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Thromb Haemost 2018; 118(05): 864-872
DOI: 10.1055/s-0038-1641153
Cellular Haemostasis and Platelets
Schattauer GmbH Stuttgart

Platelet Inhibition and Bleeding in Patients Undergoing Non-Cardiac Surgery—The BIANCA Observational Study

Elisabeth Mahla
1   Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria
,
Helfried Metzler
1   Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria
,
Helmar Bornemann-Cimenti
1   Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria
,
Florian Prueller
2   Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
,
Reinhard B. Raggam
2   Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
3   Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Gudrun Pregartner
4   Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
,
Andrea Berghold
4   Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
,
Anneliese Baumann
5   Department of Vascular Surgery, Medical University of Graz, Graz, Austria
,
Christian Goeroeg
1   Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria
,
Paul A. Gurbel
6   Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Falls Church, Virginia, United States
› Author Affiliations Funding Funding was provided by departmental resources only. Dr. Mahla received honoraria and consultant fees from Astra Zeneca and Boehringer Ingelheim. Dr. Gurbel reports grants from Haemonetics, NIH, Idorsia, Janssen, Merck, Amgen, Medicure, Bayer, Instrumentation Labs, personal fees from Bayer, Merck, Janssen, Medicure, World Medical, outside the submitted work.
Further Information

Publication History

29 November 2017

21 February 2018

Publication Date:
06 April 2018 (online)

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Abstract

Nearly 20% of patients will need non-cardiac surgery within 1 year of coronary stenting and their management is complicated by concomitant antiplatelet therapy. Platelet function testing may optimize the timing of surgery in these patients. In this prospective observational study, we explored the association between platelet reactivity and bleeding in patients undergoing non-cardiac surgery treated with clopidogrel with or without aspirin within 7 days before surgery. The timing of surgery was at the surgeon's discretion. Blood was drawn at induction of anaesthesia and platelet reactivity assessed by light transmittance aggregometry (LTA), vasodilator stimulated phosphoprotein (VASP) assay, Multiplate Analyzer and Innovance PFA-200. The primary endpoint was surgery-related thrombolysis in myocardial infarction (TIMI) bleeding. Among 197 patients enrolled, 72 and 12% underwent surgery within 24 and 48 hours of the last dose of clopidogrel, respectively. The median (interquartile range [IQR]) for pre-operative maximal adenosine diphosphate (ADP)-induced aggregation was 33.0% (21.0–57.5%), for VASP-platelet reactivity index was 61.5% (40.1–75.4%), for Multiplate was 22.0 (14.5–36.0) U*min and for Innovance PFA-200 was 224 (101.0–300.0) seconds. TIMI bleeding, observed in 25% of patients, decreased with increasing tertiles of platelet reactivity to ADP assessed by LTA (p = 0.031). Additionally, in a multivariable logistic regression analysis, platelet reactivity to ADP assessed by LTA was significantly associated with TIMI bleeding, as were age and urgency of surgery. These results demonstrate that in clopidogrel-treated patients, pre-operative platelet reactivity to ADP is associated with surgical bleeding risk. An objective assessment of pre-operative platelet function may optimize the timing of non-cardiac surgery in these patients.

Keywords

antiplatelet therapy - coronary artery disease - surgery - clopidogrel
 

  • References

  • 1 Windecker S, Kolh P, Alfonso F. , et al; Authors/Task Force members. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014; 35 (37) 2541-2619
    CrossrefPubMedGoogle Scholar
  • 2 Hawn MT, Graham LA, Richman JS, Itani KM, Henderson WG, Maddox TM. Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA 2013; 310 (14) 1462-1472
    CrossrefPubMedGoogle Scholar
  • 3 Albaladejo P, Marret E, Samama CM. , et al. Non-cardiac surgery in patients with coronary stents: the RECO study. Heart 2011; 97 (19) 1566-1572
    CrossrefPubMedGoogle Scholar
  • 4 Biondi-Zoccai GG, Lotrionte M, Agostoni P. , et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J 2006; 27 (22) 2667-2674
    CrossrefPubMedGoogle Scholar
  • 5 Devereaux PJ, Mrkobrada M, Sessler DI. , et al; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014; 370 (16) 1494-1503
    CrossrefPubMedGoogle Scholar
  • 6 Rossini R, Musumeci G, Capodanno D. , et al. Perioperative management of oral antiplatelet therapy and clinical outcomes in coronary stent patients undergoing surgery. Results of a multicentre registry. Thromb Haemost 2015; 113 (02) 272-282
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Siller-Matula JM, Petre A, Delle-Karth G. , et al. Impact of preoperative use of P2Y12 receptor inhibitors on clinical outcomes in cardiac and non-cardiac surgery: a systematic review and meta-analysis. Eur Heart J Acute Cardiovasc Care 2017; 6 (08) 753-770
    CrossrefPubMedGoogle Scholar
  • 8 Essebag V, Verma A, Healey JS. , et al; BRUISE CONTROL Investigators. Clinically significant pocket hematoma increases long-term risk of device infection: BRUISE CONTROL INFECTION study. J Am Coll Cardiol 2016; 67 (11) 1300-1308
    PubMedGoogle Scholar
  • 9 Kamel H, Johnston SC, Kirkham JC. , et al. Association between major perioperative hemorrhage and stroke or Q-wave myocardial infarction. Circulation 2012; 126 (02) 207-212
    CrossrefPubMedGoogle Scholar
  • 10 Kristensen SD, Knuuti J, Saraste A. , et al; Authors/Task Force Members. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: the Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur Heart J 2014; 35 (35) 2383-2431
    CrossrefPubMedGoogle Scholar
  • 11 Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003; 107 (23) 2908-2913
    CrossrefPubMedGoogle Scholar
  • 12 Price MJ, Walder JS, Baker BA. , et al. Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease: the recovery trial. J Am Coll Cardiol 2012; 59 (25) 2338-2343
    CrossrefPubMedGoogle Scholar
  • 13 Aradi D, Kirtane A, Bonello L. , et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J 2015; 36 (27) 1762-1771
    CrossrefPubMedGoogle Scholar
  • 14 Ferraris VA, Saha SP, Oestreich JH. , et al; Society of Thoracic Surgeons. 2012 update to the Society of Thoracic Surgeons guideline on use of antiplatelet drugs in patients having cardiac and noncardiac operations. Ann Thorac Surg 2012; 94 (05) 1761-1781
    CrossrefPubMedGoogle Scholar
  • 15 Hansson EC, Jidéus L, Åberg B. , et al. Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study. Eur Heart J 2016; 37 (02) 189-197
    CrossrefPubMedGoogle Scholar
  • 16 Held C, Asenblad N, Bassand JP. , et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (Platelet Inhibition and Patient Outcomes) trial. J Am Coll Cardiol 2011; 57 (06) 672-684
    CrossrefPubMedGoogle Scholar
  • 17 Mahla E, Prueller F, Farzi S. , et al. Does platelet reactivity predict bleeding in patients needing urgent coronary artery bypass grafting during dual antiplatelet therapy?. Ann Thorac Surg 2016; 102 (06) 2010-2017
    CrossrefPubMedGoogle Scholar
  • 18 Smith PK, Goodnough LT, Levy JH. , et al. Mortality benefit with prasugrel in the TRITON-TIMI 38 coronary artery bypass grafting cohort: risk-adjusted retrospective data analysis. J Am Coll Cardiol 2012; 60 (05) 388-396
    CrossrefPubMedGoogle Scholar
  • 19 Kernan WN, Ovbiagele B, Black HR. , et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45 (07) 2160-2236
    CrossrefPubMedGoogle Scholar
  • 20 Gurbel PA, Bliden KP, Butler K. , et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation 2009; 120 (25) 2577-2585
    CrossrefPubMedGoogle Scholar
  • 21 Tsantes A, Ikonomidis I, Papadakis I. , et al. Evaluation of the role of the new INNOVANCE PFA P2Y test cartridge in detection of clopidogrel resistance. Platelets 2012; 23 (06) 481-489
    CrossrefPubMedGoogle Scholar
  • 22 Kozek-Langenecker SA, Afshari A, Albaladejo P. , et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30 (06) 270-382
    CrossrefPubMedGoogle Scholar
  • 23 Fleisher LA, Fleischmann KE, Auerbach AD. , et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 130 (24) 2215-2245
    CrossrefPubMedGoogle Scholar
  • 24 Mehran R, Rao SV, Bhatt DL. , et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123 (23) 2736-2747
    CrossrefPubMedGoogle Scholar
  • 25 Team RC. A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2016
    Google Scholar
  • 26 Mahla E, Suarez TA, Bliden KP. , et al. Platelet function measurement-based strategy to reduce bleeding and waiting time in clopidogrel-treated patients undergoing coronary artery bypass graft surgery: the timing based on platelet function strategy to reduce clopidogrel-associated bleeding related to CABG (TARGET-CABG) study. Circ Cardiovasc Interv 2012; 5 (02) 261-269
    CrossrefPubMedGoogle Scholar
  • 27 Tantry US, Bonello L, Aradi D. , et al; Working Group on On-Treatment Platelet Reactivity. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol 2013; 62 (24) 2261-2273
    CrossrefPubMedGoogle Scholar
  • 28 Sibbing D, Aradi D, Jacobshagen C. , et al; TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet 2017; 390 (10104): 1747-1757
    CrossrefPubMedGoogle Scholar
  • 29 Ebrahimi R, Dyke C, Mehran R. , et al. Outcomes following pre-operative clopidogrel administration in patients with acute coronary syndromes undergoing coronary artery bypass surgery: the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. J Am Coll Cardiol 2009; 53 (21) 1965-1972
    CrossrefPubMedGoogle Scholar
  • 30 Eisenberg MJ, Richard PR, Libersan D, Filion KB. Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. Circulation 2009; 119 (12) 1634-1642
    CrossrefPubMedGoogle Scholar
  • 31 Mehran R, Baber U, Steg PG. , et al. Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. Lancet 2013; 382 (9906): 1714-1722
    CrossrefPubMedGoogle Scholar
  • 32 Mannacio V, Meier P, Antignano A, Di Tommaso L, De Amicis V, Vosa C. Individualized strategy for clopidogrel suspension in patients undergoing off-pump coronary surgery for acute coronary syndrome: a case-control study. J Thorac Cardiovasc Surg 2014; 148 (04) 1299-1306
    CrossrefPubMedGoogle Scholar
  • 33 Kwak YL, Kim JC, Choi YS, Yoo KJ, Song Y, Shim JK. Clopidogrel responsiveness regardless of the discontinuation date predicts increased blood loss and transfusion requirement after off-pump coronary artery bypass graft surgery. J Am Coll Cardiol 2010; 56 (24) 1994-2002
    CrossrefPubMedGoogle Scholar