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在接受血栓切除术的患者中,无论是否使用溶栓剂,原发性和继发性止血生物标志物与急性缺血性卒中结局的关联:荷兰急性缺血性卒中血管内治疗多中心随机临床试验-NO IV的事后分析

Association of primary and secondary hemostasis biomarkers with acute ischemic stroke outcome in patients undergoing thrombectomy, with or without thrombolytics: post hoc analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands-NO IV.

作者信息

Barakzie Aarazo, Jansen A J Gerard, Cavalcante Fabiano, Nagy Magdolna, Dippel Diederik W J, van der Lugt Aad, Roos Yvo B W E M, Majoie Charles B L M, Ten Cate Hugo, de Maat Moniek P M

机构信息

Department of Hematology, Erasmus Medical Center Cardiovascular Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: https://twitter.com/AarazoB.

Department of Hematology, Erasmus Medical Center Cardiovascular Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.

出版信息

J Thromb Haemost. 2025 Jan;23(1):235-247. doi: 10.1016/j.jtha.2024.10.008. Epub 2024 Oct 21.

Abstract

BACKGROUND

Intravenous thrombolysis (IVT) using recombinant tissue plasminogen activator prior to endovascular thrombectomy treatment (EVT) failed to improve treatment effect in acute ischemic stroke (AIS) patients compared with EVT alone.

OBJECTIVES

We investigated whether primary and secondary hemostasis biomarkers are associated with the effect of intravenous thrombolytics on clinical and radiological outcomes after EVT.

METHODS

In the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN)-NO IV, AIS patients were randomized to receive IVT plus EVT or EVT alone. We measured hemostatic biomarkers before and 24 hours postreperfusion to determine changes in biomarkers and the association of the biomarkers with short term stroke severity on National Institutes of Health Stroke Scale score, long-term functional outcome (modified Rankin scale [mRS] score), post-EVT extended Thrombolysis in Cerebral Infarction score, and final infarct size.

RESULTS

This substudy included 214 of the 539 AIS patients who underwent IVT + EVT (n = 108/266) or EVT alone (n = 106/273). In the EVT group, low soluble glycoprotein VI (sGPVI) and high factor (F)VIII levels before treatment were associated with severe National Institutes of Health Stroke Scale score at 24 hours and poor mRS score at 90 days posttreatment, respectively. Also, in this group, sGPVI levels 24 hours after treatment were negatively associated with final infarct size. In the IVT + EVT group, high fibrinogen before treatment was associated with good extended Thrombolysis in Cerebral Infarction score, and low a disintegrin and metalloprotease with thrombospondin motif repeats 13 activity 24 hours posttreatment was associated with an unfavorable mRS score at 90 days.

CONCLUSION

Our findings suggest that patients with high FVIII and fibrinogen and low sGPVI levels might be the most suitable candidates for IVT + EVT and that patients with low a disintegrin and metalloprotease with thrombospondin motif repeats 13 activity might be suitable for EVT alone.

摘要

背景

与单纯血管内血栓切除术(EVT)相比,在急性缺血性卒中(AIS)患者的血管内血栓切除术治疗(EVT)之前使用重组组织型纤溶酶原激活剂进行静脉溶栓(IVT)未能改善治疗效果。

目的

我们研究了原发性和继发性止血生物标志物是否与静脉溶栓对EVT后临床和影像学结局的影响相关。

方法

在荷兰进行的急性缺血性卒中血管内治疗多中心随机临床试验(MR CLEAN)-NO IV中,AIS患者被随机分配接受IVT加EVT或单纯EVT。我们在再灌注前和再灌注后24小时测量止血生物标志物,以确定生物标志物的变化以及这些生物标志物与美国国立卫生研究院卒中量表评分的短期卒中严重程度、长期功能结局(改良Rankin量表[mRS]评分)、EVT后扩展脑梗死溶栓评分和最终梗死体积的关联。

结果

该亚研究纳入了539例接受IVT + EVT(n = 108/266)或单纯EVT(n = 106/273)的AIS患者中的214例。在EVT组中,治疗前可溶性糖蛋白VI(sGPVI)水平低和因子(F)VIII水平高分别与治疗后24小时严重的美国国立卫生研究院卒中量表评分和治疗后90天不良的mRS评分相关。此外,在该组中,治疗后24小时的sGPVI水平与最终梗死体积呈负相关。在IVT + EVT组中,治疗前高纤维蛋白原水平与良好的扩展脑梗死溶栓评分相关,治疗后24小时低含血小板反应蛋白基序的解聚素和金属蛋白酶13活性与90天时不良的mRS评分相关。

结论

我们的研究结果表明,FVIII和纤维蛋白原水平高且sGPVI水平低的患者可能是IVT + EVT的最合适候选者,而含血小板反应蛋白基序的解聚素和金属蛋白酶13活性低的患者可能适合单纯EVT。

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