Hereditary/Acquired Bleeding Disorders

For the first time, a multicenter team has identified the specific structural element of von Willebrand factor (VWF) that enables it to bind to platelets and initiate clotting. This unit, which they call the discontinuous autoinhibitory molecule (AIM) “allows the VWF molecule to remain nonreactive in normal circulating blood, and activates the VWF instantly upon bleeding,” author X. Frank Zhang, from Lehigh University, commented in a news release. Dr. Zhang said the team’s research showed that caplacizumab, an FDA-approved monoclonal antibody that binds directly to VWF, “works by binding the AIM region of VWF and enhancing the force threshold to mechanically remove VWF’s autoinhibitory structures, opening up a new avenue to the development of antithrombotic drugs targeting the AIM structures.”