Sadler Figure 2 (in George et al). A model for the role of UL-VWF and ADAMTS13 in TTP.

UL-VWF is released from endothelial cells that enter the circulation (A,B) or adhere to the endothelial surface (C). VWF also binds to exposed connective tissue at sites of injury (D). Platelets adhere to VWF in solution (B) or on surfaces (C,D) through platelet glycoprotein Ib (GPIb). VWF also may recruit platelets to previously adhering platelets (E). ADAMTS13 cleaves the A2 domain of the VWF subunit, severing the multimer. This reaction is slow for VWF in solution (A) but occurs rapidly when platelets adhere to VWF under high fluid shear conditions in suspension (B) or on surfaces (C,D,E), presumably as a consequence of conformational changes induced by tensile force on the VWF multimer. Failure of this mechanism appears to cause TTP.

Adapted with permission from Sadler JE: A new name in thrombosis, ADAMTS13. Proc Natl Acad Sci USA 2002;99:11552-11554 (Copyright 2002 National Academy of Sciences, U.S.A.).