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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.
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Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion
Carless PA, Rubens FD, Anthony DM, Connell D, Henry DA
Cochrane Database of Systematic Reviews. 2011;((3):):CD004172.
Abstract
BACKGROUND Concerns regarding the safety of transfused blood have generated considerable enthusiasm for the use of technologies intended to reduce the use of allogeneic blood (blood from an unrelated donor). Platelet-rich plasmapheresis (PRP) offers an alternative approach to blood conservation. OBJECTIVES To examine the evidence for the efficacy of PRP in reducing peri-operative allogeneic red blood cell (RBC) transfusion, and the evidence for any effect on clinical outcomes such as mortality and re-operation rates. SEARCH STRATEGY We identified studies by searching MEDLINE (1950 to 2009), EMBASE (1980 to 2009), The Cochrane Library (Issue 1, 2009), the Internet (to March 2009) and the reference lists of published articles, reports, and reviews. SELECTION CRITERIA Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to PRP, or to a control group which did not receive the intervention. DATA COLLECTION AND ANALYSIS Primary outcomes measured were: the number of patients exposed to allogeneic RBC transfusion, and the amount of RBC transfused. Other outcomes measured were: the number of patients exposed to allogeneic platelet transfusions, fresh frozen plasma, and cryoprecipitate, blood loss, re-operation for bleeding, post-operative complications (thrombosis), mortality, and length of hospital stay. Treatment effects were pooled using a random-effects model. Trial quality was assessed using criteria proposed by Schulz et al (Schulz 1995). MAIN RESULTS Twenty-two trials of PRP were identified that reported data for the number of patients exposed to allogeneic RBC transfusion. These trials evaluated a total of 1589 patients. The relative risk (RR) of exposure to allogeneic blood transfusion in those patients randomised to PRP was 0.73 (95%CI 0.59 to 0.90), equating to a relative risk reduction (RRR) of 27% and a risk difference (RD) of 19% (95%CI 10% to 29%). However, significant heterogeneity of treatment effect was observed (p < 0.00001; I2 = 79%). When the four trials by Boldt are excluded, the RR is 0.76 (95% CI 0.62 to 0.93). On average, PRP did not significantly reduce the total volume of RBC transfused (weighted mean difference [WMD] -0.69, 95%CI -1.93 to 0.56 units). Trials provided inadequate data regarding the impact of PRP on morbidity, mortality, and hospital length of stay. Trials were generally small and of poor methodological quality. AUTHORS' CONCLUSIONS Although the results suggest that PRP is effective in reducing allogeneic RBC transfusion in adult patients undergoing elective surgery, there was considerable heterogeneity of treatment effects and the trials were of poor methodological quality. The available studies provided inadequate data for firm conclusions to be drawn regarding the impact of PRP on clinically important endpoints.
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Combination of acute preoperative plateletpheresis, cell salvage, and aprotinin minimizes blood loss and requirement during cardiac surgery
Li S, Ji H, Lin J, Lenehan E, Ji B, Liu J, Liu J, Long C, Crane TA
The Journal of Extra-Corporeal Technology. 2005;37((1):):9-14.
Abstract
Acute preoperative plateletpheresis (APP), cell salvage (CS) technique, and the use of aprotinin have been individually reported to be effective in reducing blood loss and blood component transfusion while improving hematological profiles in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this prospective randomized clinical study, the efficacy of these combined approaches on reducing blood loss and transfusion requirements was evaluated. Seventy patients undergoing primary coronary artery bypass grafting (CABG) were randomly divided into four groups: a control group (group I, n = 10) did not receive any of the previously mentioned approaches. An APP and CS group (group II, n = 20) experienced APP in which preoperative platelet-rich plasma was collected and reinfused after reversal of heparin, along with the cell salvage technique throughout surgery. The third group (group III, n = 22) received aprotinin in which 5,000,000 KIU Trasylol was applied during surgery, and a combination group (group IV, n = 18) was treated with all three approaches, i. e. , APP, CS, and aprotinin. Compared with group I (896+/-278 mL), the postoperative total blood loss was significantly reduced in groups II, III, and IV (468+/-136, 388+/-122, 202+/-81 mL, respectively, p < 0. 05). The requirements of packed red blood cells in the three approached groups (153+/-63, 105+/-178, 0+/-0 mL, respectively) also were reduced when compared with group I (343+/-118 mL, p < 0. 05). In group I, six patients (6/10) received fresh-frozen plasma and three patients (3/10) received platelet transfusion, whereas no patients in the other three groups required fresh-frozen plasma and platelet. In conclusion, both plateletpheresis concomitant with cell salvage and aprotinin contribute to the improvement of postoperative hemostasis, and the combination of these two approaches could minimize postoperative blood loss and requirement.
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Platelet-rich plasmapheresis in cardiac surgery: a meta-analysis of the effect on transfusion requirements
Rubens FD, Fergusson D, Wells PS, Huang M, McGowan JL, Laupacis A
Journal of Thoracic and Cardiovascular Surgery. 1998;116((4):):641-7.
Abstract
OBJECTIVE Our purpose was to determine whether intraoperative platelet-rich plasmapheresis in cardiac surgery is effective in reducing the proportion of patients exposed to allogeneic red cell transfusions. METHODS A systematic search for prospective, randomized trials of platelet-rich plasmapheresis in cardiac surgery, using MEDLINE, HEALTHSTAR, Current Contents, Biological Abstracts, and EMBASE/Excerpta Medica up to August 1997, was completed. Trials were included if they reported either the proportion of patients exposed to allogeneic red cells or the units of allogeneic red cells transfused. Trials were abstracted by 2 independent investigators and the quality of trial design was assessed with the use of a validated scale. RESULTS Seventeen references met the inclusion criteria (1369 patients (675 control: 694 platelet-rich plasmapheresis)). Plateletrich plasmapheresis reduced the likelihood of exposure to allogeneic red cells in cardiac surgery (odds ratio 0.44; 95% confidence interval 0.27, 0.72, P = .001). Platelet-rich plasmapheresis had a small but statistically significant effect on both the volume of blood lost in the first 24 hours (weighted mean difference -102 mL; 95% confidence interval -148, -55 mL, P < .0001) and the mean units transfused (weighted mean difference -0.33 units; 95% confidence interval -0.43, -0.23, P < .0001). However, platelet-rich plasmapheresis was only marginally effective (odds ratio 0.83, 95% confidence interval 0.34, 2.01, P = .68) for good quality trials, whereas it appeared very effective in trials with poor methodologic quality (odds ratio 0.33, 95% confidence interval 0.17, 0.62, P = .0007). CONCLUSIONS Although platelet-rich plasmapheresis appeared effective in decreasing the proportion of patients receiving transfusions after cardiac operations, the quality of most of the supporting trials was low and the benefit was small in trials of good quality. Further clinical trials should be completed.
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5.
Preoperative plasmapheresis in patients undergoing cardiac surgery procedures
Boldt J, von Bormann B, Kling D, Jacobi M, Moosdorf R, Hempelmann G
Anesthesiology. 1990;72((2):):282-8.
Abstract
Donor plasmapheresis that is carried out weeks before the operation has proven to be of benefit in elective orthopedic patients with regard to reducing homologous blood consumption and preserving coagulation. In this study acute preoperatively performed plasmapheresis (APP) was investigated in cardiac surgery patients. Forty-five patients scheduled for elective aortocoronary bypass surgery were randomly divided into three groups of 15 patients each: 1) removal of platelet-poor plasma (PPP), 2) removal of platelet-rich plasma (PRP), and 3) no plasmapheresis (control group). Plasma volume removed was 10 ml/kg in all APP patients, and plasma was replaced by the same amount of low-molecular weight hydroxyethylstarch solution (6% HES 200/0.5). Various laboratory data were investigated before, during, and after extracorporeal circulation (ECC). Blood loss in control patients was more pronounced than in the two APP groups; two of the control patients needed packed red cells. APP itself did not affect coagulation variables, free hemoglobin, or polymorphonuclear (PMN) elastase. At the end of the operation, 5 h after ECC, and at the first postoperative day the number of platelets was significantly lower in the control group; PRP patients showed the highest values. Fibrinogen and AT-III levels were less compromised in APP patients than in the control group. Global coagulation parameters did not differ between the groups within the whole investigation period. PMN elastase increased significantly during ECC in all groups with the greatest increase in the control group (722%) and the smallest increase in PRP patients (280%), possibly due to the removal of cellular elements in this group.(ABSTRACT TRUNCATED AT 250 WORDS)