Bleeding risk stratification in coronary artery surgery: the should-not-bleed score.

BACKGROUND: An estimated 20% of allogeneic blood transfusions in the United States are associated with cardiac surgery. It is estimated that 11% of red cell resources were used for transfusion support of patients undergoing coronary artery bypass grafting (CABG) with a documented wide variability in transfusion rate (7.8 to 92.8%). To address the issue of unnecessary transfusions within the CABG population, we developed a model to predict which patients are at low risk of bleeding for whom transfusion treatment might be considered unnecessary. Herein we present our "SHOULD-NOT-BLEED-SCORE" application developed for the Windows® software platform which is based on our previous research. METHODS: This study is aimed to develop a user-friendly application that stratifies patients with respect to bleeding risk. The statistical model we used in our previous research was focused on detection of CABG patients at low risk of bleeding. The rationale behind such an approach was to identify a CABG patient subgroup at low risk of bleeding. By identifying patients at low risk of bleeding we can define a subgroup of patients for whom transfusion treatment might be considered unnecessary. We developed a Windows platform application based on risk modelling which we previously calculated for 1426 patients undergoing elective CABG from January 2010 to January 2018. RESULTS: The SHOULD-NOT-BLEED-SCORE risk score is developed for the Windows software platform. A mathematical model that is based on multivariate analysis was used for app development. The variables that entered the scoring system were: Age; Body Mass Index; Chronic Renal Failure; Preoperative Clopidogrel Exposure; Preoperative Red Blood Cells Count; Preoperative Fibrinogen Level; Preoperative Multiplate ASPI test area under the curve (AUC) units. The SHOULD-NOT-BLEED-SCORE identifies/predicts patients without a risk for excessive bleeding with strong discriminatory performance (Receiver Operating Curve (ROC) analysis AUC 72.3%, p < 0.001). CONCLUSION: The SHOULD-NOT-BLEED risk scoring application may be useful in the preoperative risk screening process. The clinical and economic burden associated with unnecessary transfusions may be adequately addressed by a preoperative scoring system detecting patients at low risk of bleeding for whom transfusion treatment might be considered unnecessary.

Cost Analysis of Transfusion Therapy in Coronary Artery Surgery.

BACKGROUND: In patients undergoing coronary artery bypass grafting (CABG), wide variability in transfusion rate (7.8% to 92.8%) raises the question of the amount of unnecessary transfusions. The aim of the study was (1) to identify CABG patients at low risk of bleeding to whom transfusion treatment should be avoided and (2) to calculate the amount of possible cost savings that would be achieved by avoiding transfusion in low bleeding risk patients. METHODS: This retrospective observational study enrolled patients undergoing isolated elective CABG from January 2010 to January 2018. Patients were divided with respect to the presence of excessive bleeding and transfusion costs were compared between the two groups. Predictors for postoperative excessive bleeding were defined and multivariable logistic regression analysis and risk modeling were performed. The use of a model to predict patients at low risk of bleeding allowed for the estimation of transfusion cost savings assuming the patients who were found to be at low risk of bleeding should not be transfused. RESULTS: A total of 1,426 patients were enrolled in the analysis. Of those, 28.3% had excessive postoperative bleeding. The multivariate logistic regression analysis model was developed to identify/predict patients without excessive bleeding (receiver operating characteristic curve analysis, area under the curve 72.3%, p < 0.001). When applied to the existing database, the use of the developed model identifying patients at low risk of bleeding may result in a 39.1% reduction of transfusions. Specifically, cost savings would be 48.2% for packed red blood cells, 38.9% for fresh frozen plasma, 10.9% for platelets concentrate, and 17.9% for fibrinogen concentrate. CONCLUSION: The clinical and economic burdens associated with unnecessary transfusions are significant. Avoiding transfusion in CABG patients found to be at low risk of bleeding may result in significant reduction of transfusion rate and transfusion-associated costs.

Severe bleeding caused by piperacillin/tazobactam-induced platelet dysfunction
.

OBJECTIVE: Piperacillin/tazobactam (TZP ) is commonly used against multi-resistant nosocomial Pseudomonas infections. While TZP-induced thrombocytopenia is a well-known and easily diagnosed complication, we herein present an unusual case of spontaneous TZP-induced bleeding caused by platelet dysfunction. CASE SUMMARY: A 73-year-old-man experienced severe pulmonary hemorrhage and bloody diarrhea during the treatment with TZP for Pseudomonas aeruginosa ventilator-associated pneumonia. While both platelet count and coagulation tests were normal, platelet functional test revealed severely impaired ADP-dependent platelet aggregation. CONCLUSION: Platelet dysfunction is a little-known mechanism of TZP-induced bleeding. This is the second reported case of TZP-related bleeding that has been attributed to platelet dysfunction, and the first case report that has not been associated with surgery. While thrombocytopenia is easily recognized, this form of TZP-induced bleeding can be detected only by platelet functional tests.

Impact of Continuous P2Y12 Inhibition Tailoring in Acute Coronary Syndrome and Genetically Impaired Clopidogrel Absorption.

Clopidogrel is still widely used in acute coronary syndrome despite the development of more potent P2Y12 inhibitors. Previously, we conducted a trial that evaluated serial clopidogrel dose adjustment based on platelet function testing in acute coronary syndrome patients with initial high on-treatment platelet reactivity (HTPR). In this substudy, we performed post hoc analysis of the effect of ABCB1 genetic variants C3435T and G2677T/A on platelet inhibition and outcomes. There were no differences in the proportion of HTPR patients among C3435T carriers and noncarriers in both interventional and control group. G2677T carriers expressed significantly higher proportion of HTPR pattern throughout 12-month follow-up in the control group with no difference in the interventional group. There was no difference in ischemic outcomes between C3435T and G2677T carriers and noncarriers in both groups of patients. The results indicate that ABCB1 genotyping is not useful to guide clopidogrel therapy tailoring to improve high-risk patient management.

The effect of cyclic adenosine monophosphate (cAMP) on acute liver toxicity in mice induced by D-galactosamine and lipopolysaccharide.

The aim of this study was to examine the effect of cyclic adenosine monophosphate (cAMP) and its possible interference/synergism with calcium channel blocker in mice with acute liver injury induced with D-galactosamine (D-GalN) and lipopolysaccharide (LPS). C57Bl/6 mice were given i.p. simultaneously 300 mg/kg D-GalN and LPS 0.01 mg/kg. This treatment induced severe hepatitis, as evidenced by high mortality (80-90%) of control mice and large increase in concentration of aminotransferases in plasma (AST, ALT). Injection of stabile analogue of cAMP (dibutyryl-cAMP, db-cAMP) one hour before hepatotoxic agents increased survival of mice in dose-dependent manner and in medium dose significantly decreased plasma ALT level. Similar (protective) effect had also verapamil, calcium channel blocker, when given in non toxic doses and at the same time schedule as db-cAMP Combination of db-cAMP and verapamil had not synergistic effect in protection from D-GalN+LPS hepatotoxicity; the survival of mice was similar to that seen in protection caused by each agent alone.