FVIIa-AT complexes in patients with acute ischemic stroke: Impact on clinical outcomes

Plasma levels of activated factor VII-antithrombin complexes (FVIIa-AT) reflect indirectly tissue factor (TF)-FVII interaction. We investigated FVIIa-AT in acute ischemic stroke (AIS) and its prognostic value.

We prospectively studied 88 AIS patients (median age 75 years), of whom 67 (76.1 %) received thrombolysis. Plasma FVIIa-AT levels, fibrin clot properties, i.e. clot lysis time (CLT), fibrin clot permeability (Ks), and protein carbonyl (PC) levels were measured on admission, at 24 h, and at 3 months. Stroke-related mortality and functional outcomes (modified Rankin Scale, mRS) were assessed at 3 months.

Baseline FVIIa-AT (median 134.7 (IQR, 118.2-149.8 pM)), correlated with age (r = 0.51; p < 0.001), NIHSS (r = 0.54; p < 0.001), Ks (r = 0.32; p = 0.002), CLT (r = 0.34; p = 0.001), PC (r = 0.36; p < 0.001), and mRS at 3 months (r = 0.51; p < 0.001). After 24 h, FVIIa-AT increased by 8.3 % (p < 0.001) and correlated with NIHSS (r = 0.52; p < 0.001), PC (r = 0.35; p = 0.001), and mRS (r = 0.59; p < 0.001). At 24 h, thrombolysis had no impact on FVIIa-AT. After 3 months, FVIIa-AT decreased by 20.9 % compared to baseline (p < 0.0001). Baseline and 24-hour FVIIa-AT levels increased the odds of hemorrhagic transformation at 48 h (OR = 1.62, 95 %CI 1.09-2.42 and OR = 1.46, 95 %CI 1.04-2.03) and mRS > 2 at 3 months (OR = 1.48, 95 %CI 1.12-1.95 and OR = 1.61, 95 %CI 1.23-2.10, respectively). Stroke-related mortality was associated with FVIIa-AT solely at 24 h (OR = 1.59, 95 %CI 1.18-2.14).

FVIIa-AT levels are linked to acute stroke severity and worse clinical outcomes, in association with prothrombotic fibrin clot properties and enhanced protein carbonylation.