Unintended Interruption of Caplacizumab Therapy Can Compromise Outcomes in Immune-Mediated Thrombotic Thrombocytopenic Purpura: Lessons from Two Clinical Cases

Background: Caplacizumab is a cornerstone in the management of immune-mediated thrombotic thrombocytopenic purpura (iTTP), in combination with plasma exchange (PEX) and immunosuppression. Pivotal trials and real-world data have demonstrated faster platelet count recovery and improved remission rates. Nevertheless, a subset of patients still experiences exacerbations or delayed response. Observational evidence suggests that unintended treatment interruptions may contribute to these unfavorable outcomes. Methods: We report on two patients with iTTP treated with caplacizumab and immunosuppression; PEX was used in Case 1 and as escalation therapy in Case 2. Laboratory parameters including platelet count, lactate dehydrogenase (LDH), ADAMTS13 activity, and anti-ADAMTS13 autoantibodies were monitored. Results: In the first case, a 29-year-old female experienced an exacerbation and ischemic complications after two individual caplacizumab doses were unintentionally missed on days 12 and 14. Subsequent continuous administration led to stabilization and recovery. In the second case, a 42-year-old male presented with hemolytic anemia, thrombocytopenia, and ADAMTS13 activity of 1% and was initially treated with prednisolone and caplacizumab without PEX. Two individual caplacizumab doses were unintentionally missed on days 3 and 5 and were followed by delayed treatment response and microembolic infarcts. Treatment escalation to PEX and rituximab and reinitiation of continuous caplacizumab administration led to clinical stabilization. Conclusions: Even brief interruptions of caplacizumab therapy may compromise outcomes in iTTP. Continuous administration and secured availability, together with serial monitoring of ADAMTS13 activity to guide treatment duration and discontinuation, are essential to improve patient care.