Advances in rapid ADAMTS13 testing for thrombotic thrombocytopenic purpura: a systematic review of diagnostic assays and the role of clinical probability tools.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy caused by severe ADAMTS13 deficiency. This systematic review evaluates recent diagnostic advances, focusing on rapid assays, clinical prediction tools, and emerging biomarkers. METHODS: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Cochrane Library, Google Scholar, and ClinicalTrials.gov (2015-2026). We included studies evaluating ADAMTS13-based or adjunct biomarkers for TTP diagnosis, reporting diagnostic accuracy or turnaround time. Risk of bias was assessed using QUADAS-2. RESULTS: From 2,217 records and 42 registry entries, 14 studies met inclusion criteria. ADAMTS13 activity <10% remained the key diagnostic threshold. Rapid automated platforms reduced turnaround time from >72 h to 17-35 min. KEY FINDINGS INCLUDE: HemosIL AcuStar assay (100% sensitivity, 94.6%-98.9% specificity, 33-min turnaround); CLEIA (17-min turnaround, near-perfect agreement with reference methods, κ = 0.95-0.96); bedside Technoscreen assay (100% sensitivity, 90% specificity, 10-min result). Clinical prediction tools demonstrated variable performance across settings, with PLASMIC showing the most favourable balance of sensitivity and specificity (pooled sensitivity 0.85, specificity 0.89 at the conventional threshold of ≥6). Meta-analysis and multicentre data indicate that performance is influenced by patient age, laboratory parameters, and the chosen cut-off. Open-conformation ADAMTS13 assays detected abnormal conformation in 97% of acute iTTP samples, supporting relapse monitoring. CONCLUSION: TTP diagnosis is shifting from slow reference-laboratory confirmation toward an integrated strategy combining rapid automated ADAMTS13 testing, clinical probability scoring, and adjunct biomarkers. This approach enables earlier diagnosis, faster treatment initiation, and improved relapse surveillance.Systematic Review Registration: identifier CRD420261363424.