Universal Definition Of Perioperative Bleeding Research Articles

Using Machine Learning to Predict Bleeding after Cardiac Surgery.

The primary objective was to predict bleeding after cardiac surgery with machine learning using the data from the ANZSCTS (Australia New Zealand Society of Cardiac and Thoracic Surgeons) Cardiac Surgery Database, cardiopulmonary bypass perfusion database, ICU (intensive care unit) database and laboratory results. We obtained surgical, perfusion, ICU and laboratory data from a single Australian tertiary cardiac surgical hospital from February 2015 to March 2022 and included 2000 patients undergoing cardiac surgery. We trained our models to predict either the Papworth definition or Dyke et al.'s universal definition of perioperative bleeding. Our primary outcome was the performance of our machine learning algorithms using sensitivity, specificity, positive and negative predictive values, accuracy, AUROC (area under receiver operating characteristics curve) and AUPRC (area under precision recall curve). Of the 2000 patients undergoing cardiac surgery, 13.3% (226/2000) had bleeding using the Papworth definition and 17.2% (343/2000) had moderate to massive bleeding using Dyke et al.'s definition. The best performing model based on AUPRC was the Ensemble Voting Classifier model for both Papworth (AUPRC 0.310, AUROC 0.738) and Dyke definitions of bleeding (AUPRC 0.452, AUROC 0.797). Machine learning can incorporate routinely collected data from various datasets to predict bleeding after cardiac surgery.

Albumin Infusion and Blood Loss After Cardiac Surgery

BackgroundIn the recent ALBICS (ALBumin In Cardiac Surgery) trial, 4% albumin used for cardiopulmonary bypass priming and volume replacement increased perioperative bleeding compared with Ringer acetate. In the present exploratory study, albumin-related bleeding was further characterized. MethodsRinger acetate and 4% albumin were compared in a randomized, double-blinded fashion in 1386 on-pump adult cardiac surgery patients. The study end points for bleeding were the Universal Definition of Perioperative Bleeding (UDPB) class and its components. ResultsThe UDPB bleeding grades were higher in the albumin group than the Ringer group: “insignificant” (albumin vs Ringer: 47.5% vs 62.9%), “mild” (12.7% vs 8.9%), “moderate” (28.7% vs 24.4%), “severe” (10.2% vs 3.2%), and “massive” (0.9% vs. 0.6%; P < .001). Patients in the albumin group received red blood cells (45.2% vs 31.5%; odds ratio [OR], 1.80; 95% CI, 1.44-2.24; P < .001), platelets (33.3% vs 21.8%; OR, 1.79; 95% CI, 1.41-2.28; P < .001), and fibrinogen (5.6% vs 2.6%; OR, 2.24; 95% CI, 1.27-3.95; P < .05), and underwent resternotomy (5.3% vs 1.9%; OR, 2.95; 95% CI, 1.55-5.60, P < .001) more often than patients in the Ringer group. The strongest predictors of bleeding were albumin group allocation (OR, 2.18; 95% CI, 1.74-2.74) and complex (OR, 2.61; 95% CI, 2.02-3.37) and urgent surgery (OR, 1.63; 95% CI, 1.26-2.13). In interaction analysis, the effect of albumin on the risk of bleeding was stronger in patients on preoperative acetylsalicylic acid. ConclusionsPerioperative administration of albumin, compared with Ringer’s acetate, resulted in increased blood loss and higher UDBP class. The magnitude of this effect was similar to the complexity and urgency of the surgery.

THE QUANTRA PCS, PLATELET CONTRIBUTION TO CLOT STIFFNESS, PARAMETER IS CLINICALLY USEFUL TO IDENTIFY PLATELET-DEPENDENT BLEEDING IN HIGH-RISK CARDIAC SURGERY PATIENTS

<h3>Objective</h3> Postoperative use of platelet function testing in order to rule out microvascular bleeding due to platelet dysfunction after cardiac surgery still lacks strong reference data and reliable cut-off values. We investigated the performance of two different point-of-care viscoelastic devices and platelet aggregometry in expressing surgery-dependent platelet dysfunction and anticipating postoperative major bleeding in a cohort of high-risk patients. <h3>Design and Method</h3> This is a prospective cohort study on 50 adult patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) being on antiplatelet drugs discontinued for no more than 7 days (clopidogrel, prasugrel) or 5 days (ticagrelor). Coagulation and platelet function testing, including QUANTRA, ROTEM and Multiplate were assessed preoperatively and postoperatively. Chest drain blood loss was measured in the first 12 postoperative hours. Perioperative bleeding was assessed using the Universal Definition of Perioperative Bleeding (UDPB) in cardiac surgery, modified to not consider anemia-correcting packed red cells transfusions in absence of bleeding > 600 ml/12 h. Major bleeding was identified as UDPB class II or higher. <h3>Results</h3> The QUANTRA Platelet contribution to Clot Stiffness (PCS) was significantly (P=0.001) reduced after CPB. Multiplate ADPtest was significantly (P=0.001) reduced, as well, whereas TRAPtest was not. The platelet component (PC) as extrapolated by ROTEM data (EXTEM MCF – FIBTEM MCF) was unchanged after CPB, while the A10 PC (PC at 10 minutes) significantly (P=0.001) decreased. At regression analysis of the preoperative and postoperative platelet function parameters, there was a significant linear correlation (P=0.001) for the PCS, A10 PC and ADPtest. At the ROC analysis for the predictive ability of the post-CPB platelet function testing, the best discrimination was obtained by the QUANTRA PCS, with an AUC of 0.788, followed by the ROTEM A10 PC (AUC 0.765) and PC (AUC 0.758). The Multiplate tests did not achieve an AUC > 0.70. The cut off values identified for the QUANTRA PCS (10.5 hPa), the ROTEM A10 PC (38 mm) and for the ROTEM PC (47 mm) yielded a combination of a negative predictive value > 80% and a positive predictive value > 67%. <h3>Conclusions</h3> QUANTRA PCS, ROTEM A10 PC, and Multiplate ADPtest reflect the post-CPB platelet dysfunction, whereas ROTEM PC and Multiplate TRAPtest do not. Major bleeding was predicted with a moderate degree of discrimination by the post-CPB viscoelastic tests (PCS, PC, A10 PC) but not by the Multiplate tests.

Are Viscoelastic Tests Clinically Useful to Identify Platelet-Dependent Bleeding in High-Risk Cardiac Surgery Patients?

Postoperative use of platelet function testing to rule out microvascular bleeding due to platelet dysfunction after cardiac surgery still lacks strong reference data and reliable cutoff values, yielding a clinically adequate sensitivity and specificity. The present study aims to investigate the performance of two different point-of-care viscoelastic devices and platelet aggregometry in expressing surgery-dependent platelet dysfunction and anticipating postoperative major bleeding in a cohort of high-risk patients. Prospective cohort study of 50 adult patients who were on antiplatelet drugs discontinued for no more than 7 days (clopidogrel and prasugrel) or 5 days (ticagrelor) undergoing cardiac surgery with cardiopulmonary bypass (CPB). Coagulation and platelet function testing, including QUANTRA, ROTEM, and Multiplate, were assessed preoperatively and postoperatively. Chest drain blood loss was measured in the first 12 postoperative hours. Perioperative bleeding was assessed using a modified version of the Universal Definition of Perioperative Bleeding (UDPB) in cardiac surgery, modified to not consider anemia-correcting packed red cells transfusions in the absence of bleeding >600 mL/12 h. Major bleeding was identified as UDPB class II or higher. Multiplate adenosine diphosphate (ADPtest) was significantly ( P = .001) reduced after CPB, whereas TRAPtest was not. The platelet component (PC) as extrapolated by ROTEM data (EXTEM MCF-FIBTEM MCF) was unchanged after CPB, while the A10 PC (PC at 10 minutes) was significantly ( P = .001) reduced. The QUANTRA platelet contribution to clot stiffness (PCS) was significantly ( P = .001) reduced, as well. At the ROC analysis for the predictive ability of the post-CPB platelet function testing, the best discrimination was obtained by the QUANTRA PCS, with an area under the curve (AUC) (95% confidence interval [CI]) of 0.80 (0.66-0.91), P = .001, followed by the ROTEM A10 PC with AUC (95% CI) of 0.75 (0.51-0.99), P = .004, and PC with AUC (95% CI) of 0.74 (0.50-0.99), P = .009. The Multiplate ADPtest had an AUC (95% CI) of 0.67 (0.42-0.91), and the TRAPtest had an AUC (95% CI) of 0.62 (0.37-0.86). The cutoff values identified were 13 hPa for the QUANTRA PCS, 40 mm for the ROTEM A10, and 48.5 mm for the ROTEM PC, with negative predictive values of 84%, 81%, and 86%, respectively, and positive predictive values of 55%, 53%, and 69%, respectively. QUANTRA PCS, ROTEM A10 PC, and Multiplate ADPtest showed a significant decrease after CPB, whereas ROTEM PC and Multiplate TRAPtest did not. Major bleeding was predicted with a moderate to good discrimination by the post-CPB viscoelastic tests (PCS, PC, and A10 PC).

Preoperative treatment with clopidogrel and ticagrelor on bleeding complications in off-pump coronary artery bypass grafting

BackgroundDual antiplatelet therapy (DAPT) consisting of acetylsalicylic acid and clopidogrel or ticagrelor increased bleeding complications in patients undergoing coronary artery bypass grafting (CABG). We aimed to compare the bleeding risks between patients treated with clopidogrel and ticagrelor preoperatively and investigate the influence of discontinuation of clopidogrel and ticagrelor on bleeding risk in off-pump CABG (OPCABG). MethodsWe conducted a retrospective analysis of patients with DAPT who underwent OPCABG. The propensity score matching was performed given the baseline differences between clopidogrel- and ticagrelor-treated patients. Bleeding was assessed by chest tube drainage volume and universal definition of perioperative bleeding. ResultsThis study included 836 patients. Five hundred and fifty patients were treated with clopidogrel and 286 patients treated with ticagrelor before surgery. After matching, 275 patients treated with clopidogrel and 275 patients with ticagrelor were included. There were no significant differences in bleeding between clopidogrel and ticagrelor group. Patients who discontinued clopidogrel before surgery <3 d had a higher risk of severe perioperative bleeding compared with those who discontinued ≥5 d (16.4 % vs. 5.0 %, P = 0.045). By contrast, the risk of severe perioperative bleeding was comparable among patients who discontinued ticagrelor for <3 d, ≥3–5 d and ≥5 d preoperatively (16.2 % vs. 9.1 % vs. 10.1 %, P = 0.317). The multivariable analysis confirmed that time since discontinuation (<3 d vs. ≥5 d: OR = 2.732, 95 % CI: 1.332–5.605, P = 0.006) but not the types of P2Y12 receptor antagonist was an independent predictor for severe perioperative bleeding. ConclusionsThere were no significant differences in severe perioperative bleeding between clopidogrel and ticagrelor groups. Discontinuation of clopidogrel <3 d before OPCABG increased the risk of severe perioperative bleeding.

The Effect of Cell Salvage on Bleeding and Transfusion Needs in Cardiac Surgery.

Introduction Cell salvaging is well established in the blood management of cardiac patients, but there remain some concerns about its effects on perioperative bleeding and transfusion variables. This randomized controlled study investigated the potential effects of the centrifuged end-product on bleeding, transfusion rates, and other transfusion-related variables in adult cardiac surgery patients submitted to extracorporeal circulation. Materials and Methods Patients were randomly chosen to receive (cell-salvage group, 99 patients) or not to receive (control group, 110 patients) the centrifuged product of a cell salvage apparatus. Bleeding and transfusion rates according to the universal definition of perioperative bleeding (UDPB) classification, postoperative hemoglobin, coagulation, and oxygenation indices were recorded and compared between the groups. Results Both groups had almost identical bleeding and transfusion rates (median value: 2 units of red blood cells (RBC) and no units of fresh frozen plasma (FFP) and platelets (PLT) for both groups, p > 0.05). Patients in the cell-salvage group presented slightly higher hemoglobin concentrations (10.6 ± 1.1 vs. 10.1 ± 1.7 g/dL, p < 0.05, respectively) and a tendency towards better oxygenation indices (PaO2/FiO2: 241 ± 94 vs. 207 ± 84, p=0.013) in the postoperative period albeit with a tendency for prolongation of prothrombin time (INR: 1.31 ± 0.18 vs. 1.26 ± 0.12, p=0.008). Conclusion Within the study's constraints, the perioperative use of the cell salvage concentrate does not seem to affect bleeding or transfusion variables, although it could probably ameliorate postoperative oxygenation in adult cardiac surgery patients. A tendency to promote coagulation disturbances was detected.

Machine learning algorithms to predict major bleeding after isolated coronary artery bypass grafting.

ObjectivesPostoperative major bleeding is a common problem in patients undergoing cardiac surgery and is associated with poor outcomes. We evaluated the performance of machine learning (ML) methods to predict postoperative major bleeding.MethodsA total of 1,045 patients who underwent isolated coronary artery bypass graft surgery (CABG) were enrolled. Their datasets were assigned randomly to training (70%) or a testing set (30%). The primary outcome was major bleeding defined as the universal definition of perioperative bleeding (UDPB) classes 3–4. We constructed a reference logistic regression (LR) model using known predictors. We also developed several modern ML algorithms. In the test set, we compared the area under the receiver operating characteristic curves (AUCs) of these ML algorithms with the reference LR model results, and the TRUST and WILL-BLEED risk score. Calibration analysis was undertaken using the calibration belt method.ResultsThe prevalence of postoperative major bleeding was 7.1% (74/1,045). For major bleeds, the conditional inference random forest (CIRF) model showed the highest AUC [0.831 (0.732–0.930)], and the stochastic gradient boosting (SGBT) and random forest models demonstrated the next best results [0.820 (0.742–0.899) and 0.810 (0.719–0.902)]. The AUCs of all ML models were higher than [0.629 (0.517–0.641) and 0.557 (0.449–0.665)], as achieved by TRUST and WILL-BLEED, respectively.ConclusionML methods successfully predicted major bleeding after cardiac surgery, with greater performance compared with previous scoring models. Modern ML models may enhance the identification of high-risk major bleeding subpopulations.

Massive Bleeding After Surgical Repair in Acute Type A Aortic Dissection Patients: Risk Factors, Outcomes, and the Predicting Model.

BackgroundMassive bleeding throughout aortic repair in acute type A aortic dissection (ATAAD) patients is a common but severe condition that can cause multiple serious clinical problems. Here, we report our findings regarding risk factors, short-term outcomes, and predicting model for massive bleeding in ATAAD patients who underwent emergent aortic repair.MethodsA universal definition of perioperative bleeding (UDPB) class 3 and 4 were used to define massive bleeding and comprehensively evaluate patients. A total of 402 consecutive patients were enrolled in this retrospective study during 2019. Surgical strategies used to perform aortic arch procedures included total arch and hemiarch replacements. In each criterion, patients with massive bleeding were compared with remaining patients. Multivariable regression analyses were used to identify independent risk factors for massive bleeding. Logistic regression was used to build the model, and the model was evaluated with its discrimination and calibration.ResultsIndependent risk factors for massive bleeding included male sex (OR = 6.493, P < 0.001), elder patients (OR = 1.029, P = 0.05), low body mass index (BMI) (OR = 0.879, P = 0.003), emergent surgery (OR = 3.112, P = 0.016), prolonged cardiopulmonary bypass time (OR = 1.012, P = 0.002), lower hemoglobin levels (OR = 0.976, P = 0.002), increased D-dimer levels (OR = 1.000, P = 0.037), increased fibrin degradation products (OR = 1.019, P = 0.008), hemiarch replacement (OR = 5.045, P = 0.037), total arch replacement (OR = 14.405, P = 0.004). The early-stage mortality was higher in massive bleeding group (15.9 vs. 3.9%, P = 0.001). The predicting model showed a well discrimination (AUC = 0.817) and calibration (χ2 = 5.281, P = 0.727 > 0.05).ConclusionMassive bleeding in ATAAD patients who underwent emergent aortic repair is highly associated with gender, emergent surgery, increased D-dimer levels, longer CPB time, anemia, and use of a complex surgical strategy. Since massive bleeding may lead to worse outcomes, surgeons should choose suitable surgical strategies in patients who are at a high risk of massive bleeding.

Does thromboelastography predict bleeding in patients treated with clopidogrel or ticagrelor in off-pump coronary artery bypass grafting?

ObjectivesWe sought to investigate the predictive value of platelet function assessment for bleeding in clopidogrel- or ticagrelor-treated patients undergoing off-pump coronary artery bypass grafting (OPCABG). MethodsThis prospective study included patients treated with acetylsalicylic acid and clopidogrel or acetylsalicylic acid and ticagrelor and scheduled for OPCABG. The percentage of platelet aggregation was evaluated by thromboelastography. Postoperative blood loss was measured as the chest tube drainage (CTD) and excessive blood loss was settled as CTD with more than 600 mL at first postoperative 12 h. Major bleeding complications were defined by Bleeding Academic Research Consortium (BARC) type 4-CABG related bleeding or class 3 or class 4 bleeding in universal definition of perioperative bleeding (UDPB) in adult cardiac surgery. ResultsA total of 434 consecutive patients were included. There was a negative correlation (r = −0.133, P = 0.0056) between ADP-induced platelet aggregation and CTD at 12 h. The platelet aggregation exhibited a moderate performance (AUC = 0.616) for predicting excessive postoperative blood loss. Multivariable analysis showed that ADP-induced platelet aggregation <33.45% (OR = 2.976, 95% CI: 1.325–6.711, P = 0.008) was independently associated with excessive postoperative blood loss. However, the percentage of ADP-induced platelet aggregation predicted neither UDPB-defined nor BARC-defined major bleeding. Instead, P2Y12 receptor antagonist discontinuation time was independently related to the risk of major bleeding complication. ConclusionsADP-induced platelet aggregation detected by thromboelastography was negatively related to postoperative blood loss and platelet aggregation <33.45% was associated with excessive postoperative blood loss. However, platelet function assessment by thromboelastography failed to predict major bleeding complications.

Rationale and design of the safe and timely antithrombotic removal - ticagrelor (STAR-T) trial: A prospective, multi-center, double-blind, randomized controlled trial evaluating reductions in postoperative bleeding with intraoperative removal of ticagrelor by the drugsorb™-ATR device in patients undergoing cardiothoracic surgery within 48 hours from last ticagrelor dose

Ticagrelor is often administered to patients with acute coronary syndromes. However, when these patients require urgent or emergent cardiothoracic (CT) surgery the presence of ticagrelor significantly increases surgical bleeding. The goal of the current trial is to evaluate the effectiveness and safety of the DrugSorb-ATR hemoadsorption device for the intraoperative removal of ticagrelor to reduce postoperative bleeding in the above patient population. The Safe and Timely Antithrombotic Removal - Ticagrelor (STAR-T) Trial is a multi-center, double-blind, randomized, controlled trial enrolling patients who require cardiothoracic surgery on cardiopulmonary bypass (CPB) within 48 hours of last ticagrelor dose. Subjects will be randomized 1:1 to receive either the DrugSorb-ATR device or an identical sham device during CPB. The study will enroll up to 120 subjects at 20 U.S centers, and the primary outcome is the composite of fatal perioperative bleeding, moderate/severe/massive bleeding according to the Universal Definition of Perioperative Bleeding in Cardiac Surgery (UDPB), and 24 hours chest tube drainage. The components of the composite are hierarchically ranked according to clinical significance and the primary analysis will utilize the Win Ratio method. Percent change in ticagrelor levels before and after CPB (drug removal) will be the key secondary endpoint. An independent Clinical Events Committee will adjudicate all clinical endpoints including safety endpoints relating to postoperative thrombotic events. Subjects will be followed through 30 days after the index operation. The results from STAR-T, if positive, will potentially support FDA market approval for DrugSorb-ATR, and provide a solution to an important unmet clinical need.

Universal definition of perioperative bleeding in cardiac surgery adults and association with mortality in a Mexican Cardiovascular Critical Care Unit

Background Bleeding as a complication is associated with poorer results in cardiac surgery. There is increasing evidence that the use of blood products is an independent factor of increased morbidity, mortality, and hospital costs. Dyke et al. established the universal definition of perioperative bleeding (UDPB). This classification is more precise defining mortality in relation to the degree of bleeding. Methods A descriptive and analytical retrospective study of a database of patients underwent cardiac surgery from January 1, 2016, to December 31, 2017, was performed. The primary objective of the study was to look at mortality associated with the degree of bleeding using the UDPB. Results A total of 918 patients who went to cardiac surgery were obtained. Most of the population was classified as insignificant bleeding class (n = 666, 72.9%), and for massive bleeding the lowest proportion (n = 25, 2.7%). For the primary outcome of 30-day mortality, a significant difference was found between the groups, observing that it increased to a higher degree of bleeding. This was corroborated by multivariate logistic regression analysis that was adjusted to EuroScore II and cardiopulmonary bypass (CPB) duration, finding an independent association of the bleeding class with 30-day mortality (OR, 95%, 5.82 [2.22-15.26], p = 0.0001). Conclusions We found that the higher the degree in UDPB was associated with higher mortality independently to EuroScore II and CPB duration for adult patients undergoing cardiac surgery.

MiR-223 levels predicting perioperative bleeding in off-pump coronary artery bypass grafting.

BackgroundTo investigate the predictive value of platelet-related microRNAs (miRNAs) for bleeding during and after off-pump coronary artery bypass grafting (OPCABG) and the influence of dual antiplatelet therapy (DAPT) on miRNAs.MethodsThis prospective study included 59 patients scheduled for OPCABG. The plasma miR-126 and miR-223 levels were measured and platelet aggregation was determined by thromboelastography during DAPT. The plasma miRNA levels were compared between patients treated with ticagrelor or clopidogrel. Multivariable logistic regression analysis was performed to determine the independent risk factors for bleeding during and after surgery. Active bleeding was defined as a blood loss >1.5 mL/kg/h for 6 consecutive hours within the first 24 hours or in case of reoperation during the first 12 postoperative hours. Severe perioperative bleeding was defined using the universal definition of perioperative bleeding in adult cardiac surgery.ResultsHigher circulating miR-223 levels [odds ratio (OR) =1.348, 95% confidence interval (CI): 1.001–1.814, P=0.047] and lower body mass index (OR =0.648, 95% CI: 0.428–0.980, P=0.040) were independent predictors for severe perioperative bleeding in OPCABG. Ticagrelor treatment led to significant increases in circulating miR-223 levels compared with clopidogrel treatment.ConclusionsThe plasma miR-223 levels served as a predictor for bleeding during and after OPCABG. Circulating miR-223 levels were significantly elevated with ticagrelor treatment compared with clopidogrel treatment. MiR-223 may be a novel biomarker for bleeding in cardiac surgery and can help explain the different efficacies of ticagrelor and clopidogrel.

Universal definition of perioperative bleeding in cardiac surgery adults and association with mortality in a Mexican Cardiovascular Critical Care Unit.

Bleeding as a complication is associated with poorer results in cardiac surgery. There is increasing evidence that the use of blood products is an independent factor of increased morbidity, mortality, and hospital costs. Dyke et al. established the universal definition of perioperative bleeding (UDPB). This classification is more precise defining mortality in relation to the degree of bleeding. A descriptive and analytical retrospective study of a database of patients underwent cardiac surgery from January 1, 2016, to December 31, 2017, was performed. The primary objective of the study was to look at mortality associated with the degree of bleeding using the UDPB. A total of 918 patients who went to cardiac surgery were obtained. Most of the population was classified as insignificant bleeding class (n = 666, 72.9%), and for massive bleeding the lowest proportion (n = 25, 2.7%). For the primary outcome of 30-day mortality, a significant difference was found between the groups, observing that it increased to a higher degree of bleeding. This was corroborated by multivariate logistic regression analysis that was adjusted to EuroScore II and cardiopulmonary bypass (CPB) duration, finding an independent association of the bleeding class with 30-day mortality (OR, 95%, 5.82 [2.22-15.26], p = 0.0001). We found that the higher the degree in UDPB was associated with higher mortality independently to EuroScore II and CPB duration for adult patients undergoing cardiac surgery.

Genetic Polymorphisms and Perioperative Bleeding in Off-Pump Coronary Artery Bypass Grafting Surgery

Clopidogrel use before coronary artery bypass graft surgery may increase risk for perioperative hemorrhage. The effect of genetic polymorphisms related to clopidogrel responses on bleeding during or after off-pump coronary artery bypass graft surgery is unknown. This prospective study included 206 coronary artery disease patients scheduled for off-pump coronary artery bypass graft surgery. Genotypes were determined using Sequenom MassARRAY system. Severe bleeding was defined by the universal definition of perioperative bleeding in cardiac surgery. Patients carrying the ABCB1 3435 wild-type genotype (CC) had a higher risk of severe perioperative bleeding compared with patients carrying the variant genotype (CT or TT; 33.9% vs 16.5%, P= .009). Low baseline hemoglobin level (odds ratio 0.944; 95% confidence interval, 0.917 to 0.972; P < .001), low baseline estimated glomerular filtration rate (odds ratio 0.977; 95% confidence interval, 0.956 to 0.999; P= .041), discontinuing clopidogrel 5 days or less before surgery (odds ratio 2.458; 95% confidence interval, 1.044 to 5.786; P= .039), and the ABCB1 wild-type genotype (CC; odds ratio 2.941; 95% confidence interval, 1.250 to 6.944; P= .014) were independent risk factors for severe perioperative bleeding. Patients carrying the ABCB1 wild-type genotype (CC) had a higher rate of severe perioperative bleeding compared with patients carrying the variant genotype (CT or TT). Discontinuation of clopidogrel 5 days or less before surgery and the ABCB1 wild-type genotype (CC) were independent risk factors for severe perioperative bleeding.

U-shaped relationship between pre-operative plasma fibrinogen levels and severe peri-operative bleeding in cardiac surgery.

An inverse linear relationship has been reported between pre-operative fibrinogen levels and postoperative blood loss in cardiac surgery. However, recently high pre-operative fibrinogen levels have also been reported to be associated with increased blood transfusion and re-operation. We tested the hypothesis that the relationship between pre-operative fibrinogen levels and severe peri-operative bleeding is not linear. A large-scale (n = 3883) single-centre retrospective study. A tertiary care teaching hospital. We analysed data from our institutional database which includes all patients above 18 years who underwent on-pump cardiac surgery through a sternotomy between September 2010 and May 2014. Peri-operative severe bleeding adapted from the Universal Definition of Peri-operative Bleeding, class 3 or 4. The relationship between pre-operative fibrinogen levels and peri-operative severe bleeding was analysed by binary logistic regression. A cubic B-spline transformation was used to estimate the relationship between pre-operative fibrinogen level associated with excessive peri-operative bleeding. Severe peri-operative bleeding was observed in 957 (24.6%) patients. An L-shaped relationship was observed between pre-operative fibrinogen levels and 24-h postoperative blood loss. The relationship between pre-operative fibrinogen levels and severe peri-operative bleeding (i.e. Universal Definition of Peri-operative Bleeding class 3 or 4) was U-shaped: the risk of severe peri-operative bleeding bottomed at 3.3 g l when the upward sloping curve started at 5.8 g l with a steeper increase above 8.2 g l. We reported a U-shaped relationship between severe peri-operative bleeding and pre-operative fibrinogen levels. While a low-level of fibrinogen appears to be associated with a high risk of bleeding, a high level does not necessarily protect the patient against such a risk and could even be a risk factor for peri-operative bleeding.

The Prognostic Significance of Different Bleeding Classifications in off-pump coronary artery bypass grafting

BackgroundPerioperative bleeding during cardiac surgery are known to make patients susceptible to adverse outcomes and several bleeding classifications have been developed to stratify the severity of bleeding events. Further validation of different classifications was needed. The aim of present study was to validate and explore the prognostic value of different bleeding classifications in patients undergoing off-pump coronary artery bypass grafting (OPCAB).MethodsData on baseline and operative characteristics of 3988 patients who underwent OPCAB in Beijing Anzhen Hospital from February 2008 to December 2014 were available. The primary endpoint was a composite of in-hospital death and nonfatal postoperative myocardial infarction (MI). The secondary endpoint was postoperative acute kidney injury (AKI). We explored the association of major bleeding defined by the European registry of Coronary Artery Bypass Grafting (E-CABG), Universal Definition of Perioperative Bleeding (UDPB), Bleeding Academic Research Consortium (BARC) classification and Study of Platelet Inhibition and Patient Outcomes (PLATO) with primary endpoints by multivariable logistic regression analysis and investigated their significance of adverse event prediction using goodness-of-fit tests of − 2 log likelihood.ResultsIn-hospital mortality was 1.23% (n = 49) and postoperative MI was observed in 4.76% (n = 190) of patients, AKI in 24.69% (n = 985). The incidence of the primary outcome was 5.99% (n = 239). Multivariable logistic regression analysis showed that BARC type 4 (OR = 2.64, 95% CI: 1.66–4.19, P < 0.001), UDPB class 4 (OR = 3.52, 95% CI: 2.05–6.02, P < 0.001) and E-CABG class 2–3 (class 2: OR = 2.24, 95% CI: 1.36–3.70, P = 0.001; class 3: OR = 12.65, 95% CI: 2.74–18.43, P = 0.002) bleeding but not PLATO bleeding were associated with an increased risk of in-hospital death and postoperative MI. Major bleeding defined by all the four classifications mentioned above was an independent risk factor of AKI after surgery. Inclusion of major bleeding defined by these four classifications improved the predictive performance of the multivariable model with baseline characteristics.ConclusionsBleeding assessed by BARC, E-CABG and UDPB classifications were significantly associated with poorer immediate outcomes. These classifications seemed to be valuable tool in the assessment of prognostic effect of perioperative bleeding.

Absence of perioperative excessive bleeding in on-pump coronary artery bypass grafting cases performed by residents.

On-pump coronary artery bypass grafting (CABG) is associated with elevated bleeding risk. Our aim was to evaluate the role of surgical experience in postoperative blood loss. A propensity score-matched analysis was employed to compare on-pump CABG patients operated on by residents and specialists. End points included drainage volume and bleeding severity, as assessed by the Universal Definition of Perioperative Bleeding in cardiac surgery and E-CABG scale. A total of 212 matched pairs (c-statistics 0.693) were selected from patients operated on by residents (n = 294) and specialists (n = 4394) between October 2012 and May 2018. Patients did not differ in bleeding risk. There were no statistically significant differences in postoperative 6-, 12- and 24-h drainages between subjects operated on by residents and specialists, and there was no between-group difference in rethoracotomy or transfusion rate. There were no differences in Universal Definition of Perioperative Bleeding or E-CABG grades. In June 2018, after a median follow-up of 2.8 years (range 0.1-5.7 years), the overall survival was 94%, with no differences between the patients operated on by residents (95%) and specialists (92%) (P = 0.27). Patients undergoing on-pump CABG, when operated on by a resident, are not exposed to an elevated bleeding risk, as compared with patients operated on by experienced surgeons.

Bleeding in Patients Treated With Ticagrelor or Clopidogrel Before Coronary Artery Bypass Grafting

We evaluated perioperative bleeding after coronary artery bypass grafting (CABG) in patients preoperatively treated with ticagrelor or clopidogrel, stratified by discontinuation of these P2Y12 inhibitors. All patients from the prospective, European Multicenter Registry on Coronary Artery Bypass Grafting (E-CABG) treated with ticagrelor or clopidogrel undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding, stratified by P2Y12 inhibitor discontinuation. Secondary outcome measures included four additional definitions of major bleeding. Propensity score matching was performed to adjust for differences in preoperative and perioperative covariates. Of 2,311 patients who were included, 1,293 (55.9%) received clopidogrel and 1,018 (44.1%) ticagrelor preoperatively. Mean time between discontinuation and the operation was 4.5 ± 3.2 days for clopidogrel and 4.9 ± 3.0 days for ticagrelor. In the propensity score-matched cohort, ticagrelor-treated patients had a higher incidence of major bleeding according to Universal Definition of Perioperative Bleeding when ticagrelor was discontinued 0 to 2 days compared with 3 days before the operation (16.0% vs 2.7%, p= 0.003). Clopidogrel-treated patients had a higher incidence of major bleeding according to the Universal Definition of Perioperative Bleeding when clopidogrel was discontinued 0 to 3 days compared with 4 to 5 days before the operation (15.6% vs 8.3%, p= 0.031). In patients receiving ticagrelor 2 days before CABG and in those receiving clopidogrel 3 days before CABG, there was an increased rate of severe bleeding. Postponing nonemergent CABG for at least 3 days after discontinuation of ticagrelor and 4 days after clopidogrel should be considered.

Postoperative platelet function is associated with severe bleeding in ticagrelor-treated patients.

Preoperative testing of platelet function predicts bleeding risk in cardiac surgery patients treated with dual antiplatelet therapy, but the value of postoperative platelet function testing, reflecting both preoperative antiplatelet therapy and perioperative changes in platelet function, has not been evaluated. Seventy-four patients with acute coronary syndrome treated with acetylsalicylic acid and ticagrelor within 5 days before cardiac surgery were included in a prospective observational study. Platelet aggregation induced by adenosine diphosphate, arachidonic acid and thrombin receptor-activating peptide was assessed with multiple electrode impedance aggregometry immediately before surgery and 2 h after weaning off cardiopulmonary bypass. Receiver operating characteristic curves were used to determine any association between platelet aggregation and severe bleeding according to the universal definition of perioperative bleeding in adult cardiac surgery. Severe bleeding occurred in 25 of 74 patients (34%). Preoperative and postoperative adenosine diphosphate-induced platelet aggregations were associated with bleeding, with comparable areas under the receiver operating characteristic curve [0.77 (95% confidence interval 0.65-0.89) vs 0.75 (0.62-0.87)]. Postoperative arachidonic acid- and thrombin receptor-activating peptide-induced aggregation had markedly smaller areas under the curve. There were significant correlations between preoperative and postoperative platelet aggregation induced by adenosine diphosphate (r2 = 0.77, P < 0.001), arachidonic acid (r2 = 0.24, P < 0.001) and thrombin receptor-activating peptide (r2 = 0.21, P < 0.001) but with large interindividual variations. Poor postoperative platelet function was associated with severe bleeding, with accuracy comparable to that of preoperative platelet function. There was a correlation between preoperative and postoperative platelet function, but the predictability in an individual patient was limited.

Perioperative Bleeding in Patients With Acute Coronary Syndrome Treated With Fondaparinux Versus Low-Molecular-Weight Heparin Before Coronary Artery Bypass Grafting

The perioperative bleeding risk in patients receiving fondaparinux versus low-molecular weight heparin before coronary artery bypass grafting has not been reported. We evaluated perioperative coronary artery bypass grafting-related bleeding in patients with acute coronary syndrome preoperatively treated with fondaparinux or low-molecular weight heparin. All patients with acute coronary syndrome from the prospective, European multicenter registry on coronary artery bypass grafting preoperatively treated with fondaparinux or low-molecular weight heparin undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding stratified by P2Y12 inhibitor discontinuation. Secondary outcome measures included 3 additional definitions of major bleeding used in cardiac surgery trials. Propensity score matching was performed to adjust for differences in pre- and perioperative covariates. 1,525 patients were included, of whom 276 (18.1%) received fondaparinux and 1,249 (81.9%) low-molecular weight heparin preoperatively. In the propensity score-matched cohort (245 pairs), the risk of major bleeding according to the universal definition of perioperative bleeding severe or massive bleeding (11.8 vs 9.0%, p = 0.285) and the 3 other major bleeding definitions was similar between the fondaparinux and low-molecular weight heparin cohorts. In conclusion, preoperative treatment with fondaparinux compared with low-molecular weight heparin was associated with similar incidence of perioperative bleeding in patients with acute coronary syndrome who underwent coronary artery bypass grafting.