Adenosine diphosphate-induced platelet-fibrin clot strength: a new thrombelastographic indicator of long-term poststenting ischemic events

Abstract

Background: Poststenting ischemic events occur despite dual-antiplatelet therapy, suggesting that a "one size fits all" antithrombotic strategy has significant limitations. Ex vivo platelet function measurements may facilitate risk stratification and personalized antiplatelet therapy.

Methods: We investigated the prognostic utility of the strength of adenosine diphosphate (ADP)-induced (MA(ADP)) and thrombin-induced (MA(THROMBIN)) platelet-fibrin clots measured by thrombelastography and ADP-induced light transmittance aggregation (LTA(ADP)) in 225 serial patients after elective stenting treated with aspirin and clopidogrel. Ischemic and bleeding events were assessed over 3 years.

Results: Overall, 59 (26%) first ischemic events occurred. Patients with ischemic events had higher MA(ADP), MA(THROMBIN), and LTA(ADP) (P < .0001 for all comparisons). By receiver operating characteristic curve analysis, MA(ADP) >47 mm had the best predictive value of long-term ischemic events compared with other measurements (P < .0001), with an area under the curve = 0.84 (95% CI 0.78-0.89, P < .0001). The univariate Cox proportional hazards model identified MA(ADP) >47 mm, MA(THROMBIN) >69 mm, and LTA(ADP) >34% as significant independent predictors of first ischemic events at the 3-year time point, with hazard ratios of 10.3 (P < .0001), 3.8 (P < .0001), and 4.8 (P < .0001), respectively. Fifteen bleeding events occurred. Receiver operating characteristic curve and quartile analysis suggests MA(ADP) <or=31 as a predictive value for bleeding.

Conclusion: This study is the first demonstration of the prognostic utility of MA(ADP) in predicting long-term event occurrence after stenting. The quantitative assessment of ADP-stimulated platelet-fibrin clot strength measured by thrombelastography can serve as a future tool in investigations of personalized antiplatelet treatment designed to reduce ischemic events and bleeding.

Copyright 2010 Mosby, Inc. All rights reserved.

Figures

Figure 1

Comparison of receiver operating characteristic curves for MATHROMBIN, MAADP, and LTAADP.

Figure 2

Cumulative incidence of first ischemic events (Kaplan Meier) during 3-year follow-up period for platelet function parameters.

Figure 2

Cumulative incidence of first ischemic events (Kaplan Meier) during 3-year follow-up period for platelet function parameters.

Figure 3

Quartile distribution of ischemic events for each platelet function parameter.

Figure 3

Quartile distribution of ischemic events for each platelet function parameter.

Figure 4

Fourth quartile of MATHROMBIN showing MATHROMBIN with corresponding MAADP value for each patient. Left portion displays patients with repeat ischemic events and right portion without ischemic events. Dotted lines indicate cutpoints for ischemic and bleeding risk, and delineate a possible therapeutic range.