(A) Physiological action of ADAMTS13, which binds via CUB domains to D4-CK region of VWF under high shear stress. Further exosite binding of ADAMTS13 to VWF ensures alignment before VWF cleavage. (B) A cartoon to reflect the closed and open forms of ADAMTS13. ADAMTS13 is shown in a closed inactive form and an open confirmation, associated with antibody binding to the spacer domain, as detected by murine IC4 monoclonal antibody in the IC4 ELISA.