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

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Abstract 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: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000027761 Clinical Perspective What Is New? Comprehensive measurements of von Willebrand factor-related values, platelet proteins, and ristocetin-induced platelet aggregation rates were obtained in patients with left ventricular assist device support to evaluate their association with bleeding events. The von Willebrand factor large multimer index, ratio of von Willebrand factor ristocetin cofactor activity to von Willebrand factor antigen levels, and maximal ristocetin-induced platelet aggregation rate predicted bleeding events in patients implanted with a left ventricular assist device. What Are the Clinical Implications? Predictors of bleeding events in patients with left ventricular assist device support were identified in this study. Understanding how von Willebrand factor-related values are associated with bleeding events will facilitate the management of potential bleeding events. The ratio of von Willebrand factor ristocetin cofactor activity to von Willebrand factor antigen levels is a predictor of bleeding events that can be measured and evaluated relatively easily in many centers without special techniques or equipment, in contrast to analysis of the von Willebrand factor large multimer index.

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