Clinical and laboratory factors associated with shear-dependent platelet hyper-reactivity in patients on chronic aspirin therapy

Abstract

The Platelet Function Analyzer-100® (PFA-100) assesses agonist-induced platelet aggregation under high shear by measuring the closure time (CT) of a membrane aperture by the formation of a platelet plug [ [1] Hayward C.P. Harrison P. Cattaneo M. Ortel T.L. Rao A.K. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost. 2006; 4: 312-319 Crossref PubMed Scopus (343) Google Scholar ]. The two agonist cartridges currently available are designed to screen patients for defects in primary hemostasis: The collagen/epinephrine (CEPI) agonist cartridge detects the antiplatelet effects of aspirin and the collagen/ADP (CADP) agonist cartridge, which is not influenced by aspirin, is useful in identifying patients with acquired and congenital platelet disorders such as von Willebrand disease [ [2] Favaloro E.J. Clinical application of the PFA-100. Curr Opin Hematol. 2002; 9: 407-415 Crossref PubMed Scopus (169) Google Scholar ]. With both agonist cartridges, prolongation of the CT beyond the normal range indicates inhibited or impaired platelet function. Recent evidence also suggests that the PFA-100 has utility in identifying patients with platelet hyper-reactivity, indicated by an abnormally low CT. In patients with cardiovascular disease, a CEPI CT in the normal range despite aspirin therapy has been associated with an increased risk of recurrent cardiovascular events [ 3 Reny J.L. de Moerloose P. Dauzat M. Fontana P. Use of the PFA-100 closure time to predict cardiovascular events in aspirin-treated cardiovascular patients: a systematic review and meta-analysis. J Thromb Haemost. 2008; 6: 444-450 Crossref PubMed Scopus (119) Google Scholar , 4 Crescente M. Di Castelnuovo A. Iacoviello L. De Gaetano G. Cerletti C. PFA-100 closure time to predict cardiovascular events in aspirin-treated cardiovascular patients: a meta-analysis of 19 studies comprising 3,003 patients. Thromb Haemost. 2008; 99: 1129-1131 PubMed Google Scholar ]. A CADP CT below the normal range, indicative of enhanced global platelet reactivity, has been observed in patients with acute coronary syndromes and found to correlate both with the degree of myocardial damage and with recurrent ischemic events [ 5 Frossard M. Fuchs I. Leitner J.M. Hsieh K. Vlcek M. Losert H. et al. Platelet function predicts myocardial damage in patients with acute myocardial infarction. Circulation. 2004; 110: 1392-1397 Crossref PubMed Scopus (223) Google Scholar , 6 Harrison P. Mackie I. Mathur A. Robinson M.S. Hong Y. Erusalimsky J.D. et al. Platelet hyper-function in acute coronary syndromes. Blood Coagul Fibrinolysis. 2005; 16: 557-562 Crossref PubMed Scopus (43) Google Scholar , 7 Fuchs I. Frossard M. Spiel A. Riedmuller E. Laggner A.N. Jilma B. Platelet function in patients with acute coronary syndrome (ACS) predicts recurrent ACS. J Thromb Haemost. 2006; 4: 2547-2552 Crossref PubMed Scopus (119) Google Scholar ].