Persistent ADAMTS13 Inhibitor Delays Recovery of ADAMTS13 activity in Caplacizumab-Treated Japanese iTTP Patients.

For patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP), caplacizumab, a nanobody against von Willebrand factor A1 domain, has become crucial. Delayed normalization of ADAMTS13 activity during caplacizumab therapy has been identified. In a retrospective analysis, we compared platelet count, ADAMTS13 activity, its inhibitor, and anti-ADAMTS13 IgG levels in acute iTTP cases treated with caplacizumab (N=14) or without it (N=16). The median time from initial therapeutic plasma exchange (TPE) to the first rituximab administration was 12 days in the caplacizumab group (N=11) and 10 days in the group without caplacizumab (N=13). We evaluated ADAMTS13-related parameters at onset and once a week until day 28 after the first TPE. The number of days until the platelet counts reached >= 150×109/L was significantly shorter in the caplacizumab group than in the non-caplacizumab group. The median ADAMTS13 activity levels on days 14, 21, and 28 were significantly lower in the caplacizumab group than in the non-caplacizumab group. The median titers of the ADAMTS13 inhibitor and anti-ADAMTS13 IgG on the same days were significantly higher in the caplacizumab group than in the non-caplacizumab group. Furthermore, the median number of days from the first TPE until finally achieving an ADAMTS13 activity >= 10% was significantly longer in the caplacizumab group than in the non-caplacizumab group (42 days vs. 23 days, p=0.014). We observed delayed ADAMTS13 activity recovery and continued inhibitor and anti-ADAMTS13 IgG detection in acute iTTP patients on caplacizumab, possibly due to the decreased number of TPEs and delayed frontline rituximab.