Impaired Fibrinolysis in Patients with Isolated Aortic Stenosis is Associated with Enhanced Oxidative Stress

Abstract

Aortic stenosis (AS) has been associated with impaired fibrinolysis and increased oxidative stress. This study aimed to investigate whether oxidative stress could alter fibrin clot properties in AS. We studied 173 non-diabetic patients, aged 51–79 years, with isolated AS. We measured plasma protein carbonylation (PC) and thiobarbituric acid reactive substances (TBARS), along with plasma clot permeability (Ks), thrombin generation, and fibrinolytic efficiency, which were evaluated by two assays: clot lysis time (CLT) and lysis time (Lys50). Coagulation factors and fibrinolytic proteins were also determined. Plasma PC showed an association with AS severity, reflected by the aortic valve area and the mean and maximum aortic gradients. Plasma PC was positively correlated with CLT, Lys50, plasminogen activator inhibitor-1 (PAI-1), and tissue factor (TF) antigens. TBARS were positively correlated with maximum aortic gradient, Lys50, and TF antigen. Regression analysis showed that PC predicted prolonged CLT (>104 min; odds ratio (OR) 6.41, 95% confidence interval (CI) 2.58–17.83, p < 0.001) and Lys50 (>565 s; OR 5.83, 95% CI 2.23–15.21, p < 0.001). Multivariate regression analysis showed that mean aortic gradient, PC, α2-antiplasmin, PAI-1, and triglycerides were predictors of prolonged CLT, while PC, α2-antiplasmin, and fibrinogen were predictors of Lys50. Our findings suggest that elevated oxidative stress contributes to impaired fibrinolysis in AS and is associated with AS severity.

Diabetes mellitus as a risk factor for aortic stenosis: from new mechanisms to clinical implications

“…Recently, it has been shown that VICs are also able to express prothrombin and active FX [11]. Moreover, growing evidence indicates that AS patients are characterized by impaired clot susceptibility to fibrinolysis [33,34], the process closely regulated by specific inhibitors, such as plasminogen activator inhibitor type-1 and thrombin-activatable fibrinolysis inhibitor [35]. In severe AS patients, the amounts of valvular fibrin positively correlated with prolonged fibrinolysis [34].…”

“…Moreover, growing evidence indicates that AS patients are characterized by impaired clot susceptibility to fibrinolysis [33,34], the process closely regulated by specific inhibitors, such as plasminogen activator inhibitor type-1 and thrombin-activatable fibrinolysis inhibitor [35]. In severe AS patients, the amounts of valvular fibrin positively correlated with prolonged fibrinolysis [34]. Although the direct relationship between vascular calcification and blood coagulation is still open for investigation, it seems that coagulation and fibrinolysis may be of major importance in the development/progression of AS.…”

Apolipoproteins and lipoprotein(a) as factors modulating fibrin clot properties in patients with severe aortic stenosis

“…We enrolled 173 consecutive patients aged 18-80 years with documented isolated AS. Patient characteristics were presented in detail previously [17]. We excluded 30 individuals with non-severe AS and 5 due to unavailable apolipoprotein levels.…”

“…Presence of fibrin deposits within aortic valve leaflets and positive association of transvalvular pressure gradients with reduced plasma fibrinolytic capacity in AS patients suggest that impaired fibrinolysis might promote faster progression of this disease [15]. Recently, we have observed that TC and triglyceride levels, but not LDL-C, have been positively associated with longer clot lysis time in AS patients [17]. In the current study, we aimed to investigate whether dyslipidemia, in particular apolipoproteins levels, can affect fibrin clot structure and fibrinolytic potential in patients with severe AS, treated with statins or not.…”

A Modified in vitro Clot Lysis Assay Predicts Outcomes in Non-traumatic Intracerebral Hemorrhage Stroke Patients—The IRONHEART Study

“…The clot lysis assay (CLA) is a global assay of the fibrinolytic system reflecting the overall plasma fibrinolytic potential (8). This test has been used to study clot formation and fibrinolysis in a wide spectrum of pathologies, including acute ischemic stroke (8)(9)(10)(11)(12)(13). Although the CLA is feasible and has a potential for clinical use to examine fibrin clot properties and fibrinolysis, the assay is not free of analytical challenges and protocols used in different laboratories may vary significantly.…”