Therapeutic efficacy and safety of red blood cells treated with a chemical process (S-303) for pathogen inactivation: a Phase III clinical trial in cardiac surgery patients

BACKGROUND: A randomized, double-blind trial is reported of the clinical efficacy of red blood cells (RBCs) treated for pathogen inactivation with S-303, a synthetic labile alkylating agent. STUDY DESIGN AND METHODS: Patients undergoing complex cardiac surgeries were randomly assigned to receive either S-303-treated (test) or conventional (control) RBC transfusion during surgery and for 6 days thereafter. Efficacy was evaluated by comparing the occurrence of a composite primary endpoint of treatment-related morbidity (myocardial infarction and renal failure) and mortality. RESULTS: Two-hundred twenty-three patients were randomly assigned and 148 patients who received transfusions (74 with S-303-treated RBCs and 74 with control RBCs) were evaluable. The incidence of the primary endpoint was equivalent between the two groups (22 and 21% in the S-303-treated and control RBC groups, respectively). Secondary endpoints, including hemoglobin increment (mean, 1.4 vs. 1.5 g/dL), number of RBC transfusions (mean, 4.4 vs. 3.8 units), and other blood product support, were also comparable. The adverse event profile was similar between groups; however, patients who received S-303 RBCs were significantly more likely to develop constipation and less likely to suffer supraventricular extrasystoles. Four patients (2 test and 2 control) demonstrated positive indirect antiglobulin tests with reactivity for S-303 RBCs at one or more time points before or after transfusion, without evidence of hemolysis. CONCLUSION: S-303-treated and conventional RBCs were equivalent with respect to clinical efficacy and safety in supporting the transfusion needs of cardiac surgery patients. Investigations are under way to ascertain the significance of S-303 RBC antibodies and to prevent their occurrence.     

Red blood cell transfusion practice in elective orthopedic surgery: a multicenter cohort study

BACKGROUND: The indications for red blood cell (RBC) transfusions remain unclear despite published guidelines. Our hypothesis was that the transfusion practice varies inside the Centre hospitalier de l'Université de Montréal (CHUM). STUDY DESIGN AND METHODS: A total of 701 charts of patients who underwent a knee or hip arthroplasty or prosthesis revision in three hospitals of the CHUM were reviewed. Demography, hemoglobin (Hb) concentrations, details on transfusions, and postoperative adverse events (AEs) were collected up until discharge. The primary outcome was the presence or absence of RBC transfusion. Secondary outcomes were the nadir Hb, number of units transfused, discharge Hb, blood losses, and postoperative AEs. RESULTS: The rate of postoperative transfusion was 29%. We found no significant difference between odds ratios of each site for sex, coronary artery disease, chronic heart failure, type of procedure, American Society of Anesthesiologists physical status, weight, height, body mass index, body surface area, and estimated blood volume. Overall, patients were transfused at a Hb between 75 and 80 g/L. Eighty‐five percent of postoperative transfusions could be predicted using only nadir Hb and adding patient characteristics did not substantially improve the model (86.1%). Discharge Hb was below 100 g/L in 66% of patients. CONCLUSIONS: There was no difference among hospitals regarding the way RBC transfusions are used. Our data suggest that physicians mainly based their decision to transfuse on a single variable, the Hb concentration, with the use of a restrictive strategy. Future trials should focus on the optimal transfusion trigger to adopt in major orthopedic surgery.     

Variability and predictability of large-volume red blood cell transfusion in cardiac surgery: a multicenter study

BACKGROUND: In cardiac surgery, excessive blood loss requiring large-volume red blood cell (RBC) transfusion is a common occurrence that is associated with significant morbidity and mortality. The objectives of this study were to measure the interinstitution variation and predictability of large-volume RBC transfusion. STUDY DESIGN AND METHODS: Data were retrospectively collected on 3500 consecutive cardiac surgical patients at seven Canadian hospitals during 2004. The crude and risk-adjusted institutional odds ratios (ORs) for large-volume (>or=5 U) RBC transfusion were calculated with logistic regression. The predictive accuracy of an existing prediction rule for large-volume RBC transfusion was calculated for each institution. RESULTS: Large-volume RBC transfusion occurred in 538 (15%) patients. When compared to the reference hospital (median crude rate), the institutional unadjusted and adjusted ORs for large-volume RBC transfusion ranged from 0.29 to 1.26 and 0.14 to 1.15, respectively (p<0.0001 for interinstitution variation). The variation was lower, but still considerable, for excessive blood loss, defined as at least 5-U RBC transfusion or reexploration; the ORs ranged from 0.42 to 1.22 (p<0.0001). The prediction rule performed well at most sites; its pooled positive predictive value for excessive blood loss was 71 percent (range, 63%-89%), and its negative predictive value was 90 percent (range, 87%-93%). CONCLUSIONS: There is marked interinstitution variation in large-volume RBC transfusion in cardiac surgery that is not explained by patient- or surgery-related factors. Despite this variation, patients at high or low risk for large-volume RBC transfusion can be accurately identified by a prediction rule composed of readily available clinical variables.     

The effect of blood transfusion on pulmonary permeability in cardiac surgery patients: a prospective multicenter cohort study

BACKGROUND: There is an association between blood transfusion and pulmonary complications in cardiac surgery. Mediators of increased pulmonary vascular leakage after transfusion are unknown. We hypothesized that factors may include antibodies or bioactive lipids, which have been implicated in transfusion‐related acute lung injury. STUDY DESIGN AND METHODS: We performed a prospective cohort study in two university hospital intensive care units in the Netherlands. Pulmonary vascular permeability was measured in cardiac surgery patients after receiving no, restrictive (one or two transfusions), or multiple (five or more transfusions) transfusions (n = 20 per group). The pulmonary leak index (PLI), using ⁶⁷Ga‐labeled transferrin, was determined within 3 hours postoperatively. Blood products were screened for bioactive lipid accumulation and the presence of antibodies. RESULTS: The PLI was elevated in all groups after cardiac surgery. Transfused patients had a higher PLI compared to nontransfused patients (33 × 10^?3 ± 20 × 10^?3 vs. 23 × 10^?3 ± 11 × 10^?3/min, p < 0.01). The amount of red blood cell (RBC) products, but not of fresh‐frozen plasma or platelets, was associated with an increase in PLI (β, 1.6 [0.2‐3.0]). Concerning causative factors in the blood product, neither the level of bioactive lipids nor the presence of antibodies was associated with an increase in PLI. Patient factors such as surgery risk and time on cardiopulmonary bypass did not influence the risk of pulmonary leakage after blood transfusion. CONCLUSIONS: Transfusion in cardiothoracic surgery patients is associated with an increase in pulmonary capillary permeability, an effect that was dose dependent for RBC products. The level of bioactive lipids or the presence of HLA or HNA antibodies in the transfused products were not associated with increased pulmonary capillary permeability.     

Protein quality in Mirasol pathogen reduction technology–treated,apheresis‐derived fresh‐frozen plasma

BACKGROUND: The Mirasol pathogen reduction technology (PRT) system for plasma is based on a riboflavin (vitamin B₂) and ultraviolet (UV) light treatment process resulting in pathogen inactivation due to irreversible photo‐oxidative damage of nucleic acids. The purpose of this study was to evaluate the in vitro protein quality of apheresis‐derived plasma treated with riboflavin and UV light in comparison with untreated fresh‐frozen plasma (FFP). STUDY DESIGN AND METHODS: Twenty apheresis plasma samples (270 ± 10 mL) were combined with 35 ± 5 mL of riboflavin solution (500 µM), yielding a mean 60 µM final riboflavin concentration, and then exposed to UV light (6.24 J/mL). Riboflavin and UV light–treated plasma was then flash frozen, within 8 hours of collection, generating treated FFP. Treated FFP was thawed and analyzed using standard coagulation assays, and the percent retention of protein activity was reported, relative to untreated, paired controls. RESULTS: Plasma proteins demonstrated different sensitivities to riboflavin and UV treatment. The amount of total protein remained unchanged. After treatment, fibrinogen (antigen) showed 99% retention; Factor (F)XII, FXIII, ADAMTS‐13, and von Willebrand factor (ristocetin cofactor) 96% to 100%. Fibrinogen retained 77% activity, FII 80%, FVIIIc 75%, and FV 73% after treatment. Antithrombin, protein S, plasminogen, and α₂‐antiplasmin retained between 91 and 100% activity. CONCLUSION: The results from this study demonstrate that coagulant and anticoagulant proteins in riboflavin and UV light–treated (PRT) apheresis plasma are well preserved.