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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:940.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Dilation-Dependent Activation of Platelets and Prothrombin in Human Thoracic Ascending Aortic Aneurysm

Ziad Touat; Laurent Lepage; Véronique Ollivier; Patrick Nataf; Ulrich Hvass; Julien Labreuche; Martine Jandrot-Perrus; Jean-Baptiste Michel; Guillaume Jondeau

From INSERM (Z.T., L.L., V.O., M.J.-P., J.-B.M., G.J.), U698, University Paris 7, Paris, France; AP-HP (L.L., P.N., U.H., J.-B.M., G.J.) Medical and Surgical Cardiology Department, Bichat Hospital, AP-HP, Paris, France, University Paris VII Denis Diderot (Z.T., L.L., P.N., J.L., J.-B.M., G.J.), and the Centre de reference Marfan et syndromes apparentes (G.J.), Bichat Hospital, AP-HP, Paris, France.

Correspondence to Pr Guillaume Jondeau, CHU Bichat, INSERM U698, 46, rue Henri Huchard, 75018 Paris, France. E-mail guillaume. jondeau{at}bch.aphp.fr

Abstract

Objectives— The purpose of this study was to investigate whether thoracic ascending aortic aneurysm (TAAA) induces platelet activation as mural thrombus participates in aortic dilatation in abdominal aortic aneurysm and TAAA are associated with rheological factors favoring coagulation activation.

Methods and Results— We studied the relation between coagulation activation and aortic diameter in Marfan patients (MFS) with various aortic diameters (n=52). We then studied patients presenting large aneurysms associated with bicuspid aortic valve (BAV) and degenerative form. Lastly, we used immunochemistry and biochemistry to investigate prothrombin/thrombin retention within the aortic wall. Microparticles, sGPV, tissue factor, and TAT complexes were increased in plasma from MFS with large aneurysms (45 mm) compared to MFS with limited aortic dilatation (<45 mm). Similar elevations were observed in all patients with large aortic aneurysms, regardless of the etiology, the site of maximal aortic dilation, associated valvulopathy, risk factors, or treatments. P-selectin and platelet-bound fibrinogen were also increased, demonstrating platelet activation in large aneurysms. Significant increase in sCD146 plasma concentration suggested alteration of endothelium.

Conclusions— Platelet activation occurs in patients with large aneurysms of the ascending aorta, is dependent on aortic dilation, and is associated with thrombin generation, part of which appears to be retained in mucoid degeneration areas.

Platelet activation and thrombin formation were evidenced in Marfan patients with ascending aortic dilatation above 45 mm (but not below 45 mm), and in patients with large aneurysm of other aetiologies. Thrombin (susceptible to activate MMPs) present within the aortic wall suggests that it could participate in aortic dilatation.

Key Words: thoracic aortic aneurysm • coagulation • Marfan • platelets