Thrombotic Thrombocytopenic Purpura: From the Bench to the Bedside, but Not Yet to the Community

In the past 4 years, remarkable advances have been made in our understanding of the pathogenesis of thrombotic thrombocytopenic purpura (TTP). This condition is associated with a severe deficiency of von Willebrand factor–cleaving protease (1-4), now known as ADAMTS13 (5). This deficiency prevents normal processing of large von Willebrand factor multimers that are secreted from endothelial cells (6). Persistence of the large von Willebrand factor multimers in the circulation helps form microvascular platelet thrombi, the pathologic hallmark of TTP (6). Mutations of the ADAMTS13 gene may result in life-long recurrent episodes of TTP due to congenital deficiency of ADAMTS13 (7). Acquired ADAMTS13 deficiency can be caused by autoantibodies (1-3), as in the patient described by Zheng and colleagues in this issue (8).

This 42-year-old woman had recurrent severe signs and symptoms of TTP for more than 2 years. Her disease responded only transiently to plasma exchange treatment and several other therapies before cyclophosphamide and rituximab led to remission. She had a severe deficiency of ADAMTS13 and an antibody to ADAMTS13. With remission, the anti-ADAMTS13 antibody became undetectable and ADAMTS13 activity was partially restored. The success of rituximab and cyclophosphamide after other agents had failed to induce remission suggests that more intensive immunosuppression may be required in patients with prolonged critical courses of TTP caused by anti-ADAMTS13 antibodies.

This well-documented report illustrates beautifully the defining phrase of translational research, “From the bench to the bedside.” Now we must ask the next …