Unintended Interruption of Caplacizumab Therapy is a Major Risk for Exacerbation in Thrombotic Thrombocytopenic Purpura

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. Case presentation: We report two patients with iTTP treated with caplacizumab, prednisolone, and PEX. Laboratory parameters including platelet count, lactate dehydrogenase (LDH), and ADAMTS13 activity were monitored. In the first case, a 29-year-old female experienced an exacerbation and ischemic complications after two brief interruptions of caplacizumab therapy. Subsequent continuous administration led to stabilization and recovery. Caplacizumab treatment was terminated on day 26, with ADAMTS13 activity at 39%. In the second case, a 42-year-old male presented with hemolytic anemia, thrombocytopenia, and ADAMTS13 activity of approximately 1%. Unintended interruptions in caplacizumab treatment were followed by delayed treatment response and microembolic infarcts. Treatment escalation with PEX and rituximab led to clinical stabilization. Caplacizumab was discontinued on day 12 with an ADAMTS13 activity of 31%. Conclusions In conclusion, even unintended brief interruptions of caplacizumab therapy may compromise outcomes in iTTP. Continuous administration and secure availability, together with monitoring ADAMTS13 activity and potentially von Willebrand factor activity, are essential to improve patient care.