Clot control

Blood clots are needed to patch vessel injuries. But clot size must be carefully controlled, as oversized clots (thrombi) can plug up blood vessels. The combined action of protease inhibitors, which inactivate clotting factors, and fibrin-cleaving enzymes, which dissolve the fibrin meshwork of the clot, keeps clot size in check. On page 767, Chauhan and colleagues find that another enzyme—the metalloprotease ADAMTS13—is also required to limit clot size.

ADAMTS13 chops up ultra-large multimers of von Willebrand factor (UL-VWF), the blood protein that tethers platelets to injured blood vessels. The importance of dicing up UL-VWF became clear when defects in ADAMTS13 were identified as the cause of the life-threatening disease thrombotic thrombocytopenic purpura (TTP). In patients with TTP, small clots—composed largely of platelets and VWF—form in vessels, eventually breaking free and clogging downstream vessels. What...