High anti-ADAMTS13 IgG levels after plasma exchange predict delayed ADAMTS13 normalization in immune-mediated thrombotic thrombocytopenic purpura

Background: In acute immune-mediated TTP (iTTP) caplacizumab therapy has proved to be effective in achieving an early clinical response. However, the discontinuation of caplacizumab therapy before ADAMTS13 activity has at least partially recovered can potentially lead to disease recurrence. Of note, normalization of ADAMTS13 activity was reported to be delayed in caplacizumab-treated patients. Aims: To investigate delayed ADAMTS13 normalization and its potential causes. Patients/Methods: We conducted a retrospective detailed longitudinal investigation of ADAMTS13 activity and anti-ADAMTS13 IgG levels in a single-center cohort of caplacizumab-treated iTTP patients (n=10). Results were compared to iTTP patients treated according to the standard of care in the same center, without caplacizumab (historical controls, n=28). Results: We observed that ADAMTS13 activity was lower in caplacizumab-treated patients than in historical controls one week after TPE was discontinued upon first clinical response (post-TPE). The difference later gradually decreased and we observed no delay in attaining ADAMTS13 activity thresholds of 20% (partial ADAMTS13 remission, reached in median 26 vs. 25 days after the first TPE session) or higher. However, almost half of the caplacizumab-treated patients needed more than 30 days to achieve partial ADAMTS13 remission. Importantly, we found that the post-TPE anti-ADAMTS13 IgG level correlates with the time until partial ADAMTS13 remission both in caplacizumab-treated and historical control patients, and is a significant predictor of delayed ADAMTS13 normalization. Conclusions: The latter finding has important clinical implications, as it suggests that measuring post-TPE anti-ADAMTS13 IgG levels may help identify patients who need additional immunosuppressive treatment to avoid delayed ADAMTS13 normalization.