Abstract Body: Background and Purpose
Thrombolysis can improve outcome in patients with acute ischemic stroke. However, recanalization is not always complete with persisting cerebral vascular occlusion in >50% of patients despite treatment. Properties of the formed thrombus may influence thrombolysis efficiency and impede recanalization success. Here we examine whether differences thrombin generation are associated with unfavourable outcome in thrombolysis treated patients with acute ischemic stroke.
Methods
Two cohorts of patients with acute ischemic stroke treated with thrombolysis were recruited (cohort 1 n=36 patients, cohort 2 n= 42). Thrombin generation was determined by thrombin generation assay and related to stroke outcome at 90-days determined by modified Rankin Scale (mRS). The relationship of thrombin concentration to clot lysis rate was examined in vitro. Inflammatory factors associated with increased thrombin generation were also identified.
Results
An increase in peak thrombin was associated with unfavourable 90-day outcome in patients with acute ischemic stroke treated with thrombolysis. In cohort 1, patients with mRS£2 had a mean peak thrombin of 208.4nM compared to 255.5nM in those with mRS>2 (p=0.019). In cohort 2, patients with mRS£2 had a mean peak thrombin of 211.1nM compared to 251.6nM in those with mRS>2 (p=0.019). In vitro, an increase in thrombin concentration slowed the rate of clot lysis by tPA. In patients with stroke, an increase in peak thrombin was associated with increased plasma interleukin (IL)-6, interleukin-8 and a decrease in a2-macroglobulin. In vitro, IL-6 can was found to increase thrombin generation via monocyte tissue factor.
Conclusions
Increased thrombin generation on admission is associated with unfavourable outcome at 90 days in thrombolysis treated stroke patients. Higher thrombin generation may influence thrombus properties, reducing effectiveness of thrombolysis, and impairing recanalization. Further understanding regarding the relationship of thrombin generation to thrombolysis is necessary to enhance recanalization and further improve outcomes in stroke.