Delayed normalisation of ADAMTS13 activity in acute Thrombotic Thrombocytopenic Purpura in the caplacizumab era.

The benefits of caplacizumab in acute immune mediated TTP (iTTP) are well established. We identified a delay in normalisation of ADAMTS13 activity (>30%) in a subgroup of caplacizumab treated patients which was not evident in the pre-caplacizumab era. Caplacizumab treated patients (n=64) achieved ADAMTS13 activity >30% at median 31 days post PEX, compared to 11.5 days in the non-caplacizumab group (n=50, p=0.0004). 18/64 (28%) caplacizumab treated patients had an ADAMTS13 activity <10% at the time of stopping caplacizumab with a longer time to ADAMTS13 activity >30% (median 139 days after completing PEX). 18/64 (28%) of patients receiving extended caplacizumab (31-58 days) failed to achieve ADAMTS13 activity >30% at time of stopping caplacizumab compared to 4/47 (8.5%) of historical controls at similar timepoint (30+28 days, p<0.0001). Failure to achieve ADAMTS13 activity >30% within 30+28 days was 6 times more likely in caplacizumab treated patients (OR 6.3, p=0.0006). ADAMTS13 antigen level <30% at caplacizumab cessation was associated with increased iTTP recurrence (4/10 vs 0/9 in patients with ADAMTS13 antigen ≥30%). Admission anti-ADAMTS13 IgG antibody level did not predict recurrence. Anti-ADAMTS13 IgG antibody levels, immunosuppression and ethnicity did not account for differences in ADAMTS13 activity response. ADAMTS13 antigen levels ≥30% may be useful to guide stopping caplacizumab therapy after extended use in patients with ADAMTS13 activity <10%, but patients require close monitoring. The reason for delayed ADAMTS13 normalisation is unclear and requires further investigation.