THROMBOEMBOLIC COMPLICATIONS OF ABDOMINAL AORTIC ANEURYSM: PATHOGENETIC MECHANISMS AND LESSONS FROM PRINZMETALS ANGINA



S. David Gertz, M.D., Ph.D., The Hebrew University, Jerusalem, Israel

Intraluminal (mural) thrombus (ILT) is reportedly found in up to 70-80% of patients with abdominal aortic aneurysm (AAA). Statistically, critical occlusion of the aorta and distal thromboembolic events are relatively rare components of the overall threat posed by ILT in AAA. A much more frequent consequence of ILT is its profound local effect on aneurysm progression and rupture. Recent studies have shown that the high concentration of activated neutrophils in the ILT of AAA are associated with high levels of proteolytic enzymes including cathepsins, elastases, collagen proteases, and other metalloproteinases. Marked increases in various reactive oxygen species have also been found at these sites with increased inflammatory cell infiltrates from the adventitia, reduced numbers of viable smooth muscle cells, and progressive degradation and thinning of aortic wall leading to eventual rupture. It was previously thought that ILT of AAA occurs primarily because of pooling or stagnation of blood in areas of aortic out-pouching facilitated by wall damage. In this talk we present the evidence from our laboratory, as well as others, suggesting that ILT can occur at sites of ballooning, curvatures, or branch points even, and perhaps particularly, where the overall rate of flow is not reduced. We show how altered hemodynamic shear forces at such sites, compounded by any of a variety of local or systemic factors, can result in damage to the aortic wall ranging from minimal desquamation of the endothelial lining to marked trans-medial defects followed by platelet deposition and thrombus formation at these sites. We will point out the unexpected similarities to the pathogenesis and consequences of Prinzmetal’s (vasospastic) angina as well as implications of these findings for treatment for prevention of aneurysmal progression and rupture.