Long-term follow-up outcomes in congenital thrombotic thrombocytopenic purpura.

Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultrarare thrombotic microangiopathy mediated through inherited deficiency in a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13). To date, >200 ADAMTS13 genetic variants have been associated with cTTP. We report longitudinal follow-up from the UK TTP registry in 104 confirmed cTTP cases (91 consented for follow-up) in a large multiethnic national cohort of patients with cTTP, including a large Black African cTTP cohort. A total of 71 ADAMTS13 variants were identified, with N-terminal variants associated with earlier age at presentation. During the follow-up period (median, 63 months; range, 1-179), 80.2% of patients received regular (plasma derived) prophylaxis, which reduced end organ damage, including stroke/transient ischemic attack (19.0%-1.5%) and renal impairment during follow-up. Postpresentation acute TTP episodes were reduced with prophylaxis (0.68 vs 0.06 acute episodes per follow-up year). Despite regular prophylaxis, symptom control remained apparent on plasma-derived therapy (including headache 42.6%, depression/anxiety 13.2%, fatigue 16.2%, and abdominal pain 13.2%). Most patients with cTTP in the United Kingdom have now switched to recombinant ADAMTS13 (n = 43 [58.9%]), owing to inadequate symptom control (53.5%), plasma reactions (30.2%), or subclinical disease activity (16.3%). This work shows the breadth of ADAMTS13 genetic variants in cTTP and demonstrates efficacy of regular prophylaxis in (1) reducing acute TTP episodes and (2) preventing end organ damage, but despite advances, cTTP related symptoms and the use of blood products remained problematic.