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200: Determination of the platelet sensitivity to antiplatelet therapy and the role of other blood cells in it
Journal of Clinical Lipidology, Vol 2, No 5S, October 2008
(p<0.001). There was a linear correlation between anti Cp IgG antibodies and anti Cp HSP 70 IgG antibodies (p=0.05). Also we noted the correlation between HsCRP levels and Cp IgG antibodies (p=0.05). Conclusions: Molecular mimicry and autoimmunity might be the mechanisms which highlights the development and progression of atherosclerosis. HSP might be use as marker of chronic inflammation. Funding: none
200 DETERMINATION OF THE PLATELET SENSITIVITY TO ANTIPLATELET THERAPY AND THE ROLE OF OTHER BLOOD CELLS IN IT L. Buryachkovskaya, I. Uchitel, A. Sumarokov, E. Popov. Russian Cardiology Research Complex, Moscow, Russia Objective: Resistence to antiplatelet therapy and detection of the maintained high platelet activity represent a serious problem in clinical and laboratory practice. The aim of the study was to evaluate two methods of registration of platelet aggregation to ascertain the phenomen of resistence and examine the role of other blood cells in it. Methods: Platelet and red blood cell (RBC) aggregation and resistance of the latter to haemolysis were investigated in 65 patients (pts) with coronary heart disease (CHD) and 36 healthy subjects (HS) by simultaneous analysis of fluctuations of optical transmission (FOT) and turbidometric method (TM) using BIOLA Russia. ADP at doses 0.1, 0.5, 1.0 and 5.0 uM was taken as agonist. Platelet morphology and leukocyteplatelet aggregates (LPA) were assessed by electron microscopy. All patients received dual antiaplatelet therapy (75 mg aspirin, clopidogrel) for at least two month. Results: Analysis of FOT indicated that in 28.7% of pts platelets maintain high level of aggregation and in 24% pts spontaneous platelet aggregation (SPA) was registrered, which was absent in HS. SPA correlated with the number of reticulated platelets (r=0.427) and LPA (r=0.596), these were also absent in HS. TM revealed high aggregation only in 7.3% of pts, and these pts also had decreased resistance of RBC to haemolysis. Conclusions:
Platelet resistence to antiplatelet therapy depends on the presence or reticulated platelets, inflammation and RBC resistance. TM only allows detection of some of the pts resistant to antiplatelet therapy. For more correct revelation of nonresponders it is necessary to register SPA. Funding: none
201 GPIIB ILE843SER GENOTYPE INFLUENCES ANTI-PLATELET EFFECTS OF ASPIRIN M. Brambilla, K. Gertow, P. Bogani, M. Camera, F. Veglia, M.C. Nava, D. Villa, E. Tremoli, J.P. Werba. Cardiologico Monzino Center, IRCCS and Dept. of Pharmacological Sciences, U. of Milan, Milan, Italy Objective: GPIIb/IIIa protein complex plays an important role in platelet function. The GPIIIa Leu33Pro SNP is known to modulate the efficacy of aspirin (ASA). In this study we assessed the influence of the GPIIb Ile843Ser SNP on the antiplatelet effects of ASA in patients with coronary disease (CHD). Methods: Patients attending a CV prevention program (n=889, 61±8 years, 80% males, 79% CHD) were screened for the GPIIb Ile843Ser and GPIIIa Leu33Pro SNPs. Among selected subjects (males, CHD, GPIIIa Leu/Leu), 182 GPIIb Ile/Ile and 59 Ser/Ser homozygotes were identified. Out of these, 20 Ile/Ile and 18 Ser/Ser, all in therapy with ASA (100, 150, 160, or 300 mg/d), were recalled for platelet function studies. Platelets were prepared from fasting blood and analysed by aggregometry (using collagen, AA or ADP), collagen-induced TXB2 generation and PFA-100. Results: A significant ASA dose-GPIIb genotype interaction on collagen-induced aggregation (p=0.03) was observed. Indeed, a significant genotypic effect was found in patients on 100 mg ASA/d (mean [CI] Ile/Ile 55.8% [43.1-68.5], n=12; Ser/Ser 37.9% [25.4-50.4], n=11; p=0.04) but not on higher doses. There was also a trend for an ASA dose-GPIIb genotype interaction on TXB2 generation, and a significant genotypic effect in patients on 100 mg/d (mean [CI] Ile/Ile 2.19 [0.825.83]; Ser/Ser 0.51 [0.23-1.17], p=0.02) but not on higher doses. No significant differences in PFA-100 closure time were observed according to the GPIIb
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(p<0.001). There was a linear correlation between anti Cp IgG antibodies and anti Cp HSP 70 IgG antibodies (p=0.05). Also we noted the correlation between HsCRP levels and Cp IgG antibodies (p=0.05). Conclusions: Molecular mimicry and autoimmunity might be the mechanisms which highlights the development and progression of atherosclerosis. HSP might be use as marker of chronic inflammation. Funding: none
200 DETERMINATION OF THE PLATELET SENSITIVITY TO ANTIPLATELET THERAPY AND THE ROLE OF OTHER BLOOD CELLS IN IT L. Buryachkovskaya, I. Uchitel, A. Sumarokov, E. Popov. Russian Cardiology Research Complex, Moscow, Russia Objective: Resistence to antiplatelet therapy and detection of the maintained high platelet activity represent a serious problem in clinical and laboratory practice. The aim of the study was to evaluate two methods of registration of platelet aggregation to ascertain the phenomen of resistence and examine the role of other blood cells in it. Methods: Platelet and red blood cell (RBC) aggregation and resistance of the latter to haemolysis were investigated in 65 patients (pts) with coronary heart disease (CHD) and 36 healthy subjects (HS) by simultaneous analysis of fluctuations of optical transmission (FOT) and turbidometric method (TM) using BIOLA Russia. ADP at doses 0.1, 0.5, 1.0 and 5.0 uM was taken as agonist. Platelet morphology and leukocyteplatelet aggregates (LPA) were assessed by electron microscopy. All patients received dual antiaplatelet therapy (75 mg aspirin, clopidogrel) for at least two month. Results: Analysis of FOT indicated that in 28.7% of pts platelets maintain high level of aggregation and in 24% pts spontaneous platelet aggregation (SPA) was registrered, which was absent in HS. SPA correlated with the number of reticulated platelets (r=0.427) and LPA (r=0.596), these were also absent in HS. TM revealed high aggregation only in 7.3% of pts, and these pts also had decreased resistance of RBC to haemolysis. Conclusions:
Platelet resistence to antiplatelet therapy depends on the presence or reticulated platelets, inflammation and RBC resistance. TM only allows detection of some of the pts resistant to antiplatelet therapy. For more correct revelation of nonresponders it is necessary to register SPA. Funding: none
201 GPIIB ILE843SER GENOTYPE INFLUENCES ANTI-PLATELET EFFECTS OF ASPIRIN M. Brambilla, K. Gertow, P. Bogani, M. Camera, F. Veglia, M.C. Nava, D. Villa, E. Tremoli, J.P. Werba. Cardiologico Monzino Center, IRCCS and Dept. of Pharmacological Sciences, U. of Milan, Milan, Italy Objective: GPIIb/IIIa protein complex plays an important role in platelet function. The GPIIIa Leu33Pro SNP is known to modulate the efficacy of aspirin (ASA). In this study we assessed the influence of the GPIIb Ile843Ser SNP on the antiplatelet effects of ASA in patients with coronary disease (CHD). Methods: Patients attending a CV prevention program (n=889, 61±8 years, 80% males, 79% CHD) were screened for the GPIIb Ile843Ser and GPIIIa Leu33Pro SNPs. Among selected subjects (males, CHD, GPIIIa Leu/Leu), 182 GPIIb Ile/Ile and 59 Ser/Ser homozygotes were identified. Out of these, 20 Ile/Ile and 18 Ser/Ser, all in therapy with ASA (100, 150, 160, or 300 mg/d), were recalled for platelet function studies. Platelets were prepared from fasting blood and analysed by aggregometry (using collagen, AA or ADP), collagen-induced TXB2 generation and PFA-100. Results: A significant ASA dose-GPIIb genotype interaction on collagen-induced aggregation (p=0.03) was observed. Indeed, a significant genotypic effect was found in patients on 100 mg ASA/d (mean [CI] Ile/Ile 55.8% [43.1-68.5], n=12; Ser/Ser 37.9% [25.4-50.4], n=11; p=0.04) but not on higher doses. There was also a trend for an ASA dose-GPIIb genotype interaction on TXB2 generation, and a significant genotypic effect in patients on 100 mg/d (mean [CI] Ile/Ile 2.19 [0.825.83]; Ser/Ser 0.51 [0.23-1.17], p=0.02) but not on higher doses. No significant differences in PFA-100 closure time were observed according to the GPIIb
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