Elsevier

American Heart Journal

Volume 160, Issue 2, August 2010, Pages 346-354
American Heart Journal

Clinical Investigation
Interventional Cardiology
Adenosine diphosphate–induced platelet-fibrin clot strength: A new thrombelastographic indicator of long-term poststenting ischemic events

https://doi.org/10.1016/j.ahj.2010.05.034Get rights and content

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 (MAADP) and thrombin-induced (MATHROMBIN) platelet-fibrin clots measured by thrombelastography and ADP-induced light transmittance aggregation (LTAADP) 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 MAADP, MATHROMBIN, and LTAADP (P < .0001 for all comparisons). By receiver operating characteristic curve analysis, MAADP >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 MAADP >47 mm, MATHROMBIN >69 mm, and LTAADP >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 MAADP ≤31 as a predictive value for bleeding.

Conclusion

This study is the first demonstration of the prognostic utility of MAADP 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.

Section snippets

Patients

The study was approved by the Investigational Review Board of Sinai Hospital, Baltimore, MD. Two hundred twenty-five consecutive patients undergoing nonemergent PCI were prospectively enrolled between 2004 and 2005 after providing informed consent. All patients were older than 18 years. Inclusion and exclusion criteria were described previously.5 Aspirin (325 mg) was administered to all patients on the day of the procedure and daily thereafter (81-325 mg). Sixty-six percent of the patients

Demographic and procedural characteristics

Two hundred twenty-five patients undergoing PCI were enrolled. Fifty-nine patients (26%) sustained an ischemic event within 3 years after the index PCI. Patient demographics and procedural characteristics are shown in Table I, Table II, respectively. Briefly, patients with ischemic events had a higher prevalence of hyperlipidemia, diabetes, prior percutaneous transluminal coronary angioplasty (PTCA), and calcium-channel blocker use and had lower ejection fraction as compared with patients

Discussion

Thrombus formation is a dynamic and nonlinear process involving many interacting elements, most notably the vascular wall, blood components, and blood flow. Light transmittance aggregometry has long been the methodology of choice to determine platelet reactivity. However, our study suggests that the TEG MA parameters, MAADP and MATHROMBIN, provide additional information for post-PCI risk assessment. In vivo, the strength of the clot determines whether it will resist the shear forces of the

Conclusions

Management of patients using universal fixed-dosing dual-antiplatelet therapy is associated with an unacceptable rate of recurrent events. This study was able to characterize post-PCI patients according to risk for long-term recurrence of ischemic events based on selected TEG Platelet Mapping results, specifically MAADP and MATHROMBIN. This is the first study to compare the prognostic utility of conventional aggregometry with TEG for long-term events and also the first to examine the role of MA

Sources of funding

The study was supported by Sinai Hospital of Baltimore and National Institutes of Health grant R44-HL059753.

Disclosures

Paul A. Gurbel has received research funding from Astra Zeneca, Daiichi Sankyo, Lilly, Schering-Plough, Pozen, Portola Pharmaceuticals, Bayer Healthcare, Sanofi-Aventis, Haemonetics, and NIH. Eli Cohen and Irene Navickas are former employees of Haemoscope Corporation. All other authors report no conflicts of interest.

References (14)

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