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

Aarazo Barakzie; Gerard A J Jansen; Fabiano Cavalcante; Magdolna Nagy; Diederik W J Dippel; Aad van der Lugt; Yvo B W E M Roos; Charles B L M Majoie; Hugo Ten Cate; Moniek P M de Maat; Collaboration for New Treatments of Acute Stroke consortium

doi:10.1016/j.jtha.2024.10.008

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

J Thromb Haemost. 2024 Oct 21:S1538-7836(24)00615-9. doi: 10.1016/j.jtha.2024.10.008. Online ahead of print.

Affiliations

¹ Department of Hematology, Erasmus Medical Center Cardiovascular Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: https://twitter.com/AarazoB.
² Department of Hematology, Erasmus Medical Center Cardiovascular Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
³ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
⁴ Department of Biochemistry, Cardiovascular Research Institute Maastricht School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands; Thrombosis Expertise Center and Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
⁵ Department of Neurology, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands; Department of Public Health, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands.
⁶ Department of Radiology and Nuclear Medicine, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands.
⁷ Department of Hematology, Erasmus Medical Center Cardiovascular Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: m.demaat@erasmusmc.nl.

PMID: 39442626
DOI: 10.1016/j.jtha.2024.10.008

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.

Keywords: clinical and radiological outcomes; coagulation biomarkers; ischemic stroke; mechanical thrombectomy; thrombolysis.