title: Point-of-care platelet function testing predicts bleeding in patients exposed to clopidogrel undergoing coronary artery bypass grafting: Verify pre-op TIMI 45--a pilot study.
abstract: BACKGROUND
  Guidelines recommend delaying coronary artery bypass grafting (CABG) for 5 days after discontinuing clopidogrel. However, platelet function may recover quicker in certain individuals.
  
  
  OBJECTIVE
  We hypothesized that perioperative measurement of platelet function with a point-of-care P2Y12 inhibitor assay could predict bleeding during CABG in patients exposed to clopidogrel.
  
  
  METHODS
  Verify Pre-Op TIMI 45 was a prospective pilot study of 39 patients on clopidogrel who subsequently underwent CABG. Preoperative on-treatment platelet reactivity was assessed with VerifyNow P2Y12 Reaction Units (PRU), with higher PRU indicating more reactive platelets. Outcomes were stratified by PRU quartiles, as well as prespecified cutpoints for the lowest quartile (PRU 173), a cutpoint for major bleeding determined by the Youden index using receiver operator curve analysis (PRU 207), and clopidogrel resistance (PRU 230).
  
  
  RESULTS
  Patients in higher PRU quartiles experienced smaller decreases in hemoglobin and hematocrit (P < 0.05 for all comparisons), less major bleeding (P = 0.021), and less major or minor bleeding (P = 0.003). Patients above the PRU 207 and 230 cutpoints had less chest-tube output (P = 0.041 and P = 0.012, respectively), less major bleeding (P = 0.005 and P = 0.036, respectively), and less major or minor bleeding (P = 0.013 and P < 0.001, respectively). By receiver operator curve analysis, preoperative PRU ≤ 207 discriminated between patients with and without major bleeding during surgery (area under the curve: 0.76, 95% confidence interval: 0.59-0.94, P = 0.018).
  
  
  CONCLUSIONS
  In this pilot study, we found that point-of-care platelet function assessment could predict bleeding in patients recently exposed to clopidogrel undergoing CABG.
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts; Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
authors: Grant W
authors: GW
authors: Reed
authors: Amit
authors: A
authors: Kumar
authors: Jianping
authors: J
authors: Guo
authors: Sary
authors: S
authors: Aranki
authors: Prem
authors: P
authors: Shekar
authors: Arvind
authors: A
authors: Agnihotri
authors: Andrew O
authors: AO
authors: Maree
authors: Dalton S
authors: DS
authors: McLean
authors: Kenneth
authors: K
authors: Rosenfield
authors: Christopher P
authors: CP
authors: Cannon
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D001026:Coronary Artery Bypass / Q000009:adverse effects; D004351:Drug Resistance; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D010979:Platelet Function Tests / Q000379:methods*; D019095:Point-of-Care Systems; D011237:Predictive Value of Tests; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects*; D012372:ROC Curve; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects*; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D014481:United States
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine
references: N Engl J Med. 2001 Aug 16;345(7):494-502
references: 11519503
references: Cancer. 1950 Jan;3(1):32-5
references: 15405679
references: Ann Thorac Surg. 2004 Nov;78(5):1536-41
references: 15511426
references: Ann Thorac Surg. 2005 Apr;79(4):1210-6
references: 15797051
references: Circulation. 2006 Apr 4;113(13):1667-74
references: 16567570
references: J Am Coll Cardiol. 2006 Jul 18;48(2):281-6
references: 16843176
references: Am J Cardiol. 2006 Sep 1;98(5):681-4
references: 16923461
references: Eur Heart J. 2008 Apr;29(8):992-1000
references: 18263931
references: Am J Cardiol. 2008 Sep 15;102(6):790-5
references: 18774008
references: J Am Coll Cardiol. 2008 Sep 30;52(14):1128-33
references: 18804738
references: J Am Coll Cardiol. 2008 Nov 18;52(21):1693-701
references: 19007688
references: Am Heart J. 2009 Mar;157(3):562.e1-9
references: 19249429
references: Circulation. 2009 May 19;119(19):2625-32
references: 19451364
references: Circulation. 2009 Dec 22;120(25):2577-85
references: 19923168
references: Lancet. 2010 Jan 23;375(9711):283-93
references: 20079528
references: Ann Thorac Surg. 2010 Feb;89(2):397-402
references: 20103308
references: Circulation. 2010 Mar 16;121(10):1188-99
references: 20194878
references: Am J Cardiol. 2011 Apr 1;107(7):995-1000
references: 21256470
references: Ann Thorac Surg. 2011 Mar;91(3):944-82
references: 21353044
references: JAMA. 2011 Mar 16;305(11):1097-105
references: 21406646
references: Eur Heart J. 2011 Dec;32(23):2970-88
references: 21609973
references: Catheter Cardiovasc Interv. 2012 Feb 15;79(3):498; author reply 499-500
references: 21805612
references: J Am Coll Cardiol. 2011 Dec 6;58(24):e123-210
references: 22070836
references: JACC Cardiovasc Interv. 2012 Mar;5(3):281-9
references: 22440493
references: Ann Thorac Surg. 2012 Nov;94(5):1761-81
references: 23098967
references: Eur J Cardiothorac Surg. 2013 Aug;44(2):e133-40
references: 23660554
references: Clin Cardiol. 2014 May;37(5):285-92
references: 24452828