Examination of acquired coagulopathy in patients with aortic stenosis

Mirac Tonyalı, Derya Baykız, Elif A. Govdeli, Abdurrahman F. Aydin, Aytac Oncul

Abstract

Background: Aortic stenosis (AS) is one of the cardiovascular diseases with an increasing prevalence and is associated with high morbidity. In this patient population, bleeding diathesis represents a significant challenge in clinical management. Although the acquired coagulopathy detected in patients with AS has yielded heterogeneous results in the literature, it has been associated with alterations in von Willebrand factor (vWF) levels and activity and is commonly defined as acquired type 2A von Willebrand disease. The aim of this study was to investigate the relationship between von Willebrand factor antigen (vWF:Ag), von Willebrand factor activity (vWF:Ac), Factor VIII (FVIII) activity, and the vWF:Ac/vWF:Ag ratio with the severity and aetiology of AS and bleeding diathesis.
Methods: The study was conducted using a prospective observational design. A total of 78 individuals were included in the study, comprising 48 patients diagnosed with AS and 30 control group participants. The demographic data, echocardiography findings, vWF:Ag, vWF:Ac, FVIII activity, and the vWF:Ac/vWF:Ag and FVIII/vWF:Ag ratios of all participants were evaluated. Patients were divided into subgroups based on the severity of AS, its aetiology, and the presence of a bleeding history, and subgroup analyses were performed.
Results: Compared with controls, patients with AS had significantly higher vWF:Ag (p = 0.031) and a lower vWF:Ac/vWF:Ag ratio (p < 0.001), whereas vWF:Ac and FVIII activity were comparable between the groups. The vWF:Ac/vWF:Ag ratio remained significantly lower in both mild and severe AS and across different aetiologies compared with controls. Among patients without bleeding, vWF:Ac and the vWF:Ac/vWF:Ag ratio were significantly lower than that in both patients with bleeding and controls. ROC analysis identified vWF:Ag > 121.7% and FVIII > 136.7% as markers associated with the primary composite endpoint, with 73.3% sensitivity and 60.3% specificity. However, in multivariable Cox regression analysis, only diabetes mellitus, higher FVIII activity, and lower haemoglobin levels remained independent predictors of the primary composite endpoint.
Conclusion: Alterations in coagulation parameters in patients with AS do not fully correspond to acquired type 2A von Willebrand disease, suggesting that bleeding diathesis is likely a multifactorial process rather than the consequence of a single mechanism. In addition, the association of vWF:Ag and FVIII activity with the primary composite endpoint suggests potential prognostic value beyond bleeding risk. However, these findings should be interpreted with caution and require confirmation in larger prospective studies before routine clinical application.