Renewal of Mural Thrombus Releases Plasma Markers and Is Involved in Aortic Abdominal Aneurysm Evolution

Abstract

Human abdominal aortic aneurysm (AAA) expansion has been linked to the presence of a mural thrombus. Here we explored the mechanism of the continual luminal renewal of this thrombus and its ability to release biological markers potentially detectable in plasma. We also explored the ability of platelet inhibition to pacify the thrombus and to limit aneurysm progression in an experimental model. Blood samples and mural thrombi were collected in 20 AAA patients. In parallel, segments of sodium dodecyl sulfate-decellularized guinea pig aorta were xenografted onto the abdominal aorta of 30 rats to induce aneurysms. Fifteen rats received abciximab treatment and fifteen received irrelevant immunoglobulins. Procoagulant activity and platelet activation markers (microparticles, sP-selectin, sGPV, sCD40L) were increased threefold to fivefold in eluates from the luminal thrombus layer compared to other layers. All these markers were increased twofold to fivefold in patients' plasma compared to matched controls (P < 0.005). In the rat model, abciximab reduced both thrombus area and aneurysmal enlargement (P < 0.05). Platelet aggregation is probably responsible for the renewal of the thrombus in AAA. The luminal thrombus released markers of platelet activation that could easily be detected in plasma. Platelet inhibition limited aortic aneurysm expansion in a rat model, providing new therapeutic perspectives in the prevention of AAA enlargement.

Technetium 99m–Labeled Annexin V Scintigraphy of Platelet Activation in Vegetations of Experimental Endocarditis

“…As proposed by some authors 5 and shown in the present study, nonbacterial and bacterial thrombotic endocarditis share common pathological consequences, mainly linked to platelet procoagulant 22,32 and proteolytic activities conveyed by thrombus formation and degradation, 12 which are greatly amplified by biological activities conveyed by the bacteria themselves. 11,33 Therefore, whatever their predominant source, platelet proaggregant and procoagulant activities participate in the development of vegetations, fibrinolytic activities contribute to sepsis diffusion and embolic potential, and numerous proteases are involved in tissue destruction in relation to their ability to damage extracellular matrix and to induce cell death.…”

“…6,35 During activation, aggregation, and disintegration, platelets expose negatively charged phosphatidylserines, which are necessary for the assembly of tenase and prothrombinase complexes and thrombin generation, at the interface with circulating hemostatic blood components. 32,36 Therefore, platelet-exposed phosphatidylserine is the biological link between platelet activation and fibrin clot formation. Annexin V specifically binds with nanomolar affinity to phosphatidylserines.…”

Abdominal Aortic Aneurysm Growth Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide

“…Intraluminal thrombus is a consistent feature of AAA and usually has a laminar appearance with the mural component having been deposited first and subsequent growth of the thrombus occurring by further deposition of fibrin, platelets, and red blood cells on the inner luminal aspect. 29 The universal finding of a large change in T2* value in the periluminal region of the aneurysm is therefore likely to reflect trapping of USPIO in fresh potentially gelatinous thrombus that is typically friable and highly cellular because of its close proximity to flowing blood. 30 It was interesting to observe that this region also enhanced rapidly with gadolinium, consistent with a less selective and more generalized uptake of contrast agents in this region.…”

Thrombosis Heralding Aneurysmal Rupture: An Exploration of Potential Mechanisms in a Novel Giant Swine Aneurysm Model

“…Our findings suggest that thrombosis is accompanied by degeneration of the aneurysm wall, as found in other experimental or human aortic aneurysms. [9][10][11][12] Inflammation of the venous wall was present in unruptured and in ruptured cases. In our model, the distinguishing factor was the presence of recanalization between the thrombus and the necrosing wall.…”

“…7,8 Thrombusprecipitating rupture has also been implicated in abdominal aortic aneurysms. [9][10][11][12] However, because thrombosis followed by organization and neointimal closure of the neck is required for successful occlusion of aneurysms by endovascular embolization, 11,[13][14][15][16][17][18] there must be additional factors to account for thrombosis leading to rupture rather than occlusion. Such discriminating factors have not been explored experimentally, to our knowledge.…”