Antithrombotic drug removal with hemoadsorption during off-pump coronary artery bypass grafting.

BACKGROUND: Patients requiring coronary artery bypass grafting (CABG) are often loaded with antithrombotic drugs (AT) and are at an increased risk for perioperative bleeding complications. Active AT removal by a hemoadsorption cartridge integrated in the cardiopulmonary bypass circuit is increasingly used in this setting to reduce bleeding, and herein we describe the extension of this application in patients on AT undergoing off-pump coronary artery bypass (OPCAB). METHODS: Ten patients (80% male; mean age: 67.4 ± 9.2years) were treated with ticagrelor (eight patients), rivaroxaban and ticagrelor (one patient), and rivaroxaban (one patient) prior to OPCAB surgery. AT's were discontinued one day before surgery in nine patients and on the day of surgery in one patient, and all patients were also on aspirin. The cohort mean EuroSCORE-II was 2.9 ± 1.5%. A hemoadsorption cartridge was integrated into a dialysis device (n=4) or a stand-alone apheresis pump (n=6) periprocedural, for a treatment time of 145 ± 33 min. Outcome measures included bleeding according to Bleeding Academic Research Consortium (BARC)-4 and 24-hour chest-tube-drainage (CTD). RESULTS: Mean operation time was 184 ± 35 min. All patients received a left internal thoracic artery with a mean of 2.3 ± 0.9 total grafts. One patient had a BARC-4 bleeding event and there were no surgical re-explorations for bleeding. Mean 24-hours CTD was 680 ± 307mL. During follow-up of 19.5 ± 17.0 months, none of the patients died or required further reinterventions. No device-related adverse events were reported. CONCLUSIONS: Hemoadsorption via a stand-alone apheresis pump during OPCAB surgery was feasible and safe. This innovative and new approach showed favorable bleeding rates in patients on antithrombotic drugs requiring bypass surgery.

A New Apheresis Device for Antithrombotic Drug Removal during Off-Pump Coronary Artery Bypass Surgery.

Background and Objectives: The hemoadsorption device CytoSorb® (CytoSorbents Inc., Princeton, NJ, USA) has been shown to efficiently remove ticagrelor from whole blood in vitro. A promising clinical experience was made with the integration of the hemoadsorption cartridge on the cardiopulmonary bypass (CPB) circuit during cardiac surgery to reduce adverse events. Materials and Methods: In this report, we describe a novel approach using a new apheresis platform, PUR-01 (Nikkisio Co., Ltd., Tokyo, Japan), which was used as the extracorporeal circuit where CytoSorb® could be installed for the removal of ticagrelor during off-pump coronary artery bypass (OPCAB) procedures. Results: In a 74-year-old male (index case) with coronary artery disease and dual antiplatelet therapy, hemoadsorption was initiated with a skin incision for OPCAB surgery and was continued for 221 min to eliminate ticagrelor. The blood volume that had circulated through the CytoSorb® was 39.04 L in total. Thus far, this treatment strategy has been used in four cases with CHD and DAPT who needed OPCAB surgery. The intraoperative and postoperative courses were uneventful in all patients. No device-related adverse events occurred. Conclusions: The combination of the PUR-01 apheresis pump and hemoadsorption with the CytoSorb® column during OPCAB procedures appears to be safe and effective in eliminating antiplatelet drugs.

Catalytically Active Inclusion Bodies─Benchmarking and Application in Flow Chemistry.

In industries, enzymes are often immobilized to obtain stable preparations that can be utilized in batch and flow processes. In contrast to traditional immobilization methods that rely on carrier binding, various immobilization strategies have been recently presented that enable the simultaneous production and in vivo immobilization of enzymes. Catalytically active inclusion bodies (CatIBs) are a promising example for such in vivo enzyme immobilizates. CatIB formation is commonly induced by fusion of aggregation-inducing tags, and numerous tags, ranging from small synthetic peptides to protein domains or whole proteins, have been successfully used. However, since these systems have been characterized by different groups employing different methods, a direct comparison remains difficult, which prompted us to benchmark different CatIB-formation-inducing tags and fusion strategies. Our study highlights that important CatIB properties like yield, activity, and stability are strongly influenced by tag selection and fusion strategy. Optimization enabled us to obtain alcohol dehydrogenase CatIBs with superior activity and stability, which were subsequently applied for the first time in a flow synthesis approach. Our study highlights the potential of CatIB-based immobilizates, while at the same time demonstrating the robust use of CatIBs in flow chemistry.