Platelet activation and induction of tissue factor in acute and chronic atrial fibrillation: Involvement of mononuclear cell-platelet interaction

Abstract

Background Atrial fibrillation (AF) is associated with a prothrombotic state. The aim of this study was to analyze platelet activation and tissue factor (TF) induction in mononuclear cells (MNCs) and granulocytes downstream of cell-cell interactions in AF patients. Methods Blood samples were obtained from patients with paroxysmal AF (n = 14) at sinus rhythm and at 15 min after induction of AF during an electrophysiological study, and from control subjects (n = 13) and patients with chronic AF (n = 14) in the outpatient clinic. The expression of CD41a, CD42b, P-selectin, and P-selectin glycoprotein ligand-1 (PSGL-1) on platelets and microparticles in platelet-rich plasma (PRP), and on MNCs and granulocytes in whole blood were examined by flow cytometry. MNC-platelet interaction was investigated ex vivo. Results The expression of CD41a and CD42b on platelets and microparticles was comparable between the control and chronic AF groups, and unchanged after AF induction. Acute induction of AF significantly increased the expression of P-selectin on platelets and microparticles, and to a similar extent, P-selectin-positive MNCs and granulocytes and P-selectin/PSGL-1-double positive MNCs. However, AF induction had no effect on platelet-MNC interactions ex vivo or TF expression on MNCs and granulocytes. Only patients with chronic AF showed platelet-MNC interaction ex vivo and TF overexpression on MNCs. Conclusions Acute-onset AF activates platelets within minutes to initiate platelet-MNC interaction. The subsequent platelet binding induced TF expression in patients with chronic AF. These findings support the efficacy of anticoagulant therapeutics in chronic AF and suggest the underlying utility of antiplatelet therapeutics in early phase of AF occurrence.