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

来源：

JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH | 2014年 / 7卷 / 01期

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

页码：126 / 132

页数：7

共 30 条

[11] Obesity is associated with poor response to clopidogrel and an increased susceptibility to protease activated receptor-1 mediated platelet activation [J].

Gremmel, Thomas ;

Steiner, Sabine ;

Seidinger, Daniela ;

Koppensteiner, Renate ;

Panzer, Simon ;

Kopp, Christoph W. .

TRANSLATIONAL RESEARCH, 2013, 161 (05) :421-429

[12] Clinical, genetic and confounding factors determine the dynamics of the in vitro response/non response to clopidogrel [J].

Gremmel, Thomas ;

Panzer, Simon .

THROMBOSIS AND HAEMOSTASIS, 2011, 106 (02) :211-218

[13] Thrombin generation, a function test of the haemostatic-thrombotic system [J].

Hemker, H. Coenraad ;

Al Dieri, Raed ;

De Smedt, Erik ;

Beguin, Suzette .

THROMBOSIS AND HAEMOSTASIS, 2006, 96 (05) :553-561

[14] Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation [J].

Hron, Gregor ;

Kollars, Marietta ;

Binder, Bernd R. ;

Eichinger, Sabine ;

Kyrle, Paul A. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 296 (04) :397-402

[15] Platelets in patients with acute ischemic stroke are exhausted and refractory to thrombin, due to cleavage of the seven-transmembrane thrombin receptor (PAR-I) [J].

Jurk, K ;

Jahn, UR ;

Van Aken, H ;

Schriek, C ;

Droste, DW ;

Ritter, MA ;

Ringelstein, EB ;

Kehrel, BE .

THROMBOSIS AND HAEMOSTASIS, 2004, 91 (02) :334-344

[16] Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin [J].

Kahn, ML ;

Nakanishi-Matsui, M ;

Shapiro, MJ ;

Ishihara, H ;

Coughlin, SR .

JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (06) :879-887

[17] Protease-activated receptors 1 and 4 do not stimulate Gi signaling pathways in the absence of secreted ADP and cause human platelet aggregation independently of Gi signaling [J].

Kim, S ;

Foster, C ;

Lecchi, A ;

Quinton, TM ;

Prosser, DM ;

Jin, JG ;

Cattaneo, M ;

Kunapuli, SP .

BLOOD, 2002, 99 (10) :3629-3636

[18] Protease-activated receptors in cardiovascular diseases [J].

Leger, Andrew J. ;

Covic, Lidija ;

Kuliopulos, Athan .

CIRCULATION, 2006, 114 (10) :1070-1077

[19] Rivaroxaban in Patients with a Recent Acute Coronary Syndrome [J].

Mega, Jessica L. ;

Braunwald, Eugene ;

Wiviott, Stephen D. ;

Bassand, Jean-Pierre ;

Bhatt, Deepak L. ;

Bode, Christoph ;

Burton, Paul ;

Cohen, Marc ;

Cook-Bruns, Nancy ;

Fox, Keith A. A. ;

Goto, Shinya ;

Murphy, Sabina A. ;

Plotnikov, Alexei N. ;

Schneider, David ;

Sun, Xiang ;

Verheugt, Freek W. A. ;

Gibson, C. Michael .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (01) :9-19

[20] Vorapaxar in the Secondary Prevention of Atherothrombotic Events [J].

Morrow, David A. ;

Braunwald, Eugene ;

Bonaca, Marc P. ;

Ameriso, Sebastian F. ;

Dalby, Anthony J. ;

Fish, Mary Polly ;

Fox, Keith A. A. ;

Lipka, Leslie J. ;

Liu, Xuan ;

Nicolau, Jose Carlos ;

Ophuis, A. J. Oude ;

Paolasso, Ernesto ;

Scirica, Benjamin M. ;

Spinar, Jindrich ;

Theroux, Pierre ;

Wiviott, Stephen D. ;

Strony, John ;

Murphy, Sabina A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (15) :1404-1413

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