Impact of Primary Hemostasis Disorders on Late Major Bleeding Events among Anticoagulated Atrial Fibrillation Patients Treated by TAVR.

Laurent Dietrich,Anh Mai Trung,Laurence Jesel,Antonin Trimaille,Marion Kibler,Bamba Diop,Benjamin Marchandot,Olivier Morel,Adrien Carmona,Phi Dinh Truong,Kensuke Matsushita,Antje Reydel,Sébastien Hess,Annie Trinh,Patrick Ohlmann

doi:10.3390/jcm11010212

Abstract

Background: Bleeding events are among the striking complications following transcatheter aortic valve replacement (TAVR), and bleeding prediction models are crucially warranted. Several studies have highlighted that primary hemostasis disorders secondary to persistent loss of high-molecular-weight (HMW) multimers of the von Willebrand factor (vWF) and assessed by adenosine diphosphate closure time (CT-ADP) may be a strong predictor of late major/life-threatening bleeding complications (MLBCs). Pre-existing atrial fibrillation (AF) is a frequent comorbidity in TAVR patients and potentially associated with increased bleeding events after the procedure. Objectives: This study evaluated the impact of ongoing primary hemostasis disorders, as assessed by post-procedural CT-ADP > 180 s, on clinical events after TAVR among anticoagulated AF patients. Methods: An ongoing primary hemostasis disorder was defined by post-procedure CT-ADP > 180 s. Bleeding complications were assessed according to the Valve Academic Research Consortium-2 (VARC-2) criteria. The primary endpoint was the occurrence of late MLBCs at one-year follow-up. The secondary endpoint was a composite of mortality, stroke, myocardial infarction, and rehospitalization for heart failure. Results: In total, 384 TAVR patients were included in the analysis. Of these patients, 57 patients (14.8%) had a prolongated CT-ADP > 180 s. Increased MLBCs were observed in patients with CT-ADP > 180 s (35.1% versus 1.2%; p < 0.0001). Conversely, the occurrence of the composite endpoint did not differ between the groups. Multivariate analysis identified CT-ADP > 180 s (HR 28.93; 95% CI 9.74–85.95; p < 0.0001), bleeding history, paradoxical aortic stenosis (AS), and major vascular complications following TAVR as independent predictors of late MLBCs. Conclusion: Among patients with anticoagulated AF, a post-procedural CT-ADP > 180 s was identified as a strong independent predictor of late MLBCs. These findings suggest that persistent primary hemostasis disorders contribute to a higher risk of late bleeding events and should be considered for a tailored, risk-adjusted antithrombotic therapy after TAVR.

Highlights

We aimed to evaluate the impact of ongoing primary hemostasis disorders, as assessed by CT ADP > 180 s on major/life-threatening bleeding complications (MLBCs) among patients with anticoagulated
546 (48.5%) patients without a history of atrial fibrillation (AF) or new onset AF, 92 (8.2%) patients with non-anticoagulated AF, and 72 (6.4%) patients without available Closure time with adenosine diphosphate (CT-ADP) value were excluded from the analysis
In the seminal work by Généreux et al derived from a large cohort of 2401 patients enrolled in the PARTNER trial [1], late MLBCs occurred in 5.9% of patients 1 y after transcatheter aortic valve replacement (TAVR) and were associated with a four-fold increase in late mortality

Summary

Introduction

Whilst significant advances in transcatheter aortic valve replacement (TAVR) device technology have enabled a drastic reduction of periprocedural bleeds and intraoperative complications, the rates of late bleedings events after TAVR are still consistent over time and have been associated with increased mortality [1,2,3,4,5,6].Despite continuous progress in techniques and methods to minimize periprocedural complications including paravalvular leak or bleeds [7,8,9], several studies have suggested that primary hemostasis disorders secondary to persistent loss of high-molecular-weight (HMW) multimers of the von Willebrand factor (vWF) may still contribute to late bleeding complications [2,10]. vWF is a multimeric protein secreted by endothelial cells and platelets.This HMW glycoprotein mediates the adhesion of platelets to sites of vascular damage through glycoprotein Ib-vWF interactions [11].Closure time with adenosine diphosphate (CT-ADP) as assessed with the platelet function analyzer PFA-100 (Siemens Healthcare Diagnostics, Marburg, Germany) is a primary hemostasis point-of-care test used as a surrogate marker of HMW multimer defects. Despite continuous progress in techniques and methods to minimize periprocedural complications including paravalvular leak or bleeds [7,8,9], several studies have suggested that primary hemostasis disorders secondary to persistent loss of high-molecular-weight (HMW) multimers of the von Willebrand factor (vWF) may still contribute to late bleeding complications [2,10]. Persistent prolongation of CT-ADP (>180 s) after TAVR was highlighted as a strong predictor of late major/life-threatening bleeding complications (MLBCs) [10] and was predictive of increased mortality one year after the procedure [13]. Several studies have highlighted that primary hemostasis disorders secondary to persistent loss of highmolecular-weight (HMW) multimers of the von Willebrand factor (vWF) and assessed by adenosine diphosphate closure time (CT-ADP) may be a strong predictor of late major/life-threatening bleeding complications (MLBCs). Bleeding complications were assessed according to the Valve Academic Research Consortium-2 (VARC-2)

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