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Background: Cardiac surgery is associated with a high rate of intraoperative transfusion, requiring pre- ordering or ordering of packed red blood cell (PRBC) before surgery. Our institutional strategy is based on a systematic type and screen (T/S) ordering of 3 PRBCs at the blood bank then stored in a dedicated refrigerator in the operating room for each patient scheduled for cardiac surgery. However, these PRBC units are not always transfused and are therefore at risk of destruction if temperature fluctuations are detected during transport and storage processes. In addition, these orders represent a burden for the blood bank. Therefore, it is relevant to move towards a more tailored PRBC order before cardiac surgery and challenge the systematic ordering protocol. Methods: The Transfusion Understanding Scoring Tool (TRUST) and the Transfusion Risk and Clinical Knowledge (TRACK) Score are designed to stratify blood transfusion needs in cardiac surgery. We retrospectively performed both scores for each patient scheduled for cardiac surgery. Then, we compared their performance to predict PRBC transfusion and determined the optimal threshold to optimize the preoperative PRBC order reflecting the needs of our population managed with our local standards. Results: Receiver operating characteristic (ROC) curves for prediction of PRBC transfusion using the two scores were computed for the whole cohort (n=1249). Both scores performed well (areas under ROC curves: 0.81 and 0.82 (95% CI) using the TRACK Score and the TRUST, respectively). A TRUST < 3 identified a subgroup of patients (53.6%) at low risk of transfusion. The availability of 1 T/S PRBC in the OR would cover the needs of the majority (92.5%) of this group. Conclusions: In our institution, the use of the TRUST preoperatively could offer a more tailored T/S PRBC order for the intraoperative period, especially in the low-risk transfusion group.

Postoperative pulmonary complications (PPC) remain a main issue after cardiac surgery. The objective was to report the incidence and identify risk factors of PPC after cardiac surgery. An international multicenter prospective study (42 international centers in 9 countries). A total of 707 adult patients who underwent cardiac surgery under cardiopulmonary bypass. None MEASUREMENTS AND MAIN RESULTS: During a study period of 2 weeks, the investigators included all patients in their respective centers and screened for PPCs. PPC was defined as the occurrence of at least 1 pulmonary complication among the following: atelectasis, pleural effusion, respiratory failure, respiratory infection, pneumothorax, bronchospasm, or aspiration pneumonitis. Among 676 analyzed patients, 373 patients presented with a PPC (55%). The presence of PPC was significantly associated with a longer intensive care length of stay and hospital length of stay. One hundred ninety (64%) patients were not intraoperatively ventilated during cardiopulmonary bypass. Ventilation settings were similar regarding tidal volume, respiratory rate, inspired oxygen. In the regression model, age, the Euroscore II, chronic obstructive pulmonary disease, preoxygenation modality, intraoperative positive end-expiratory pressure, the absence of pre- cardiopulmonary bypass ventilation, the absence of lung recruitment, and the neuromuscular blockade were associated with PPC occurrence. Both individual risk factors and ventilatory settings were shown to explain the high level of PPCs. These findings require further investigations to assess a bundle strategy for optimal ventilation strategy to decrease PPC incidence.

Introduction: Estimation of residual apixaban plasma concentrations may be requested in the management of emergencies. This study aims at assessing the performance of specific anti-Xa assays calibrated with apixaban on real-life samples with low apixaban plasma concentrations (®-Liquid Anti-Xa assay (STA ® LAX) and the low and normal procedures of the Biophen ®Direct Factor Xa Inhibitors (DiXaI) assay was tested on 134 blood samples, collected from patients on apixaban, wherefrom 74 patients received LMWH after apixaban cessation. The results were compared with the liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) measurements. Results: The Biophen ®DiXaI, Biophen ®DiXaI LOW, and STA ®LAX showed very good correlation with LC-MS/MS measurements in patients without LMWH administration (Spearman r.95,.99, and.98, respectively). Their limits of quantitation were defined at 48, 24, and 12 ng/mL, respectively. The Bland-Altman test measured mean bias (SD) at 5.6 (13.1), −2.5 (5.0), and −0.8 (6.1) ng/ml, respectively. The Spearman r of the Biophen ®DiXaI decreased to 0.64 in presence of low apixaban concentrations. The Spearman r of the Biophen ®DiXaI LOW and STA ®LAX decreased to 0.39 and 0.26, respectively, in presence of LMWH. Conclusions: The accuracy of the low methodologies (Biophen ®DiXaI LOW and STA ®LAX) is slightly improved for low apixaban plasma concentrations, compared with the normal procedure of Biophen ®DiXaI. The interference of LMWH on the low methodologies is measurable, however, less important than the previously reported interference of LMWH on rivaroxaban calibrated specific anti-Xa assays.

La COVID-19 est une maladie infectieuse émergente virale causée par la souche de coronavirus SARSCoV-2. Après presque deux années de pandémie, les cliniciens ont beaucoup progressé dans les connaissances des manifestations cliniques de la maladie, notamment en mettant en avant la place du glycocalyx endothélial. Ce dernier est une structure complexe micro-fibrillaire située au pôle apical de la cellule endothéliale, constituant la barrière histologique entre la cellule et la lumière vasculaire et se comportant comme un organe à part entière. L’étude physiopathologique de ce dernier a permis de mettre en évidence l’intérêt de celui-ci dans la compréhension de la COVID-19 et de ses complications. Cette revue a donc pour but d’appréhender cette maladie sous un angle différent et se propose de résumer les données pertinentes pour le clinicien que nous avons apprises depuis deux ans.

Summary Background To address the unmet medical need for an effective prophylactic vaccine against Ebola virus we assessed the safety and immunogenicity of three different two-dose heterologous vaccination regimens with a replication-deficient adenovirus type 26 vector-based vaccine (Ad26.ZEBOV), expressing Zaire Ebola virus glycoprotein, and a non-replicating, recombinant, modified vaccinia Ankara (MVA) vector-based vaccine, encoding glycoproteins from Zaire Ebola virus, Sudan virus, and Marburg virus, and nucleoprotein from the Tai Forest virus. Methods This randomised, observer-blind, placebo-controlled, phase 2 trial was done at seven hospitals in France and two research centres in the UK. Healthy adults (aged 18–65 years) with no history of Ebola vaccination were enrolled into four cohorts. Participants in cohorts I–III were randomly assigned (1:1:1) using computer-generated randomisation codes into three parallel groups (randomisation for cohorts II and III was stratified by country and age), in which participants were to receive an intramuscular injection of Ad26.ZEBOV on day 1, followed by intramuscular injection of MVA-BN-Filo at either 28 days (28-day interval group), 56 days (56-day interval group), or 84 days (84-day interval group) after the first vaccine. Within these three groups, participants in cohort II (14:1) and cohort III (10:3) were further randomly assigned to receive either Ad26.ZEBOV or placebo on day 1, followed by either MVA-BN-Filo or placebo on days 28, 56, or 84. Participants in cohort IV were randomly assigned (5:1) to receive one dose of either Ad26.ZEBOV or placebo on day 1 for vector shedding assessments. For cohorts II and III, study site personnel, sponsor personnel, and participants were masked to vaccine allocation until all participants in these cohorts had completed the post-MVA-BN-Filo vaccination visit at 6 months or had discontinued the trial, whereas cohort I was open-label. For cohort IV, study site personnel and participants were masked to vaccine allocation until all participants in this cohort had completed the post-vaccination visit at 28 days or had discontinued the trial. The primary outcome, analysed in all participants who had received at least one dose of vaccine or placebo (full analysis set), was the safety and tolerability of the three vaccination regimens, as assessed by participant-reported solicited local and systemic adverse events within 7 days of receiving both vaccines, unsolicited adverse events within 42 days of receiving the MVA-BN-Filo vaccine, and serious adverse events over 365 days of follow-up. The secondary outcome was humoral immunogenicity, as measured by the concentration of Ebola virus glycoprotein-binding antibodies at 21 days after receiving the MVA-BN-Filo vaccine. The secondary outcome was assessed in the per-protocol analysis set. This study is registered at ClinicalTrials.gov , NCT02416453 , and EudraCT, 2015-000596-27. Findings Between June 23, 2015, and April 27, 2016, 423 participants were enrolled: 408 in cohorts I–III were randomly assigned to the 28-day interval group (123 to receive Ad26.ZEBOV and MVA-BN-Filo, and 13 to receive placebo), the 56-day interval group (124 to receive Ad26.ZEBOV and MVA-BN-Filo, and 13 to receive placebo), and the 84-day interval group (117 to receive Ad26.ZEBOV and MVA-BN-Filo, and 18 to receive placebo), and 15 participants in cohort IV were assigned to receive Ad26.ZEBOV and MVA-BN-Filo (n=13) or to receive placebo (n=2). 421 (99·5%) participants received at least one dose of vaccine or placebo. The trial was temporarily suspended after two serious neurological adverse events were reported, one of which was considered as possibly related to vaccination, and per-protocol vaccination was disrupted for some participants. Vaccinations were generally well tolerated. Mild or moderate local adverse events (mostly pain) were reported after 206 (62%) of 332 Ad26.ZEBOV vaccinations, 136 (58%) of 236 MVA-BN-Filo vaccinations, and 11 (15%) of 72 placebo injections. Systemic adverse events were reported after 255 (77%) Ad26.ZEBOV vaccinations, 116 (49%) MVA-BN-Filo vaccinations, and 33 (46%) placebo injections, and included mostly mild or moderate fatigue, headache, or myalgia. Unsolicited adverse events occurred after 115 (35%) of 332 Ad26.ZEBOV vaccinations, 81 (34%) of 236 MVA-BN-Filo vaccinations, and 24 (33%) of 72 placebo injections. At 21 days after receiving the MVA-BN-Filo vaccine, geometric mean concentrations of Ebola virus glycoprotein-binding antibodies were 4627 ELISA units (EU)/mL (95% CI 3649–5867) in the 28-day interval group, 10 131 EU/mL (8554–11 999) in the 56-day interval group, and 11 312 mL (9072–14106) in the 84-day interval group, with antibody concentrations persisting at 1149–1205 EU/mL up to day 365. Interpretation The two-dose heterologous regimen with Ad26.ZEBOV and MVA-BN-Filo was safe, well tolerated, and immunogenic, with humoral and cellular immune responses persisting for 1 year after vaccination. Taken together, these data support the intended prophylactic indication for the vaccine regimen. Funding Innovative Medicines Initiative and Janssen Vaccines & Prevention BV. Translation For the French translation of the abstract see Supplementary Materials section.

P2Y12 inhibitor discontinuation is essential before most surgical interventions to limit bleeding complications. Based on pharmacokinetic data, fixed discontinuation durations have been recommended. However, as platelet function recovery is highly variable among patients, a more individualized approach based on platelet function testing (PFT) has been proposed. The aim of this retrospective single-centre study was to determine whether PFT using whole blood adenosine diphosphate&ndash, multiple electrode aggregometry (ADP&ndash, MEA) was associated with a safe reduction of preoperative waiting time. Preoperative ADP&ndash, MEA was performed for 29 patients on P2Y12 inhibitors. Among those, 17 patients underwent a coronary artery bypass graft. Twenty one were operated with an ADP&ndash, MEA &ge, 19 U (quantification of the area under the aggregation curve), and the waiting time was shorter by 1.6 days (median 1.8 days, IQR 0.5&ndash, 2.9), by comparison with the current recommendations (five days for clopidogrel and ticagrelor, seven days for prasugrel). Platelet function recovery was indeed highly variable among individuals. With the 19 U threshold, high residual platelet inhibition was associated with perioperative platelet transfusion. These results suggest that preoperative PFT with ADP&ndash, MEA could help reduce waiting time before urgent surgery for patients on P2Y12 inhibitors.

Background Guidelines recommend performing atrial fibrillation (AF) catheter ablation without interruption of a direct oral anticoagulants (DOACs) and to administer unfractionated heparin (UFH) for an activated clotting time (ACT) ≥300 seconds, by analogy with vitamin K antagonist (VKA). Nevertheless, pharmacological differences between DOACs and VKA, especially regarding ACT sensitivity and UFH response, prevent extrapolation from VKA to DOACs. Hypothesis The level of anticoagulation at the time of the procedure in uninterrupted DOAC-treated patients is unpredictable and would complicate intraprocedural UFH administration and monitoring. Methods This prospective study included interrupted DOAC-treated patients requiring AF ablation. Preprocedural DOAC concentration ([DOAC]), intraprocedural UFH administration, and ACT values were recorded. A cohort of DOAC-treated patients requiring flutter catheter ablation was considered to illustrate [DOAC] without DOAC interruption. Results Forty-eight patients underwent AF and 14 patients underwent flutter ablation, respectively. In uninterrupted DOAC-treated patients, [DOAC] ranged from ≤30 to 466 ng/mL. When DOAC were interrupted, from 54 to 218 hours, [DOAC] were minimal (maximum: 36 ng/mL), preventing DOAC-ACT interference. Anyway, ACT values were poorly correlated with UFH doses (R 2 = 0.2256). Conclusions Our data showed that uninterrupted DOAC therapy resulted in an unpredictable and highly variable initial level of anticoagulation before catheter ablation. Moreover, even with DOAC interruption preventing interference between DOAC, UFH, and ACT, intraprocedural UFH monitoring was complex. Altogether, our exploratory results call into question the appropriateness of transposing UFH dose protocols, as well as the relevance of ACT monitoring in uninterrupted DOAC-treated patients.

Aims Patients receiving direct oral anticoagulants (DOACs) frequently undergo elective invasive procedures. Their management is challenging. We aimed to determine the optimal duration of DOAC discontinuation that ensures a minimal anticoagulant effect during the procedure. Methods and results This prospective multicentre study included 422 DOAC-treated patients requiring an invasive procedure. Pre-procedural DOAC concentration ([DOAC]) and routine haemostasis assays were performed to determine i/the proportion of patients who achieved a minimal pre-procedural [DOAC] (≤30 ng/mL) according to the duration of DOAC discontinuation, ii/the predictors of minimal [DOAC] and, iii/the ability of routine assays to predict minimal [DOAC]. Lastly, we assessed the predictors of peri-procedural bleeding events. The duration of DOAC discontinuation ranged from 1 to 218 h and pre-procedural [DOAC] from ≤30 to 527 ng/mL. After a 49-72-h discontinuation, 95% of the [DOAC] were ≤30 ng/mL. A 72-h discontinuation predicted concentrations ≤30 ng/mL with 91% specificity. In multivariable analysis, duration of DOAC discontinuation, creatinine clearance

P2Y inhibitor discontinuation is essential before most surgical interventions to limit bleeding complications. Based on pharmacokinetic data, fixed discontinuation durations have been recommended. However, as platelet function recovery is highly variable among patients, a more individualized approach based on platelet function testing (PFT) has been proposed. The aim of this retrospective single-centre study was to determine whether PFT using whole blood adenosine diphosphate-multiple electrode aggregometry (ADP-MEA) was associated with a safe reduction of preoperative waiting time. Preoperative ADP-MEA was performed for 29 patients on P2Y inhibitors. Among those, 17 patients underwent a coronary artery bypass graft. Twenty one were operated with an ADP-MEA ≥ 19 U (quantification of the area under the aggregation curve), and the waiting time was shorter by 1.6 days (median 1.8 days, IQR 0.5-2.9), by comparison with the current recommendations (five days for clopidogrel and ticagrelor, seven days for prasugrel). Platelet function recovery was indeed highly variable among individuals. With the 19 U threshold, high residual platelet inhibition was associated with perioperative platelet transfusion. These results suggest that preoperative PFT with ADP-MEA could help reduce waiting time before urgent surgery for patients on P2Y inhibitors.

INTRODUCTION: Andexanet alfa is a recombinant modified factor Xa protein that has been developed to reverse factor Xa inhibitors. Since May 2018, the FDA has approved its utilization in patients treated with apixaban and rivaroxaban in case of life-threatening or uncontrolled bleeding. On 28 of February 2019, the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a conditional marketing authorization for andexanet alfa in Europe. Area covered: The authors provide an overview of andexanet alfa development and its pharmacokinetic and pharmacodynamic properties. The results of the clinical phase III trial ANNEXA as well as current limitations related to andexanet alfa are also discussed. Expert opinion: Although phase I and II studies have proven that andexanet alfa can be effective in reversing the effect of factor Xa inhibitors, its efficacy in major bleeding patients has only been shown for apixaban and rivaroxaban, without any comparator group. Well-designed studies comparing the efficacy and safety of andexanet alfa to other reversal strategies are required to confirm preliminary data. The benefit of andexanet alfa in specific settings needs to be investigated and its use in clinical practice needs to be facilitated by the implementation of international guidelines.

Background: The perioperative management of antiplatelet therapy in noncardiac surgery patients who have undergone previous percutaneous coronary intervention (PCI) remains a dilemma. Continuing dual antiplatelet therapy (DAPT) may carry a risk of bleeding, while stopping antiplatelet therapy may increase the risk of perioperative major adverse cardiovascular events (MACE). Methods: Occurrence of Bleeding and Thrombosis during Antiplatelet Therapy In Non-Cardiac Surgery (OBTAIN) was an international prospective multicentre cohort study of perioperative antiplatelet treatment, MACE, and serious bleeding in noncardiac surgery. The incidences of MACE and bleeding were compared in patients receiving DAPT, monotherapy, and no antiplatelet therapy before surgery. Unadjusted risk ratios were calculated taking monotherapy as the baseline. The adjusted risks of bleeding and MACE were compared in patients receiving monotherapy and DAPT using propensity score matching. Results: A total of 917 patients were recruited and 847 were eligible for inclusion. Ninety-six patients received no antiplatelet therapy, 526 received monotherapy with aspirin, and 225 received DAPT. Thirty-two patients suffered MACE and 22 had bleeding. The unadjusted risk ratio for MACE in patients receiving DAPT compared with monotherapy was 1.9 (0.93–3.88), P=0.08. There was no difference in MACE between no antiplatelet treatment and monotherapy 1.03 (0.31–3.46), P=0.96. Bleeding was more frequent with DAPT 6.55 (2.3–17.96) P=0.0002. In a propensity matched analysis of 177 patients who received DAPT and 177 monotherapy patients, the risk ratio for MACE with DAPT was 1.83 (0.69–4.85), P=0.32. The risk of bleeding was significantly greater in the DAPT group 4.00 (1.15–13.93), P=0.031. Conclusions: OBTAIN showed an increased risk of bleeding with DAPT and found no evidence for protective effects of DAPT from perioperative MACE in patients who have undergone previous PCI.

Here, we report a 71-year-old Caucasian male with a chronic spinal cord injury at the level of T4, who underwent a coronary artery bypass grafting for a 3-vessel disease. During surgery an almost fatal hypotension took place in the presence of an autonomic dysregulation, requiring to go back on cardiopulmonary bypass. A few other episodes of hyper- and hypotension occurred perioperatively. We discuss the issues with the anesthesia and surgical cardiac procedures in the light of this acute blood pressure variability called autonomic dysreflexia.