Caplacizumab Is Effective in Achieving Early Platelet Recovery and Maintaining Stability in Immune-Mediated Thrombotic Thrombocytopenic Purpura with Post–Plasma Exchange Rebound of Anti-ADAMTS13 Antibodies: Case Series

Caplacizumab, an anti–von Willebrand factor nanobody, has been shown to accelerate platelet count recovery and shorten plasma exchange (PE) and hospitalization in phase 2 and 3 trials of immune-mediated thrombotic thrombocytopenic purpura (iTTP) (N Engl J Med 2016;374:511–22; N Engl J Med 2019;380:335–46). However, real-world longitudinal data on ADAMTS13 activity and anti-ADAMTS13 antibody (inhibitor) titers during and after PE remain limited. We investigated clinical courses and laboratory profiles—including platelet count, ADAMTS13 activity, and inhibitor titers—in iTTP patients treated with PE and caplacizumab at our institution.

Between April 2012 and July 2025, eight iTTP patients received PE and caplacizumab. Six patients, for whom ADAMTS13 activity and inhibitor levels were measured at Nara Medical University, were included in this analysis. The primary outcome was defined as a clinical response, indicated by either a sustained platelet count of ≥150,000/μL for at least two consecutive days, or a stable plateau of platelet count within the normal or supranormal range for three consecutive days. Complete ADAMTS13 remission was defined as ADAMTS13 activity >50% (Blood 2021;137:1855–61). Patients were ranked P1–P6 according to time to complete ADAMTS13 remission. The Japanese iTTP severity score was evaluated to assess disease severity.

Baseline Japanese iTTP severity scores ranged from 2 to 4 (moderate to severe). All patients received PE (1.1–1.5 plasma volumes per session, replaced with fresh-frozen plasma), prednisolone, rituximab, and caplacizumab. P5 additionally received cyclosporine, and P6 received cyclophosphamide. PE was discontinued 2–3 days after a clinical response was achieved. Following initiation of treatment, inhibitor titers declined in all patients, and platelet count stabilization was achieved within 8 days (median, 5 days). The six patients were divided into two groups: three patients (P1, P2, and P3) in whom ADAMTS13 inhibitor titers did not re-elevate after the completion of PE (non-rebound group), and three patients (P4, P5, and P6) in whom inhibitor titers re-elevated after PE (rebound group). In the rebound group, inhibitor titers rebounded within 0–2 days after the cessation of PE. Time to complete ADAMTS13 remission was prolonged in the rebound group (45, 61, 172 days) compared with the non-rebound group (27, 28, 40 days). P4 and P6, who continued caplacizumab, maintained stable platelet counts despite inhibitor rebound. In contrast, P5 experienced a transient platelet decline following a temporary interruption of caplacizumab due to hematuria, which recovered after treatment was resumed.

In the treatment of iTTP, PE is known to suppress disease activity by replenishing ADAMTS13 and removing circulating inhibitors, which differs mechanistically from caplacizumab. However, some patients showed inhibitor re-elevation after completion of PE. Even in these cases, caplacizumab was effective in achieving early platelet count normalization and maintaining stability. These observations suggest that, in addition to platelet count, serial monitoring of ADAMTS13 activity and inhibitor titers is critical for assessing disease activity. Caplacizumab may help maintain platelet count stability during transient inhibitor rebound, but careful immunologic follow-up is warranted to guide treatment optimization.