Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management

Authors: Sukumar, S; Lämmle, B; Cataland, SR.

Affiliations: Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, CH 3010 Bern, Switzerland; Center for Thrombosis and Hemostasis, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany; Haemostasis Research Unit, University College London, London WC1E 6BT, UK.

Publication: Journal of Clinical Medicine; 2021; 10

Abstract: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. TTP results from a severe deficiency of the specific von Willebrand factor (VWF)-cleaving protease, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13). ADAMTS13 deficiency is most commonly acquired due to anti-ADAMTS13 autoantibodies. It can also be inherited in the congenital form as a result of biallelic mutations in the ADAMTS13 gene. In adults, the condition is most often immune-mediated (iTTP) whereas congenital TTP (cTTP) is often detected in childhood or during pregnancy. iTTP occurs more often in women and is potentially lethal without prompt recognition and treatment. Front-line therapy includes daily plasma exchange with fresh frozen plasma replacement and immunosuppression with corticosteroids. Immunosuppression targeting ADAMTS13 autoantibodies with the humanized anti-CD20 monoclonal antibody rituximab is frequently added to the initial therapy. If available, anti-VWF therapy with caplacizumab is also added to the front-line setting. While it is hypothesized that refractory TTP will be less common in the era of caplacizumab, in relapsed or refractory cases cyclosporine A, N-acetylcysteine, bortezomib, cyclophosphamide, vincristine, or splenectomy can be considered. Novel agents, such as recombinant ADAMTS13, are also currently under investigation and show promise for the treatment of TTP. Long-term follow-up after the acute episode is critical to monitor for relapse and to diagnose and manage chronic sequelae of this disease.