Multicentric evaluation of the new HemosIL Acustar^® chemiluminescence ADAMTS13 activity assay

Abstract

Introduction Thrombotic thrombocytopenic purpura (TTP) is a rare life‐threatening thrombotic microangiopathy (TMA) characterized by the severe deficiency of ADAMTS13 activity (<10%). Rapid ADAMTS13 testing is crucial for early diagnosis and optimal management of TTP patients and other TMAs. The objective of this study was to retrospectively evaluate the performance of the recently commercialized HemosIL Acustar® ADAMTS13 activity chemiluminescent immunoassay (Instrumentation Laboratory, Bedford, Massachusetts, United States) in a multicentric study between Spain and Portugal. Methods A comparison method was performed to compare HemosIL Acustar® with an in‐house FRETS‐VWF73 assay and two commercial ELISA assays: the TECHNOZYM® ADAMTS13 Activity (Technoclone GmbH, Vienna, Austria) and the DG‐EIA ADAMTS‐13 Activity (Diagnostic Grifols, SA, Barcelona, Spain). A set of 241 frozen plasma samples with known ADAMST13 levels was used. Agreement between methods was assessed with focus on two cut‐off ADAMTS13 activity values: <10% (the clinical accepted cut‐off value to confirm TTP diagnosis) and <5%. Results HemosIL AcuStar® showed high agreement with the other methods in correctly classify patients with ADAMTS13 values below 10% (Kappa = 0.89) and even below 5% (Kappa = 0.94) with no false negatives and few false positives (5.40%; 95% CI: 2.20 to 8.60%). However, it also tended to underestimate ADAMTS13 levels, especially for the high assay range values (>40%) (absolute mean bias of 8.40% (95% CI: 6.53 to 10.42%)) when compared to other assays. Conclusions HemosIL AcuStar® is highly sensitive to detect ADAMTS13 values below 10% and 5%. A large prospective validation study is needed to corroborate its utility in clinical practice.

ADAMTS13 activity testing: evaluation of commercial platforms for diagnosis and monitoring of thrombotic thrombocytopenic purpura

“…In 7 of 51 follow-up samples (14%), AcuStar showed much lower values to an extent that could impact on treatment. Other studies have also noted this discrepancy in some follow-up samples; however, details regarding the timing of the follow-up samples has not been available [12][13][14]. We found that this discrepancy was found in patients in clinical remission after an acute episode (defined as platelets >150 × 10 9 /L, LDH <1.5 × ULN, no new/progressive ischemic injury [15]).…”

Incidence, diagnosis, and outcome of immune‐mediated thrombotic thrombocytopenic purpura: A nationwide survey by the Spanish registry of thrombotic thrombocytopenic purpura

“…Until now, the main problems in making ADAMTS13 determinations before treatment have been the impossibility of performing them in the same center and the expense of time and qualified personnel to carry out the analyses. Recently, new techniques have been described that will foreseeably facilitate the diagnosis in an automated way and with greater speed, which we hope will have an impact on the greater monitoring capacity to monitor patients 18,19 …”

Economic impact of a rapid, on‐demand ADAMTS‐13 activity assay for the diagnosis of thrombotic thrombocytopenic purpura

“…The final diagnosis of TTP is clinical, and the model assumes that clinical diagnosis is accurate regardless of the assay used, as it will be based on overall clinical picture and not solely assay results. A high level of agreement has been reported between the Hemosil AcuStar ADAMTS13 Activity and other ADAMTS13 activity assays, with sensitivity ranging from 90.1% to 100%, and specificity from 94.6% to 100% 5,16,17 . If in some cases clinical picture is not consistent with rapid assay results, additional ADAMTS‐13 activity testing through reference laboratories may be needed 16 …”

“…A high level of agreement has been reported between the Hemosil AcuStar ADAMTS13 Activity and other ADAMTS13 activity assays, with sensitivity ranging from 90.1% to 100%, and specificity from 94.6% to 100%. 5,16,17 If in some cases clinical picture is not consistent with rapid assay results, additional ADAMTS-13 activity testing through reference laboratories may be needed. 16…”