From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Neurology. 2018 Mar 20;90(12):e995-e1004. doi: 10.1212/WNL.0000000000005162. Epub 2018 Feb 14.
We aimed to analyze ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in relation to arterial recanalization in patients treated with IV tissue plasminogen activator (tPA) and in relation to futile recanalization in patients treated with mechanical thrombectomy.
Acute ischemic stroke patients (n = 108) with documented arterial occlusions treated with IV-tPA were selected. ADAMTS13 activity was measured by ELISA in samples collected before treatment. Recanalization was assessed at 2 hours by transcranial Doppler. In 78 consecutive patients treated with endovascular thrombectomy, ADAMTS13 antigen was measured by ELISA and futile recanalization was defined as complete recanalization plus modified Rankin Scale score >2 at 3 months. Independent predictors of recanalization and futile recanalization were determined by logistic regression, adjusted by age, NIH Stroke Scale score, and time from stroke onset.
Patients who achieved tPA-induced recanalization had higher baseline ADAMTS13 activity (78.1% [68%-88%] vs 70.1% [61%-79%], = 0.021). In logistic regression analysis, ADAMTS13 activity >75% was an independent predictor of recanalization (odds ratio = 6.76 [1.52-30.02], = 0.012), together with absence of early ischemic signs and Oxfordshire Community Stroke Project classification. Regarding endovascular therapies, a reduced ADAMTS13 concentration (<982 ng/mL) was an independent predictor of futile recanalization (odds ratio = 67.4 [1.4-3,282.1], = 0.034), together with age and diabetes mellitus. The addition of ADAMTS13 to clinical predictors of tPA-induced recanalization and futile recanalization improved discrimination and reclassification (integrated discrimination improvement = 10.06% and 28.4%, net reclassification improvement = 61.0% and 107.4%, respectively).
A reduced ADAMTS13 was associated with poor response to recanalization therapies. If confirmed in future prospective studies, a panel of blood biomarkers including ADAMTS13 might be a useful tool to guide reperfusion therapies.
我们旨在分析 ADAMTS13（解整合素和金属蛋白酶与血小板反应素 1 型基序，成员 13）与接受 IV 组织型纤溶酶原激活剂（tPA）治疗的患者的动脉再通以及与接受机械血栓切除术治疗的患者的无效再通的关系。
选择了 108 例接受 IV-tPA 治疗的有记录的动脉闭塞的急性缺血性脑卒中患者。在治疗前采集样本，通过 ELISA 测量 ADAMTS13 活性。通过经颅多普勒在 2 小时评估再通。在连续 78 例接受血管内血栓切除术治疗的患者中，通过 ELISA 测量 ADAMTS13 抗原，并将完全再通加 3 个月时改良 Rankin 量表评分 >2 定义为无效再通。通过逻辑回归确定再通和无效再通的独立预测因子，通过年龄、NIH 卒中量表评分和卒中发作后的时间进行调整。
达到 tPA 诱导再通的患者基线 ADAMTS13 活性更高（78.1% [68%-88%] vs 70.1% [61%-79%]， = 0.021）。在逻辑回归分析中，ADAMTS13 活性 >75%是再通的独立预测因子（优势比=6.76 [1.52-30.02]， = 0.012），同时伴有早期缺血迹象和牛津郡社区卒中项目分类缺失。对于血管内治疗，ADAMTS13 浓度降低（<982ng/mL）是无效再通的独立预测因子（优势比=67.4 [1.4-3,282.1]， = 0.034），同时伴有年龄和糖尿病。将 ADAMTS13 添加到 tPA 诱导再通和无效再通的临床预测因子中，可以提高区分度和重新分类（综合区分改善=10.06%和 28.4%，净重新分类改善=61.0%和 107.4%）。
ADAMTS13 减少与再通治疗反应差有关。如果在未来的前瞻性研究中得到证实，包括 ADAMTS13 在内的一组血液生物标志物可能是指导再灌注治疗的有用工具。
