von Willebrand factor-related values can predict bleeding events in patients with left ventricular assist devices

Background Recent advances in left ventricular assist device (LVAD) therapy have significantly contributed to the improved management of severe heart failure. The unignorable risk of bleeding events associated with the device therapy, however, remains to be addressed. Predictive factors for bleeding events are not fully defined. Methods Patients implanted with various types of LVADs were assessed for von Willebrand factor (VWF)-related values and platelet proteins from 2011 to 2023 at Tohoku University Hospital. We evaluated the relationship between these parameters and bleeding events at remote periods after LVAD implantation. Results The VWF large multimer index (VWF-LMI), the ratio of VWF ristocetin cofactor activity to VWF antigen level (VWF:RCo/VWF:Ag), and maximal ristocetin (1.2 µg/mL) induced platelet aggregation (RIPA) rates decreased in a pump speed- and device type-dependent manner. Major bleeding events, defined according to the Interagency Registry for Mechanically Assisted Circulatory Support criteria, occurred in 28.8% (19/66) of the patients. Kaplan–Meier methods, log-rank tests, and Cox regression analyses revealed that VWF-LMI <42.3 (p=0.0002), VWF:RCo/VWF:Ag <0.52 (p=0.0239), and maximal RIPA rate <79.2 (p=0.0012) predicted bleeding events with hazard ratios of 6.96, 2.89, and 13.4, respectively. The platelets of the patients with LVAD support exhibited significantly reduced expression levels of glycoprotein (GPVI; p=0.0334) and glycoprotein b (GPIb; p=0.0061) compared with healthy subjects. Nevertheless, patients with bleeding events did not exhibit reduced GPVI (p=0.5267) or GPIb (p=0.6674) levels compared to those without bleeding events. Conclusions VWF-related values, including VWF-LMI, VWF:RCo/VWF:Ag, and maximal RIPA rate, but not reduced platelet proteins, predicted bleeding events in patients with LVADs. Registration URL: ; Unique identifier: UMIN000027761 What Is New? What Are the Clinical Implications? ### Competing Interest Statement A part of this study was performed in collaboration with Sysmex Corporation. ### Funding Statement This research was supported by Japan Agency for Medical Research and Development grant 22ek0109475h0003 and Japan Society for the Promotion of Science KAKENHI grant 20H03760. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the Institutional Ethics Committee in Tohoku University (Certification number; 2017-1-386 and 2020-1-935) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.