A multicenter evaluation of the Technoscreen ADAMTS13 activity semi‐quantitative screening test for thrombotic thrombocytopenic purpura diagnosis and exclusion

Abstract

AbstractIntroductionThrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal microangiopathy, with an untreated mortality rate of around 90%. TTP is caused by severe deficiency in ADAMTS13, which results in accumulation of ultra large von Willebrand factor multimers, triggering a consumptive thrombocytopenia, microangiopathic hemolytic anemia and end‐organ dysfunction and damage. Demonstration of severe ADAMTS13 deficiency is diagnostic for TTP, but long turnaround times for quantitative activity testing often necessitates empirical plasma exchange and/or caplacizumab treatment.MethodsMultisite (n = 4) assessment of the Technoscreen ADAMTS13 activity assay (semi‐quantitative flow through screening assay) for diagnosis/exclusion of TTP compared to current standard practice of quantitative assays (ELISA or chemiluminescence AcuStar).ResultsA total of 128 patient samples were analyzed, with quantitative ADAMTS13 values ranging from 0% to 150%. The Technoscreen assay demonstrated high sensitivity and negative predictive value (NPV) for ADAMTS13 deficiency, but low specificity and positive predictive value (PPV), especially with one lot of reagent. Good inter‐observer reliability was demonstrated. Excluding one possibly compromised batch and other test failures, results of 80 samples yielded sensitivity of 100% (95% CI = 84–100), specificity of 90% (80–95), PPV 77% (58–89) and NPV 100% (93–100).ConclusionThe Technoscreen assay appears to be a reliable screening test for ADAMTS13 activity to exclude TTP in routine clinical practice. However, the assay falsely identified ADAMTS13 deficiency in many cases, partially batch related, which mandates confirmation with a quantitative assay, as well as initial assessment of kits as ‘fit for purpose’ prior to use for patient testing.