Assessment of platelet-derived thrombogenicity with the total thrombus-formation analysis system in coronary artery disease patients receiving antiplatelet therapy

J Thromb Haemost. 2016 Apr;14(4):850-9. doi: 10.1111/jth.13256. Epub 2016 Feb 19.

Abstract

Background: Accurate evaluation of thrombogenicity helps to prevent thrombosis and excessive bleeding. The total thrombus-formation analysis system (T-TAS) was developed for quantitative analysis of platelet thrombus formation by the use of microchips with thrombogenic surfaces (collagen, platelet chip [PL-chip]; collagen plus tissue factor, atherome chip [AR-chip]). We examined the utility of the T-TAS in the assessment of the efficacy of antiplatelet therapy in patients with coronary artery disease (CAD).

Methods and results: In this cross-sectional study, 372 consecutive patients admitted to the cardiovascular department were divided into three groups: patients not receiving any antiplatelet therapy (control, n = 56), patients receiving aspirin only (n = 69), and patients receiving aspirin and clopidogrel (n = 149). Blood samples were used for the T-TAS to measure the platelet thrombus-formation area under the curve (AUC) at various shear rates (1500 s(-1) [PL18 -AUC10 ] and 2000 s(-1) [PL24 -AUC10 ] for the PL-chip; 300 s(-1) [AR10 -AUC30 ] for the AR-chip). The on-clopidogrel platelet aggregation was measured by the use of P2Y12 reaction units (PRUs) with the VerifyNow system. The mean PL24 -AUC10 levels were 358 ± 111 (± standard deviation) (95% confidence interval [CI] 328.9-387.1) in the control group, 256 ± 108 (95% CI 230.5-281.5) in the aspirin group, and 113 ± 91 (95% CI 98.4-127.6) in the aspirin/clopidogrel group. In the aspirin/clopidogrel group, the PL24 -AUC10 was higher in poor metabolizers (PMs) with cytochrome P450 2C19(CYP2C19) polymorphisms (152 ± 112, 95% CI 103.4-200.6) than in the non-PM group (87 ± 74, 95% CI 73.8-100.2).

Conclusions: Our findings suggest that the PL24 -AUC10 level measured by the T-TAS is a potentially suitable index for the assessment of antiplatelet therapy in CAD patients.

Keywords: CYP2C19; antiplatelet therapy; clopidogrel; new device; percutaneous coronary intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Area Under Curve
  • Aspirin / administration & dosage
  • Blood Platelets / drug effects*
  • Clopidogrel
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / drug therapy*
  • Cross-Sectional Studies
  • Cytochrome P-450 CYP2C19 / genetics
  • Electrocardiography
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors / blood
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Polymorphism, Genetic
  • Thrombosis / blood
  • Thrombosis / drug therapy
  • Thrombosis / genetics
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Ticlopidine
  • Aspirin