Neurological Impact of Caplacizumab in Refractory iTTP Survivors: A Comparative Study of Blood-Brain-Barrier Integrity and Cognitive Outcomes

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) causes systemic microvascular thrombosis, often leading to long-term neurological complications and cognitive decline despite achieving hematologic remission. Persistent blood-brain barrier (BBB) dysfunction is a suspected driver of these chronic sequelae. This study investigated whether adding caplacizumab to standard of care (SOC) improves long-term BBB integrity and cognitive outcomes in refractory iTTP survivors compared with SOC alone. METHODS: We analyzed 16 patients with iTTP categorized into SOC-only (n=7) or SOC plus caplacizumab (n=9) cohorts. Patients underwent computed tomography perfusion imaging to measure BBB permeability (PS product), blood flow, and blood volume at baseline (30 days postremission) and 12-month follow-up. Cognitive function was assessed using Creyos (URL: https://www.clinicaltrials.gov; Unique identifier: NCT03187652). RESULTS: <0.05, Benjamini-Hochberg corrected). CONCLUSIONS: Caplacizumab may provide a neuroprotective benefit by facilitating BBB repair, even in initially refractory patients. These findings suggest that targeting microvascular integrity during acute episodes can mitigate long-term cognitive decline in iTTP survivors. By facilitating long-term BBB repair, caplacizumab may mitigate chronic cognitive decline and improve the quality of life for refractory iTTP survivors.