Association between coagulation activity and clinical and imaging outcomes in acute ischemic stroke patients: A sub-study of the MR CLEAN NO-IV trial

Background: 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. Aims: 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. Methods: 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 ₀), 1 h post-EVT (T ₁) and 24 h post-EVT (T ₂). Multivariable regressions were performed to investigate the associations and effect modification. Results: In the total cohort of 116 patients, a significant increase at T ₁ 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 ₂ 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 ₁ 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. Conclusion: 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.