Antithrombotic therapy in abdominal aortic aneurysm: beneficial or detrimental?

Abstract

Abdominal aortic aneurysm (AAA) is a degenerative vascular pathology resulting in significant morbidity and mortality in older adults due to rupture and sudden death. Despite 150,000 new cases and nearly 15,000 deaths annually, the only approved treatment for AAA is surgical or endovascular intervention when the risk for aortic rupture is increased. The goal of the scientific community is to develop novel pharmaceutical treatment strategies to reduce the need for surgical intervention. As most clinically-relevant AAAs contain a complex structure of fibrin, inflammatory cells, platelets, and red blood cells in the aneurysmal sac known as an intraluminal thrombus (ILT), antithrombotic therapies have emerged as potential pharmaceutical agents for the treatment of AAA progression. However, the efficacy of these treatments has not been shown, and the effects of shrinking the ILT may be as detrimental as they are beneficial. This review discusses the prospect of anticoagulant and antiplatelet (termed collectively as antithrombotic) therapies in AAA. Herein, we discuss the role of the coagulation cascade and platelet activation in human and animal models of AAA, the composition of ILT in AAA, a possible role of the ILT in aneurysm stabilization, and the implications of antithrombotic drugs in AAA treatment.

Noninvasive imaging of vascular permeability to predict the risk of rupture in abdominal aortic aneurysms using an albumin-binding probe

“…*Nonenhancing intraluminal thrombus area; ROC: Receiver operating characteristic; TOF-MRA: time-of-flight magnetic resonance angiography; +: vascular lumen in arterial TOF. www.nature.com/scientificreports www.nature.com/scientificreports/ and maintaining its stability 17,18 , another concept focus on the intraluminal thrombus as a biologically active entity. According to this concept, the secreted molecules contribute to an inflammatory response and proteolytic injury of the arterial wall, culminating in aortic thinning and expansion 19 .…”

Platelets Are at the Nexus of Vascular Diseases

“…The adventitia neovascularization induces inflammatory cells (lymphocytes, neutrophils and macrophages) infiltration in the aortic vessel wall, maintaining a continuous level of inflammation. This process contributes to the intra-luminal thrombus (ILT) formation (194), which involves platelets and coagulation activation. Overall, the ILT thromboinflammatory status contributes to the outward remodeling and eventually to the disruption of wall integrity (195, 196).…”

“…In order to understand the mechanisms in the early steps, different animal models have been used, including mice and rats. The role of platelets and coagulation in ILT formation during AAA has been recently reviewed elsewhere (194). To study the role of platelets in AAA, two major models were used in mice and rats.…”

Abdominal Aortic Aneurysm: Roles of Inflammatory Cells

“…In the meanwhile, due to destruction of ECM structure and loss of resistance of tunica media, soluble blood components like inflammatory cells are transferred and accumulated in tunica media through the highly vascularized adventitia, resulting in infiltration of inflammatory cells into the vascular media. These processes together with platelet accumulation and coagulation system activation promote intraluminal thrombosis, and subsequently causes aortic dilation and increased vulnerability to AAA rupture ( 12 ). Intraluminal thrombosis is capable to create an inflammatory microenvironment containing neutrophils, cytokines, proteases, and reactive oxygen species, and thereby decrease aortic wall strength.…”