Correlation Between the CYP2C19 Phenotype Status and the Results of Three Different Platelet Function Tests in Cardiovascular Disease Patients Receiving Antiplatelet Therapy: An Emphasis on Newly Introduced Platelet Function Analyzer-200 P2Y Test

BACKGROUND: An association has been reported between CYP2C19 polymorphism and the altered antiplatelet activity of clopidogrel. We investigated this association using the newly introduced platelet function analyzer (PFA)-200 (INNOVANCE PFA-200 System; Siemens Healthcare, Germany) P2Y test. METHODS: Polymorphisms of CYP2C19*2, *3, *17 and the degree of inhibition of platelet function were determined in 83 patients. Three different platelet function tests were used to evaluate the degree of platelet inhibition and to check the association with genotype. RESULTS: The post-procedure PFA-200 values of extensive metabolizers (EM) patients (285.3+/-38.8) were higher than those of intermediate metabolizers (IM) and poor metabolizers (PM) patients (227.7+/-98.3 and 133.7+/-99.2, respectively; P=0.024). Light transmittance aggregometry (LTA) and the VerifyNow system showed that the post-procedure values for EM patients were lower than those of IM and PM patients (LTA: 24.4+/-15.7, 34.1+/-17.6, and 42.2+/-16.9, respectively, P<0.001; VerifyNow: 133.2+/-60.5, 171.5+/-42.6, and 218.7+/-59.3, respectively, P<0.001). The high residual platelet reactivity (HPR) rates were significantly different among the EM, IM, and PM groups using PFA-200 (PM:IM:EM=82.4:40.6:11.8, P<0.001). CONCLUSIONS: Approximately, 59.0% of Korean patients with cardiovascular disease receiving clopidogrel had CYP2C19 loss-of-function genotypes classified as IM or PM, and the frequency was similar to the data from Asian people. The PFA-200, LTA, and VerifyNow platelet function tests revealed evidence of a significant association between the efficacy of clopidogrel and CYP2C19 genotypes.

Reconfirmation of Preanalytical Variables and Establishment of Reference Intervals of Platelet Function Analyzer-100 Closure Times in Korean Adults / 대한진단검사의학회지

BACKGROUND: Platelet Function Analyzer-100 (PFA-100, Dade-Behring, Germany) is an instrument that simulates in vivo hemostatic plug formation under high shear flow by measuring the time required to occlude aperture. We performed this study to reconfirm preanalytical variables and establish the reference intervals of Korean adults. METHODS: A total of 120 healthy individuals were enrolled. Closure times (CT) with the collagen/ epinephrine (CEPI) and the collagen/ADP (CADP) cartridges were measured. RESULTS: The reference intervals by the central 95th percentile were 82-182 sec for CEPI-CT and 62-109 sec for CADP-CT. Females had significantly longer CEPI- and CADP-CT than males (P=0.034 and 0.022, respectively). Individuals over 40 yr showed shorter CEPI- and CADP-CT compared with younger ones (P=0.002 and 0.003, respectively). CEPI- and CADP-CT values measured in the afternoon were significantly longer than corresponding ones in the morning (P<0.0001 in both conditions). Group O blood groups were related to longer CEPI- and CADP-CT compared with non-O blood groups (P=0.0003 and <0.0001, respectively). CADP-CT was weakly correlated with hematocrit (r=-0.296, P=0.001), but not CEPI-CT. CONCLUSIONS: We reconfirmed the preanalytical variables and established the reference intervals of PFA-100 CT in Korean adults. It is recommended that reference interval of this test should be verified according to age, diurnal variation, and ABO blood groups for optimal utilization.

Platelet aggregometric study on whole blood of patients with ischaemic heart disease.

Platelet aggregation is an important in vitro test to assess platelet aggregation response in IHD. The present prospective case control study was undertaken to evaluate the platelet aggregation response in IHD and the effects of aspirin therapy on it. Platelet aggregation was conducted on whole blood by the Chrono- Log whole blood Aggrometer model 540-VS. Various agonists used for platelet aggregation were collagen, ADP, Epinephrine and Thrombin. High platelet aggregation was observed in-patients of IHD as compared to controls by few or all of the reagents used. Platelet aggregation was high in both MI and angina as compared to control cases. However, cases of MI showed higher response than those of angina. Aspirin intake was associated with a decrease in platelet aggregation in patients of IHD. The platelet aggregation response was higher in PRP as compared to whole blood with similar concentration of reagents, however whole blood was equally effective as PRP in detecting hyper-responsive platelets in--patients of IHD.