Abstract Number: OC 43.3
Meeting: ISTH 2021 Congress
Background: Bleeding is the most frequent complication in left ventricular assist device (LVAD) patients and is linked to the occurrence of acquired von Willebrand syndrome (aVWS). LVADs cause an increased shear-induced proteolysis of von Willebrand factor (VWF) by ADAMTS13, leading to aVWS. We previously showed that an inhibitory monoclonal antibody (mAb) against ADAMTS13 prevented the loss of high molecular weight (HMW) VWF multimers in in vitro LVAD experiments using human blood. The efficacy of this drug in a preclinical animal model has not been investigated yet.
Aims: To investigate if blocking ADAMTS13 using our in-house developed inhibitory anti-ADAMTS13 mAb 17C7 rescues aVWS in a preclinical calf model.
Methods: Bovine blood was circulated through an in vitro Impella system (n=3) with either mAb 17C7 (20 µg/mL) or PBS. VWF multimers and function (collagen binding activity) were determined at different time points (Figure 1A). Next, Impella pumps were implanted in calves (n=4) and the calves were injected with PBS and subsequently treated with mAb 17C7 (Figure 1B). VWF, ADAMTS13 and blood parameters were determined.
Results: Perfusion of bovine blood supplemented with PBS through the in vitro system resulted in a decrease of of HMW VWF multimers and VWF function (Figure A-B; blue). In contrast, blocking bovine ADAMTS13 using mAb 17C7 could prevent the loss of HMW VWF multimers and VWF function in the in vitro system (Figure A-B; red). Implantation of LVADs in calves resulted in aVWS (Figure C-D; white). Treatment with PBS had no effect (Figure C-D; blue). Interestingly, ADAMTS13 inhibition using mAb 17C7 could rescue the loss of HMW VWF multimers and VWF function (Figure C-D; red). Importantly, blocking ADAMTS13 in calves did not lead to severe thrombocytopenia nor hemolytic anemia.
Conclusions: Blocking ADAMTS13 rescues aVWS in a preclinical calf model and could become a promising therapy to treat aVWS-induced bleeding in LVAD patients.
To cite this abstract in AMA style:J Deconinck S, Nix C, Barth S, Bennek-Schöpping E, Schelpe A-, Roose E, Pareyn I, Vandenbulcke A, Muia J, Vandenbriele C, Meyns B, Tersteeg C, F De Meyer S, Jacobs S, Vanhoorelbeke K. Inhibition of ADAMTS13 Rescues Acquired von Willebrand Syndrome in a Preclinical Left Ventricular Assist Device Animal Model [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/inhibition-of-adamts13-rescues-acquired-von-willebrand-syndrome-in-a-preclinical-left-ventricular-assist-device-animal-model/. Accessed September 24, 2021.
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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/inhibition-of-adamts13-rescues-acquired-von-willebrand-syndrome-in-a-preclinical-left-ventricular-assist-device-animal-model/