Stubbs, Matthew James; Keogh, Louisa; Gounder, Praveen; Carter, Matthew; Lester, William A; Taylor, Alice; Clark, Amanda; ... Scully, Marie; + view all Stubbs, Matthew James; Keogh, Louisa; Gounder, Praveen; Carter, Matthew; Lester, William A; Taylor, Alice; Clark, Amanda; Thomas, Will; Dutt, Tina; Hermans, Joannes; Van Veen, Joost J; Evans, Rachel; Alamelu, Jayanthi; Desborough, Michael Jr; Westwood, John-Paul; Scully, Marie; - view fewer (2025) Long term follow-up outcomes in congenital thrombotic thrombocytopenic purpura. Blood 10.1182/blood.2025029789. (In press).

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Abstract

Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombotic microangiopathy mediated through inherited deficiency in ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13). To date more than 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 multi-ethnic national cTTP patient cohort, including a large Black African cTTP cohort. 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/TIA (19.0% to 1.5%) and renal impairment during follow-up. Post presentation acute TTP episodes were reduced with prophylaxis (0.68 vs 0.06 acute episodes/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%). The majority of cTTP patients in the UK 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 (i) reducing acute TTP episodes, and (ii) preventing end organ damage, but despite advances, cTTP related symptoms and the use of blood products, remained problematic.

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