[Acquired von Willebrand syndrome associated with mechanical circulatory support]

Acquired von Willebrand syndrome (AVWS) is an acquired hemostatic abnormality characterized by quantitative or qualitative defects of von Willebrand factor (VWF). In high-shear conditions, such as aortic stenosis (AS) or mechanical circulatory support (MCS), excessive proteolytic cleavage of von Willebrand factor (VWF) by its specific protease ADAMTS13 leads to the loss of large-molecular-weight VWF multimers. AVWS is increasingly recognized as a potential risk factor for bleeding in patients on MCS. Current management strategies for AVWS associated with MCS include VWF supplementation with fresh frozen plasma or VWF concentrate; however, the therapeutic effect is only transient due to persistent VWF degradation. Our research group developed a humanized anti-ADAMTS13 antibody (HA10), and we are currently developing a novel therapeutic strategy to control bleeding symptoms associated with AVWS by inhibiting ADAMTS13 activity. We demonstrated the efficacy of HA10 in inhibiting VWF degradation in MCS-implanted male cynomolgus monkeys and further established its safety profile in a GLP-grade single-dose intravenous toxicity study in male cynomolgus monkeys. Our data indicate a potentially low risk of thrombotic thrombocytopenic purpura, a potentially severe complication associated with HA10.