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Bedside Allogeneic Erythrocyte Washing with a Cell Saver to Remove Cytokines, Chemokines, and Cell-derived Microvesicles
Welsby IJ, Norris PJ, Mauermann WJ, Podgoreanu MV, Conn CM, Meade L, Cannon T, Keating SM, Silliman CC, Kehler M, et al
Anesthesiology. 2021
Abstract
BACKGROUND Removal of cytokines, chemokines, and microvesicles from the supernatant of allogeneic erythrocytes may help mitigate adverse transfusion reactions. Blood bank-based washing procedures present logistical difficulties; therefore, we tested the hypothesis that on-demand bedside washing of allogeneic erythrocyte units is capable of removing soluble factors and is feasible in a clinical setting. METHODS There were in vitro and prospective, observation cohort components to this a priori planned substudy evaluating bedside allogeneic erythrocyte washing, with a cell saver, during cardiac surgery. Laboratory data were collected from the first 75 washed units given to a subset of patients nested in the intervention arm of a parent clinical trial. Paired pre- and postwash samples from the blood unit bags were centrifuged. The supernatant was aspirated and frozen at -70°C, then batch-tested for cell-derived microvesicles, soluble CD40 ligand, chemokine ligand 5, and neutral lipids (all previously associated with transfusion reactions) and cell-free hemoglobin (possibly increased by washing). From the entire cohort randomized to the intervention arm of the trial, bedside washing was defined as feasible if at least 75% of prescribed units were washed per protocol. RESULTS Paired data were available for 74 units. Washing reduced soluble CD40 ligand (median [interquartile range]; from 143 [1 to 338] ng/ml to zero), chemokine ligand 5 (from 1,314 [715 to 2,551] to 305 [179 to 488] ng/ml), and microvesicle numbers (from 6.90 [4.10 to 20.0] to 0.83 [0.33 to 2.80] × 106), while cell-free hemoglobin concentration increased from 72.6 (53.6 to 171.6) mg/dl to 210.5 (126.6 to 479.6) mg/dl (P < 0.0001 for each). There was no effect on neutral lipids. Bedside washing was determined as feasible for 80 of 81 patients (99%); overall, 293 of 314 (93%) units were washed per protocol. CONCLUSIONS Bedside erythrocyte washing was clinically feasible and greatly reduced concentrations of soluble factors thought to be associated with transfusion-related adverse reactions, increasing concentrations of cell-free hemoglobin while maintaining acceptable (less than 0.8%) hemolysis.
2.
Fresh red blood cell transfusion and short-term pulmonary, immunologic, and coagulation status: a randomized clinical trial
Kor DJ, Kashyap R, Weiskopf RB, Wilson GA, Buskirk CM, Winters JL, Malinchoc M, Hubmayr RD, Gajic O
American Journal of Respiratory and Critical Care Medicine. 2012;185((8):):842-50.
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Abstract
RATIONALE Transfusion-related pulmonary complications are leading causes of morbidity and mortality attributed to transfusion. Observational studies suggest an important role for red blood cell (RBC) storage duration in these adverse outcomes. OBJECTIVES To evaluate the impact of RBC storage duration on short-term pulmonary function as well as immunologic and coagulation status in mechanically ventilated patients receiving RBC transfusion. METHODS This is a double-blind, randomized, clinical trial comparing fresh (<=5 d of storage) versus standard issue single-unit RBC transfusion in adult intubated and mechanically ventilated patients. The primary outcome is the change in pulmonary gas exchange as assessed by the partial pressure of arterial oxygen to fraction of inspired oxygen concentration ratio (?Pa (O (2))/Fi (O (2))). Secondary outcomes include changes in immune and coagulation status. MEASUREMENTS AND MAIN RESULTS Fifty patients were randomized to receive fresh RBCs and an additional 50 patients to standard issue RBCs. Median storage age was 4.0 days (interquartile range, 3.0-5.0) and 26.5 days (interquartile range, 21.0-36.0) in the fresh RBC group and standard issue RBC group, respectively. No differences were noted in the primary outcome of ?Pa (O (2))/Fi (O (2)) (difference between the mean ?Pa (O (2))/Fi (O (2)) in the standard issue RBC group vs. the fresh RBC group, -11.5; 95% confidence interval, -35.3 to 12.3; P = 0.22). Similarly, no significant differences were noted in markers of immunologic or coagulation status. CONCLUSIONS In this randomized clinical trial, no differences were noted in early measures of pulmonary function or in immunologic or coagulation status when comparing fresh versus standard issue single-unit RBC transfusion. Clinical trial registered with ClinicalTrials.gov (NCT00751322).