Abstract Number: PB1559
Meeting: ISTH 2020 Congress
Background: Bleeding is the most frequent adverse event in patients with continuous flow mechanical circulatory support (CF-MCS) and has been linked to the occurrence of acquired von Willebrand syndrome (aVWS). MCS devices cause an increased shear-induced proteolysis of von Willebrand factor (VWF) by ADAMTS13, leading to aVWS. We previously showed that blocking human ADAMTS13 is an efficient way to prevent aVWS in in vitro CF-MCS experiments. The efficacy of this therapy in a preclinical animal model remains to be determined.
Aims: To investigate if blocking ADAMTS13 using an in-house inhibitory anti-ADAMTS13 monoclonal antibody (mAb) 17C7 rescues the loss of high molecular weight (HMW) VWF multimers in a preclinical CF-MCS calf model.
Methods: Bovine blood was circulated through an in vitro Impella 5.5 heart-pump with mAb 17C7 or PBS and VWF multimers were analyzed. Next, Impella 5.5 pumps were implanted in calves and VWF multimers were determined. One dose of mAb 17C7 (600 µg/kg) was injected eight days after Impella implantation and plasma was reanalyzed for VWF multimers.
Results: Blocking bovine ADAMTS13 using mAb 17C7 could prevent the loss of HMW VWF multimers in the in vitro Impella system, showing that the calf is a good preclinical animal model to study the in vivo effect of this novel therapy. Impella implantation led to a decrease in HMW VWF multimers (Figure A and B), similar to what is seen in patients with an Impella device. Hence, this preclinical animal model represents the VWF laboratory features of MCS-induced aVWS. Interestingly, the loss of HMW VWF multimers after pump implantation could be rescued after injection of mAb 17C7 (Figure A and B), demonstrating the therapeutic potential of 17C7 to rescue the loss of HMW VWF multimers.
Conclusions: Blocking ADAMTS13 rescues MCS-induced VWF proteolysis in calves and could become a promising therapeutic strategy to rescue aVWS-induced bleeding in MCS patients.
To cite this abstract in AMA style:Deconinck S, Jacobs S, Nix C, Bennek-Schöpping E, Vandenbriele C, Schelpe A-, Roose E, Pareyn I, Meyns B, Tersteeg C, De Meyer SF, Vanhoorelbeke K. Inhibition of ADAMTS13 Rescues Acquired von Willebrand Syndrome in a Preclinical Mechanical Circulatory Support Animal Model [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/inhibition-of-adamts13-rescues-acquired-von-willebrand-syndrome-in-a-preclinical-mechanical-circulatory-support-animal-model/. Accessed November 30, 2023.
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