Abstract
Introduction: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy (TMA) caused by severely reduced activity of the von Willebrand factor–cleaving protease ADAMTS13. Current treatment includes therapeutic plasma exchange, glucocorticoids, caplacizumab, and anti-CD20 rituximab. During hematologic remission, a decrease in ADAMTS13 activity (≤20%) is associated with an increased risk of clinical relapse. This is commonly managed with a single dose of rituximab followed by serial monitoring and re-dosing based on ADAMTS13 levels. However, the optimal dose and duration of preemptive rituximab remain uncertain.
Methods: We retrospectively identified four asymptomatic patients with ≥1 prior iTTP relapses or exacerbations and persistently low ADAMTS13 activity (<20%) after their most recent treatment, followed at the University of Oklahoma between 2019 and 2025. All patients had normal blood counts and received fixed-dose rituximab (375 mg/m² IV) every 3 months for 2 years, regardless of ADAMTS13 response after the initial dose. ADAMTS13 activity was monitored every 3 months. One patient had incomplete follow-up ADAMTS13 data and was excluded from ADAMTS13 response analysis but was included in the safety and relapse assessments during post-treatment follow-up.
Results: All four patients (2 males, 2 females; ages 26–61) had ADAMTS13 activity <3% prior to initiating rituximab, with normal platelet and hemoglobin counts. Two patients began preemptive rituximab immediately after an acute iTTP episode, while two initiated rituximab during hematologic remission. Three patients completed 7–8 rituximab doses; one received 6 doses due to insurance limitations. One patient had incomplete ADAMTS13 follow-up data and was excluded from response analysis. All three patients evaluable for response outcomes achieved ADAMTS13 activity >60%, which was sustained throughout treatment and follow-up. For the four patients evaluable for safety outcomes, no infusion reactions, infections, or other adverse events were observed. All four remained relapse-free throughout post-treatment follow-up (median follow-up after completion of the last rituximab dose: 17.5 months; range: 3–68 months).
Conclusion: Fixed-interval rituximab maintenance every 3 months for 2 years appeared feasible and well tolerated in a small cohort of patients with recurrent iTTP and persistently low ADAMTS13 activity. Among the three evaluable patients, all achieved ADAMTS13 remission, and all four patients remained relapse-free during follow-up. While limited by sample size, this case series suggests that a proactive, standardized approach may offer clinical benefit compared to reactive or ADAMTS13-guided regimens. Prospective studies are warranted to validate efficacy, optimize treatment duration, evaluate cost-effectiveness, and refine patient selection criteria for this approach.
