Association of Thrombin Generation Potential with Platelet PAR-1 Regulation and P-Selectin Expression in Patients on Dual Antiplatelet Therapy

被引:5
作者
Eslam, Roza Badr [1 ]
Posch, Florian [2 ]
Lang, Irene M. [1 ]
Gremmel, Thomas [3 ]
Eichelberger, Beate [4 ]
Ay, Cihan [2 ]
Panzer, Simon [4 ]
机构
[1] Med Univ Vienna, Dept Med 2, Div Cardiol, A-1090 Vienna, Austria
[2] Med Univ Vienna, Dept Med 1, Clin Div Haematol & Haemostaseol, A-1090 Vienna, Austria
[3] Med Univ Vienna, Dept Med 2, Div Angiol, A-1090 Vienna, Austria
[4] Med Univ Vienna, Dept Blood Grp Serol & Transfus Med, A-1090 Vienna, Austria
关键词
Thrombin generation; Thienopyridine treatment; PAR-1; regulation; P-selectin; PROTEASE-ACTIVATED RECEPTOR-1; ACUTE CORONARY SYNDROMES; VENOUS THROMBOEMBOLISM; METABOLIC SYNDROME; GLYCOPROTEIN-IB; ISCHEMIC-STROKE; CLOPIDOGREL; INHIBITION; OBESITY; VORAPAXAR;
D O I
10.1007/s12265-013-9531-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We studied the association of thrombin generation potential with platelet protease activated receptor (PAR)-1 regulation and platelet activation in 52 stable coronary artery disease patients on continuous therapy with aspirin and clopidogrel (n = 42) or prasugrel (n = 10). Compared to controls, peak thrombin generation potential was elevated in only 11 patients (p > 0.05), while F1.2 was elevated in 26 patients (p < 0.0001). PAR-1 and thrombin inducible P-selectin expression were significantly elevated in patients compared to controls (p < 0.001). There were no significant correlations between levels of thrombin generation potential or F1.2 and PAR-1 regulation. However, there was a significant inverse correlation between levels of peak thrombin generation potential and in vitro thrombin-inducible expression of P-selectin (p = 0.002), suggesting in vivo depletion of platelet alpha granules due to ongoing platelet activation.
引用
收藏
页码:126 / 132
页数:7
相关论文
共 30 条
[1]   Glycoprotein Ib-mediated platelet activation - A signalling pathway triggered by thrombin [J].
Adam, F ;
Guillin, MC ;
Jandrot-Perrus, M .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2003, 270 (14) :2959-2970
[2]   Prediction of Venous Thromboembolism in Patients With Cancer by Measuring Thrombin Generation: Results From the Vienna Cancer and Thrombosis Study [J].
Ay, Cihan ;
Dunkler, Daniela ;
Simanek, Ralph ;
Thaler, Johannes ;
Koder, Silvia ;
Marosi, Christine ;
Zielinski, Christoph ;
Pabinger, Ingrid .
JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (15) :2099-2103
[3]   Thrombin generation in morbid obesity: significant reduction after weight loss [J].
Ay, L. ;
Kopp, H. -P. ;
Brix, J. -M. ;
Ay, C. ;
Quehenberger, P. ;
Schernthaner, G. -H. ;
Pabinger, I. ;
Schernthaner, G. .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2010, 8 (04) :759-765
[4]   The measurement and application of thrombin generation [J].
Baglin, T .
BRITISH JOURNAL OF HAEMATOLOGY, 2005, 130 (05) :653-661
[5]   Resistance to antiplatelet drugs: molecular mechanisms and laboratory detection [J].
Cattaneo, M. .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2007, 5 :230-237
[6]   The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity [J].
Dörmann, D ;
Clemetson, KJ ;
Kehrel, BE .
BLOOD, 2000, 96 (07) :2469-2478
[7]   Clopidogrel does not suppress blood markers of coagulation activation in aspirin-treated patients with non-ST-elevation acute coronary syndromes [J].
Eikelboom, JW ;
Weitz, JI ;
Budaj, A ;
Zhao, F ;
Copland, I ;
Maciejewski, P ;
Johnston, M ;
Yusuf, S .
EUROPEAN HEART JOURNAL, 2002, 23 (22) :1771-1779
[8]   Human platelet protease-activated receptor-1 responsiveness to thrombin related to P2Y12 inhibition [J].
Eslam, Roza Badr ;
Lang, Irene M. ;
Kaider, Alexandra ;
Panzer, Simon .
TRANSLATIONAL RESEARCH, 2013, 161 (05) :414-420
[9]   Regulation of PAR-1 in patients undergoing percutaneous coronary intervention: effects of unfractionated heparin and bivalirudin [J].
Eslam, Roza Badr ;
Reiter, Nina ;
Kaider, Alexandra ;
Eichinger, Sabine ;
Lang, Irene M. ;
Panzer, Simon .
EUROPEAN HEART JOURNAL, 2009, 30 (15) :1831-1836
[10]  
Gremmel T., 2008, EUR J CLIN INVEST, V43, P689