 6. 5 AS rejuvenated at 7 weeks of storage yielded RBC 24-hour recoveries of 77. 3 +/- 12. 5 percent after 10 weeks' storage time. After a second rejuvenation at Week 11, six subjects' units demonstrated a recovery of 75. 9 +/- 7. 3 percent at 12 weeks of storage. CONCLUSION Extended RBC storage may be achieved using anaerobic conditions combined with low-pH AS and rejuvenation during storage.
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9.
Anaerobic storage of red blood cells in a novel additive solution improves in vivo recovery
Dumont LJ, Yoshida T, Herschel L, Dumont D, Waters S, Baker S, AuBuchon JP
Transfusion. 2008;48((S2):):38A.. Abstract No. S101-030M.
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10.
Donor dependent glycolysis rates for platelets stored in plasma
Dumont LJ, Vandenbroeke T
Transfusion. 2004;44((s1):):29A.. Abstract No. S88-040G.