title: Thrombin-induced platelet-fibrin clot strength: relation to high on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes.
abstract: The relationship between thrombin-induced platelet-fibrin clot strength (MATHROMBIN), genotype and high on-treatment platelet reactivity (HPR) is unknown. The aim of this study is to assess the influence of MATHROMBIN 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. MATHROMBIN, platelet aggregation, genotype, and two-year MACE were assessed in 197 PCI-treated patients. HPR was defined as 5 µM ADP-induced PR ≥ 46% measured by conventional aggregometry. Both high MATHROMBIN(≥ 68 mm) and CYP2C19*2 allele carriage were independently associated with ADP-induced platelet aggregation (β coefficient: 8.3% and 12.0%, respectively). The combination of CYP2C19*2 allele carriage and high MATHROMBIN 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 MATHROMBIN were both associated with MACE (hazard ratio: 3.09 and 2.24, respectively), and patients with both HPR and high MATHROMBIN 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.
authors: Young-Hoon
authors: YH
authors: Jeong
authors: Kevin P
authors: KP
authors: Bliden
authors: Alan R
authors: AR
authors: Shuldiner
authors: Udaya S
authors: US
authors: Tantry
authors: Paul A. Gurbel, MD, Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, 2401 W. Belvedere Ave, Baltimore, MD 21215, USA, Tel.: +1 410 601 9600, Fax: +1 410 601 9601, E-mail: pgurbel@lifebridgehealth.org.
authors: Paul A
authors: PA
authors: Gurbel
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000188:drug therapy; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D013916:Thrombelastography; D013917:Thrombin / Q000378:metabolism*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D005337:Fibrin; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013917:Thrombin; D013988:Ticlopidine; D001241:Aspirin
keywords: Percutaneous coronary intervention; clopidogrel; clot strength; cytochrome P450; platelet