A simplified view of thrombotic challenges in the context of ADAMTS13 deficiency or platelet-expressed ADAMTS13. (A) In the blood vessel of an Adamts13-deficient mouse after Shiga toxin challenge, the damaged endothelium attracts the accumulation of platelets and VWF. In the absence of sufficient ADAMTS13 activity, platelets and VWF accumulate and form embolic microthrombi. The vessel of a wild-type mouse is shown with ADAMTS13 deficiency caused by anti-ADAMTS13 antibodies after injection of superphysiologic amounts of VWF. Here, any available ADAMTS13 is neutralized by injected antibody and VWF-rich emboli form. (B) The same prothrombotic challenges in a transgenic mouse showing recombinant ADAMTS13 expressed in platelets. Despite the 2 different prothrombotic challenges, the transgenic mouse is able to maintain anticoagulant ADAMTS13 activity and prevent the formation of VWF-rich microthrombi. Professional illustration by Patrick Lane, ScEYEnce Studios.