ADAMTS13: The Key to Keeping VWF Trim

The discovery of ADAMTS13 in 2001 provided the master key to unlocking the molecular mysteries of thrombotic thrombocytopenic purpura (TTP). Since then, a flurry of activity has resulted in remarkable progress towards defining the pathophysiology of TTP and provided a beginning to develop new diagnostic and therapeutic tools. This year’s ASH annual meeting offers many exciting opportunities to find out what researchers in this area have been up to for the past three years.

If you had to choose one source for your TTP update (and fortunately, you don’t), then today’s Education Session on Recent Advances in TTP at 10:15 a.m. is a must-see. ADAMTS13 and TTP are the focus of this session chaired by Dr. Evan Sadler. The session will lead off with the latest in TTP pathophysiology by TTP pioneer Dr. Joel Moake. Dr. Moake first described ultra-large von Willebrand Factor (ulVWF) multimers in relapsing TTP in the early 1980s, at which time he insightfully proposed a deficiency of a VWF-trimming enzyme. His talk today should be a riveting tale of the interplay between the two key actors in TTP: ulVWF and its cleaving enzyme, ADAMTS13. Dr. Toshiyuki Miyata will then take the podium to discuss the much anticipated development of VWF-cleaving protease activity assays. In addition to making significant contributions to the growing body of evidence for defects in ADAMTS13 in congenital TTP, Dr. Miyata has worked to define VWF-ADAMTS13 molecular interactions. Recently, Dr. Miyata reported that a critical 73 amino acid region in the VWF A2 domain (VWF73) is specifically cleaved by ADAMTS13. We could find out today whether or not VWF73 holds promise for a rapid clinical VWF-cleaving protease test. The TTP grand finale will be presented by Dr. James George, who will translate the clinical applications of these recent TTP advances. Dr. George’s unique study experience with apharesis patients at the Oklahoma Blood Institute has provided a TTP touchstone for clinicians and scientists alike. We anticipate a lively lecture on the challenges of the clinical heterogeneity of TTP, the conundrum of TTP and HUS, and the correlation of ADAMTS13 activity with TTP subtype.

In addition to the TTP Education Session, we recommend sampling at least part of the ADAMTS13/TTP whirlwind in the posters and simultaneous sessions beginning Sunday afternoon. The Monday morning session on VWF/ADAMTS13 includes two interesting talks, one detailing ADAMTS13 epitopes recognized by autoantibodies and the other describing TTP triggers in ADAMTS13 knock-out mice. The Acquired Thromobocytopenias session also offers multiple relevant clinical abstracts, with several other TTP/ADAMTS13 presentations scattered throughout the meeting.