In this video lecture, Dr. Spero Cataland discusses:
- The difference between exacerbations and relapses in iTTP, and how caplacizumab and rituximab play complementary roles in prevention.
- The importance of regular ADAMTS13 monitoring and preemptive rituximab to identify and reduce relapse risk.
- Why long-term complications including cardiovascular disease, neurocognitive impairment, and headaches, require ongoing care even during remission.
Dr. Spero Cataland is a Professor of Internal Medicine in the Division of Hematology at the Wexner Medical Center at The Ohio State University. He is also the Director of the Benign Hematology Program at Ohio State University. Dr. Cataland’s clinical and research interests include thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) with an emphasis on immune-mediated TTP (iTTP). Dr. Cataland has a long-standing interest in the development of long-term complications in patients with a prior history of TTP and the mechanisms for their development. Dr. Cataland has also worked to establish the United States Thrombotic Microangiopathy Clinical Consortium, an organization of over 25 academic medical centers that was organized to conduct collaborative research in TTP and aHUS.
(Video Lecture Summary)
Introduction
Dr. Spero Cataland discusses strategies for managing patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) after discharge from the hospital. He emphasizes the importance of preventing exacerbations, monitoring long-term relapse risk, and addressing complications that persist even during remission.
Exacerbations and Relapse
Exacerbations, defined as recurrent thrombocytopenia within 30 days of the last plasma exchange or anti–von Willebrand factor (VWF) therapy, are common and occur in about one-third of patients, typically within the first two weeks post-discharge. These episodes are clinically significant, requiring readmission, central line placement, and repeat plasma exchange. Relapse, in contrast, is a distinct episode occurring beyond 30 days. Risk factors for exacerbation include low ADAMTS13 activity and Black race, which has been associated with higher rates of both exacerbations and relapses.
Role of Therapies in Preventing Early Recurrence
Traditional immunosuppressive treatments such as corticosteroids and rituximab gradually improve ADAMTS13 activity but often too slowly to prevent early exacerbations. Caplacizumab, by directly blocking VWF-platelet interactions, significantly reduces the rate of exacerbations in the high-risk early period, shortening time to platelet recovery. Rituximab, on the other hand, is more effective in preventing longer-term relapses, though racial differences in response have been observed, with Black patients deriving less benefit.
Monitoring and Preemptive Therapy
Monitoring ADAMTS13 activity every 3–6 months is crucial for predicting relapse. Lower activity levels, especially in younger patients, are associated with higher relapse risk. Preemptive rituximab in patients with persistently low ADAMTS13 activity has been shown to delay or prevent relapses, though regular monitoring can be burdensome and costly. Updated international guidelines now incorporate definitions of ADAMTS13 relapse to guide earlier intervention.
Long-Term Complications
Even in remission, patients with a history of iTTP face reduced life expectancy, primarily due to cardiovascular complications such as stroke and microvascular disease. Studies show a fivefold increased risk of stroke and evidence of impaired myocardial perfusion on cardiac MRI, even in patients with near-normal ADAMTS13 levels. Quality of life is also affected by persistent issues such as short-term memory deficits, neurocognitive impairment, depression, anxiety, and chronic headaches, all of which can significantly impair daily functioning.
Conclusion
Dr. Cataland underscores that post-discharge care for iTTP extends beyond preventing relapse. Clinicians must remain vigilant for early exacerbations, use ADAMTS13 monitoring and preemptive rituximab to reduce long-term relapse risk, and address cardiovascular and neurocognitive complications that impact survival and quality of life.