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Gandini L, de Veer SJ, Chan CHH, Passmore MR, Liu K, Lundon B, Rachakonda R, White N, Rhodes M, Shanahan E, Yap K, See Hoe LE, Semenzin C, Li Bassi G, Fraser JF, Craik DJ, Suen JY. Anticoagulation during Extracorporeal Membrane Oxygenation (ECMO): A Selective Inhibitor of Activated Factor XII Compared to Heparin in an Ex Vivo Model. ACS Pharmacol Transl Sci 2025; 8:1260-1269. [PMID: 40405900 PMCID: PMC12093806 DOI: 10.1021/acsptsci.4c00352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 02/19/2025] [Accepted: 03/27/2025] [Indexed: 05/26/2025]
Abstract
Extracorporeal membrane oxygenation (ECMO) is a form of life support for critically ill patients with severe respiratory or cardiac failure. Interactions between patient blood and ECMO biomaterials increase the risk of thrombosis, necessitating concurrent anticoagulation treatment, with the standard of care being heparin. However, hemostatic complications such as thrombosis and bleeding remain prevalent. Activated factor XII (FXIIa) inhibitors are selective anticoagulants and offer a potential alternative to heparin. We aimed to evaluate the efficacy of IMB-F12, a cyclotide-based FXIIa inhibitor, in human blood using an ex vivo ECMO model. Ten circuits were randomly allocated to heparin or IMB-F12 and ran for 6 h. Primary hemostasis was assessed by full blood cell count, aggregometry, flow cytometry, and von Willebrand factor multimer analysis; secondary hemostasis by activated clotting time (ACT), rotational thromboelastometry (ROTEM), prothrombin time, and activated partial thromboplastin time. All circuits ran successfully for 6 h with stable oxygenator resistance (pressure drop, flow). ACT was higher in the IMB-F12 group than in the heparin group (p = 0.008). Significant differences were observed between ROTEM INTEM and HEPTEM in both IMB-F12 (clotting time (CT) p = 0.001, clot formation time (CFT) = 0.0004, maximum clot firmness (MCF) p = 0.03) and heparin (CT p = 0.01, CFT = 0.004, MCF p = 0.02) groups. Collagen- and thrombin receptor activating peptide (TRAP)-induced platelet aggregation were better preserved in the IMB-F12 group (p = 0.004 and 0.005, respectively). In conclusion, IMB-F12 provides an effective alternative to heparin anticoagulation with an improved preservation of collagen- and TRAP-induced platelet aggregation in an ex vivo model.
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Affiliation(s)
- Lucia Gandini
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Faculty
of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Department
of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy
| | - Simon J. de Veer
- Institute
for Molecular Bioscience, Australian Research Council Centre of Excellence
for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Chris H. H. Chan
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- School
of Engineering and Built Environment, Griffith
University, Gold Coast, QLD 4215, Australia
| | - Margaret R. Passmore
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Faculty
of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Keibun Liu
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Faculty
of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Non-Profit
Organization, ICU Collaboration Network
(ICON), Tokyo 113-0033, Japan
| | - Brooke Lundon
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Faculty
of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Reema Rachakonda
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Faculty
of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Nicole White
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Faculty
of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Madeleine Rhodes
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Queensland
University of Technology, Brisbane, QLD 4001, Australia
| | - Emma Shanahan
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Queensland
University of Technology, Brisbane, QLD 4001, Australia
| | - Kuok Yap
- Institute
for Molecular Bioscience, Australian Research Council Centre of Excellence
for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Louise E. See Hoe
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Faculty
of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Clayton Semenzin
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- School
of Engineering and Built Environment, Griffith
University, Gold Coast, QLD 4215, Australia
| | - Gianluigi Li Bassi
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Faculty
of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Intensive
Care Unit, St. Andrews War Memorial Hospital, Brisbane, QLD 4001, Australia
- Institut
d’Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain
- Wesley Research Institute, Auchenflower, QLD 4066, Australia
| | - John F. Fraser
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Faculty
of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- Intensive
Care Unit, St. Andrews War Memorial Hospital, Brisbane, QLD 4001, Australia
| | - David J. Craik
- Institute
for Molecular Bioscience, Australian Research Council Centre of Excellence
for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Jacky Y. Suen
- Critical
Care Research Group, The Prince Charles
Hospital, Brisbane, QLD 4032, Australia
- Faculty
of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
- School
of Pharmacy and Medical Sciences, Griffith
University, Gold Coast, QLD 4215, Australia
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Mansouritorghabeh H, Monard A, Heubel‐Moenen F, Leentjens J, Stroobants A, Henskens Y. The Utility of Total Thrombus-Formation Analysis System (T-TAS) in the Thrombosis and Hemostasis Field: A Scoping Review. Int J Lab Hematol 2025; 47:201-211. [PMID: 39659111 PMCID: PMC11885686 DOI: 10.1111/ijlh.14403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 10/07/2024] [Accepted: 11/06/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND A wide variety of laboratory hemostasis tests is available, but the majority is plasma-based, static and unable to assess platelet function and fibrin formation simultaneously. The Total Thrombus-Formation Analysis System (T-TAS) is a microchip-based flow chamber system that simulates in vivo conditions for evaluating whole blood thrombogenicity. AIM A comprehensive overview of its applicability in different thrombosis and hemostasis related clinical situations is lacking and therefore this scoping review was performed. MATERIALS & METHODS A literature search was done using the electronic databases PubMed, Scopus and Embase on January 7, 2024. Original studies assessing the usefulness of the T-TAS in thrombosis and hemostasis related clinical situations were eligible for this scoping review. RESULTS A total of 28 studies were included; six studies investigating the role of the T-TAS in congenital bleeding disorders, five studies using the T-TAS to assess 1-year bleeding risk in patients on antiplatelet or anticoagulant medications, four studies investigating the effects of thrombocytopenia and hemodialysis on thrombus formation as measured by the T-TAS, 11 studies testing the applicability of the T-TAS in the monitoring of anticoagulant and antiplatelet therapies and eventually two studies on the ability of the T-TAS to assess the thrombogenicity in different disease entities. DISCUSSION & CONCLUSION The T-TAS method is an interesting technology that mimics the complex biological coagulation process using shear forces, creating a "blood vessel component on a chip". More research is needed, but it could eventually function as a screening test for platelet function and coagulation. Moreover, it could be used to detect the presence of anticoagulant and/or antiplatelet medication.
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Affiliation(s)
- H. Mansouritorghabeh
- Central Diagnostic Laboratories, Ghaem HospitalMashhad University of Medical SciencesMashhadIran
- Department of Internal Medicine, Division of Thrombosis and HemostasisEinthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical CenterLeidenThe Netherlands
| | - A. Monard
- Department of Internal Medicine – HematologyMaastricht University Medical Centre+MaastrichtThe Netherlands
- CARIM–School for Cardiovascular DiseaseMaastricht UniversityMaastrichtThe Netherlands
| | - F. Heubel‐Moenen
- Department of Internal Medicine – HematologyMaastricht University Medical Centre+MaastrichtThe Netherlands
| | - J. Leentjens
- Department of Internal Medicine–Vascular MedicineRadboud University Medical Center, RadboudUMCNijmegenThe Netherlands
| | - A. Stroobants
- Department of Clinical ChemistryRadboud University Medical Center, RadboudUMC Laboratory for Diagnostics and Laboratory for HematologyNijmegenThe Netherlands
| | - Y. Henskens
- CARIM–School for Cardiovascular DiseaseMaastricht UniversityMaastrichtThe Netherlands
- Central Diagnostic Laboratory, Unit for Hemostasis and TransfusionMaastricht University Medical Centre+MaastrichtThe Netherlands
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Authors/Task Force Members:, Jeppsson A, (Co-Chairperson) (Sweden), Rocca B, (Co-Chairperson) (Italy), Hansson EC, (Sweden), Gudbjartsson T, (Iceland), James S, (Sweden), Kaski JC, (United Kingdom), Landmesser U, (Germany), Landoni G, (Italy), Magro P, (Portugal), Pan E, (Finland), Ravn HB, (Denmark), Sandner S, (Austria), Sandoval E, (Spain), Uva MS, (Portugal), Milojevic M, (Serbia), EACTS Scientific Document Group
. 2024 EACTS Guidelines on perioperative medication in adult cardiac surgery. Eur J Cardiothorac Surg 2024; 67:ezae355. [PMID: 39385505 DOI: 10.1093/ejcts/ezae355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Collaborators] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 08/14/2024] [Accepted: 09/26/2024] [Indexed: 10/12/2024] Open
Affiliation(s)
| | - Anders Jeppsson
- Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Bianca Rocca
- Department of Medicine and Surgery, LUM University, Casamassima, Bari, Italy
- Department of Safety and Bioethics, Catholic University School of Medicine, Rome, Italy
| | | | - Emma C Hansson
- Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Tomas Gudbjartsson
- Department of Cardiothoracic Surgery, Landspitali University Hospital, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | | | - Stefan James
- Department of Medical Sciences, Uppsala University Uppsala Sweden
| | | | - Juan Carlos Kaski
- Molecular and Clinical Sciences Research Institute, St. George's University of London, UK
| | | | - Ulf Landmesser
- Department of Cardiology, Angiology and Intensive Care Medicine; Deutsches Herzzentrum Charité, Campus Benjamin Franklin, Berlin, Germany
- Charité-University Medicine Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), partner site Berlin, Berlin, Germany
- Berlin Institute of Health (BIH) at Charité Berlin, Universitätsmedizin Berlin, Germany
| | | | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | | | - Pedro Magro
- Department of Cardiac Surgery, Hospital Santa Cruz, Carnaxide, Portugal
| | | | - Emily Pan
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland
| | | | - Hanne Berg Ravn
- Department of Anaesthesia, Odense University Hospital, Institute of Clinical Medicine, University of Southern, Denmark
| | | | - Sigrid Sandner
- Department of Cardiac Surgery, Medical University Vienna, Vienna, Austria
| | | | - Elena Sandoval
- Department of Cardiovascular Surgery, Hospital Clinic, Barcelona, Spain
| | | | - Miguel Sousa Uva
- Department of Cardiac Surgery, Hospital Santa Cruz, Carnaxide, Portugal
- Cardiovascular Research Centre, Department of Surgery and Physiology, Faculty of Medicine-University of Porto, Porto, Portugal
| | | | - Milan Milojevic
- Department of Cardiac Surgery and Cardiovascular Research, Dedinje Cardiovascular Institute, Belgrade, Serbia
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Collaborators
Matthias Siepe, Vesa Anttila, Lauren Barron, Dobromir Dobrev, Fabio Guarracino, Ziad Hijazi, Andreas Koster, Tomislav Kostic, Vladimir Lomivorotov, Vojislava Neskovic, Bjorn Redfors, Lars Peter Riber, Andrea Székely, Juan Tamargo, Theis Tönnessen, Alicja Zientara,
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Petricevic M, Goerlinger K, Milojevic M, Petricevic M. Methodological Considerations for Studies Evaluating Bleeding Prediction Using Hemostatic Point-of-Care Tests in Cardiac Surgery. J Clin Med 2024; 13:6737. [PMID: 39597881 PMCID: PMC11595064 DOI: 10.3390/jcm13226737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 10/28/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024] Open
Abstract
A certain proportion of patients undergoing cardiac surgery may experience bleeding complications that worsen outcomes. Numerous studies have investigated bleeding in cardiac surgery and some evaluate the role of hemostatic point-of-care tests in cardiac surgery patients. The prevalence of excessive bleeding varies in the literature, and such variability stems from the lack of a standardized definition of excessive bleeding. Herein, we report numerous definitions of excessive bleeding and methodological considerations for studies evaluating bleeding using hemostatic point-of-care tests in cardiac surgery patients. We evaluated the role of hemostatic point-of-care devices in contemporary research on bleeding complications and hemostatic management in cardiac surgery. The type of studies (prospective vs. retrospective, interventional vs. observational), patient selection (less complex vs. complex cases), as well as data analysis with comprehensive statistical considerations have also been provided. This article provides a comprehensive insight into the research field of bleeding complications in cardiac surgery and may help readers to better understand methodological flaws and how they influence current evidence.
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Affiliation(s)
- Mirna Petricevic
- University Department of Health Studies, University of Split, 21000 Split, Croatia;
| | - Klaus Goerlinger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45127 Essen, Germany;
- Medical Department, Tem Innovations, 80331 Munich, Germany
| | - Milan Milojevic
- Department of Cardiac Surgery and Cardiovascular Research, Dedinje Cardiovascular Institute, 101801 Belgrade, Serbia;
| | - Mate Petricevic
- University Department of Health Studies, University of Split, 21000 Split, Croatia;
- School of Medicine, University Hospital of Split, University of Split, 21000 Split, Croatia
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Antonijevic N, Mitrovic P, Gosnjic N, Orlic D, Kadija S, Ilic Mostic T, Savic N, Birovljev L, Lekovic Z, Matic D. Successful Caesarean Section on Ticagrelor Treatment One Day after Primary Percutaneous Coronary Intervention. J Pers Med 2023; 13:1344. [PMID: 37763112 PMCID: PMC10532752 DOI: 10.3390/jpm13091344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 08/22/2023] [Accepted: 08/28/2023] [Indexed: 09/29/2023] Open
Abstract
Caesarean section is a challenging intervention in patients treated with dual antiplatelet therapy. We present a case of a 32-year-old pregnant woman experiencing large acute myocardial infarction (MI) of the anterolateral wall, complicated by cardiogenic shock in the 38th week of pregnancy, and treated with drug-eluting stent implantation and dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor. Less than 24 h after the MI delivery started, an urgent Caesarean section was indicated. As multiplate aggregometry testing showed a relatively insufficient level of ticagrelor platelet inhibition and a moderate level of aspirin platelet inhibition, a Caesarean section was performed without discontinuation of ticagrelor, which was decided due to the need for emergency surgery. Local hemostatic measures including administration of tranexamic acid were applied. The patient did not experience excessive bleeding. A healthy male baby was born. To the best of our knowledge, this is the first reported case of surgery in pregnant women treated with DAPT without ticagrelor discontinuation.
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Affiliation(s)
- Nebojsa Antonijevic
- Clinic for Cardiology, University Clinical Center of Serbia, 11 000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia
| | - Predrag Mitrovic
- Clinic for Cardiology, University Clinical Center of Serbia, 11 000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia
| | - Nikola Gosnjic
- Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11 000 Belgrade, Serbia
| | - Dejan Orlic
- Clinic for Cardiology, University Clinical Center of Serbia, 11 000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia
| | - Sasa Kadija
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia
- Clinic for Gynecology and Obstetrics, University Clinical Center of Serbia, 11 000 Belgrade, Serbia
| | - Tanja Ilic Mostic
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia
- Clinic for Gynecology and Obstetrics, University Clinical Center of Serbia, 11 000 Belgrade, Serbia
| | - Nebojsa Savic
- Clinic for Vascular Surgery, Transfusion, University Clinical Center of Serbia, 11 000 Belgrade, Serbia
| | - Ljubica Birovljev
- Clinic for Cardiology, University Clinical Center of Serbia, 11 000 Belgrade, Serbia
| | - Zaklina Lekovic
- Clinic for Cardiology, University Clinical Center of Serbia, 11 000 Belgrade, Serbia
| | - Dragan Matic
- Clinic for Cardiology, University Clinical Center of Serbia, 11 000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia
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Simonte G, Guglielmini G, Falcinelli E, Isernia G, Mezzasoma AM, Gresele P, Lenti M. High-on-treatment platelet reactivity predicts adverse outcome after carotid artery stenting: A prospective study. Thromb Res 2023; 222:117-123. [PMID: 36640567 DOI: 10.1016/j.thromres.2022.12.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 12/15/2022] [Accepted: 12/22/2022] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND PURPOSE High-on-treatment platelet reactivity (HTPR) has been established as a predictor of major adverse cardiovascular events (MACE) in patients undergoing percutaneous coronary interventions on dual antiplatelet therapy (DAPT), but no data are available on its predictive value in patients on DAPT after carotid artery stenting (CAS). We aimed to evaluate the possible association between HTPR in patients on aspirin plus clopidogrel therapy after CAS and subsequent MACE. METHODS All consecutive patients treated with CAS in a single institution were enrolled in a prospective clinical study. HTPR was evaluated with 5 different laboratory assays carried out just before CAS. MACE incidence (cerebral ischemia, myocardial infarction, stent thrombosis, acute limb ischemia and vascular death) was evaluated at 30 days and thereafter at yearly visits. RESULTS A total of 300 patients were enrolled in the study, and eight were then excluded because blood samples resulted unsuitable for the laboratory testing or CAS aborted for technical problems. Median follow-up was 5.8 years and during this period 47 MACE occurred. HTPR detected by multiplate electronic aggregometry (MEA) and the VASP phosphorylation assay (VASP) were associated with a significantly enhanced risk of MACE (p = 0.048 and p = 0.038, respectively). However, HTPR to three tests (HTPR3) was more strongly predictive of increased risk of a vascular event at follow up (p = 0.005) at bivariate analysis and also at Cox regression multivariate analysis (p = 0.002). CONCLUSIONS HTPR to three different assays (mainly to VASP + PFA P2Y+ VerifyNow) in patients on DAPT after CAS has predictive value for subsequent MACE. Prospective studies to assess whether platelet function testing-guided antiplatelet therapy is superior to standard DAPT in patient undergoing CAS should be considered.
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Affiliation(s)
- G Simonte
- Unit of Vascular Surgery, S. Maria della Misericordia Hospital, Perugia, Italy
| | - G Guglielmini
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - E Falcinelli
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - G Isernia
- Unit of Vascular Surgery, S. Maria della Misericordia Hospital, Perugia, Italy
| | - A M Mezzasoma
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - P Gresele
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
| | - M Lenti
- Unit of Vascular Surgery, S. Maria della Misericordia Hospital, Perugia, Italy
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Zanetto A, Northup P, Roberts L, Senzolo M. Haemostasis in cirrhosis: Understanding destabilising factors during acute decompensation. J Hepatol 2023; 78:1037-1047. [PMID: 36708812 DOI: 10.1016/j.jhep.2023.01.010] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/03/2023] [Accepted: 01/17/2023] [Indexed: 01/27/2023]
Abstract
Hospitalised patients with decompensated cirrhosis are in a rebalanced haemostatic state due to a parallel decline in both pro- and anti-haemostatic pathways. However, this rebalanced haemostatic state is highly susceptible to perturbations and may easily tilt towards hypocoagulability and bleeding. Acute kidney injury, bacterial infections and sepsis, and progression from acute decompensation to acute-on-chronic liver failure are associated with additional alterations of specific haemostatic pathways and a higher risk of bleeding. Unfortunately, there is no single laboratory method that can accurately stratify an individual patient's bleeding risk and guide pre-procedural prophylaxis. A better understanding of haemostatic alterations during acute illness would lead to more rational and individualised management of hospitalised patients with decompensated cirrhosis. This review will outline the latest findings on haemostatic alterations driven by acute kidney injury, bacterial infections/sepsis, and acute-on-chronic liver failure in these difficult-to-treat patients and provide evidence supporting more tailored management of bleeding risk.
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Affiliation(s)
- Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale - Università Padova, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Patrick Northup
- Division of Gastroenterology and Hepatology, NYU Grossman School of Medicine, NYU Transplant Institute, New York, NY, USA
| | - Lara Roberts
- King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital, London, UK
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale - Università Padova, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
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Baryshnikova E, Di Dedda U, Ranucci M. Are Viscoelastic Tests Clinically Useful to Identify Platelet-Dependent Bleeding in High-Risk Cardiac Surgery Patients? Anesth Analg 2022; 135:1198-1206. [PMID: 36227767 DOI: 10.1213/ane.0000000000006231] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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).
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Affiliation(s)
- Ekaterina Baryshnikova
- From the Department of Cardiothoracic and Vascular Anesthesia and Intensive Care, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan, Italy
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9
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Xu FWX, Lim NA, Sim MA, Lean LL, Loh NHW, Ng KT, Chua VTY, Chew STH, Ti LK. Point-of-care platelet function testing for guided transfusion in neurosurgical management of intracranial hemorrhage: a systematic review. Eur J Med Res 2022; 27:191. [PMID: 36182926 PMCID: PMC9526957 DOI: 10.1186/s40001-022-00819-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 09/06/2022] [Indexed: 11/14/2022] Open
Abstract
Given the rising prevalence of antiplatelet therapy, rapid preoperative identification of patients with bleeding diathesis is necessary for the guidance of blood product administration. This is especially relevant in neurosurgery for intracranial hemorrhage (ICH), where indiscriminate transfusions may lead to further hemorrhagic or thromboembolic injury. Point-of-care (POC) testing of platelet function is a promising solution to this dilemma, as it has been proven effective in cardiac surgery. However, to date, POC platelet function testing in neurosurgery has not been extensively evaluated. This systematic review appraises the use of POC platelet function test (PFT) in emergency neurosurgery in terms of its impact on patient outcomes. A comprehensive search was conducted on four electronic databases (Pubmed, MEDLINE, Embase, and Cochrane) for relevant English language articles from their respective inceptions until 1 June 2022. We included all randomized controlled trials and cohort studies that met the following inclusion criteria: (i) involved adult patients undergoing neurosurgery for ICH; (ii) evaluated platelet function via POC PFT; (iii) reported a change in perioperative blood loss; and/or (iv) reported data on treatment-related adverse events and mortality. Assessment of study quality was conducted using the Newcastle Ottawa Quality Assessment Scale for Cohort Studies and Case–Control Studies, and the JBI Critical Appraisal Checklist for Case Series. The search yielded 2,835 studies, of which seven observational studies comprising 849 patients met the inclusion criteria for this review. Overall, there is evidence that the use of POC PFT to assess bleeding risk reduced bleeding events, thromboembolic adverse outcomes, and the length of hospitalization. However, there is currently insufficient evidence to suggest that using POC PFT improves blood product use, functional outcomes or mortality.
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Affiliation(s)
- Flora Wen Xin Xu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Nicole-Ann Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ming Ann Sim
- Department of Anesthesia, Singapore General Hospital, Singapore, Singapore
| | - Lyn Li Lean
- Department of Anesthesia, Ng Teng Fong General Hospital, Singapore, Singapore
| | - Ne-Hooi Will Loh
- Department of Anesthesia, National University Hospital, Singapore, Singapore
| | - Ka Ting Ng
- Department of Anesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Vanessa Tze Yuh Chua
- Department of Anesthesia, Singapore General Hospital, Singapore, Singapore.,Department of Anesthesia, National University Hospital, Singapore, Singapore
| | | | - Lian Kah Ti
- Department of Anesthesia, National University Hospital, Singapore, Singapore. .,Department of Anesthesia, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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10
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Saleem Y, Darbari A, Sharma R, Vashisth A, Gupta A. Recent advancements in pediatric cardiopulmonary bypass technology for better outcomes of pediatric cardiac surgery. THE CARDIOTHORACIC SURGEON 2022. [DOI: 10.1186/s43057-022-00084-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Pediatric cardiac surgery is in itself very enigmatic and individualized. Presently, there has been a slew of new developments aimed primarily toward pediatric cardiopulmonary bypass for safer, patient-centered pediatric cardiac surgery. Still, lot of technological challenges need to be resolved, and their safer application in pediatric and neonate patients requires further refinement.
Main body of the abstract
Considering various significant yet unresolved issues of pediatric cardiac bypass, an exhaustive literature search was done on various internet databases with standard keywords. There are various new recent improvements; as the first oxygenator explicitly designed for neonatal patients; pediatric oxygenators with low prime volumes and surface areas that allow flows up to 2 L/min; pediatric oxygenators with integrated arterial filters; and miniature ultrafiltration devices that allow for high rates of ultrafiltrate removal. These advancements can significantly reduce cardiopulmonary bypass circuit surface areas and prime volumes. These advancements could reduce or eliminate the requirement for homologous red blood cells during or after surgery with reduction or eliminate bypass-related hemodilution, and inflammation. Because of the immaturity of the neonatal hemostatic system, conventional coagulation tests alone are insufficient to guide neonatal hemostatic therapy. Myocardial preservation techniques, safe temperature with duration are still debatable and yet to be fully explored.
Short conclusion
This review is based on Standards for Quality Improvement Reporting Excellence guidelines to provide a framework for reporting new knowledge to find better management strategy for pediatric cardiac cases.
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11
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Application of a TEG-Platelet Mapping Algorithm to Guide Reversal of Antiplatelet Agents in Adults with Mild-to-Moderate Traumatic Brain Injury: An Observational Pilot Study. Neurocrit Care 2022; 37:638-648. [PMID: 35705826 DOI: 10.1007/s12028-022-01535-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 05/13/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Traumatic intracranial hemorrhages expand in one third of cases, and antiplatelet medications may exacerbate hematoma expansion. However, the reversal of an antiplatelet effect with platelet transfusion has been associated with harm. We sought to determine whether a thromboelastography platelet mapping (TEG-PM)-guided algorithm could limit platelet transfusion in patients with hemorrhagic traumatic brain injury (TBI) prescribed antiplatelet medications without a resultant clinically significant increase in hemorrhage volume, late hemostatic treatments, or delayed operative intervention. METHODS A total of 175 consecutive patients with TBI were admitted to our university-affiliated, level I trauma center between March 2016 and December 2019: 54 preintervention patients (control) and 121 patients with TEG-PM (study). After exclusion for anticoagulant administration, availability of neuroimaging and emergent neurosurgery, 62 study patients and 37 control patients remained. Intervention consisted of administration of desmopressin (DDAVP) for nonsurgical patients with significant inhibition at the arachidonic acid or adenosine diphosphate receptor sites. For surgical patients with significant inhibition, dual therapy with DDAVP and platelet transfusion was employed. Study patients were compared with a group of historical controls, which were identified from a prospectively maintained registry and typically treated with empiric platelet transfusion. RESULTS Median age was 75 years (interquartile range 85-67) and 77 years (interquartile range 81-65) in the TEG-PM and control patient groups, respectively. Admission hemorrhage volumes were similar (10.7 cm3 [20.1] in patients with TEG-PM vs. 14.1 cm3 [19.7] in controls; p = 0.41). There were no significant differences in admission Glasgow Coma Scale, mechanism of trauma, or baseline comorbidities. A total of 57% of controls versus 10% of patients with TEG-PM (p < 0.001) were transfused platelets; 52% of intervention patients and 0% controls were treated with DDAVP. Expansion hemorrhage volumes were not significantly different (14.0 cm3 [20.2] patients with TEG-PM versus 13.6 cm3 [23.7] controls; p = 0.93). There was no significant difference in rates of clinical deterioration, delayed neurosurgical intervention, or late platelet transfusion between groups. CONCLUSIONS Among patients with hemorrhagic TBI prescribed preinjury antiplatelet therapy, our study suggests that the use of a TEG-PM algorithm may reduce platelet transfusions without a concurrent increase in clinically significant hematoma expansion. Further study is required to prove a causative relationship.
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12
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Hensley NB, Ariyo PT, Holmes SD, Williams MS, Joseph Robert Whitman G, Ad N, Metkus TS. Center Variation in Use of Preoperative Dual Antiplatelet Therapy and Platelet Function Testing at the Time of Coronary Artery Bypass Grafting in Maryland. Anesth Analg 2022; 135:567-575. [PMID: 35426835 DOI: 10.1213/ane.0000000000005964] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Patients presenting with acute coronary syndrome are administered a P2Y12 inhibitor and aspirin before coronary catheterization to prevent further myocardial injury from thrombosis. Guidelines recommend a standard waiting period between the time patients are administered dual antiplatelet therapy (DAPT) and elective cardiac surgery. Since 25% to 30% of the population may be considered nonresponders to clopidogrel, platelet function testing can be utilized for timing of surgery and to assess bleeding risks. The extent to which a standard waiting period or platelet function testing is used across centers is not established, representing an important opportunity to standardize practice. METHODS We conducted a retrospective cohort study from 2011 to 2020 using data from the Maryland Cardiac Surgical Quality Initiative, a consortium of all 10 hospitals in the state performing cardiac surgery. The proportion of patients administered DAPT within 5 days of surgery was examined by hospital over the time period. Mixed-effects multivariable logistic regressions were used to examine the association of preoperative DAPT with ischemic and bleeding outcomes. Centers were surveyed on use or nonuse of preoperative platelet function testing, and bleeding outcomes were compared. RESULTS There was significant heterogeneity of preoperative DAPT usage across centers ranging from 2% to 54% (P < .001). DAPT within 5 days of isolated coronary artery bypass grafting (CABG) was associated with higher odds of reoperation for bleeding (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.19-2.01; P = .001), >2 units of red blood cells (RBCs) transfused (OR, 1.62; 95% CI, 1.44-1.81; P < .001), and >2 units of non-RBCs transfused (OR, 1.79; 95% CI, 1.60-2.00; P < .001). In the 5 hospitals using preoperative platelet function testing to guide timing of surgery, there were greater odds for DAPT within 5 days (OR, 1.33; 95% CI, 1.22-1.45; P < .001), fewer RBCs >2 units transfusions (22% vs 33%; P < .001), and non-RBCs >2 units (17% vs 28%; P < .001) transfusions within DAPT patients. CONCLUSIONS There is significant variability in DAPT usage within 5 days of CABG between hospital centers. Preoperative platelet function testing may allow for earlier timing of surgery for those on DAPT without increased bleeding risks.
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Affiliation(s)
- Nadia B Hensley
- From the Division of Cardiothoracic Anesthesiology, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Promise T Ariyo
- From the Division of Cardiothoracic Anesthesiology, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sari D Holmes
- Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland
| | - Marlene S Williams
- Department of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Glenn Joseph Robert Whitman
- Division of Cardiac Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; and
| | - Niv Ad
- Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland.,Division of Cardiac Surgery, Adventist Health Care White Oak Medical Center, Silver Spring, Maryland
| | - Thomas Stephen Metkus
- Department of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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13
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Schoerghuber M, Pregartner G, Berghold A, Lindenau I, Zweiker R, Voetsch A, Mahla E, Zirlik A. How do type of preoperative P2Y 12 receptor inhibitor and withdrawal time affect bleeding? Protocol of a systematic review and individual patient data meta-analysis. BMJ Open 2022; 12:e060404. [PMID: 35351733 PMCID: PMC8961154 DOI: 10.1136/bmjopen-2021-060404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 02/23/2022] [Indexed: 11/05/2022] Open
Abstract
INTRODUCTION In order to reduce the risk of bleeding in patients on P2Y12 receptor inhibitors presenting for non-emergent coronary artery bypass grafting (CABG), current guidelines recommend a preoperative discontinuation period of at least three, five and seven days for ticagrelor, clopidogrel and prasugrel, respectively, to allow for recovery of platelet function. However, there is still substantial interinstitutional variation in preoperative management and relevant covariates of CABG-related bleeding are largely elusive so far. METHODS AND ANALYSIS We will search PubMed (July 2013 to November 2021) and EMBASE (January 2014 to November 2021) using the following terms, MeSH terms and their synonyms: clopidogrel, prasugrel, ticagrelor, dual antiplatelet, P2Y12 receptor inhibitor, CABG, bleeding, haemorrhage. Two independent reviewers will screen all abstracts and full papers for eligibility. Disagreements will be solved by consulting with a third reviewer.The primary outcome is the incidence of Bleeding Academic Research Consortium type-4 bleeding depending on type of P2Y12 receptor inhibitor and preoperative withdrawal period. The secondary outcomes are mortality and ischaemic events according to the Academic Research Consortium 2 Consensus Document. We will perform an individual patient data meta-analysis (IPD-MA) with drug-specific preoperative withdrawal time and adjust for demographic and procedural variables. Subgroup analyses will be performed for anaemic patients and patients undergoing non-emergent versus urgent/emergent surgery. ETHICS AND DISSEMINATION This IPD-MA consists of secondary analyses of existing non-identifiable data and meets the criteria for waiver of ethics review by the local Research Ethics Committee. Data sharing and transfer will be subject to a confidentiality agreement and a data use agreement. Findings will be disseminated through peer-reviewed publication and conference presentation. PROSPERO REGISTRATION NUMBER CRD42022291946.
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Affiliation(s)
- Michael Schoerghuber
- Division of Anesthesiology for Cardiovascular Surgery and Intensive Care Medicine, Medical University of Graz, Graz, Austria
| | - Gudrun Pregartner
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Andrea Berghold
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Ines Lindenau
- Division of Anesthesiology for Cardiovascular Surgery and Intensive Care Medicine, Medical University of Graz, Graz, Austria
- Department of Anesthesiology and Intensive Care Medicine, Hospital Hochsteiermark, Steiermarkische Krankenanstaltengesellschaft mbH, Leoben, Austria
| | - Robert Zweiker
- Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Andreas Voetsch
- Department of Cardiovascular and Endovascular Surgery, Paracelsus Medical University Salzburg, Salzburg, Austria
| | - Elisabeth Mahla
- Division of Anesthesiology for Cardiovascular Surgery and Intensive Care Medicine, Medical University of Graz, Graz, Austria
| | - Andreas Zirlik
- Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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14
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Abstract
Massive diffuse bleeding is still a problem in cardiovascular surgery. The first line treatment is platelet concentrate transfusion, although there is still insufficient information regarding efficacy, quantity, and timing. The objective of this prospective cohort study was to find out whether the amount of 4 apheresis platelet concentrates could reduce intraoperative bleeding and improve viscoelasticity and aggregometry.10 patients were enrolled intraoperatively because of life-threatening diffuse bleeding after cardiopulmonary bypass and received 4 apheresis platelet concentrates back-to-back. The units were given every 5 minutes. After every unit, thromboelastometry, performed by ROTEM®, and aggregometry, performed by Multiplate®, were done together with Hematocrit, Hemoglobin, and Platelet Count.Hematocrit and Hemoglobin showed a statistically significant decrease of 14%, whereas Platelet Count showed a statistically significant increase of 205%. MCE-EXTEM increased statistically significant: 46%. There was no statistically significant increase in both ADP and COL results.Even a series of 4 platelet concentrates did not comprehensively improve both essential components of an adequate hemostasis: viscoelasticity and aggregation. Just the transfusion of platelet concentrates alone did not build a sufficient strategy improving hemostasis and reducing bleeding. A positive effect of surgical packing on stopping the bleeding could be seen.
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Affiliation(s)
- Lisa Blath
- Department for Anesthesiology and Intensive Care Medicine, Franziskus Hospital Bielefeld, Bielefeld, Germany
| | - Jörg Martens
- Institute for Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Niels Rahe-Meyer
- Department for Anesthesiology and Intensive Care Medicine, Franziskus Hospital Bielefeld, Bielefeld, Germany.,Department for Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany
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15
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Sharan S, Kapoor PM, Choudhury M, Prakash M, Chowdhury UK, Hote M, Ravi V. Platelet Function Test in Coronary Artery Bypass Grafting: Does It Predict Postoperative Bleeding? JOURNAL OF CARDIAC CRITICAL CARE TSS 2022. [DOI: 10.1055/s-0042-1742402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
Abstract
Background Patients undergoing on-pump coronary artery bypass grafting (CABG) are at increased risk of perioperative bleeding and morbidity associated with transfusion as a result of acquired and pharmacologically induced impaired platelet function.
Settings and Design In this a prospective observational study where 52 patients underwent on-pump CABG were analyzed with ROTEM platelet aggregometry.
Materials and Methods Patients were assigned to the “nonexcessive” and “excessive” postoperative bleeding groups according to the postoperative chest tube drainage over 24 hours. Platelet function was assessed by ROTEM platelet using three different activators (arachidonic acid, adenosine diphosphate, and thrombin receptor-activating peptide), at two perioperative time points (T1, before heparinization and T2, 5–10 minutes after protamine administration).
Results There were no differences regarding demographic, pre–cardiopulmonary bypass (CPB) platelet count and antiplatelet therapy. Platelet function was impaired over the time course in all parameters with three different activators. At T2 point, area under the curve (AUC) of all the three platelet indices, that is, TRAPTEM, ARATEM, and ADPTEM, showed significant difference between excessive and nonexcessive groups. At both T1 and T2 points, the amplitude after 6 minutes (A6) and maximum slope (MS) parameters of TRAPTEM, ARATEM, and ADPTEM tests were not significantly different in excessive and nonexcessive groups. At T1 point, AUC was also not significantly different in all three ROTEM platelet tests. Results after protamine administration showed correlation with postoperative chest tube drainage. Cut-off values, as determined by receiver operating characteristics (ROC) analyses, had a consistently weak positive predictive value for all tests at T2 time point, whereas negative predictive values were higher.
Conclusion Platelet function analysis using ROTEM platelet can help to exclude platelet dysfunction as the reason for bleeding after cardiac surgery. Point-of-care platelet function analysis, particularly in combination with viscoelastic testing can reduce perioperative bleeding and transfusion requirements, as well as improve patient outcomes in cardiac surgery.
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Affiliation(s)
- Sandeep Sharan
- Department of Cardiac Anaesthesia, All India Institute of Medical Sciences, New Delhi, India
| | - Poonam Malhotra Kapoor
- Department of Cardiac Anaesthesiology, All India Institute of Medical Sciences, New Delhi, India
| | - Minati Choudhury
- Department of Cardiac Anaesthesiology, All India Institute of Medical Sciences, New Delhi, India
| | - Mohit Prakash
- Department of Cardiac Anaesthesia, All India Institute of Medical Sciences, New Delhi, India
| | - Ujjwal K. Chowdhury
- Department of Cardio Thoracic Vascular Surgery (CTVS), All India Institute of Medical Sciences, New Delhi, India
| | - Milind Hote
- Department of Cardio Thoracic Vascular Surgery (CTVS), All India Institute of Medical Sciences, New Delhi, India
| | - Vajala Ravi
- Department of Statistics, Delhi University, Lady Sriram College, New Delhi, India
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16
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Jourdi G, Godier A, Lordkipanidzé M, Marquis-Gravel G, Gaussem P. Antiplatelet Therapy for Atherothrombotic Disease in 2022—From Population to Patient-Centered Approaches. Front Cardiovasc Med 2022; 9:805525. [PMID: 35155631 PMCID: PMC8832164 DOI: 10.3389/fcvm.2022.805525] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 01/06/2022] [Indexed: 12/20/2022] Open
Abstract
Antiplatelet agents, with aspirin and P2Y12 receptor antagonists as major key molecules, are currently the cornerstone of pharmacological treatment of atherothrombotic events including a variety of cardio- and cerebro-vascular as well as peripheral artery diseases. Over the last decades, significant changes have been made to antiplatelet therapeutic and prophylactic strategies. The shift from a population-based approach to patient-centered precision medicine requires greater awareness of individual risks and benefits associated with the different antiplatelet strategies, so that the right patient gets the right therapy at the right time. In this review, we present the currently available antiplatelet agents, outline different management strategies, particularly in case of bleeding or in perioperative setting, and develop the concept of high on-treatment platelet reactivity and the steps toward person-centered precision medicine aiming to optimize patient care.
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Affiliation(s)
- Georges Jourdi
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
- Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada
- *Correspondence: Georges Jourdi
| | - Anne Godier
- Université de Paris, Innovative Therapies in Haemostasis, INSERM UMR_S1140, Paris, France
- Department of Anesthesiology and Critical Care, AP-HP, Université de Paris, Hôpital Européen Georges Pompidou, Paris, France
| | - Marie Lordkipanidzé
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
- Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada
| | - Guillaume Marquis-Gravel
- Research Center, Montreal Heart Institute, Montreal, QC, Canada
- Faculty of Medicine, Université de Montréal, Montreal, QC, Canada
| | - Pascale Gaussem
- Université de Paris, Innovative Therapies in Haemostasis, INSERM UMR_S1140, Paris, France
- Service d'Hématologie Biologique, AP-HP, Université de Paris, Hôpital Européen Georges Pompidou, Paris, France
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17
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Baryshnikova E, Di Dedda U, Ranucci M. A Comparative Study of Multiple Electrode Aggregometry Technologies in Cardiac Surgery: Different Values, Same Clinical Relevance. J Cardiothorac Vasc Anesth 2021; 36:1927-1933. [PMID: 34949522 DOI: 10.1053/j.jvca.2021.11.030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 11/16/2021] [Accepted: 11/17/2021] [Indexed: 11/11/2022]
Abstract
OBJECTIVES The assessment of platelet function in cardiac surgery patients who recently received dual-antiplatelet therapy is considered in the existing guidelines. Among available devices, Multiplate (MP) and ROTEM Platelet (RP) are both based on electrical impedance. This study aimed to determine the agreement between MP and RP in cardiac surgery patients under dual-antiplatelet therapy discontinued before surgery. Secondarily, it compared the ability of the MP and RP in predicting postoperative bleeding and the need for platelet transfusion. DESIGN A prospective cohort study. SETTING A hospital in Milan, Italy. PARTICIPANTS Fifty adult patients preoperatively and postoperatively tested. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Patients were studied with adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP) testing on both of the devices. The mean preoperative ADP tests were below the respective lower limit of the reference value, thus reflecting a good ability of these tests to detect the residual or ongoing effects of antiplatelet drugs acting on the P2Y12 receptor. The agreement between the 2 methodologies was very poor for both the ADP and TRAP tests, with a percentage error of 80%. The preoperative ADP tests were predictive for the need of platelet concentrate transfusion, with cut-off values at 35 U for the ADP-MP and 60 Ω/min for the ADP-RP. No correlation was found for postoperative bleeding. CONCLUSION Both technologies seemed to offer potential benefits in the surgical approach to patients who preoperatively received antiplatelet drugs. However, the results of these tests are not interchangeable, and different cut-off values should be applied.
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Affiliation(s)
- Ekaterina Baryshnikova
- Department of Cardiothoracic and Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, Milan, Italy
| | - Umberto Di Dedda
- Department of Cardiothoracic and Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, Milan, Italy
| | - Marco Ranucci
- Department of Cardiothoracic and Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, Milan, Italy.
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18
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Görlinger K, Gandhi A. Utility of Platelet Function Testing in Cardiac Surgery in 2021. JOURNAL OF CARDIAC CRITICAL CARE TSS 2021. [DOI: 10.1055/s-0041-1732839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Affiliation(s)
- Klaus Görlinger
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Medical Affairs, TEM Innovations GmbH, Munich, Germany
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19
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Sharan S, Kapoor PM, Choudhury M, Devagourou V, Choudhury UK, Ravi V. Role of Platelet Function Test in Predicting Postoperative Bleeding Risk after Coronary Artery Bypass Grafting: A Prospective Observational Study. JOURNAL OF CARDIAC CRITICAL CARE TSS 2021. [DOI: 10.1055/s-0041-1728978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
AbstractPatients undergoing cardiac surgery are at risk of excessive bleeding and its associated complications. Excessive bleeding during and after cardiac surgery has an incidence of ~20%. Massive bleeding and subsequent requirement for blood product administration and mediastinal reexploration are associated with significant morbidity and mortality. Postoperative, nonsurgical bleeding in cardiac surgical patients is often multifactorial. Platelet dysfunction, excessive fibrinolysis, hypothermia, preoperative anemia, and deficiency of coagulation factors or their dilution are all suggested etiologies of postoperative bleeding. In the Arachidonic Acid Thromboelastometry (ARATEM) test, platelets are activated with arachidonic acid; in Adenosine diphosphate Thromboelastometry (ADPTEM) test, platelets are activated with adenosine diphosphate; and in TRAPTEM test, platelets are activated with thrombin receptor-activating peptide 6. Measurement time is 6 minutes, and results are expressed in three different parameters: A6 (amplitude at 6 minutes, in Ohm); MS (maximum slope of the aggregation curve in Ohm/min), and AUC (area under the curve in Ohm.min). Algorithm-based point-of-care platelet function testing helped us to preemptively give the right blood component therapy, avoiding fibrinolytic bleeding in the postoperative period.
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Affiliation(s)
- Sandeep Sharan
- Department of Cardiac Anaesthesia, CTC, AIIMS, New Delhi, India
| | | | | | - V Devagourou
- Department of CTVS, CTC, AIIMS, New Delhi, India
| | | | - Vajala Ravi
- Department of Statistics, Lady Shri Ram College, University of Delhi New Delhi, India
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20
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Challenges in Patient Blood Management for Cardiac Surgery: A Narrative Review. J Clin Med 2021; 10:jcm10112454. [PMID: 34205971 PMCID: PMC8198483 DOI: 10.3390/jcm10112454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/27/2021] [Accepted: 05/28/2021] [Indexed: 11/16/2022] Open
Abstract
About 15 years ago, Patient Blood Management (PBM) emerged as a new paradigm in perioperative medicine and rapidly found support of all major medical societies and government bodies. Blood products are precious, scarce and expensive and their use is frequently associated with adverse short- and long-term outcomes. Recommendations and guidelines on the topic are published in an increasing rate. The concept aims at using an evidence-based approach to rationalize transfusion practices by optimizing the patient's red blood cell mass in the pre-, intra- and postoperative periods. However, elegant as a concept, the implementation of a PBM program on an institutional level or even in a single surgical discipline like cardiac surgery, can be easier said than done. Many barriers, such as dogmatic ideas, logistics and lack of support from the medical and administrative departments need to be overcome and each center must find solutions to their specific problems. In this paper we present a narrative overview of the challenges and updated recommendations for the implementation of a PBM program in cardiac surgery.
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21
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Tescione M, Vadalà E, Marano G, Battaglia E, Bruni A, Garofalo E, Longhini F, Rovida S, Polimeni N, Squillaci R, Lascala S, Franco G, Labate D, Caracciolo M, Macheda S. Platelet aggregometry for hip fracture surgery in patients treated with clopidogrel: a pilot study. J Clin Monit Comput 2021; 36:823-828. [PMID: 33956283 DOI: 10.1007/s10877-021-00714-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 04/23/2021] [Indexed: 11/25/2022]
Abstract
Surgery for hip fractures should be performed within 48 h from patient's admission. However, several factors including chronic antiplatelet therapy could delay operation. Among the totality of patients taking clopidogrel, up to 30% are resistant to the drug and have a normal platelets reactivity. We propose thromboelastography (TEG) with an ADP Platelet Mapping assay kit to assess platelet aggregation, a safe tool that could help to avoid surgery delay in those patients treated with antiplatelet therapy. A patient's blood sample was collected for aggregometry. If MA-ADP and platelets aggregation (%) were within normal values, the patient was fit for immediate surgery with neuraxial anesthesia and ultrasound-guided nerve block. If one of the two parameters or both were deranged, a mortality risk assessment was estimated. In the low risk category, the patients waited till normalization of the parameters, whereas in the high-risk group a general anesthesia and peripheral antalgic block was carried out. Nine patients were enrolled. Four of them showed normal aggregometry and surgery was performed within 24 h from admission. Two patients were classified as high mortality risk and surgery was carried out under general anesthesia. Three patients awaited operation till normalization of parameters. No peri or post-operative complications were reported. An aggregometry-guided protocol can safely expedite hip fracture surgery in patients taking clopidogrel. Nonetheless, in presence of a normal platelets function, clinician can opt for a neuraxial instead of general anesthesia reducing the incidence of postoperative delirium and cognitive dysfunction.Trial registration: prospectively registered at clinicaltrials.gov (NCT04642209; date of registration: 23rd November 2020).
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Affiliation(s)
- Marco Tescione
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy.
| | - Eugenio Vadalà
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Graziella Marano
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Enzo Battaglia
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Andrea Bruni
- Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Eugenio Garofalo
- Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Federico Longhini
- Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Serena Rovida
- Department of Emergency Medicine, Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Nicola Polimeni
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Rosalba Squillaci
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Stefano Lascala
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Gaetana Franco
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Demetrio Labate
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Massimo Caracciolo
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Sebastiano Macheda
- Anesthesia and Intensive Care Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy
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22
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Dias JD, Pottgiesser T, Hartmann J, Duerschmied D, Bode C, Achneck HE. Comparison of three common whole blood platelet function tests for in vitro P2Y12 induced platelet inhibition. J Thromb Thrombolysis 2021; 50:135-143. [PMID: 31620937 PMCID: PMC7293977 DOI: 10.1007/s11239-019-01971-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In the context of interventional cardiology, platelet function testing may identify patients treated with P2Y12-inhibitors at an increased risk of mortality, thrombosis and bleeding. Several whole blood point-of-care platelet function analyzers are available; however, inter-device differences have not been examined systematically. To compare three platelet function tests under standardized in vitro conditions. Healthy volunteer (n = 10) blood samples were spiked with increasing concentrations of ticagrelor (0–7500 ng/mL) and/or ASA (0–3280 ng/mL), measured on three platelet function analyzers (TEG®6s, Multiplate®, and VerifyNow®) and respective Effective Concentration (EC) levels EC10, EC50 and EC90 were calculated. Repeatability was assessed in a separate group of pooled blood samples (n = 10) spiked with ticagrelor at EC10, EC50 and EC90. ASA had no impact on ADP-activated channels for all three devices. TEG®6s was able to distinguish (p ≤ 0.05) between all ticagrelor EC zones; VerifyNow® and Multiplate® were able to distinguish between three and two zones, respectively. Multiplate® showed the largest window between EC10 and EC90 (19–9153 ng/mL), followed by TEG®6s (144–2589 ng/mL), and VerifyNow® (191–1100 ng/mL). Drug effect models distribution of disagreements were identified for TEG®6s (5.0%), VerifyNow® (8.3%), and Multiplate® (13.3%). TEG®6s showed the smallest average coefficient of variation between EC conditions (5.1%), followed by Multiplate® (14.1%), and VerifyNow® (17.7%). Linear models could be generated between TEG®6s and Multiplate®, but not VerifyNow®. Significant differences were found between whole blood point-of-care platelet function analyzers and the clinical impact of these differences needs to be further investigated.
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Affiliation(s)
| | - Torben Pottgiesser
- Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany
| | | | - Daniel Duerschmied
- Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany
| | - Christoph Bode
- Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany
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23
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Anaya R, Rodriguez M, Gil JM, Vilalta N, Merchan-Galvis A, Moral V, Mateo J, Martinez-Zapata MJ. Correlation between PlateletWorks ® and PFA-100 ® for Measuring Platelet Function before Urgent Surgery in Patients with Chronic Antiplatelet Therapy. J Clin Med 2021; 10:jcm10020255. [PMID: 33445597 PMCID: PMC7827156 DOI: 10.3390/jcm10020255] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 01/05/2021] [Accepted: 01/06/2021] [Indexed: 11/16/2022] Open
Abstract
Hemostasis is crucial for reducing bleeding during surgical procedures. The points-of-care based on the platelet function test could be useful to minimize the complications related to chronic antiplatelet therapy during surgery. The present study is aimed at comparing two point-of-care platelet function devices-Platelet Function Analyzer PFA-100® (Siemens Canada, Mississauga, ON, Canada) and Plateletworks®(Helena Laboratories, Beaumont, TX, USA). Our objective is to evaluate if they provide comparable and useful information to manage anti-aggregate patients before surgery. We included patients with a femoral fracture receiving chronic antiplatelet therapy and a median age of 89 years (range from 70 to 98). A platelet function evaluation was performed on all patients before surgery using both devices-Plateletworks® and PFA-100®. The correlation between Plateletworks® and PFA-100® was performed using Cohen's Kappa coefficient. Twenty consecutive patients participated in the trial; 16 patients were under treatment with 75 mg/day of clopidogrel, three with >300 mg/day of acetylsalicylic acid (ASA), and only one was in treatment with both antiplatelet agents. Cohen's Kappa coefficient was 0.327 comparing PFA-100®-ADP (adenosine diphosphate) and Plateletworks® and, 0.200 comparing PFA-100®-EPI (epinephrine) and Plateletworks®. In conclusion, we found a weak concordance comparing PFA-100® and Plateletworks®. This could partially be due to the advanced age of the included patients. However, given the limited sample size, more studies are necessary to confirm these results.
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Affiliation(s)
- Rafael Anaya
- Anesthesiology Service, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; (R.A.); (M.R.); (J.M.G.); (N.V.); (V.M.)
| | - Mireia Rodriguez
- Anesthesiology Service, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; (R.A.); (M.R.); (J.M.G.); (N.V.); (V.M.)
| | - José María Gil
- Anesthesiology Service, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; (R.A.); (M.R.); (J.M.G.); (N.V.); (V.M.)
| | - Noelia Vilalta
- Anesthesiology Service, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; (R.A.); (M.R.); (J.M.G.); (N.V.); (V.M.)
| | - Angela Merchan-Galvis
- Iberoamerican Cochrane Centre-Public Health and Clinical Epidemiology, IIBSant Pau, 08025 Barcelona, Spain;
- Departamento de Medicina Social y Salud Familiar, Universidad del Cauca, 190003 Popayán, Colombia
| | - Victoria Moral
- Anesthesiology Service, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; (R.A.); (M.R.); (J.M.G.); (N.V.); (V.M.)
| | - José Mateo
- Thrombosis and Hemostasis Unit, Hematology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain;
| | - María José Martinez-Zapata
- Iberoamerican Cochrane Centre-Public Health and Clinical Epidemiology, IIBSant Pau, 08025 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 08025 Barcelona, Spain
- Correspondence:
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24
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Matkovic M, Novakovic T, Bilbija I, Lazovic JM, Tutus V, Cubrilo M, Aleksic N, Mikic A, Petrovic E, Peric V, Milojevic A, Putnik S. The routine use of platelet function tests in elective coronary artery bypass grafting: A prospective observational trial. J Card Surg 2021; 36:629-636. [PMID: 33403686 DOI: 10.1111/jocs.15284] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/30/2020] [Accepted: 12/16/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND Preoperative use of platelet function tests contributes to the decrease of re-intervention rate due to bleeding and the necessity of transfusion in coronary artery bypass grafting (CABG) patients. The aim was to investigate the predictive value and to justify routine preoperative use of multiple electrode aggregometry in these patients. METHODS A prospective observational trial which included 416 consecutive patients subjected to elective isolated CABG was conducted. The Multiplate® test was used to assess platelet function. Platelet function test results, postoperative blood loss, and transfusion requirements were compared between high and low bleeding risk patients. Receiver operating characteristic analysis was performed to assess the sensitivity and specificity of the arachidonic acid (ASPI) and adenosine di-phosphate high sensitive (ADPHS) tests. RESULTS ADPHS and ASPI test results significantly predicted total bleeding > 1000 ml (AUC, 0.685, p < .001; 0.695, p = .039). Sensitivity and specificity were 62.9% and 40.0%, for ADPHS ≤602, and 70.8% and 41.8%, for ASPI ≤ 453. The sensitivity and specificity of cut-off values recommended by the manufacturer were 84.2% and 40.0% for ADPHS ≤ 500, while for ASPI < 600 the values were 54.7% and 62.2%. More platelets and cryoprecipitate were transfused in patients with ADPHS ≤ 602.5 (p < .001; p = .035). Patients with ADPHS ≤ 500 had a higher rate of red blood count, platelet and cryoprecipitate transfusion (p<.001p<.001; p = .013). The manufacturer's ASPI test cut-off values showed no statistically significant prediction for a higher transfusion rate. CONCLUSION Preoperative platelet function tests should be conducted systematically for all elective CABG patients who were on dual antiplatelet therapy after adjusting test cut-off values for each population.
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Affiliation(s)
- Milos Matkovic
- Department for Cardiac Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Tina Novakovic
- Department for Biostatistics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ilija Bilbija
- Department for Cardiac Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jelena Milin Lazovic
- Department for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia
| | - Vladimir Tutus
- Department for Anesthesiology and Intensive Care, Clinical Center of Serbia, Belgrade, Serbia
| | - Marko Cubrilo
- Department for Cardiac Surgery, Clinical Center of Serbia, Belgrade, Serbia
| | - Nemanja Aleksic
- Department for Cardiac Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Aleksandar Mikic
- Department for Cardiac Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Emilija Petrovic
- Department for Cardiac Surgery, Clinical Center of Serbia, Belgrade, Serbia
| | - Valerija Peric
- Department for Cardiac Surgery, Clinical Center of Serbia, Belgrade, Serbia
| | | | - Svetozar Putnik
- Department for Cardiac Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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25
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A Pilot Trial of Platelets Stored Cold versus at Room Temperature for Complex Cardiothoracic Surgery. Anesthesiology 2020; 133:1173-1183. [PMID: 32902572 DOI: 10.1097/aln.0000000000003550] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND This pilot trial focused on feasibility and safety to provide preliminary data to evaluate the hemostatic potential of cold-stored platelets (2° to 6°C) compared with standard room temperature-stored platelets (20° to 24°C) in adult patients undergoing complex cardiothoracic surgery. This study aimed to assess feasibility and to provide information for future pivotal trials. METHODS A single center two-stage exploratory pilot study was performed on adult patients undergoing elective or semiurgent complex cardiothoracic surgery. In stage I, a two-armed randomized trial, platelets stored up to 7 days in the cold were compared with those stored at room temperature. In the subsequent single-arm stage II, cold storage time was extended to 8 to 14 days. The primary outcome was clinical effect measured by chest drain output. Secondary outcomes were platelet function measured by multiple electrode impedance aggregometry, total blood usage, immediate and long-term (28 days) adverse events, length of stay in intensive care, and mortality. RESULTS In stage I, the median chest drain output was 720 ml (quartiles 485 to 1,170, n = 25) in patients transfused with room temperature-stored platelets and 645 ml (quartiles 460 to 800, n = 25) in patients transfused with cold-stored platelets. No significant difference was observed. The difference in medians between the room temperature- and cold-stored up to 7 days arm was 75 ml (95% CI, -220, 425). In stage II, the median chest drain output was 690 ml (500 to 1,880, n = 15). The difference in medians between the room temperature arm and the nonconcurrent cold-stored 8 to 14 days arm was 30 ml (95% CI, -1,040, 355). Platelet aggregation in vitro increased after transfusion in both the room temperature- and cold-stored platelet study arms. Total blood usage, number of adverse events, length of stay in intensive care, and mortality were comparable among patients receiving cold-stored and room temperature-stored platelets. CONCLUSIONS This pilot trial supports the feasibility of platelets stored cold for up to 14 days and provides critical guidance for future pivotal trials in high-risk cardiothoracic bleeding patients. EDITOR’S PERSPECTIVE
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26
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Platelet Function Testing in Patients on Antiplatelet Therapy before Cardiac Surgery. Anesthesiology 2020; 133:1263-1276. [DOI: 10.1097/aln.0000000000003541] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Based on variable pharmacodynamic responsiveness and platelet reactivity recovery after discontinuation of P2Y12 receptor inhibitors, preoperative platelet function testing may individualize discontinuation and be a part of transfusion algorithm triggering targeted postpump hemostatic management.
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27
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Schultz-Lebahn A, Skipper MT, Hvas AM, Larsen OH. Optimized tool for evaluation of platelet function measured by impedance aggregometry. Platelets 2020; 32:842-845. [PMID: 32865092 DOI: 10.1080/09537104.2020.1809644] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Platelet aggregation measured by impedance aggregometry is highly dependent on platelet count. We previously developed a tool to interpret impedance aggregometry based on the strong linear correlation between platelet counts and platelet aggregation at reduced platelet counts. The present study aimed to optimize the tool by expanding the model to include normal platelet counts. We combined data from three previous studies on 266 healthy individuals measuring impedance aggregometry with four agonists (collagen, adenosine diphosphate, thrombin receptor activating peptide-6, and ristocetin). Reduced platelet counts were established in vitro. The investigated platelet counts ranged from 26-425x109/L. A positive linear correlation was found between platelet counts and platelet aggregation across normal and reduced platelet counts (all p-values <0.001). We established 95% prediction intervals for healthy platelet aggregation in relation to platelet count. The new expanded model serves as an optimized tool for evaluation of platelet aggregation at normal and reduced platelet counts.
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Affiliation(s)
- Anna Schultz-Lebahn
- Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| | | | - Anne-Mette Hvas
- Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Ole Halfdan Larsen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
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28
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Auci E, Vetrugno L, Riccardi I, Brussa A, Orso D, Baroselli A, Gigante A, Cecotti R, Bassi F, Livi U, Bove T. Multiple Electrode Aggregometry After Cardiopulmonary Bypass to Assess Platelet (Dys)-Function and Transfusion Threshold: A Concordance Study. J Cardiothorac Vasc Anesth 2020; 34:3306-3313. [PMID: 32684430 DOI: 10.1053/j.jvca.2020.06.060] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 05/31/2020] [Accepted: 06/17/2020] [Indexed: 01/31/2023]
Abstract
OBJECTIVE Cardiac surgery patients have a high risk of postoperative bleeding. Historically, the platelet count has been one of the main parameters used to establish the need for platelet transfusions, and the recent introduction of point-of-care tests for platelet function has allowed clinicians to rationalize platelet transfusion needs by assessing the platelet (dys-)function of the patient. For the present study, the authors evaluated how the introduction of one of these systems-the adenosine diphosphate (ADP) test, performed using a Multiplate electrode analyzer (Roche Diagnostics, Basel, Switzerland)-into their clinical practice had modified their platelet transfusion practice. The relationship between the platelet count and the functional evaluation of platelet aggregation (via the ADP test) also was examined. DESIGN This was a retrospective, single-center, observational study. SETTING Cardiac surgery department of a tertiary care center in North-east Italy. PARTICIPANTS Cardiac surgery patients requiring cardiac bypass in 2017 and 2019. INTERVENTIONS The primary outcome was to compare platelet transfusion practice before and after the implementation of a platelet function test (the ADP test) into the institution's transfusion algorithm, which replaced the platelet count as the trigger. Secondary outcomes were assessing whether the incorporation of the ADP test into their transfusion algorithm brought about a reduction in the frequency of platelet transfusions compared with previous rates (when only platelets counts were used); assessing patient blood loss in the first 12 postoperative hours; and ascertaining the percentage of patients requiring surgical reexplorations. MEASUREMENTS AND MAIN RESULTS The study comprised 110 patients undergoing cardiac surgery from the platelet count period (2017) and 110 patients from the ADP test period (2019). Agreement between platelet counts versus ADP tests in determining the need for platelet transfusion was moderate (κ = 0.483; 95% confidence interval [CI] 0.239-0.728), and the general linear regression relationship between platelet counts and the ADP test (Akaike information criterion = 2536; p < 0.001) was determined. Since the introduction of ADP testing, a highly significant reduction in platelet transfusions has occurred: 41.82% (platelet count period) versus 13.64% (ADP test period) (p < 0.001); average blood loss in the 12 hours postsurgery also was less in the ADP test period (p < 0.001) at 300 mL (95% CI 150-730) compared with 440 mL in the platelet count period (95% CI 135-900). Furthermore, a decreasing trend was observed in the number of patients requiring reexploration to optimize hemostasis in the first 12 hours postsurgery (6.36% v 2.73%); however, this trend did not achieve statistical significance (p = 0.195). CONCLUSION The application of new Multiplate analyzer technologies, like the ADP test, have the potential to reduce platelet transfusion rates in cardiac surgery patients compared with the use of platelet counts alone; this point-of-care test may constitute an important strategy to help spare the use of allogeneic blood products. Additional studies are needed to confirm this trend and establish the best cutoff values to apply.
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Affiliation(s)
- Elisabetta Auci
- Department of Anesthesia and Intensive Care Medicine, ASUFC "Santa Maria della Misericordia" University Hospital of Udine, Udine, Italy
| | - Luigi Vetrugno
- Department of Anesthesia and Intensive Care Clinic, ASUFC "Santa Maria della Misericordia" University Hospital of Udine, Udine, Italy; Department of Medicine, University of Udine, Udine, Italy.
| | - Ilaria Riccardi
- Department of Anesthesia and Intensive Care Clinic, ASUFC "Santa Maria della Misericordia" University Hospital of Udine, Udine, Italy
| | - Alessandro Brussa
- Department of Anesthesia and Intensive Care Clinic, ASUFC "Santa Maria della Misericordia" University Hospital of Udine, Udine, Italy
| | - Daniele Orso
- Department of Medicine, University of Udine, Udine, Italy
| | - Antonio Baroselli
- Department of Anesthesia and Intensive Care Medicine, ASUFC "Santa Maria della Misericordia" University Hospital of Udine, Udine, Italy
| | - Andrea Gigante
- Department of Anesthesia and Intensive Care Medicine, ASUFC "Santa Maria della Misericordia" University Hospital of Udine, Udine, Italy
| | - Roberta Cecotti
- Department of Anesthesia and Intensive Care Medicine, ASUFC "Santa Maria della Misericordia" University Hospital of Udine, Udine, Italy
| | - Flavio Bassi
- Department of Anesthesia and Intensive Care Medicine, ASUFC "Santa Maria della Misericordia" University Hospital of Udine, Udine, Italy
| | - Ugolino Livi
- Department of Cardiothoracic Surgery, ASUFC "Santa Maria della Misericordia" University Hospital of Udine, Udine, Italy; Department of Medicine, University of Udine, Italy
| | - Tiziana Bove
- Department of Anesthesia and Intensive Care Clinic, ASUFC "Santa Maria della Misericordia" University Hospital of Udine, Udine, Italy; Department of Medicine, University of Udine, Udine, Italy
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29
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Bolliger D, Lancé MD, Siegemund M. Point-of-Care Platelet Function Monitoring: Implications for Patients With Platelet Inhibitors in Cardiac Surgery. J Cardiothorac Vasc Anesth 2020; 35:1049-1059. [PMID: 32807601 DOI: 10.1053/j.jvca.2020.07.050] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 07/13/2020] [Accepted: 07/15/2020] [Indexed: 12/13/2022]
Abstract
Although most physicians are comfortable managing the limited anticoagulant effect of aspirin, the recent administration of potent P2Y12 receptor inhibitors in patients undergoing cardiac surgery remains a dilemma. Guidelines recommend discontinuation of potent P2Y12 inhibitors 5- to- 7 days before surgery to reduce the risk of postoperative hemorrhage. Such a strategy might not be feasible before urgent surgery, due to ongoing myocardial ischemia or in patients at high risk for thromboembolic events. Recently, different point-of-care devices to assess functional platelet quality have become available for clinical use. The aim of this narrative review was to evaluate the implications and potential benefits of platelet function monitoring in guiding perioperative management and therapeutic options in patients treated with antiplatelets, including aspirin or P2Y12 receptor inhibitors, undergoing cardiac surgery. No objective superiority of one point-of-care device over another was found in a large meta-analysis. Their accuracy and reliability are generally limited in the perioperative period. In particular, preoperative platelet function testing has been used to assess platelet contribution to bleeding after cardiac surgery. However, predictive values for postoperative hemorrhage and transfusion requirements are low, and there is a significant variability between and within these tests. Further, platelet function monitoring has been used to optimize the preoperative waiting period after cessation of dual antiplatelet therapy before urgent cardiac surgery. Furthermore, studies assessing their value in therapeutic decisions in bleeding patients after cardiac surgery are scarce. A general and liberal use of perioperative platelet function testing is not yet recommended.
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Affiliation(s)
- Daniel Bolliger
- Department for Anesthesia, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, Basel, Switzerland.
| | - Marcus D Lancé
- Department of Anesthesiology, Intensive Care Unit and Perioperative Medicine, Weill-Cornell Medicine-Qatar, Hamad Medical Corporation, Doha, Qatar
| | - Martin Siegemund
- Intensive Care Medicine, University Hospital Basel, Basel, Switzerland
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30
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Verdoia M, Nardin M, Gioscia R, Negro F, Marcolongo M, Suryapranata H, Kedhi E, De Luca G. Higher neutrophil-to-lymphocyte ratio (NLR) increases the risk of suboptimal platelet inhibition and major cardiovascular ischemic events among ACS patients receiving dual antiplatelet therapy with ticagrelor. Vascul Pharmacol 2020; 132:106765. [PMID: 32681888 DOI: 10.1016/j.vph.2020.106765] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 04/11/2020] [Accepted: 07/10/2020] [Indexed: 01/04/2023]
Abstract
BACKGROUND Neutrophil to lymphocyte ratio (NLR) has emerged as a useful and easy-to-assess prognostic tool and biomarker of cardiovascular risk. However, few studies have evaluated its role on platelet inhibition among patients on dual antiplatelet therapy (DAPT), and especially in the settings of acute coronary syndromes (ACS). We aimed at assessing the impact of NLR on platelet reactivity and the risk of major ischemic events at long-term follow-up among ACS patients on DAPT with ticagrelor. METHODS Patients on dual antiplatelet therapy with ASA + ticagrelor (90 mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by Multiple Electrode Aggregometry (MEA). Suboptimal platelet inhibition (HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome, target vessel revascularization) at longest available follow-up. RESULTS We included 397 patients, that were divided according to NLR tertiles. Patients with higher NLR were older (p < .001), less frequently smokers (p = .03), with higher rates of renal failure (p = .001), previous bypass surgery (p = .05) and use of statins (p = .03) and diuretics (p = .01). Higher white blood cells count and C-reactive protein (p < .001) and lower haemoglobin (p = .001) were associated with NLR. Mean platelet reactivity and the prevalence of high platelet reactivity (HRPR) on ticagrelor were significantly associated to higher NLR tertiles values (7% vs 12% vs 14.3%, p = .04), with a significant relationship between NLR and platelet reactivity being confirmed for all the different activating stimuli. At a mean follow-up of 939 ± 581.4 days, 21.2% of the patients experienced the primary composite endpoint, with a trend for a higher risk of events across NLR tertiles (15.4% vs 24.2% vs 24.4%, p = .09), that became statistically significant after correction for baseline confounders (adjusted HR[95%CI] = 1.13[1.008-1.26], p = .036). Moreover, NLR was significantly associated to overall mortality and recurrent ACS (adjusted p = .008, p = .06 and p = .02 respectively). CONCLUSIONS In the present study we found that among ACS patients treated with ASA and ticagrelor after PCI, suboptimal platelet inhibition despite DAPT was significantly increased for higher values of Neutrophil-to-Lymphocyte Ratio. Moreover, mortality and the risk of recurrent major ischemic events at long-term were associated to NLR.
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Affiliation(s)
- Monica Verdoia
- Division of Cardiology, Ospedale degli Infermi, ASL, Biella, Italy; Department of Translational Medicine, Eastern Piedmont University, Novara, Italy
| | - Matteo Nardin
- Department of Translational Medicine, Eastern Piedmont University, Novara, Italy
| | - Rocco Gioscia
- Department of Translational Medicine, Eastern Piedmont University, Novara, Italy; Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy
| | - Federica Negro
- Department of Translational Medicine, Eastern Piedmont University, Novara, Italy
| | - Marco Marcolongo
- Division of Cardiology, Ospedale degli Infermi, ASL, Biella, Italy
| | | | - Elvin Kedhi
- Department of Cardiology, St-Jan Hospital, Brugge, Belgium
| | - Giuseppe De Luca
- Department of Translational Medicine, Eastern Piedmont University, Novara, Italy; Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
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Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Jüni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2020; 40:87-165. [PMID: 30165437 DOI: 10.1093/eurheartj/ehy394] [Citation(s) in RCA: 4441] [Impact Index Per Article: 888.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Wang L, Valencia O, Phillips S, Sharma V. Implementation of Perioperative Point-of-Care Platelet Function Analyses Reduces Transfusion Requirements in Cardiac Surgery: A Retrospective Cohort Study. Thorac Cardiovasc Surg 2020; 69:710-718. [DOI: 10.1055/s-0040-1710582] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Abstract
Background Platelet dysfunction is a common cause of bleeding, perioperative blood transfusion, and surgical re-exploration in cardiac surgical patients. We evaluated the effect of incorporating a platelet function analyzer utilizing impedance aggregometry (Multiplate, Roche, Munich, Germany) into our local transfusion algorithm on the rate of platelet transfusion and postoperative blood loss in patients undergoing coronary artery bypass grafting (CABG) surgery.
Methods Data were collected on patients undergoing CABG surgery from January 2015 to April 2017. Patients who underwent surgery before and after introduction of this algorithm were classified into prealgorithm and postalgorithm groups, respectively. The primary outcome was the rate of platelet transfusion before and after implementation of the Multiplate-based transfusion algorithm. Secondary outcomes included transfusion rate of packed red blood cells, postoperative blood loss at 12 and 24 hours, length of stay in the intensive care unit, and the hospital and mortality.
Results A total of 726 patients were included in this analysis with 360 and 366 patients in the pre- and postalgorithm groups, respectively. Transfusion rates of platelets (p = 0.01) and packed red blood cells (p = 0.0004) were significantly lower following introduction of the algorithm in patients (n = 257) who had insufficient time to withhold antiplatelet agents. Receiver operating characteristic curves defined optimal cutoff points of arachidonic acid and adenosine diphosphate assays on the Multiplate to predict future platelet transfusion were 23AU and 43AU, respectively.
Conclusions The introduction of a Multiplate-based platelet transfusion algorithm showed a statistically significant reduction in the administration of platelets to patients undergoing urgent CABG surgery.
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Affiliation(s)
- Lihui Wang
- Department of Clinical Perfusion, St George's Hospital, London, United Kingdom
| | - Oswaldo Valencia
- Department of Cardiac Surgery, St George's Hospital, London, United Kingdom
| | - Simon Phillips
- Department of Clinical Perfusion, St George's Hospital, London, United Kingdom
| | - Vivek Sharma
- Department of Anaesthesia, St George's Hospital, London, United Kingdom
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33
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Nakamura M, Kimura K, Kimura T, Ishihara M, Otsuka F, Kozuma K, Kosuge M, Shinke T, Nakagawa Y, Natsuaki M, Yasuda S, Akasaka T, Kohsaka S, Haze K, Hirayama A. JCS 2020 Guideline Focused Update on Antithrombotic Therapy in Patients With Coronary Artery Disease. Circ J 2020; 84:831-865. [DOI: 10.1253/circj.cj-19-1109] [Citation(s) in RCA: 115] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
- Masato Nakamura
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center
| | - Kazuo Kimura
- Division of Cardiology, Yokohama City University Medical Center
| | - Takeshi Kimura
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
| | - Masaharu Ishihara
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine
| | - Fumiyuki Otsuka
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center
| | - Ken Kozuma
- Division of Cardiology, Department of Internal Medicine, Teikyo University School of Medicine
| | - Masami Kosuge
- Division of Cardiology, Yokohama City University Medical Center
| | - Toshiro Shinke
- Division of Cardiology, Department of Medicine, Showa University School of Medicine
| | - Yoshihisa Nakagawa
- Division of Cardiovascular Medicine, Department of Internal Medicine, Shiga University of Medical Science
| | | | - Satoshi Yasuda
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center
| | - Takashi Akasaka
- Department of Cardiovascular Medicine, Wakayama Medical University
| | - Shun Kohsaka
- Department of Cardiology, Keio University School of Medicine
| | - Kazuo Haze
- Department of Cardiology, Kashiwara Municipal Hospital
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34
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Söderberg M, Holm M, Gupta A. Assessment of platelet function after discontinuation of ticagrelor. Acta Anaesthesiol Scand 2020; 64:526-531. [PMID: 31828756 DOI: 10.1111/aas.13524] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 11/22/2019] [Accepted: 11/27/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND Patients presenting with acute coronary syndromes (ACS) are often treated by percutaneous coronary intervention (PCI) with insertion of coronary artery stents and a majority receive dual antiplatelet therapy (DAPT), usually a combination of a COX-1 inhibitor (aspirin) and a P2Y12 inhibitor (eg ticagrelor). Not seldom the question arises as to when DAPT should be discontinued prior to interventional surgery. This study was done with the primary aim of investigating thrombocyte function immediately prior to and after discontinuation of ticagrelor. MATERIALS AND METHODS In this prospective, longitudinal, observational study including 24 patients, venous blood was obtained from patients on day 0, before stopping maintenance dose of 90 mg ticagrelor twice daily, and then on days 1, 3, 5, and 8, after discontinuation. Samples were analyzed using Multiplate® and VerifyNow® . RESULTS Prior to urgent surgery platelet aggregation >30 aggregation units (Multiplate® ) and >208 P2Y12 reaction units (VerifyNow® ) have been shown to correlate with reduced risk of peri- and postoperative bleeding risk. On day 3 after ticagrelor discontinuation, 100% (P = .016) and 67% (P=<.001) of patients had reached these levels on Multiplate® and VerifyNow® , respectively. On day 5, the corresponding figures were 100% (P = .016) and 78% (P=<.001). CONCLUSION Discontinuation of ticagrelor for 3 days resulted in return of adequate platelet function in all patients on Multiplate® and in a majority of patients on VerifyNow® , indicating a lower bleeding risk. A bedside test for platelet function may be considered if time to anticipated surgery is less than 5 days after ticagrelor discontinuation.
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Affiliation(s)
- Martin Söderberg
- Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
| | - Manne Holm
- Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
| | - Anil Gupta
- Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
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35
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Reduction of Preoperative Waiting Time before Urgent Surgery for Patients on P2Y 12 Inhibitors Using Multiple Electrode Aggregometry: A Retrospective Study. J Clin Med 2020; 9:jcm9020424. [PMID: 32033153 PMCID: PMC7074528 DOI: 10.3390/jcm9020424] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 01/30/2020] [Accepted: 01/31/2020] [Indexed: 12/18/2022] Open
Abstract
P2Y12 inhibitor discontinuation is essential before most surgical interventions to limit bleeding complications. Based on pharmacodynamic 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 P2Y12 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 P2Y12 inhibitors.
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36
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Ow KW, Parker WAE, Porter MM, Hanson J, Judge HM, Briffa NP, Thomas MR, Storey RF. Offset of ticagrelor prior to coronary artery bypass graft surgery for acute coronary syndromes: effects on platelet function and cellular adenosine uptake. Platelets 2020; 31:945-951. [PMID: 31893974 DOI: 10.1080/09537104.2019.1709631] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Ticagrelor is an antagonist of both platelet adenosine diphosphate (ADP) receptor P2Y12 and equilibrative nucleoside transporter-1. Optimal timing of ticagrelor cessation prior to coronary artery bypass grafting (CABG) remains unclear. We characterized the offset of ticagrelor's effects on platelets and cellular adenosine uptake in ticagrelor-treated patients (n = 13) awaiting CABG. Blood was drawn prior to CABG at multiple timepoints 2 to 120 (h) after the last dose of ticagrelor. Platelet function (n = 13) was assessed with multiple electrode aggregometry (MEA), expressed as arbitrary units (U) derived from area-under-the-curve (AUC) in response to ADP, and inhibition of adenosine uptake by high-performance liquid chromatography (n = 7). Mean±SD AUC was 20.3 ± 8.2 U (2 h post-ticagrelor), 33.0 ± 18.3U (24 h), 56.6 ± 30.6U (48 h), 61.4 ± 20.2U (72 h), 82.8 ± 24.2U (96 h) and 96.0 ± 15.3U (120 h). There was a significant difference between 72 h and 120 h (p = .007), but not between 96 h and 120 h (p > .99). By 96 h, all patients had AUC >31U, an accepted cutoff below which surgical bleeding risk is increased. Adenosine uptake showed no significant differences between the timepoints. These data suggest it takes 4 days for platelet reactivity to recover sufficiently after cessation of ticagrelor to avoid the excess risk of CABG-related bleeding. Discontinuing ticagrelor had no measurable effect on cellular adenosine uptake.
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Affiliation(s)
- Kok Weng Ow
- Department of Infection, Immunity and Cardiovascular Disease, The Medical School, University of Sheffield , Sheffield, UK
| | - William A E Parker
- Department of Infection, Immunity and Cardiovascular Disease, The Medical School, University of Sheffield , Sheffield, UK.,South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust , Sheffield, UK
| | - Mark M Porter
- Manchester Royal Infirmary, Manchester University NHS Foundation Trust , Manchester, UK
| | - Jessica Hanson
- Department of Infection, Immunity and Cardiovascular Disease, The Medical School, University of Sheffield , Sheffield, UK
| | - Heather M Judge
- Department of Infection, Immunity and Cardiovascular Disease, The Medical School, University of Sheffield , Sheffield, UK
| | - Norman P Briffa
- Department of Infection, Immunity and Cardiovascular Disease, The Medical School, University of Sheffield , Sheffield, UK.,South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust , Sheffield, UK
| | - Mark R Thomas
- Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham , Birmingham, UK
| | - Robert F Storey
- Department of Infection, Immunity and Cardiovascular Disease, The Medical School, University of Sheffield , Sheffield, UK.,South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust , Sheffield, UK
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37
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Swan D, Loughran N, Makris M, Thachil J. Management of bleeding and procedures in patients on antiplatelet therapy. Blood Rev 2020; 39:100619. [DOI: 10.1016/j.blre.2019.100619] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 07/31/2019] [Accepted: 10/10/2019] [Indexed: 02/06/2023]
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Olsson A, Alfredsson J, Thelander M, Svedjeholm R, Berglund JS, Berg S. Activated platelet aggregation is transiently impaired also by a reduced dose of protamine. SCAND CARDIOVASC J 2019; 53:355-360. [PMID: 31476919 DOI: 10.1080/14017431.2019.1659396] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Objectives: Protamine reduces platelet aggregation after cardiopulmonary bypass (CPB). We studied the inhibitory effect of a reduced protamine dose, the duration of impaired platelet function and the possible correlation to postoperative bleeding. Design: Platelet function was assessed by impedance aggregometry in 30 patients undergoing cardiac surgery with CPB at baseline, before protamine administration, after 70% and 100% of the calculated protamine dose, after 20 minutes and at arrival to the intensive care unit. Adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used as activators. Blood loss was measured during operation and three hours after surgery. Results are presented as median (25th-75th percentile). Results: Platelet aggregation decreased markedly after the initial dose of protamine (70%) with all activators; ADP 89 (71-110) to 54 (35-78), TRAP 143 (116-167) to 109 (77-136), both p < .01; AA 25 (16-49) to 17 (12-24) and COL 92 (47-103) to 60 (38-81) U, both p < .05. No further decrease was seen after 100% protamine. The effect was transient and after twenty minutes platelet aggregation had started to recover; ADP 76 (54-106), TRAP 138 (95-158), AA 20 (10-35), COL 70 (51-93) U. Blood loss during operation correlated to aggregometry measured at baseline and after protaminization. Conclusions: Protamine after CPB induces a marked decrease in platelet aggregation already at a protamine-heparin ratio of 0.7:1. The impairment seems to be transient and recovery had started after 20 minutes.
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Affiliation(s)
- A Olsson
- Department of Health Science, Blekinge Institute of Technology, Karlskrona, Sweden.,Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.,Department of Cardio-Thoracic Surgery, Blekinge Hospital, Karlskrona, Sweden
| | - J Alfredsson
- Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.,Department of Cardiology, Linköping University, Linköping, Sweden
| | - M Thelander
- Department of Cardio-Thoracic Surgery, Blekinge Hospital, Karlskrona, Sweden
| | - R Svedjeholm
- Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.,Department of Cardio-Thoracic and Vascular Surgery, Linköping University, Linköping, Sweden
| | - J Sanmartin Berglund
- Department of Health Science, Blekinge Institute of Technology, Karlskrona, Sweden
| | - S Berg
- Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.,Department of Cardiovascular Anesthesia and Intensive Care, Linköping University, Linköping, Sweden
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Nicola H, Ho KM. Aspirin Resistance Incidence and Associations Between Aspirin Effect and Outcomes in Cardiac Surgery. Ann Thorac Surg 2019; 108:1815-1821. [PMID: 31238032 DOI: 10.1016/j.athoracsur.2019.04.114] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 03/23/2019] [Accepted: 04/29/2019] [Indexed: 11/24/2022]
Abstract
BACKGROUND When, and on whom, aspirin should be ceased before elective cardiac surgery is controversial. This study assessed the incidence of preoperative aspirin resistance and whether the quantitative antiplatelet effect of aspirin was associated with perioperative outcomes. METHODS Aspirin-induced antiplatelet effect was measured by multiple electrode aggregometry in 250 adult cardiac surgical patients within 24 hours before surgery. Aspirin resistance was defined by a normal platelet function testing result for those who had continued taking aspirin until the day before the platelet function testing. RESULTS Aspirin resistance was observed in 16 (11.9%) patients (95% confidence interval [CI], 7.4-18.4). Of the 250 patients included, 75 (30%) required allogeneic blood product transfusion subsequently. Aspirin induced antiplatelet effect (odds ratio [OR], 0.991 per unit increment in the area under the curve on the platelet function testing, with a smaller area indicating more platelet inhibition; 95% CI, 0.982-0.999; P = .035), a higher EuroSCORE [European System for Cardiac Operative Risk Evaluation] II risk (OR, 1.184 per EuroSCORE II risk percentage increment; 95% CI, 1.017-1.379; P = .001), and a lower body mass index (OR, 0.926 per unit increment; 95% CI, 0.867-0.990; P = .024) were the only factors independently associated with requiring perioperative allogeneic blood product transfusion. CONCLUSIONS The degree of aspirin effect immediately before cardiac surgery was weakly associated with the risks of postoperative bleeding and allogeneic blood product transfusion, suggesting that measuring aspirin-induced antiplatelet effect before cardiac surgery may be useful as an adjunct in optimizing patient blood management for patients who are at high risk of bleeding and requiring allogeneic blood transfusion.
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Affiliation(s)
- Henrique Nicola
- Intensive Care Unit, Royal Perth Hospital, Perth, Western Australia, Australia; Intensive Care Unit, Mount Hospital, Perth, Western Australia, Australia.
| | - Kwok M Ho
- Intensive Care Unit, Royal Perth Hospital, Perth, Western Australia, Australia; Intensive Care Unit, Mount Hospital, Perth, Western Australia, Australia; University of Western Australia, Perth, Western Australia, Australia; Murdoch University, Perth, Western Australia, Australia
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40
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Bolliger D, Tanaka KA. Platelet Count and Function—Can We Kill Two Birds With an Ultrasound Wave? J Cardiothorac Vasc Anesth 2019; 33:1599-1600. [DOI: 10.1053/j.jvca.2019.02.038] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/19/2019] [Indexed: 11/11/2022]
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41
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Godier A, Garrigue D, Lasne D, Fontana P, Bonhomme F, Collet JP, de Maistre E, Ickx B, Gruel Y, Mazighi M, Nguyen P, Vincentelli A, Albaladejo P, Lecompte T. Management of antiplatelet therapy for non elective invasive procedures of bleeding complications: proposals from the French working group on perioperative haemostasis (GIHP), in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR). Anaesth Crit Care Pain Med 2019; 38:289-302. [DOI: 10.1016/j.accpm.2018.10.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Accepted: 10/07/2018] [Indexed: 12/12/2022]
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Görlinger K, Pérez-Ferrer A, Dirkmann D, Saner F, Maegele M, Calatayud ÁAP, Kim TY. The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management. Korean J Anesthesiol 2019; 72:297-322. [PMID: 31096732 PMCID: PMC6676023 DOI: 10.4097/kja.19169] [Citation(s) in RCA: 136] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 05/08/2019] [Indexed: 02/07/2023] Open
Abstract
Rotational thromboelastometry (ROTEM) is a point-of-care viscoelastic method and enables to assess viscoelastic profiles of whole blood in various clinical settings. ROTEM-guided bleeding management has become an essential part of patient blood management (PBM) which is an important concept in improving patient safety. Here, ROTEM testing and hemostatic interventions should be linked by evidence-based, setting-specific algorithms adapted to the specific patient population of the hospitals and the local availability of hemostatic interventions. Accordingly, ROTEM-guided algorithms implement the concept of personalized or precision medicine in perioperative bleeding management (‘theranostic’ approach). ROTEM-guided PBM has been shown to be effective in reducing bleeding, transfusion requirements, complication rates, and health care costs. Accordingly, several randomized-controlled trials, meta-analyses, and health technology assessments provided evidence that using ROTEM-guided algorithms in bleeding patients resulted in improved patient’s safety and outcomes including perioperative morbidity and mortality. However, the implementation of ROTEM in the PBM concept requires adequate technical and interpretation training, education and logistics, as well as interdisciplinary communication and collaboration.
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Affiliation(s)
- Klaus Görlinger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.,Tem Innovations, Munich, Germany
| | - Antonio Pérez-Ferrer
- Department of Anesthesiology, Infanta Sofia University Hospital, San Sebastián de los Reyes, Madrid, Spain
| | - Daniel Dirkmann
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Fuat Saner
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Marc Maegele
- Department for Trauma and Orthopedic Surgery, CologneMerheim Medical Center (CMMC), Cologne, Germany.,Institute for Research in Operative Medicine (IFOM), University Witten/Herdecke (UW/H), Campus Cologne-Merheim, Cologne, Germany
| | - Ángel Augusto Pérez Calatayud
- Terapia Intensiva Adultos, Hospital de Especialidades del Niño y la Mujer, Coordinador Grupo Mexicano para el Estudio de la Medicina Intensiva, Colegio Mexicano de Especialistas en Obstetrica Critica (COMEOC), Queretarco, Mexico
| | - Tae-Yop Kim
- Department of Anesthesiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
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Opheim EN, Apelseth TO, Stanworth SJ, Eide GE, Hervig T. Multiple electrode aggregometry and thromboelastography in thrombocytopenic patients with haematological malignancies. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2019; 17:181-190. [PMID: 30747706 PMCID: PMC6596372 DOI: 10.2450/2018.0140-18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 11/07/2018] [Indexed: 01/22/2023]
Abstract
BACKGROUND In thrombocytopenic patients better assessment of bleeding risk than that provided by platelet count alone is required. Multiplate® aggregometry and thromboelastography (TEG) could be used, but information on their role in such patients is limited. The primary aim of this study was to investigate the feasibility of Multiplate® analyses in patients with haematological malignancies. A secondary aim was to explore whether a multiple logistic regression model combining Multiplate®, TEG, clinical and laboratory variables was associated with risk of bleeding. MATERIALS AND METHODS This was an exploratory, prospective observational study of thrombocytopenic patients with haematological malignancies. Total platelet count (TPC), white blood cell count, C-reactive protein (CRP) level, temperature and bleeding status were recorded daily. TEG and Multiplate® analyses with four agonists were performed on weekdays. RESULTS Ten patients were enrolled into the study. The median number of days in a study period was 21. Bleeding was observed on 64 of 298 study days. TPC <20×109/L and <10×109/L occurred on 119 and 25 days, respectively. When TPC was <33×109/L, many samples showed no aggregation, regardless of bleeding status. Despite this, the odds of World Health Organization (WHO) grade 2 bleeding decreased significantly as aggregation increased and Multiplate® had a negative predictive value (NPV) of 96% and a positive predictive value (PPV) of 19% for significant bleeding. In the multiple logistic regression model collagen-activated Multiplate® aggregation, TEG angle, TEG reaction time and CRP significantly affected the odds of WHO grade 2 bleeding. The combined model had a NPV of 99% and a PPV of 19%. DISCUSSION Our findings suggest that the markers of platelet function and haemostasis provided by Multiplate® aggregometry and TEG may add information to support prediction of bleeding, although platelet count still remains the most accessible analysis for routine testing.
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Affiliation(s)
- Elin N. Opheim
- Department of Clinical Science, University of Bergen, Norway
- Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
| | - Torunn O. Apelseth
- Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
- Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway
| | - Simon J. Stanworth
- NHS Blood and Transplant/Oxford University Hospitals NHS Trust, “John Radcliffe” Hospital, Oxford, United Kingdom
| | - Geir E. Eide
- Department of Global Public Health and Primary Care, University of Bergen, Norway
- Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway
| | - Tor Hervig
- Department of Clinical Science, University of Bergen, Norway
- Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
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Gasecka A, Konwerski M, Pordzik J, Soplińska A, Filipiak KJ, Siller-Matula JM, Postuła M. Switching between P2Y12 antagonists – From bench to bedside. Vascul Pharmacol 2019; 115:1-12. [DOI: 10.1016/j.vph.2019.01.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2018] [Revised: 01/01/2019] [Accepted: 01/12/2019] [Indexed: 01/14/2023]
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Bolliger D, Buser A, Tanaka KA. Transfusion Requirements in Anesthesia and Intensive Care. CURRENT ANESTHESIOLOGY REPORTS 2019. [DOI: 10.1007/s40140-019-00320-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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46
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Godier A, Garrigue D, Lasne D, Fontana P, Bonhomme F, Collet JP, de Maistre E, Ickx B, Gruel Y, Mazighi M, Nguyen P, Vincentelli A, Albaladejo P, Lecompte T. Management of antiplatelet therapy for non-elective invasive procedures or bleeding complications: Proposals from the French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Thrombosis and Haemostasis (GFHT), in collaboration with the French Society for Anaesthesia and Intensive Care (SFAR). Arch Cardiovasc Dis 2019; 112:199-216. [DOI: 10.1016/j.acvd.2018.10.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Accepted: 10/09/2018] [Indexed: 12/21/2022]
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Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Jüni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferović PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO. 2018 ESC/EACTS Guidelines on myocardial revascularization. EUROINTERVENTION 2019; 14:1435-1534. [PMID: 30667361 DOI: 10.4244/eijy19m01_01] [Citation(s) in RCA: 373] [Impact Index Per Article: 62.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Franz-Josef Neumann
- Department of Cardiology & Angiology II, University Heart Center Freiburg-Bad Krozingen, Bad Krozingen, Germany
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Hassan K, Kannmacher J, Wohlmuth P, Budde U, Schmoeckel M, Geidel S. Cytosorb Adsorption During Emergency Cardiac Operations in Patients at High Risk of Bleeding. Ann Thorac Surg 2019; 108:45-51. [PMID: 30684482 DOI: 10.1016/j.athoracsur.2018.12.032] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 11/14/2018] [Accepted: 12/10/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND The purpose of this study was to analyze the results of Cytosorb (CytoSorbents, Monmouth Junction, NJ) adsorption during emergency open heart operations in patients at high risk of bleeding due to treatment with coagulation-active substances. METHODS We investigated 55 consecutive patients (median age 70 years; interquartile range: 60 to 77) who underwent emergency cardiac surgery at our institution between June 2016 and June 2018. All patients were receiving therapy with either ticagrelor (n = 43) or rivaroxaban (n = 12). In 39 of 55 cases, we routinely installed standardized Cytosorb adsorption into the heart-lung machine. Bleeding complications during and after surgery were analyzed in detail and compared with 16 patients without adsorption. RESULTS In the Cytosorb adsorption group, no rethoracotomies had to be performed. Drainage volumes in 24 hours were only 350 mL (interquartile range: 300 to 450 mL) after ticagrelor administration and 390 mL (interquartile range: 310 to 430 mL) after rivaroxaban therapy. In the majority of patients, transfusions of blood products were not needed. Compared with that group, among the group of patients without adsorption, multiple bleeding complications occurred. These were associated with longer total operation (p = 0.0042), higher drainage volumes (p = 0.0037), more transfusions of red blood cells (p = 0.0119) and platelets (p = 0.0475), a significantly higher rethoracotomy rate (p = 0.0003), significantly prolonged stay in the intensive care unit (p = 0.0141), and a longer hospital stay (p = 0.0244). CONCLUSIONS The intraoperative use of Cytosorb adsorption of ticagrelor and rivaroxaban in emergency open heart operations is reported for the first time. The data show that the strategy is safe and is an effective method to reduce bleeding complications. We recommend the use for safety in patients with ticagrelor or rivaroxaban undergoing emergency cardiac surgery.
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Affiliation(s)
- Kambiz Hassan
- Department of Cardiac Surgery, Asklepios Klinik St. Georg, Hamburg, Germany.
| | - Jochen Kannmacher
- Department of Anesthesiology and Intensive Care Medicine, Asklepios Klinik St. Georg, Hamburg, Germany
| | | | - Ulrich Budde
- Section of Hemostaseology, Medilys Laborgesellschaft, Hamburg, Germany
| | - Michael Schmoeckel
- Department of Cardiac Surgery, Asklepios Klinik St. Georg, Hamburg, Germany
| | - Stephan Geidel
- Department of Cardiac Surgery, Asklepios Klinik St. Georg, Hamburg, Germany
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Gresele P, Bury L, Mezzasoma AM, Falcinelli E. Platelet function assays in diagnosis: an update. Expert Rev Hematol 2019; 12:29-46. [DOI: 10.1080/17474086.2019.1562333] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Paolo Gresele
- Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
| | - Loredana Bury
- Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
| | - Anna Maria Mezzasoma
- Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
| | - Emanuela Falcinelli
- Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
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Kizilay M, Aslan Z, Vural U, Balci AY, Aglar AA, Yilmaz S. Is Preoperative Clopidogrel Resistance a Predictor of Bleeding and Risks in Patients Undergoing Emergency CABG Surgery? Braz J Cardiovasc Surg 2019; 33:330-338. [PMID: 30184029 PMCID: PMC6122766 DOI: 10.21470/1678-9741-2018-0005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 02/27/2018] [Indexed: 11/23/2022] Open
Abstract
Objective The aims of this study were to determine whether the detection of
preoperative clopidogrel resistance in patients undergoing cardiac surgery
while using clopidogrel could play a guiding role in the prediction of
postoperative excessive bleeding, transfusion requirements, and risks and to
provide clinically significant data. Methods Two hundred and twenty-two patients [median age: 59.4 (38-83) years;
38 females] undergoing emergency and elective coronary artery bypass
graft (CABG) surgeries in our clinic were evaluated prospectively. Patients
with multiple systemic diseases, other than diabetes mellitus (DM) and
hypertension (HT), were excluded. Patients receiving clopidogrel were also
evaluated for clopidogrel resistance and grouped according to the results of
this test. Assessments of platelet functions were performed by multiplate
impedance aggregometry method and adenosine diphosphate test. Results The use of postoperative fresh blood replacement and platelet transfusion was
higher in patients receiving clopidogrel than in those not receiving it
(P=0.001, P=0.018). DM, HT, myocardial
infarction, and the number of presentation to the emergency room were
significantly higher in patients receiving clopidogrel than in those not
receiving it (P<0.05). No significant difference was
determined between patients with and without clopidogrel resistance
regarding the amount of bleeding during and after surgery, erythrocyte
suspension and fresh-frozen plasma transfusion rates, preoperative troponin
values, ejection fraction values, and length of hospital stays
(P>0.05). Conclusion We think that resistance studies in patients receiving clopidogrel before
cardiac surgery are not efficient to predict bleeding and bleeding-related
complications in patients undergoing emergency and elective CABG
surgeries.
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Affiliation(s)
- Mehmet Kizilay
- Department of Cardiovascular Surgery, Dr. Siyami Ersek Training and Research Hospital, University of Health Sciences, İstanbul, Turkey
| | - Zeynep Aslan
- Department of Cardiovascular Surgery, Derince Training and Research Hospital, University of Health Sciences, Derince, Kocaeli, Turkey
| | - Unsal Vural
- Department of Cardiovascular Surgery, Dr. Siyami Ersek Training and Research Hospital, University of Health Sciences, İstanbul, Turkey
| | - Ahmet Yavuz Balci
- Department of Cardiovascular Surgery, Dr. Siyami Ersek Training and Research Hospital, University of Health Sciences, İstanbul, Turkey
| | - Ahmet Arif Aglar
- Department of Cardiovascular Surgery, Dr. Siyami Ersek Training and Research Hospital, University of Health Sciences, İstanbul, Turkey
| | - Sahin Yilmaz
- Department of Anesthesiology, Dr. Siyami Ersek Training and Research Hospital, University of Health Sciences, İstanbul, Turkey
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