Extracorporeal assays of thrombosis

Platelet deposition, adhesion/aggregation, to the damaged vessel wall or atherosclerotic plaque components has shown to play a major role in hemostasis, thrombosis, and the development of atherosclerosis. Platelet-vessel wall interaction and thrombus formation is driven by blood flow rheology/hemodynamics (changes in local flow conditions), the nature of the flowing blood, and the characteristics of the triggering substrate (lesion type). An extracorporeal perfusion system (the Badimon chamber) was developed to investigate the dynamics of platelet deposition and thrombus formation on: (a) different surfaces (biological and synthetic); (b) under controlled blood flow conditions with varying degrees of stenosis mimicking various vascular conditions (patent and stenotic arteries); and (c) with varying perfusing blood treatments. In the following chapter, we thoroughly describe this experimental approach that has helped to improve the understanding of the pathophysiology of the acute coronary syndromes (Badimon et al., Arteriosclerosis 6:312-320, 1986; Badimon et al., J Lab Clin Med 110:706-718, 1987; Badimon et al., Blood 73:961-967, 1989; Mailhac et al., Circulation 90:988-996, 1994) and is a useful tool for the study and screening of new antithrombotic and platelet-inhibitory compounds (Badimon et al., Thromb Haemost 71:511-516, 1994; Vilahur et al., Circulation 110:1686-1693; Vilahur et al., Thromb Haemost 92:191-200, 2004; Vilahur et al., Cardiovasc Res 61:806-816; Vilahur et al., Thromb Haemost 98:662-669, 2007; Vilahur et al., Thromb Haemost 97:650-657, 2007; Zafar et al., J Thromb Haemost 5:1195-1200, 2007; Lev et al., J Am Coll Cardiol 43:966-971) and for the evaluation of the thrombogenicity associated to synthetic/prosthetic surfaces (Badimon et al., J Biomater Appl 5:27-48, 1990; Badimon et al., ASAIO Trans 33:621-625, 1987) and/or plasma components (cholesterol, glucose levels, etc.) (Badimon et al., Arterioscler Thromb 11:395-402, 1991; Osende et al., J Am Coll Cardiol 38:1307-1312; 2001).