Bedside Allogeneic Erythrocyte Washing with a Cell Saver to Remove Cytokines, Chemokines, and Cell-derived Microvesicles
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.
Effects of platelet-rich plasmapheresis during cardiovascular surgery: A meta-analysis of randomized controlled clinical trials
Journal of clinical anesthesia. 2019;56:88-97
OBJECTIVE This study aimed to explore the effects of platelet-rich plasmapheresis (PRP) on the amount of postoperative blood loss and the requirements for allogeneic fresh frozen plasma (FFP) and red blood cell (RBC) transfusions during cardiovascular surgery. METHODS A literature search of 7 online databases was conducted. Randomized control trials (RCT) comparing intraoperative PRP or appropriate control groups were considered suitable for this current study. RESULTS Fifteen RCTs enrolling a total of 1002 patients, including 501 patients who received PRP and 501 control patients. Meta-analysis of the data from these trials showed that PRP reduced the total volume of postoperative blood loss (standardized mean difference [SMD], -0.74; 95% confidence interval [CI], -1.18 to -0.31; P<0.05), reduced postoperative fresh frozen plasma (FFP) transfusion (SMD, -0.38; 95%CI, -0.69 to -0.08; P<0.05), reduced postoperative RBCs transfusion (SMD, -0.44; 95%CI, -0.77 to -0.10; P<0.05), and reduced the proportion of patients receiving postoperative allogeneic RBC transfusions (relative risk [RR], 0.44; 95%CI, 0.21-0.91, P<0.05) during cardiovascular surgery. CONCLUSION Conducting PRP before cardiopulmonary bypass (CPB) and transfusing autologous platelet-rich plasma (aPRP) after reversal of heparin could reduce postoperative blood loss, the requirements for blood products transfusion during cardiovascular surgery. A higher mean platelet count in aPRP may improve the final outcome. However, there was a high degree of undetermined heterogeneity among the analyzed trials, and larger and more precise RCTs are needed to confirm these conclusions.
Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion
Cochrane Database of Systematic Reviews. 2011;((3):):CD004172.
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.
Plateletpheresis the day before cardiac surgery and the impairment of platelet function
European Journal of Anaesthesiology. 2003;20((4):):338-40.
The pathogenesis of the platelet qualitative defect after cardiopulmonary bypass (CPB) remains incompletely elucidated . Theoretically, the collection of platelets before CPB followed by their transfusion immediately at the end of CPB would result in improved haemostasis. We decided to study the effect of autologous plateletpheresis the day before surgery on platelet function and mediastinal blood loss. After institutional review board approval and written informed consent, patients scheduled for cardiac surgery were prospectively enrolled. Cardiac procedures with expected CPB longer than 2 h represented the target population. Twenty patients with normal coagulation function, platelet counts and withdrawal of antiplatelet drugs for at least 7 days before the operation were randomized for either the control group (n =10) or the apheresis group (n =10). The day before surgery, platelet collection was performed with a cell separator (COBE Spectra LRS®, Denver, CO, USA). The platelets were stored for 24 h in an incubator (Helmer, Nobelsville, IA, USA). Surgical procedures were performed with standard CPB techniques at moderate systemic hypothermia (32°C). Aprotinin was infused to all patients. Heparin was given at an initial dosage of 300 IU kg-1, supplemented to maintain an activated coagulation time (ACT) greater than 480 s and ‘reversed’ with protamine sulphate to return ACT to baseline. Autologous platelets were infused at the end of CPB. Blood samples were collected after induction of anaesthesia (T1), after completion of CPB and protamine-induced heparin neutralization (T2), 30 min after protamineinduced antagonism of heparin and after completion of autologous platelet infusion in the apheresis group (T3), 4 h after heparin neutralization (T4) for measurements of platelet count, haemoglobin concentration and platelet aggregation. Photo-optical aggregometry was used (Platelet Aggregation Profiler-4®; Bio Data Corporation, Hatboro, PA, USA). Briefly, platelet-rich and -poor plasmas were obtained by centrifuging whole blood at 1000 and 3000 rpm, respectively. The aggregometer was calibrated. One agonist was added to platelet-rich plasma: ristocetin (Paesel Lorei®, Hanau, Germany) 1.2mgmL_1, adenine diphosphate (ADP®; Boehringer, Mannheim, Germany) 5 µmol L-1, collagen (collagen reagent Horin®, Munich, Germany) 2.5 µgmL-1. In both groups, the same algorithm was applied for transfusion requirements. Mediastinal blood loss was recorded during the second, 12th and 24th h. Continuous variables were expressed as mean ± standard deviation. Blood losses were expressed as median and interquartile ranges (2575%). Comparisons for continuous variables between groups were made using the U-test; comparisons between the groups, for discrete variables, were made with Fisher’s exact test; a Spearman’s rank correlation test was used. P < 0.05 was considered as being statistically significant. Patient characteristics and preoperative haematological variables were similar among patients of both groups. The control and apheresis groups did not differ significantly for the duration of CPB (137 ± 20 vs. 144 ± 36 min). In the apheresis group, a mean of 13 ± 2 1011 platelets was collected. Mediastinal blood losses were quite similar with a median of 720 (640975) mL during the first 24 h in the control group vs. 820 (745885) mL in the apheresis group. No difference was noted at any time with reference to haemoglobin concentration or platelet aggregation (Table 1). Four hours after infusion of the autologous stored platelets (T4), the platelet count was not significantly higher in the apheresis group than in the control group (162 ± 50 vs. 154 ± 55 103µL-1). One of the most important findings of the study in the apheresis group was that platelet aggregation did not improve either after platelet infusion or 4 h after completion of CPB. After protamine administration, ADP and ristocetin induced-platelet aggregation demonstrated a significant negative correlation with a mediastinal blood loss at the 12th postoperative hou
Platelet pheresis is not a useful adjunct to blood-sparing strategies in cardiac surgery
Journal of Cardiothoracic & Vascular Anesthesia. 2002;16((3):):321-9.
OBJECTIVE To examine whether specific platelet pheresis (minimal plasma harvested) would contribute toward reduced blood loss and allogenic blood requirements after cardiac surgery. DESIGN A prospective randomized trial. SETTING A large cardiothoracic surgical center. PARTICIPANTS Consenting patients undergoing routine coronary artery or valve surgery (n = 54). INTERVENTIONS Patients in the pheresis group underwent platelet pheresis in the anesthetic preparation room before general anesthesia. Pheresed platelets were stored during cardiopulmonary bypass and were returned to the patients after reversal of heparin with protamine toward the end of surgery. Control patients underwent their operations without this intervention. MEASUREMENTS AND MAIN RESULTS Primary endpoints were blood loss and transfusion requirements. There were no differences between the 2 groups (pheresis v control: median loss, 960 mL v 1100 mL, p = 0.15; median blood transfused, 896 mL v 635 mL, p = 0.71). Secondary endpoints included analysis of platelet counts, platelet function, and surface markers. Counts remained the same after retransfusion of platelets up to 2 hours after surgery. Platelet aggregation to ristocetin was well preserved, but adenosine diphosphate caused almost no aggregation of the harvested platelets. Flow cytometry revealed the platelets to have a reduced surface density of the glycoprotein 1b receptor, and 13% of them were irreversibly activated. CONCLUSION Platelet pheresis activates a proportion of the harvested platelets and impairs the function of the remainder; this may explain its failure to reduce postoperative blood loss and transfusion requirements. Copyright 2002, Elsevier Science (USA). All rights reserved.
Intraoperative use of platelet-plasmapheresis in vascular surgery
Journal of Clinical Anesthesia. 2002;14((1):):10-4.
STUDY OBJECTIVE To determine, in a pilot study, whether pheresis of plasma and platelets before surgical blood loss, with reinfusion of the autologous plasma and platelets after completion of the aortic reconstruction, will result in decreased bleeding and decreased transfusion of allogenic blood components in patients undergoing elective aortic reconstruction. DESIGN Randomized study. SETTING University medical center. INTERVENTIONS Patients were randomized to perioperative (acute) platelet plasmapheresis (APP group) versus conventional blood component therapy (control group). In the APP group, blood was withdrawn after induction of anesthesia, to sequester approximately 300 mL of platelet rich plasma (PRP); platelet poor plasma (PPP) and red blood cells (RBC) were sequestered as well. An autotransfusion device was used to collect and re-infuse autologous RBC during the course of the operation in both groups. After completion of the aortic reconstruction, autologous PRP and PPP were re-infused in the APP group. Blood loss, volume of blood component transfusions, and preoperative and postoperative hemoglobin (Hb), hematocrit (Hct), platelet, international normalized ratio (INR), and activated partial thromboplastin time (aPTT) were recorded. MEASUREMENTS AND MAIN RESULTS There was no difference between groups in demographics, preoperative laboratory values, or surgical procedures, although more patients were treated for aneurysms (73% vs. 60%) and fewer for occlusive disease (20% vs. 40%) in the control versus APP group. Also, there were no differences between the control and APP groups in duration of operation, blood loss, volume of colloid infused, or volume of allogenic RBC and plasma transfused. Patients in the APP group received a greater volume of crystalloid solution (9.1 +/- 3.4 L vs. 6.8 +/- 3.0 L; p = 0.002), but fewer units of allogenic platelets than the control group (0.7 +/- 1.0 units vs. 0.2 +/- 0.4 units; p < 0.04). There were no differences in postoperative Hb, Hct, INR, aPTT, or fibrinogen. The platelet count was lower in the APP group than in the control group (123 +/- 40 x 10(3)/mm(3) vs. 182 +/- 51 x 10(3)/mm(3); p = 0.004). CONCLUSIONS Perioperative platelet plasmapheresis led to fewer allogenic platelet transfusions in patients undergoing elective aortic reconstruction. However, there was no decrease in blood loss and no reduction in transfusion of allogenic RBC or plasma. Perioperative platelet plasmapheresis is not recommended for routine use in elective aortic reconstruction.
Intraoperative plateletpheresis and autologous platelet gel do not reduce chest tube drainage or allogeneic blood transfusion after reoperative coronary artery bypass graft
Anesthesia & Analgesia. 2001;93((3):):536-42.
Platelet-rich plasma (PRP) is postulated to decrease postoperative mediastinal chest tube drainage (MCTD) and allogeneic blood transfusions (ABT) after surgery with cardiopulmonary bypass. However, recent metaanalysis of the literature reveals that few good quality (therapeutic yield) trials that show a benefit have been published. The potential hemodynamic instability caused by plateletpheresis has not been emphasized. We studied the effect of plateletpheresis on MCTD, ABT, and hemodynamic stability in reoperative coronary artery bypass graft patients, a group perceived to be at high risk for ABT. Ninety patients were randomly assigned to Pheresis or Control groups. epsilon-Aminocaproic acid was given to all patients. Hemodynamic instability was assessed by degree of volume and inotrope resuscitation required. Part of the sequestered platelet volume was used to make autologous platelet gel, which was applied as a wound sealant. Mean pheresis yield was 30% +/- 7% of the circulating platelet mass or 6.4 +/- 2.2 allogeneic platelet unit equivalents. Total MCTD did not differ between the groups. There were no differences in mean packed red blood cell, platelet, and plasma transfusion rates. Overall, 52% of the Pheresis group received ABT, versus 55% of the Control group. Fifty-three percent of the Pheresis group patients exhibited significant hemodynamic instability, versus 27% of the Control group (P < 0.05). This study was unable to show any reduction in MCTD or ABT, although the plateletpheresis technique may offset platelet dysfunction caused by aspirin or increased blood exposure to nonbiologic surfaces, or it may compensate for lack of antifibrinolytic use. The significantly increased incidence of hemodynamic instability in the Pheresis group means that the risk/benefit ratio must be determined for individual cardiac surgical units.
Systemic leukocyte filtration during cardiopulmonary bypass
Perfusion. 2001;16((1 Suppl):):11-18.
Cardiopulmonary bypass (CPB) induces a whole body inflammatory response leading to postoperative lung dysfunction. Activated leukocytes may play a role in the pathogenesis of pulmonary dysfunction. We evaluated postoperative lung function after the use of leukocyte-depleting filters incorporated in the extracorporeal circuit during CPB. From November 1997 to March 2000, 40 patients underwent isolated coronary artery bypass grafting. Patients were randomly allocated to the leukocyte-depletion group (group F, 20 patients) or to the control group (group C, 20 patients). There was no significant difference between the two groups with respect to age, sex, weight, height, body surface area, haemoglobin and haematocrit levels, preoperative left ventricular ejection fraction, cooling temperature, aortic crossclamping and CBP duration. Blood samples were drawn preoperatively, at aortic declamping, 60 min after CPB, after arriving at the intensive care unit (ICU) and 24 h after the operation. We analysed blood cell count, elastase, interleukin-8 (IL-8) and tumour necrosis factor (TNF-alpha) levels and continuous monitoring of arterial blood gases in the intensive care unit (ICU). The analysis of total circulating white blood cells (WBCs) showed a significant reduction of WBCs in both groups soon after aortic declamping [from the right atrium: 6.4 x 10(9)/l +/- 1.4 x 10(9)/l in group F vs 10.3 +/- 1.8 x 10(9)/l in group C (p<0.05); from the left atrium: 5.8 +/- 1.3 x 10(9)/l in group F vs 8.4 +/- 1.9 x 10(9)/l in group C (p<0.05)] and after 60 min of CPB [7.1 +/- 2.2 x 10(9)/l in group F vs 10.4 +/- 1.8 x 10(9)/l in group C (p<0.05)]. The analysis of circulating neutrophils showed similar findings in both groups. Elastase levels increased during CPB in both groups with a peak at the end of CPB without significant difference between the two groups (group C: 260 +/- 148 microg/l vs group F: 371 +/- 68 microg/l). The decrease of plasmatic elestase levels was observed, for both groups, in the 24 h after CPB. There was no difference in intubation time between the two groups (16.4 h for group C vs 11.2 h for group F). Pulmonary function tested by pulmonary respiratory index [RI = partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2 x 100)] did not show significant difference between the two groups, either arriving in the ICU (group C RI 265 vs group F RI 322), or after 3 h (group RI 304 vs group F RI 305) or after 6 h (group C RI 292 vs group F RI 319). Leukocyte-depleting filters reduce with blood cells count during CPB, but, in this study, WBC depletion did not significantly improve clinical conditions or laboratory finding.
Does platelet-rich plasmapheresis reduce allogeneic transfusions in cardiac surgery?
Transfusion. 1999;39((S10):):55S.. Abstract No. S242-P.
Platelet-rich plasmapheresis in cardiac surgery: a meta-analysis of the effect on transfusion requirements
Journal of Thoracic and Cardiovascular Surgery. 1998;116((4):):641-7.
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.