Flow cytometric measurement of platelet-leukocyte aggregates: A possible target to monitor platelet function?

被引:19
作者
Klinkhardt, U
Harder, S
机构
[1] Univ Hosp Frankfurt, Inst Clin Pharmacol, Pharmazentrum Frankfurt, D-60590 Frankfurt, Germany
[2] Univ Hosp Frankfurt, Inst Clin Pharmacol, Frankfurt, Germany
关键词
platelet-leukocyte-aggregates; flow cytometry; clopidogrel dose response; PAOD patients;
D O I
10.1055/s-2005-916673
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Increased platelet-leukocyte-aggregate (PLA) formation has been reported in acute coronary syndromes (ACS) and during cardiopulmonary bypass, and PLA formation has been acknowledged as a possible target for antiplatelet therapy in ACS and coronary interventions. It has also been suggested as a monitoring tool for risk stratification parameters. In a controlled study design as well as under clinical conditions we investigated the effect of antiplatelet agents by flow cytometric measurement of PLA formation. We were able to demonstrate considerable reduction in PLA formation under experimental and clinical clopidogrel therapy alone or in combination with aspirin. In healthy volunteers the percentage of monocyte-PLAs decreased significantly to 55 to 75% of the baseline under clopidogrel, depending on the type and concentration of the activating agent. In patients with severe peripheral artery disease, formation of monocyte-PLAs at baseline and after stimulation with thrombin receptor activating peptide (TRAP) or adenosine diphosphate (ADP) was significantly lower under combined therapy when compared with patients under aspirin alone or without antiplatelet treatment. Flow cytometric measurement of PLA formation appears to be well suited for dose response of antiplatelet agents in healthy volunteers and a valuable tool in establishing the clinical significance of circulating PLAs. It may also be a qualified method to monitor platelet function in long-term treatment with antiplatelet agents that interfere with the degranulation process. It is not suited for acute situations.
引用
收藏
页码:400 / 403
页数:4
相关论文
共 19 条
[1]   Modulation of monocyte-endothelial cell interactions by platelet microparticles [J].
Barry, OP ;
Praticò, D ;
Savani, RC ;
FitzGerald, GA .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (01) :136-144
[2]   Association of neutrophils with platelet aggregates in unstable angina - Should we alter therapy? [J].
Entman, ML ;
Ballantyne, CM .
CIRCULATION, 1996, 94 (06) :1206-1208
[3]   Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease [J].
Furman, MI ;
Benoit, SE ;
Barnard, MR ;
Valeri, CR ;
Borbone, ML ;
Becker, RC ;
Hechtman, HB ;
Michelson, AD .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1998, 31 (02) :352-358
[4]   Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction [J].
Furman, MI ;
Barnard, MR ;
Krueger, LA ;
Fox, ML ;
Shilale, EA ;
Lessard, DM ;
Marchese, P ;
Frelinger, AL ;
Goldberg, RJ ;
Michelson, AD .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2001, 38 (04) :1002-1006
[5]   Soluble CD40 ligand in acute coronary syndromes [J].
Heeschen, C ;
Dimmeler, S ;
Hamm, CW ;
van den Brand, MJ ;
Boersma, E ;
Zeiher, AM ;
Simoons, ML ;
CAPTURE Study Investigators .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (12) :1104-1111
[6]   Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease [J].
Klinkhardt, U ;
Bauersachs, R ;
Adams, J ;
Graff, J ;
Lindhoff-Last, E ;
Harder, S .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2003, 73 (03) :232-241
[7]   Clopidogrel, but not abciximab, reduces platelet leukocyte conjugates and P-selectin expression in a human ex vivo in vitro model [J].
Klinkhardt, U ;
Graff, J ;
Harder, S .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2002, 71 (03) :176-185
[8]  
May AE, 1997, EUR HEART J, V18, P1913
[9]   Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin - Studies in baboons, human coronary intervention, and human acute myocardial infarction [J].
Michelson, AD ;
Barnard, MR ;
Krueger, LA ;
Valeri, CR ;
Furman, MI .
CIRCULATION, 2001, 104 (13) :1533-1537
[10]  
NAGATA K, 1993, J IMMUNOL, V151, P3267