In this panel discussion moderated by Dr. Brian Carney, listen to three leading experts in the field of TTP as they discuss the practical aspects of diagnosis and patient care, from recognizing the first clues to managing treatment and long-term follow-up.
Meet the Moderator and Panelists:
Brian Carney, MD is an attending physician in the Division of Hematology and Hematologic Malignancies at Beth Israel Deaconess Medical Center (BIDMC) and an Assistant Professor of Medicine at Harvard Medical School. He is a clinical investigator with an interest in thrombotic microangiopathies. He serves as Medical Director of Apheresis Services at BIDMC.
Dr. Pavan “Tem” Bendapudi holds a joint faculty appointment at Beth Israel Deaconess Medical Center (BIDMC) and Massachusetts General Hospital (MGH) in Boston and is assistant professor of medicine at Harvard Medical School. He is board-certified in hematology, oncology, and transfusion medicine. Dr. Bendapudi currently serves as principal investigator of the Harvard Thrombotic Microangiopathies Research Collaborative, an interdisciplinary, multi-institutional clinical research effort that studies thrombotic thrombocytopenic purpura (TTP) and allied disorders.
Dr. Marie Scully is a Consultant Haematologist at University College London Hospitals (UCLH), currently acting as the clinical lead for haemostasis and thrombosis, having spent ten years as the clinical lead for blood transfusion. She has considerable experience in within complex tertiary cases within obstetrics, neurosurgery, intensive care and haematooncology associated haemostasis and thrombosis complications. Her particular area of interest is acquired haemostasis and platelet disorders, specifically Immune Thrombocytopenic Purpura (ITP). She runs specialist ITP and TTP clinics and works on obstetric haematology, as part of a team that specialises in treating varied and complex thrombosis, acquired and inherited bleeding disorders.
Long Zheng, MD, PhD, is the Russel J Eilers Professor and Chair of Pathology and Laboratory Medicine at the University of Kansas Medical Center, Kansas City, Kansas. Dr. Zheng was among the first group of scientists who identified and cloned ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. The deficiency of ADAMTS13 results in thrombotic thrombocytopenic purpura (TTP). Over the past decades, Dr. Zheng’s laboratory has made seminal contributions towards our understandings of the structure-function and regulation of ADAMTS13 protease and pathogenesis of TTP, and the role of ADAMTS13 in other inflammatory thrombotic disorders. Dr. Zheng’s research group have published more than 160 manuscripts in peer-reviewed journals including five chapters on TTP and related disorders in highly sought reference books.
(Video Lecture Summary)
Introduction
In this panel discussion moderated by Dr. Brian Carney, Drs. Marie Scully, Long Zheng, and Tem Bendapudi explore current challenges and evolving practices in the management of thrombotic thrombocytopenic purpura (TTP). The conversation highlights differences in international approaches, new therapeutic considerations, and practical issues surrounding diagnosis, treatment, and follow-up.
Diagnostic Strategies and ADAMTS13 Testing
A central focus of the discussion was the turnaround time for ADAMTS13 activity assays. Dr. Zheng emphasized that institutions with access to rapid automated platforms can achieve results within hours, fundamentally changing patient management. In contrast, Dr. Scully noted that the United Kingdom has organized TTP care into nine regional centers, with standardized systems ensuring results within 24 hours. Concerns were raised about the reliability of some rapid assays, including potential sensitivity issues, underscoring the importance of expert interpretation and confirmatory testing when clinical and laboratory findings diverge.
The panel also reflected on the role of clinical scoring systems, such as the PLASMIC and French scores. While these tools may assist non-specialists in recognizing potential cases, experienced centers often rely more on integrated laboratory-clinical services and clinical acumen. Scores are viewed as rule-out rather than definitive rule-in tools, highlighting the continuing primacy of ADAMTS13 testing in diagnosis.
Therapeutic Approaches and Timing of Intervention
Plasma exchange remains the cornerstone of therapy, but panelists acknowledged the logistical challenges of timely access, particularly in rural or resource-limited settings. Both rapid initiation and a defined “door-to-pheresis” goal of within four hours were stressed as critical quality measures. In circumstances where plasma exchange is delayed, bridging strategies such as fresh frozen plasma infusion or early use of caplacizumab were discussed, though with recognition of their limitations.
The introduction of caplacizumab has reshaped treatment thresholds and duration of plasma exchange. Panelists agreed that platelet count normalization now provides an earlier and more reliable stopping point than in the pre-caplacizumab era. However, there was debate regarding its empirical use in patients with intermediate pretest probability, with some advocating caution due to risks of overtreatment.
Immunosuppression and Steroid Management
Discussion turned to adjunctive therapies, particularly immunosuppression. Steroids remain standard, but the consensus favored early initiation of rituximab to address the underlying autoimmune process. Most panelists reported rapid steroid tapering within two to three weeks to minimize side effects, with rituximab typically introduced within days of presentation. While dosing strategies varied, from rheumatologic regimens to lymphoma-based protocols, there was agreement that flexibility and institutional comfort shaped practice.
Follow-Up and Long-Term Monitoring
The panel concluded by addressing follow-up of patients after remission. Practices ranged from frequent inpatient monitoring of ADAMTS13 activity to structured outpatient schedules, often weekly initially and then extending over time. A decline in ADAMTS13 levels, even in asymptomatic patients, was generally met with consideration of pre-emptive rituximab, sometimes supplemented with additional immunosuppressive agents such as mycophenolate mofetil. The importance of individualized care, attention to relapse risk, and adapting to resource availability were emphasized.
Conclusion
The panel underscored the evolving landscape of TTP management. Rapid diagnostic testing, integration of novel therapeutics, and refined strategies for plasma exchange and immunosuppression are reshaping care. While international practices differ, the shared goal remains consistent: timely, expert-driven treatment to reduce mortality and improve long-term outcomes.