Abstract 52: Early Elevation of Plasma Plasminogen Activator Inhibitor-1 is Associated with Vasospasm following Subarachnoid Hemorrhage

Abstract

Background: While the mechanism of early brain injury following subarachnoid hemorrhage (SAH) remains unclear, animal studies suggest that SAH is associated with significant changes in the fibrinolytic cascade. Human data shows that SAH-related brain ischemia is associated with the polymorphism in plasminogen activator inhibitor 1 (PAI-1) promotor linked to higher plasma PAI-1 levels. However, human plasma PAI-1 has not been previously studied in SAH. We hypothesize that elevated plasma PAI-1 is associated with VSP and poor outcome in SAH. Methods: In a prospective cohort of 61 SAH subjects, we compared plasma PAI-1 levels by ELISA (R&D Systems) on post-SAH days 1, 5, 7 and 14 with respect to angiographic VSP and to functional outcome at 3- and 6-months. Angiographic VSP was defined as >50% reduction in vessel caliber on post-SAH day 6-8 angiography. Poor functional outcome was defined as a modified Rankin score >2. Biomarker levels were compared using Wilcoxon rank sum test. Bonferroni correction was applied for multiple comparisons. Results: Subjects with (n=25) and without VSP (n=36) were comparable in gender, Fisher and Hunt and Hess (HH) grade distribution, aneurysm treatment modality, and incidence of hydrocephalus. Subjects with VSP had lower mean age (50 vs. 56). Elevated plasma PAI-1 on post-SAH day 1 was strongly association with VSP (3.28 vs. 1.82 ng/mL; p=.0058) and showed a trend towards association with VSP on post-SAH day 5 (2.65 vs 1.83 ng/mL, p=0.05). Plasma PAI-1 levels were not associated with functional outcome at 3 or 6 months. Elevated plasma PAI-1 on post-SAH day 1 remained significantly associated with VSP (p=0.0155) after adjustment for age and HH and Fisher grades by logistic regression. Conclusion: Early elevation of plasma PAI-1 on post-SAH day 1 is strongly and independently associated with angiographic VSP in this small prospective SAH cohort and may be a candidate biomarker for VSP. Future mechanistic studies with simultaneous measurements of tissue plasminogen activator (tPA) and tPA-PAI complex and larger clinical studies are necessary to understand the utility of PAI-1 as potential biomarker in SAH.