PURPOSE: Atrial fibrillation (AF) is associated with a systemic pro-coagulant state. Coagulation involves complex interactions between endothelial and circulating cells, cell-derived microparticles and plasma proteins. The purpose of this study was to investigate the levels of leukocyte, endothelial cell and platelet activation and markers of cellular interactions among patients with AF.
METHODS: We investigated the levels of endothelial and platelet microparticles, leukocyte and platelet activation, and cell interactions in 48 patients with non-valvular AF and compared them to normal controls. We performed flow cytometry in periheral venous blood to measure (1) Platelet expression of P-selectin, (2) Platelet microparticles; (3) Platelet-leukocyte conjugates; (4) Leukocyte expression of CD11b; (5) Endothelial microparticles (EMP) positive for CD31 and negative for CD42 (EMP31), EMP positive for E-selectin (EMP62E), CD54 (EMP54), or CD51 (EMP51); (6) EMP54- and EMP62E-leukocyte conjugates.
RESULTS: Patients with AF had significantly higher levels of platelet P-selectin expression and platelet-leukocyte conjugates (p<0.05). P-selectin expression strongly correlated with platelet-leukocyte conjugate levels (r=0.77; p<0.001). Patients with AF also demonstrated increased levels of free EMP31, EMP62E and EMP51, as well as EMP62E-lymphocyte, -monocyte and -neutrophil conjugates (all p<0.05). Levels of free EMP54 were lower, whereas EMP54- neutrophil and EMP54-lymphocyte conjugates were higher among patients with AF (p<0.05). EMP62E-neutrophil conjugates correlated with leukocyte expression of activation marker CD11b (r=0.42; p=0.003) and predicted CD11b expression independently of platelet-leukocyte conjugates (r2 increase=16%; p=0.003).
CONCLUSION: Patients with AF have increased levels of platelet and leukocyte activation, circulating endothelial microparticles, and binding of endothelial microparticles and platelets to leukocytes. The formation of EMP62E-neutrophil conjugates is a major determining factor for circulating leukocyte activation in AF.
CLINICAL IMPLICATIONS: The interaction between platelets and leuckocytes and between EMP and leukocytes may represent novel markers for thromboembolism risk and potential therapeutic targets in AF.
DISCLOSURE: Julio Chirinos, None.