Abstract Number: PB1000
Meeting: ISTH 2022 Congress
Background: Acquired von Willebrand syndrome has been linked to bleedings observed in mechanical circulatory support (MCS) device patients. We previously showed that blocking ADAMTS13, using the inhibitory anti-ADAMTS13 monoclonal antibody (mAb) 17C7, prevented von Willebrand factor (VWF) degradation in in vitro MCS device systems with human and bovine blood. Surprisingly, blocking ovine ADAMTS13 did not prevent the loss of high molecular weight (HMW) VWF multimers in an in vitro MCS system.
Aims: To determine if other mechanisms (besides ADAMTS13) linked to the presence of blood cells could also contribute to the shear-induced VWF degradation in sheep.
Methods: Ovine blood or plasma was supplemented with PBS (control) or mAb 17C7 (30 µg/mL) and vortexed for 10 minutes at 2500 rotations per minute using a vortex device (n=4). The vortex assay allowed us to use smaller blood or plasma volumes compared to in vitro MCS device experiments. Next, VWF multimers were analyzed and the percentage of HMW VWF multimers was calculated relative to baseline (no shear set at 100% HMW VWF multimers).
Results: In line with our previous MCS device experiments with ovine blood, mAb 17C7 was not able to significantly prevent HMW VWF multimer loss in ovine blood after vortexing (26±14% HMW VWF multimers in control versus 57±15% in mAb 17C7-treated ovine blood, P=0.06). In contrast, vortexing ovine plasma in the presence of mAb 17C7 resulted in a significant inhibition of VWF degradation compared to control plasma (33±14% HMW VWF multimers in control versus 81%±14% in mAb 17C7-treated plasma, P=0.03) and compared to mAb 17C7-treated ovine blood (57±15%, P=0.04).
Conclusion(s): In sheep, shear-induced VWF degradation is most likely a result of other blood cell proteases or the formation of VWF-platelet complexes whereas it is mainly ADAMTS13-dependent in human and bovine blood. Hence, these important differences between species should be taken into account when performing preclinical research.
To cite this abstract in AMA style:Deconinck S, Schelpe A, Pareyn I, Vandenbulcke A, Tersteeg C, De Meyer S, Vanhoorelbeke K. The Loss of High Molecular Weight Von Willebrand Factor Multimers under Shear Conditions in Sheep is Not Solely ADAMTS13 Dependent [abstract]. https://abstracts.isth.org/abstract/the-loss-of-high-molecular-weight-von-willebrand-factor-multimers-under-shear-conditions-in-sheep-is-not-solely-adamts13-dependent/. Accessed September 26, 2022.
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