Rapid ADAMTS13 activity assays for thrombotic thrombocytopenic purpura: a systematic review and meta-analysis

Abstract Thrombotic thrombocytopenic purpura (TTP) is a rare, potentially fatal thrombotic microangiopathy caused by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13) deficiency. Prompt treatment improves survival; however, reference standard enzyme-linked immunosorbent assay and FRETS-VWF73 ADAMTS13 activity assays have long turnaround times (TATs) that necessitate empiric treatment of many patients who ultimately are found not to have TTP. Rapid assays with analytical TATs <1 hour have recently become available. We conducted a systematic review and meta-analysis of the performance characteristics of rapid assays relative to reference standard assays for ADAMTS13 activity for patients with suspected or confirmed TTP. Nineteen studies representing 3 rapid ADAMTS13 assays and 4207 patient samples were included. The HemosIL AcuStar chemiluminescence immunoassay (CLIA) demonstrated high sensitivity (0.98; 95% confidence interval [CI], 0.94-1.00), specificity (0.99; 95% CI, 0.97-1.00), and positive (PPV) (0.96; 95% CI, 0.90-0.98) and negative predictive values (NPV) (0.99; 95% CI, 0.99-1.00). The Technofluor fluorescence resonance energy transfer (FRET) and Technoscreen assays had sensitivity of 0.93 (95% CI, 0.86-0.96) and 0.98 (95% CI, 0.42-1.00), specificity of 0.98 (95% CI, 0.95-0.99) and 0.87 (95% CI, 0.76-0.94), PPV of 0.97 (95% CI, 0.85-1.00) and 0.71 (95% CI, 0.59-0.80), and NPV of 0.96 (95% CI, 0.93-0.98) and 0.99 (95% CI, 0.72-1.00), respectively. The proportion of discrepant results (relative to reference standard assays) was 0.04 (95% CI, 0.03-0.05) for HemosIL AcuStar, 0.04 (95% CI, 0.02-0.06) for Technofluor FRET, and 0.11 (95% CI, 0.07-0.16) for the Technoscreen assay. With rapid TAT and high sensitivity, the HemosIL AcuStar CLIA seems able to reliably avert empiric plasma exchange, corticosteroids, and caplacizumab in patients without TTP.