Thrombotic thrombocytopenic purpura (TTP) is a life-threatening medical emergency due to platelet thrombi in the microvasculature leading to thrombocytopenia, microangiopathic hemolytic anemia, and potential end-organ damage and death. The majority of cases of TTP are acquired, caused by autoantibodies that decrease the activity of the von Willebrand factor (VWF)-cleaving protease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), resulting in the accumulation of ultralarge VWF multimers.
The session will cover the utility of real-time ADAMTS13 assays, pharmacologic management, and current research in characterizing anti-ADAMTS13 autoantibodies that could yield novel therapies.
Part 1, ADAMTS13 Assays: The first session will cover the diagnostic value and limitations of ADAMTS13 activity and inhibitor assays, and additionally, the utility of having in-house ADAMTS13 assays for real-time clinical use to differentiate TTP from other causes of hemolytic anemia. Beyond clinical diagnosis, the potential value of ADAMTS13 assays to monitor therapy, guide treatment decisions and predict prognosis will also be explored.
Part 2, Pharmacologic Management: The second session will address pharmacologic management options. The discussion will include optimal dosing and timing of corticosteroids and rituximab to prevent relapse. Also discussed will be treatment options for refractory TTP, e.g., the potential role of cyclosporin, cyclophosphamide, vincristine and intravenous immunoglobulin as adjunctive salvage therapy. Finally, the emphasis will be on the potential of caplacizumab, scheduled to undergo priority review by the food and drug administration (FDA), to transform TTP management.
Part 3, Anti-ADAMTS13 Autoantibodies: The third session will address pathogenic inhibitory anti-ADAMTS13 autoantibodies. It will explore the exciting possibility of using the epitope specificities of polyclonal pathogenic autoantibodies as a tool for developing animal models of acquired TTP to study disease immunobiology and develop novel therapies.
Overall, this session will provide the audience with a current perspective on the real-time clinical utility of ADAMTS13 assays. Currently available pharmacologic management options will be addressed along with the potential of caplacizumab as a new TTP management option, finally, the potential of understanding anti-ADAMTS13 autoantibodies to comprehend TTP pathophysiology and further advance TTP therapy.
Evaluate the utility and limitations of ADAMTS13 assays
Appraise pharmacologic management options for TTP
Appreciate how characterizing anti-ADAMTS13 autoantibodies can be used to develop novel therapies
Sanofi: Consultant, Grant/Research Support (Secondary Investigators need not disclose) I Genentech: Consultant, Grant/Research Support (Secondary Investigators need not disclose) I Takeda: Consultant, Grant/Research Support (Secondary Investigators need not disclose)