Aspirin therapy is associated with less compact fibrin networks and enhanced fibrinolysis in patients with abdominal aortic aneurysm

Bailey, Marc A.; Aggarwal, R. K.; Bridge, Katherine; Griffin, Kathryn J.; Iqbal, Farrukh; Phoenix, Fladia; Purdell-Lewis, Jeremy; Trian, Thomas; Johnson, Anne B.; Ariëns, Robert A. S.; Scott, Daniel; Ajjan, R. A.

doi:10.1111/jth.12872

Cited by 14 publications

(11 citation statements)

References 31 publications

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“…11 Indeed, inhibition of both isotypes as with aspirin not only decrease inflammation, but has also been reported to reduce the formation of fibrin networks that stabilize AAA thrombus via fibrinolysis. 12,13 Our findings support other studies which have illustrated the importance between thrombus, antiplatelet activity, and aneurysm growth. In an observational study, AAA expansion rate for patients on low-dose aspiring was significantly less in mm/year as compared to non-users.…”

Section: Discussionsupporting

confidence: 90%

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Aspirin use is associated with decreased radiologically-determined thrombus sac volume in abdominal aortic aneurysms

et al. 2018

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Introduction Formation and renewal of intramural thrombus is associated with inflammation, and contributes to the complexity of aneurysm repair. Current cardiovascular pharmacotherapy includes several inflammatory modulators such as aspirin, statins, clopidogrel, and angiotensin-converting enzyme inhibitors. The purpose of our study was to investigate the effect of these inflammatory modulators on radiographically-determined thrombus sac volume. Methods Pre-operative computed tomography scans were reviewed in patients who underwent elective infrarenal aortic aneurysm repair. Thrombus sac volume was obtained using a Hounsfield unit restricted region growth algorithm. Co-morbid conditions such as diabetes mellitus and post-operative complications were evaluated compared to thrombus sac volume. Receiver-operator characteristic curves were generated for thrombus sac volume and patients on the various cardiovascular pharmacotherapies. Results A total of 266 patients (mean age = 72.6 ± 0.6 years; mean thrombus sac volume = 58.7 (34.4-89.0) cm) were identified. Acetylsalicylic acid use was associated with a decreased thrombus sac volume ≤50 cm (AUC = 0.616, p = 0.013) whereas statins ( p = 0.26), angiotensin-converting enzyme inhibitors ( p = 0.46), and clopidogrel ( p = 0.62) had no correlation to thrombus sac volume. Diabetes mellitus was not associated with thrombus sac volume ( p = 0.31). Conclusion Acetylsalicylic acid use is associated with decreased thrombus sac volume in a patient population undergoing elective abdominal aortic aneurysms repair. The effect of acetylsalicylic acid over other anti-inflammatory and anti-platelet agents is possibly attributable to its distinct mechanism of cyclooxygenase-1 inhibition. Diabetes mellitus, a known correlate of aneurysm incidence, is not associated with thrombus burden. The potential to alter aneurysm thrombus volume, thereby affecting aneurysm morphology, may yield a more favorable aneurysmal repair.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Aspirin use is associated with decreased radiologically-determined thrombus sac volume in abdominal aortic aneurysms

et al. 2018

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“…564 Moreover, the use of aspirin or P2Y12 inhibitors has been associated with a reduced rate of death among patients with AAA. 428 In a study of the potential mechanisms underlying the benefits of aspirin therapy, Bailey and colleagues 565 showed that aspirin therapy in patients was associated with enhanced fibrinolysis and less compact fibrin networks. In a metaanalysis of a few trials, the use of aspirin was associated with lower expansion rates and less need for later surgical repair in patients with larger AAA ( > 35 mm).…”

Section: Platelet Inhibitorsmentioning

confidence: 99%

Molecular pathogenesis of genetic and sporadic aortic aneurysms and dissections

Shen

LeMaire

2017

Current Problems in Surgery

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the descending thoracic aorta; and 10% involve the thoracoabdominal aorta. 3 Thoracic aortic dissection (TAD) is estimated to occur at a rate of 3 cases per 100,000 individuals per year. [4][5][6][7] The prevalence of infrarenal abdominal aortic aneurysms (AAA) is estimated to be between 2.2% and 5% in men older than 55 years of age. 3,8,9 AAD are highly lethal conditions that often necessitate surgical treatment. Operative treatment generally involves replacing the diseased segment with a prosthetic graft by using an open surgical, endovascular, or hybrid approach. Despite significant improvements in the surgical treatment of AAD, they cause more than 10,000 deaths in the United States each year. Although AAD are a leading cause of death in people 55 years of age or older, 10,11 AAD are also a significant cause of morbidity and mortality in children and young adults. 12 Recent reports indicate that the mortality rate of acute TAAD is 16%. 2 AAD are particularly lethal when they involve the ascending aorta. The current incidence of in-hospital death is 24% for patients presenting with acute ascending aortic dissection (ie, DeBakey type I or II dissection and Stanford type A dissection). 13 Normal structure and function of the aorta Histology of the aortic wallThe aortic wall is composed of 3 layers (Fig 3A): a thin inner layer (the intima), a thick medial layer (the media), and a thin outer layer (the tunica adventitia). The intima is lined with a monolayer of endothelial cells that not only separates the aortic wall from circulating blood but also regulates vascular functions. 30

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“…Several mechanisms appear to be involved including reducing tissue factor production by platelets and immune cells with the acetylation of thrombin and prothrombin also playing an important role [ 172 ] (reviewed by Undas et al [ 173 ]). In addition, high dose aspirin (greater than 300 mg/day) appears to increase the efficiency of fibrinolysis [ 174 , 175 ]. Ingestion of aspirin also leads to the upregulation of lipoxin A4 in humans and animals [ [176] , [177] , [178] , [179] ] via a mechanism involving the irreversible acetylation of COX2 [ 180 , 181 ] (reviewed by Romano et al [ 182 ]).…”

Section: Suggestions For Therapeutic Interventionmentioning

confidence: 99%

Preventing the development of severe COVID-19 by modifying immunothrombosis

Morris

Bortolasci

Puri³

et al. 2021

Life Sciences

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Background COVID-19-associated acute respiratory distress syndrome (ARDS) is associated with significant morbidity and high levels of mortality. This paper describes the processes involved in the pathophysiology of COVID-19 from the initial infection and subsequent destruction of type II alveolar epithelial cells by SARS-CoV-2 and culminating in the development of ARDS. Main body The activation of alveolar cells and alveolar macrophages leads to the release of large quantities of proinflammatory cytokines and chemokines and their translocation into the pulmonary vasculature. The presence of these inflammatory mediators in the vascular compartment leads to the activation of vascular endothelial cells platelets and neutrophils and the subsequent formation of platelet neutrophil complexes. These complexes in concert with activated endothelial cells interact to create a state of immunothrombosis. The consequence of immunothrombosis include hypercoagulation, accelerating inflammation, fibrin deposition, migration of NET producing neutrophils into the alveolar apace, activation of the NLRP3 inflammazome, increased alveolar macrophage destruction and massive tissue damage by pyroptosis and necroptosis Therapeutic combinations aimed at ameliorating immunothrombosis and preventing the development of severe COVID19 are discussed in detail.

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Aspirin therapy is associated with less compact fibrin networks and enhanced fibrinolysis in patients with abdominal aortic aneurysm

Cited by 14 publications

References 31 publications

Aspirin use is associated with decreased radiologically-determined thrombus sac volume in abdominal aortic aneurysms

Aspirin use is associated with decreased radiologically-determined thrombus sac volume in abdominal aortic aneurysms

Molecular pathogenesis of genetic and sporadic aortic aneurysms and dissections

Preventing the development of severe COVID-19 by modifying immunothrombosis

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