Ceulemans Angelique, Barakzie Aarazo, Spronk Henri M H, de Maat Moniek P M, van Beusekom Heleen M M, Taha Aladdin, Emmer Bart J, Roos Yvo B W E M, Dippel Diederik W J, Majoie Charles B L M, van Zwam Wim H, Ten Cate Hugo, van Oostenbrugge Robert J, Nagy Magdolna
Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Disease (CARIM), Maastricht University, the Netherlands.
Department of Hematology, Erasmus MC Cardiovascular Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Thromb Res. 2025 Jan;245:109212. doi: 10.1016/j.thromres.2024.109212. Epub 2024 Nov 8.
The MR CLEAN NO-IV trial showed neither superiority nor noninferiority of endovascular treatment (EVT) alone compared to intravenous thrombolysis (IVT; Alteplase) before EVT in acute ischemic stroke (AIS) patients with large vessel occlusion of the anterior circulation. Although the treatment effect is largely attributable to EVT, IVT may affect hypercoagulability during AIS.
To investigate the association between activated coagulation and final infarct volume and clinical outcomes (modified Rankin Scale 3-6 and mortality 90 days post-EVT), and whether this effect is modified by IVT administration.
Enzyme-linked immunosorbent assays were used to quantify activated coagulation markers (activated coagulation factor (F) XIIa-C1 esterase inhibitor (C1inh); FXIIa-antithrombin (AT), FXIa-C1inh, FXIa-AT, FIXa-AT, FXa-AT, T-AT, FVIIa-AT) in plasma samples obtained on admission (T), 1 h post-EVT (T) and 24 h post-EVT (T). Multivariable regressions were performed to investigate the associations and effect modification.
In the total cohort of 116 patients, a significant increase at T was seen in FIXa-AT (p = .001), FXa-AT (p < .001), T-AT (p < .001), and FVIIa-AT (p = .012), while there was a significant increase at T in FXIIa-C1inh (p < .001). Similar results were seen in the IVT+EVT subgroup. The EVT alone subgroup showed a significant temporary increase at T in FXa-AT (p < .001) and T-AT (p = .014). Neither the enzyme:inhibitor complexes nor the interaction with IVT were significantly associated with the outcome measures.
Despite temporary significant increases in enzyme:inhibitor complexes in the IVT+EVT group, but not in the EVT alone group, there were no significant associations with final infarct volume and clinical outcomes.
MR CLEAN NO-IV试验表明，对于前循环大血管闭塞的急性缺血性卒中（AIS）患者，单纯血管内治疗（EVT）与EVT前静脉溶栓（IVT；阿替普酶）相比，既不具有优越性也不具有非劣效性。尽管治疗效果很大程度上归因于EVT，但IVT可能会影响AIS期间的高凝状态。
研究活化凝血与最终梗死体积及临床结局（EVT后90天改良Rankin量表评分3-6分及死亡率）之间的关联，以及IVT给药是否会改变这种效应。
采用酶联免疫吸附测定法对入院时（T0）、EVT后1小时（T1）和EVT后24小时（T2）采集的血浆样本中的活化凝血标志物（活化凝血因子（F）XIIa-C1酯酶抑制剂（C1inh）；FXIIa-抗凝血酶（AT）、FXIa-C1inh、FXIa-AT、FIXa-AT、FXa-AT、总抗凝血酶（T-AT）、FVIIa-AT）进行定量。进行多变量回归分析以研究这些关联和效应修正。
在116例患者的整个队列中，T0时FIXa-AT（p = 0.001）、FXa-AT（p < 0.001）、T-AT（p < 0.001）和FVIIa-AT（p = 0.012）显著升高，而T1时FXIIa-C1inh显著升高（p < 0.001）。在IVT+EVT亚组中也观察到类似结果。单纯EVT亚组在T1时FXa-AT（p < 0.001）和T-AT（p = 0.014）出现显著的短暂升高。酶：抑制剂复合物以及与IVT的相互作用均与结局指标无显著关联。
尽管IVT+EVT组中酶：抑制剂复合物有短暂显著升高，但单纯EVT组没有，且这些升高与最终梗死体积和临床结局均无显著关联。
