ADAMTS13 activity and clinical outcomes: a targeted literature review in congenital thrombotic thrombocytopenic purpura and other related thrombotic conditions

INTRODUCTION: Severe ADAMTS13 deficiency causes congenital thrombotic thrombocytopenic purpura (cTTP), a potentially life-threatening thrombotic microangiopathy. Considering ADAMTS13 regulates thrombosis, ADAMTS13 activity might correlate with clinical outcomes in cTTP; however, evidence evaluating this relationship remains limited. AREAS COVERED: We conducted a targeted literature review examining associations between ADAMTS13 activity and clinical outcomes and/or treatment patterns in cTTP. Given the ultra-rarity of cTTP and extremely few cTTP-specific studies, we reviewed findings from TTP and non-TTP populations for contextual insight. The 34 included studies (MEDLINE database search: 2014-2024) statistically assessed relationships between ADAMTS13 activity and outcomes including mortality, cardiovascular events, organ damage, renal signs, or treatment frequency/patterns. EXPERT OPINION: Lower ADAMTS13 activity appears associated with increased mortality and cardiovascular risk in non-TTP populations, providing exploratory guidance for potential protective thresholds in cTTP. Only one cTTP study met inclusion criteria, and it did not evaluate activity-outcome associations. With only four studies in immune-mediated/unspecified TTP, evidence is insufficient to draw conclusions regarding ADAMTS13 activity thresholds, prognostic value or therapeutic targets in cTTP. Future research should prioritize cTTP-specific studies, including evaluating prophylaxis and temporal peak/trough activity, to define actionable ADAMTS13 activity thresholds to guide personalized management and prevent breakthrough events or long-term complications in cTTP.