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Semin Thromb Hemost 2017; 43(07): 699-705
DOI: 10.1055/s-0037-1603366
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Antiplatelet Therapy, Platelet Function Testing, and Bleeding Complications in Cardiac Surgery Patients

Emma C. Hansson
1   Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
2   Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
,
Anders Jeppsson
1   Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
2   Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
› Author Affiliations
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Publication History

Publication Date:
01 June 2017 (online)

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Abstract

Antiplatelet therapy with acetylsalicylic acid, alone or in combination with a P2Y12 inhibitor, reduces thromboembolic events in patients with coronary artery disease but increases the risk for spontaneous and perioperative bleeding complications. Both the antiplatelet effect and the risk for bleeding complications are larger with the new generation P2Y12 inhibitors prasugrel and ticagrelor than with clopidogrel. In this review, the perioperative handling of acetylsalicylic acid and the P2Y12 inhibitors clopidogrel, prasugrel, and ticagrelor will be discussed. In addition, the concept of platelet function testing in the surgical setting will be covered.

Keywords

antiplatelet therapy - acetylsalicylic acid - P2Y12 inhibitors - bleeding - coronary artery bypass grafting - platelet function testing
 

  • References

  • 1 Lewis Jr HD, Davis JW, Archibald DG. , et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study. N Engl J Med 1983; 309 (07) 396-403
    CrossrefPubMedGoogle Scholar
  • 2 Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. ; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345 (07) 494-502
    CrossrefPubMedGoogle Scholar
  • 3 Wiviott SD, Braunwald E, McCabe CH. , et al; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357 (20) 2001-2015
    CrossrefPubMedGoogle Scholar
  • 4 Wallentin L, Becker RC, Budaj A. , et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361 (11) 1045-1057
    CrossrefPubMedGoogle Scholar
  • 5 Roffi M, Patrono C, Collet JP. , et al; Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37 (03) 267-315
    CrossrefPubMedGoogle Scholar
  • 6 Steg PG, James SK, Atar D. , et al; Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33 (20) 2569-2619
    CrossrefPubMedGoogle Scholar
  • 7 Windecker S, Kolh P, Alfonso F. , et al; Authors/Task Force members. 2014 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2014; 35 (37) 2541-2619
    CrossrefPubMedGoogle Scholar
  • 8 Dyke C, Aronson S, Dietrich W. , et al. Universal definition of perioperative bleeding in adult cardiac surgery. J Thorac Cardiovasc Surg 2014; 147 (05) 1458-1463.e1
    CrossrefPubMedGoogle Scholar
  • 9 Stone GW, Clayton TC, Mehran R. , et al. Impact of major bleeding and blood transfusions after cardiac surgery: analysis from the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial. Am Heart J 2012; 163 (03) 522-529
    CrossrefPubMedGoogle Scholar
  • 10 Fröjd V, Jeppsson A. Reexploration for bleeding and its association with mortality after cardiac surgery. Ann Thorac Surg 2016; 102 (01) 109-117
    CrossrefPubMedGoogle Scholar
  • 11 Dixon B, Santamaria JD, Reid D. , et al. The association of blood transfusion with mortality after cardiac surgery: cause or confounding? (CME). Transfusion 2013; 53 (01) 19-27
    CrossrefPubMedGoogle Scholar
  • 12 Ranucci M, Bozzetti G, Ditta A, Cotza M, Carboni G, Ballotta A. Surgical reexploration after cardiac operations: why a worse outcome?. Ann Thorac Surg 2008; 86 (05) 1557-1562
    CrossrefPubMedGoogle Scholar
  • 13 Vivacqua A, Koch CG, Yousuf AM. , et al. Morbidity of bleeding after cardiac surgery: is it blood transfusion, reoperation for bleeding, or both?. Ann Thorac Surg 2011; 91 (06) 1780-1790
    CrossrefPubMedGoogle Scholar
  • 14 Surgenor SD, Kramer RS, Olmstead EM. , et al; Northern New England Cardiovascular Disease Study Group. The association of perioperative red blood cell transfusions and decreased long-term survival after cardiac surgery. Anesth Analg 2009; 108 (06) 1741-1746
    CrossrefPubMedGoogle Scholar
  • 15 Murphy GJ, Pike K, Rogers CA. , et al; TITRe2 Investigators. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015; 372 (11) 997-1008
    CrossrefPubMedGoogle Scholar
  • 16 Paparella D, Brister SJ, Buchanan MR. Coagulation disorders of cardiopulmonary bypass: a review. Intensive Care Med 2004; 30 (10) 1873-1881
    CrossrefPubMedGoogle Scholar
  • 17 Patrono C. Aspirin A2. In: Michelson AD. . Platelets, ed. London, UK: Academic Press; 2013: 1099-1115
    Google Scholar
  • 18 Hastings S, Myles P, McIlroy D. Aspirin and coronary artery surgery: a systematic review and meta-analysis. Br J Anaesth 2015; 115 (03) 376-385
    CrossrefPubMedGoogle Scholar
  • 19 Myles PS, Smith JA, Forbes A. , et al; ATACAS Investigators of the ANZCA Clinical Trials Network. Stopping vs. continuing aspirin before coronary artery surgery. N Engl J Med 2016; 374 (08) 728-737
    CrossrefPubMedGoogle Scholar
  • 20 Hansson EC, Shams Hakimi C, Åström-Olsson K. , et al. Effects of ex vivo platelet supplementation on platelet aggregability in blood samples from patients treated with acetylsalicylic acid, clopidogrel, or ticagrelor. Br J Anaesth 2014; 112 (03) 570-575
    CrossrefPubMedGoogle Scholar
  • 21 Martin AC, Berndt C, Calmette L. , et al. The effectiveness of platelet supplementation for the reversal of ticagrelor-induced inhibition of platelet aggregation: An in-vitro study. Eur J Anaesthesiol 2016; 33 (05) 361-367
    CrossrefPubMedGoogle Scholar
  • 22 O'Connor SA, Amour J, Mercadier A. , et al; ACTION Study Group. Efficacy of ex vivo autologous and in vivo platelet transfusion in the reversal of P2Y12 inhibition by clopidogrel, prasugrel, and ticagrelor: the APTITUDE study. Circ Cardiovasc Interv 2015; 8 (11) e002786
    CrossrefPubMedGoogle Scholar
  • 23 Mangano DT. ; Multicenter Study of Perioperative Ischemia Research Group. Aspirin and mortality from coronary bypass surgery. N Engl J Med 2002; 347 (17) 1309-1317
    CrossrefPubMedGoogle Scholar
  • 24 Wallentin L. P2Y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J 2009; 30 (16) 1964-1977
    CrossrefPubMedGoogle Scholar
  • 25 Fox KA, Mehta SR, Peters R. , et al; Clopidogrel in Unstable angina to prevent Recurrent ischemic Events Trial. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial. Circulation 2004; 110 (10) 1202-1208
    CrossrefPubMedGoogle Scholar
  • 26 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
  • 27 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
  • 28 Becker RC, Bassand JP, Budaj A. , et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 2011; 32 (23) 2933-2944
    CrossrefPubMedGoogle Scholar
  • 29 Buchanan A, Newton P, Pehrsson S. , et al. Structural and functional characterization of a specific antidote for ticagrelor. Blood 2015; 125 (22) 3484-3490
    CrossrefPubMedGoogle Scholar
  • 30 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
  • 31 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
  • 32 Gherli R, Mariscalco G, Dalén M. , et al. Safety of preoperative use of ticagrelor with or without aspirin compared with aspirin alone in patients with acute coronary syndromes undergoing coronary artery bypass grafting. JAMA Cardiol 2016; 1 (08) 921-928
    CrossrefPubMedGoogle Scholar
  • 33 Tomšič A, Schotborgh MA, Manshanden JS, Li WW, de Mol BA. Coronary artery bypass grafting-related bleeding complications in patients treated with dual antiplatelet treatment. Eur J Cardiothorac Surg 2016; 50 (05) 849-856
    CrossrefPubMedGoogle Scholar
  • 34 Malm CJ, Hansson EC, Åkesson J. , et al. Preoperative platelet function predicts perioperative bleeding complications in ticagrelor-treated cardiac surgery patients: a prospective observational study. Br J Anaesth 2016; 117 (03) 309-315
    CrossrefPubMedGoogle Scholar
  • 35 Teng R, Carlson GF, Nylander S, Andersson TL. Effects of autologous platelet transfusion on platelet inhibition in ticagrelor-treated and clopidogrel-treated subjects. J Thromb Haemost 2016; 14 (12) 2342-2352
    CrossrefPubMedGoogle Scholar
  • 36 Angiolillo DJ, Firstenberg MS, Price MJ. , et al; BRIDGE Investigators. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA 2012; 307 (03) 265-274
    CrossrefPubMedGoogle Scholar
  • 37 Deo SV, Dunlay SM, Shah IK. , et al. Dual anti-platelet therapy after coronary artery bypass grafting: is there any benefit? A systematic review and meta-analysis. J Card Surg 2013; 28 (02) 109-116
    CrossrefPubMedGoogle Scholar
  • 38 Verma S, Goodman SG, Mehta SR. , et al. Should dual antiplatelet therapy be used in patients following coronary artery bypass surgery? A meta-analysis of randomized controlled trials. BMC Surg 2015; 15: 112
    CrossrefPubMedGoogle Scholar
  • 39 Storey RF, Bliden KP, Ecob R. , et al. Earlier recovery of platelet function after discontinuation of treatment with ticagrelor compared with clopidogrel in patients with high antiplatelet responses. J Thromb Haemost 2011; 9 (09) 1730-1737
    CrossrefPubMedGoogle Scholar
  • 40 Hansson EC, Malm CJ, Hesse C. , et al. Platelet function recovery after ticagrelor withdrawal in patients awaiting urgent coronary surgery. Eur J Cardiothorac Surg 2017; 51 (04) 633-637
    PubMedGoogle Scholar
  • 41 Born GV, Cross MJ. Effect of adenosine diphosphate on the concentration of platelets in circulating blood. Nature 1963; 197: 974-976
    CrossrefPubMedGoogle Scholar
  • 42 Corredor C, Wasowicz M, Karkouti K, Sharma V. The role of point-of-care platelet function testing in predicting postoperative bleeding following cardiac surgery: a systematic review and meta-analysis. Anaesthesia 2015; 70 (06) 715-731
    CrossrefPubMedGoogle Scholar
  • 43 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
  • 44 Ranucci M, Baryshnikova E, Soro G, Ballotta A, De Benedetti D, Conti D. ; Surgical and Clinical Outcome Research (SCORE) Group. Multiple electrode whole-blood aggregometry and bleeding in cardiac surgery patients receiving thienopyridines. Ann Thorac Surg 2011; 91 (01) 123-129
    CrossrefPubMedGoogle Scholar
  • 45 Ranucci M, Colella D, Baryshnikova E, Di Dedda U. ; Surgical and Clinical Outcome Research (SCORE) Group. Effect of preoperative P2Y12 and thrombin platelet receptor inhibition on bleeding after cardiac surgery. Br J Anaesth 2014; 113 (06) 970-976
    CrossrefPubMedGoogle Scholar
  • 46 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