Beranger Nicolas, Benghezal Sandrine, Joly Bérangère S, Capdenat Sophie, Delton Adeline, Stepanian Alain, Coppo Paul, Veyradier Agnès
Service d'hématologie Biologique Hôpital Lariboisière, AP-HP.Nord and EA3518 Institut de Recherche Saint-Louis Université de Paris Paris France.
French National Reference Centre for Thrombotic Microangiopathies Assistance Publique - Hôpitaux de Paris France.
Res Pract Thromb Haemost. 2020 Dec 15;5(1):81-93. doi: 10.1002/rth2.12461. eCollection 2021 Jan.
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy (TMA) caused by a severe functional deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I repeats-13), the specific von Willebrand factor (VWF) cleaving protease. ADAMTS13 activity is essential to diagnose TTP but remains challenging to assess, as reference ADAMTS13 activity assays are manual and time consuming. Current techniques also lack robustness in low detectable ADAMTS13 activity range, which could prove problematic for therapy-driven monitoring.
The HemosIL AcuStar ADAMTS13 activity assay is a fast, automated chemiluminescent assay, the performance of which remains to be evaluated prospectively on very large cohorts of patients with TMA and in real-life conditions.
Our study was conducted over two successive sequences: a retrospective evaluation followed by a "real-life" prospective evaluation. Overall, we evaluated the HemosIL AcuStar ADAMTS13 activity assay on 539 citrated plasma samples. We extensively studied linearity, limit of detection, contamination, intra-assay and interassay precisions with a specific focus on levels < 25 IU/dL. Diagnostic performances for the detection of < 10 IU/dL ADAMTS13 activity and overall method comparison were conducted with the fluorescence resonance energy transfer (FRETS)-VWF73 assay as the reference method.
Technical performance proved excellent. Robustness in low detectable ADAMTS13 activity range was good, potentially qualifying this assay for therapy-driven monitoring. Comparison with the FRETS-VWF73 assay was satisfactory ( = .83, < .0001) as were the diagnostic performances for acute-phase TTP (specificity, 99.7%; positive predictive value, 99.2%).
The HemosIL AcuStar ADAMTS13 activity assay is a fast, reliable, automated technique well adapted as a first-line ADAMTS13 activity assay for TTP diagnosis and follow-up.
血栓性血小板减少性紫癜（TTP）是一种由ADAMTS13（一种含Ⅰ型血小板反应蛋白基序的解聚素和金属蛋白酶-13）严重功能缺陷引起的危及生命的血栓性微血管病（TMA），ADAMTS13是特异性的血管性血友病因子（VWF）裂解蛋白酶。ADAMTS13活性对TTP的诊断至关重要，但评估仍具有挑战性，因为参考ADAMTS13活性检测方法是手工操作且耗时。目前的技术在低可检测ADAMTS13活性范围内也缺乏稳健性，这可能给治疗驱动的监测带来问题。
HemosIL AcuStar ADAMTS13活性检测是一种快速、自动化的化学发光检测方法，其性能仍有待在大量TMA患者队列和实际临床环境中进行前瞻性评估。
我们的研究分两个连续阶段进行：回顾性评估，随后是“真实世界”前瞻性评估。总体而言，我们对539份枸橼酸盐血浆样本进行了HemosIL AcuStar ADAMTS13活性检测评估。我们广泛研究了线性、检测限、污染、批内和批间精密度，特别关注低于25 IU/dL的水平。以荧光共振能量转移（FRETS）-VWF73检测作为参考方法，对低于10 IU/dL的ADAMTS13活性检测的诊断性能及整体方法比较进行了研究。
技术性能表现出色。在低可检测ADAMTS13活性范围内具有良好的稳健性，这可能使该检测方法适用于治疗驱动的监测。与FRETS-VWF73检测的比较结果令人满意（r = 0.83，P < 0.0001），急性期TTP的诊断性能也令人满意（特异性为99.7%；阳性预测值为99.2%）。
HemosIL AcuStar ADAMTS13活性检测是一种快速、可靠、自动化的技术，非常适合作为TTP诊断和随访的一线ADAMTS13活性检测方法。
