High rate of ticagrelor and prasugrel- non-responder in patients in therapeutic hypothermia after cardiac arrest. K. Ibrahim, M.C. Christoph, S. Schmeinck, ...
Thrombosis and antithrombotic therapy
complications was higher in non obese than in obese patients: 10% (119/1206) vs. 6% (20/336), OR [95% CI]: 1.7 [1.1-2.8], p=0.03. Conclusion: BMI has a strong impact on response to thienopyridine with a linear relationship between BMI and on treatment platelet reactivity. We also reported in obese patients higher incidence of HTPR, lower incidence of LTPR and lower incidence of bleeding complications.
P4879 | BENCH Mean platelet volume and platelet count in acute coronary syndrome patients: role of a genetic variants on chr7q22.3 and chr3p13-p21 B. Giusti 1 , R. Marcucci 1 , C. Saracini 1 , A.M. Gori 1 , R. Valenti 2 , G. Parodi 2 , G.F. Gensini 1 , D. Antoniucci 2 , R. Abbate 1 . 1 University of Florence, Thrombosis Centre, Dpt of Medical and Surgical Critical Care, Florence, Italy; 2 Careggi University Hospital, Department of Cardiology, Florence, Italy Several studies have demonstrated an association between elevated mean platelet volume (MPV), low platelet count (Plt) and coronary artery disease (CAD). Animal and twin studies demonstrated that MPV and Plt are genetically determined. Genome-wide association studies on healthy subjects identify several loci associated with MPV and Plt phenotypes, among which rs342293 polymorphism on chr7q22.3 and rs12485738 polymorphism on chr3p13-p21. No data are available on the possible association between these polymorphisms and platelet phenotypes in patients with CAD. Aim of our study was to evaluate the association of these two polymorphisms with MPV and Plt in a cohort of acute coronary syndrome patients undergoing PCI with stent implantation (RECLOSE 2 ACS study). We genotyped 1433 ACS patients by TaqMan technology and specific assay. The two polymorphisms were in Hardy-Weinberg equilibrium. The genotype distribution and minor allele frequencies were consistent with those reported in literature and dbSNP: rs342293 CC 36.1%, CG 46.4%, GG 17.5%, MAF G=0.407; rs12485738 GG 35.7, GA 47.0%, AA 17.3% MAF A=0.408. Concerning MPV and rs342293 polymorphism, in GG homozygous patients MPV values were significantly higher than in heterozygous and wild-type homozygous patients [9.3 (6.0-19.3) fL vs 8.8 (6.2-37.1) fL, p=0.001]. Concerning Plt and rs342293, patients carriers of the G allele showed lower Plt than CC wild-type homozygous patients [219 (80-805) plateletsx103/microL vs 226 (77-1360) plateletsx103/microL, p=0.038]. No association between MPV, Plt and rs12485738 polymorphism was observed. At the linear regression analysis adjusted for age, sex, and Plt rs342293 polymorphism was a significant and independent predictor of MPV [Beta=0.230, standard error=0.113, p=0.042]. In conclusion, our results confirm and extend in ACS patients the role of rs342293 polymorphism on MPV phenotype.
P4880 | BEDSIDE Obesity is associated with poor response to clopidogrel and an increased susceptibility to protease activated receptor-1 mediated platelet activation T. Gremmel, S. Steiner, D. Seidinger, R. Koppensteiner, S. Panzer, C.W. Kopp. Medical University of Vienna, Vienna, Austria Purpose: Obesity is associated with a prothrombotic state resulting from increased thrombin generation, platelet hyper-reactivity and decreased fibrinolysis. Data on the influence of obesity on clopidogrel-mediated platelet inhibition are conflicting and limited to platelet function tests. Moreover, there are no data on thrombin-inducible platelet activation in obese patients. We therefore investigated response to clopidogrel therapy and Protease Activated Receptor (PAR)-1 mediated platelet activation in obese and non-obese patients undergoing angioplasty and stenting for cardiovascular disease. Methods: The Vasodilator-Stimulated Phosphoprotein (VASP) phosphorylation assay, Multiple Electrode Aggregometry (MEA) with adenosine diphosphate (ADP), and surface expressions of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to ADP and Thrombin Receptor Activating Peptide (TRAP)-6 were assessed in 71 obese and 245 non-obese patients. Results: Obesity was independently associated with higher residual platelet reactivity by the VASP assay and MEA ADP, and with platelet surface expressions of P-selectin and activated GPIIb/IIIa in response to ADP (all p≤0.04). Further, high on-treatment residual ADP-inducible platelet reactivity by the VASP assay and by MEA ADP were significantly more frequent in obese patients compared to non-obese patients (both p≤0.04). Finally, PAR-1 mediated platelet activation as assessed by expression of P-selectin and activated GPIIb/IIIa in response to TRAP-6 was significantly more pronounced in obese patients than in patients without obesity (both p≤0.02). Conclusion: Obese patients undergoing angioplasty and stenting exhibit a diminished response to clopidogrel and an increased susceptibility to TRAP-6 inducible platelet activation.
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P4881 | BEDSIDE Modulation of complement C3 levels and fibrin clot structure: the role of aspirin dose K.A. Hess 1 , Z. Kurdee 2 , N. Oxley 2 , F. Phoenix 2 , N. Marx 1 , R. King 2 , R.F. Storey 3 , P.J. Grant 2 , R.A. Ajjan 2 . 1 RWTH University Hospital Aachen, Internal Medicine I, Cardiology, Pulmonology & Vascular Medicine, Aachen, Germany; 2 University of Leeds, Leeds, United Kingdom; 3 University of Sheffield, Department of Cardiovascular Science, Sheffield, United Kingdom Purpose: Fibrin clot structure predicts predisposition to cardiovascular events and complement C3 plasma levels are associated with vascular disease, which may be partly related to the effect of C3 on fibrinolysis. Although aspirin has been shown to directly modulate the fibrin network and facilitate fibrinolysis, in vivo studies are scarce, the optimal dose is unclear and the effect on C3 plasma levels is unknown. Therefore, this study assessed the role of aspirin dose in modulating fibrin clot structure/lysis and complement C3 plasma levels. Methods: A double blind cross-over study including 45 healthy individuals (mean age 24.4[18-49]) with no past medical history was undertaken. Aspirin was given at 75 or 300 mg/day for 2 weeks, followed by a 3 weeks wash-out period and another two weeks of aspirin therapy (300 or 75 mg/day). Blood was taken on 4 occasions with fibrin clot structure/lysis assessed using turbidimetric assays, recording: maximum absorbance, a measure of clot density, clot lysis time, analysing fibrinolysis potential, and lysis area, a complex measure of clot density and susceptibility to lysis. Plasma levels of complement C3 were analyzed by ELISA. Results: Clot lysis time and lysis area correlated with C3 plasma levels (r=0.36 and r=0.32 respectively; p
