Relapse and beyond: Navigating the long-term clinical impacts of immune thrombotic thrombocytopenic purpura

Abstract

Immune Thrombotic thrombocytopenic purpura (iTTP) is a rare but life-threatening thrombotic microangiopathy characterized by an autoantibody against ADAMTS13, leading to accumulation of ultra-large von Willebrand multimers, systemic platelet microthrombi, end-organ damage, and mortality if untreated. Therapeutic plasma exchange and corticosteroids have been the mainstay therapy for decades, but there exists significant relapse potential after the initial acute episode. While more recent advances in the use of immunotherapy (e.g. rituximab and caplacizumab) have significantly improved acute survival and short-term exacerbation/relapse prevention, long-term complications of the disease remain a concern for survivors. This narrative review discusses challenges of optimizing post-remission care after iTTP, highlighting disease impact on neurological, cardiovascular, and psychological health. Chronic cognitive impairment, increased risk of hypertension and ischemic events, and mental health challenges such as anxiety and depression are reported in iTTP survivors. Moreover, recurrence risk and persistent ADAMTS13 deficiency may define the need for long-term monitoring and individualized treatment of potential relapse. We emphasize the importance of multidisciplinary, patient-centered management, not only in the management and prevention of iTTP relapse episodes, but to improve quality of life and reduce morbidity in survivors of this rare disease. Providers should possess heightened awareness of long-term complications and atypical manifestations of relapse in survivors. We advocate for further research and observational cohort studies to formulate standardized guidelines for surveillance and intervention to mitigate the chronic burden of iTTP.

Keywords: ADAMTS13 deficiency; Cardiovascular risk; Immune thrombotic thrombocytopenic purpura (iTTP); Long-term complications; Neurocognitive impairment; Relapse prevention.