A novel therapy to treat Left Ventricular Assist Device (LVAD) induced bleeding in end stage heart disease patients

Acquired von Willebrand syndrome (aVWS) has been linked to the bleeding diathesis observed in patients treated with an LVAD as these patients have a loss of high molecular weight (HMW) von Willebrand factor (VWF) multimers. The high shear stress in the LVAD increases the shear-induced proteolysis of VWF by ADAMTS13 leading to a loss of HMW VWF multimers. We showed for the first time that specifically blocking ADAMTS13, using the inhibitory anti-ADAMTS13 monoclonal antibody (mAb) 17C7, prevented the loss of HMW VWF multimers in an in vitro Impella (heart pump used for short term support) circuit with human and bovine blood. In addition, we succesfully demonstrated that the loss of HMW VWF multimers could be rescued in a preclinical bovine Impella model when ADAMTS13 was blocked using the inhibitory mAb 17C7. Hence, in the current translational project we aim at determining the therapeutic window and safety of the humanized inhibitory mAb 17C7 to treat LVAD-induced aVWS before bringing our preclinical candidate drug to enter CMC, non-clinical development and clinical development.

Keywords:bleeding, heart patients, assist device, therapy

Disciplines:Cardiology, Non-clinical studies