Validation of Three Platelet Function Tests for Bleeding Risk Stratification During Dual Antiplatelet Therapy Following Coronary Interventions

Overview

Journal Clin Cardiol

Specialty Cardiology & Vascular Diseases

Date 2016 Jun 30

PMID 27355612

Citations 4

Authors

Moo Hyun Kim

Sun Young Choi

Soo Yeon An

Victor Serebruany

Affiliations

Soon will be listed here.

Abstract

Background: Although low platelet reactivity (LPR) is commonly detected during bleeding, a validated threshold for reliable DAPT bleeding risk stratification is lacking. We tested the diagnostic utility of 3 conventional platelet-activity assays to define the predictive value (if any) of LPR for bleeding.

Hypothesis: We hypothesized whether one of these tests be better than any others for predicting bleeding events.

Methods: Patients (n = 800) following drug-eluting stent implantation received DAPT. Bleeding was assessed by Bleeding Academic Research Consortium (BARC) classification and events were collected for 1 year after stenting. Platelet reactivity was measured by light transmittance aggregometry (LTA), VerifyNow, and multiple electrode aggregometry (MEA). The LPR values for bleeding event stratification were defined as ≤15% for LTA, ≤139 PRU for VerifyNow, and ≤25 U for MEA.

Results: Bleeding events occurred in 18 patients (2.3%). All tests distinguished LPR as an independent predictor for bleeding by univariate analysis ([HR]: 5.00, 95% [CI]: 1.8-14.0, P = 0.002 for LTA; HR: 21.3, 95% CI: 6.2-73.0, P < 0.0001 for VerifyNow; and HR: 7.4, 95% CI: 2.2-25.5, P = 0.002 for MEA). Multivariate analysis revealed that only VerifyNow (HR: 11.5, 95% CI: 2.9-45.7, P < 0.0004) remained an independent predictor for bleeding. However, the specificity (81.5%, 60.2%, and 81.7%, respectively) and sensitivity (61.1%, 83.3%, and 83.2%, respectively) of all 3 tests were quite low.

Conclusions: Among 3 conventional platelet-activity assays, VerifyNow was better than LTA or MEA for triaging future bleeding risks. However, all 3 tests failed to reliably predict future bleeding.

Citing Articles

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References

Fattorutto M, Pradier O, Schmartz D, Ickx B, Barvais L . Does the platelet function analyser (PFA-100) predict blood loss after cardiopulmonary bypass?. Br J Anaesth. 2003; 90(5):692-3. DOI: 10.1093/bja/aeg110. View

Malinin A, Pokov A, Spergling M, DeFranco A, Schwartz K, Schwartz D . Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12(R) rapid analyzer: the VERIfy Thrombosis risk ASsessment (VERITAS) study. Thromb Res. 2006; 119(3):277-84. DOI: 10.1016/j.thromres.2006.01.019. View

van Werkum J, van der Stelt C, Seesing T, Hackeng C, Ten Berg J . A head-to-head comparison between the VerifyNow P2Y12 assay and light transmittance aggregometry for monitoring the individual platelet response to clopidogrel in patients undergoing elective percutaneous coronary intervention. J Thromb Haemost. 2006; 4(11):2516-8. DOI: 10.1111/j.1538-7836.2006.02187.x. View

Toth O, Calatzis A, Penz S, Losonczy H, Siess W . Multiple electrode aggregometry: a new device to measure platelet aggregation in whole blood. Thromb Haemost. 2006; 96(6):781-8. View

Harrison P, Frelinger 3rd A, Furman M, Michelson A . Measuring antiplatelet drug effects in the laboratory. Thromb Res. 2007; 120(3):323-36. DOI: 10.1016/j.thromres.2006.11.012. View

Wiviott S, Braunwald E, McCabe C, Montalescot G, Ruzyllo W, Gottlieb S . Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007; 357(20):2001-15. DOI: 10.1056/NEJMoa0706482. View

Lordkipanidze M, Pharand C, Nguyen T, Schampaert E, Palisaitis D, Diodati J . Comparison of four tests to assess inhibition of platelet function by clopidogrel in stable coronary artery disease patients. Eur Heart J. 2008; 29(23):2877-85. DOI: 10.1093/eurheartj/ehn419. View

Wallentin L, Becker R, Budaj A, Cannon C, Emanuelsson H, Held C . Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361(11):1045-57. DOI: 10.1056/NEJMoa0904327. View

Breet N, van Werkum J, Bouman H, Kelder J, Ten Berg J, Hackeng C . High on-aspirin platelet reactivity as measured with aggregation-based, cyclooxygenase-1 inhibition sensitive platelet function tests is associated with the occurrence of atherothrombotic events. J Thromb Haemost. 2010; 8(10):2140-8. DOI: 10.1111/j.1538-7836.2010.04017.x. View

10.

Mehran R, Rao S, Bhatt D, Gibson C, Caixeta A, Eikelboom J . Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011; 123(23):2736-47. DOI: 10.1161/CIRCULATIONAHA.110.009449. View

11.

Steg P, Huber K, Andreotti F, Arnesen H, Atar D, Badimon L . Bleeding in acute coronary syndromes and percutaneous coronary interventions: position paper by the Working Group on Thrombosis of the European Society of Cardiology. Eur Heart J. 2011; 32(15):1854-64. DOI: 10.1093/eurheartj/ehr204. View

12.

Parodi G, Marcucci R, Valenti R, Gori A, Migliorini A, Giusti B . High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI. JAMA. 2011; 306(11):1215-23. DOI: 10.1001/jama.2011.1332. View

13.

Brar S, Berg J, Marcucci R, Price M, Valgimigli M, Kim H . Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol. 2011; 58(19):1945-54. DOI: 10.1016/j.jacc.2011.06.059. View

14.

Tricoci P, Huang Z, Held C, Moliterno D, Armstrong P, Van de Werf F . Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2011; 366(1):20-33. DOI: 10.1056/NEJMoa1109719. View

15.

Aradi D, Komocsi A, Price M, Cuisset T, Ari H, Hazarbasanov D . Efficacy and safety of intensified antiplatelet therapy on the basis of platelet reactivity testing in patients after percutaneous coronary intervention: systematic review and meta-analysis. Int J Cardiol. 2012; 167(5):2140-8. DOI: 10.1016/j.ijcard.2012.05.100. View

16.

Windecker S, Kolh P, Alfonso F, Collet J, Cremer J, Falk V . 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.... Eur Heart J. 2014; 35(37):2541-619. DOI: 10.1093/eurheartj/ehu278. View

17.

Mishra P, Thekkudan J, Sahajanandan R, Gravenor M, Lakshmanan S, Fayaz K . The role of point-of-care assessment of platelet function in predicting postoperative bleeding and transfusion requirements after coronary artery bypass grafting. Ann Card Anaesth. 2015; 18(1):45-51. PMC: 4900327. DOI: 10.4103/0971-9784.148321. View

18.

Reed G, Kumar A, Guo J, Aranki S, Shekar P, Agnihotri A . 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. Clin Cardiol. 2015; 38(2):92-8. PMC: 6711068. DOI: 10.1002/clc.22357. View

19.

Aradi D, Kirtane A, Bonello L, Gurbel P, Tantry U, Huber K . 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):1762-71. DOI: 10.1093/eurheartj/ehv104. View

20.

Debernardi Venon W, Ponzo P, Sacco M, Mengozzi G, Raso S, Valpreda A . Usefulness of thromboelastometry in predicting the risk of bleeding in cirrhotics who undergo invasive procedures. Eur J Gastroenterol Hepatol. 2015; 27(11):1313-9. DOI: 10.1097/MEG.0000000000000442. View