Thrombin-induced platelet-fibrin clot strength: Relation to high on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes

Young-Hoon Jeong; Kevin P. Bliden; Alan R. Shuldiner; Udaya S. Tantry; Paul A. Gurbel

doi:10.1160/TH13-08-0643

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 111(04): 713-724
DOI: 10.1160/TH13-08-0643

Platelets and Blood Cells

Schattauer GmbH

Thrombin-induced platelet-fibrin clot strength: Relation to high on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes

Authors

Young-Hoon Jeong

¹Sinai Center for Thrombosis Research, Baltimore, Maryland, USA

²Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University, Jinju, Korea
Kevin P. Bliden

¹Sinai Center for Thrombosis Research, Baltimore, Maryland, USA
Alan R. Shuldiner

³Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
Udaya S. Tantry

¹Sinai Center for Thrombosis Research, Baltimore, Maryland, USA
Paul A. Gurbel

¹Sinai Center for Thrombosis Research, Baltimore, Maryland, USA

Abstract

Summary

The relationship between thrombin-induced platelet-fibrin clot strength (MA_THROMBIN), genotype and high on-treatment platelet reactivity (HPR) is unknown. The aim of this study is to assess the influence of MA_THROMBIN measured by thrombelastography on HPR and long-term major adverse cardiovascular events (MACE) in percutaneous coronary intervention (PCI)-treated patients during aspirin and clopidogrel therapy. MA_THROMBIN, platelet aggregation, genotype, and two-year MACE were assessed in 197 PCI-treated patients. HPR was defined as 5 µM ADP-induced PR46% measured by conventional aggregometry. Both high MA_THROMBIN ( 68 mm) and CYP2C19*2 allele carriage were independently associated with ADP-induced platelet aggregation ([uni03B2] coefficient: 8.3% and 12.0%, respectively). The combination of CYP2C19*2 allele carriage and high MA_THROMBIN increased the predictive value for the risk of HPR (odds ratio: 13.89; 95% confidence interval: 3.41 to 55.56; p < 0.001). MACE occurred in 25 patients (12.7%). HPR and high MA_THROMBIN were both associated with MACE (hazard ratio: 3.09 and 2.24, respectively), and patients with both HPR and high MA_THROMBIN showed an increased risk for MACE (adjusted hazard ratio: 5.56; 95% confidence interval: 1.85 to 16.67; p = 0.002). In conclusion, this is the first study to demonstrate that high platelet-fibrin clot strength is an independent determinant of HPR in PCI-treated patients. Combining the measurements of platelet aggregation and platelet-fibrin clot strength may enhance post-PCI risk stratification and deserves further study.

Keywords

Percutaneous coronary intervention - clot strength - platelet - clopidogrel - cytochrome P450

Full Text

References

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