Effect of Factor VIII Elevation on Outcomes in Post-tPA Acute Ischemic Stroke.

Background: Elevation of factor VIII (FVIII), a significant part of the clotting cascade, has been shown to increase incidence of acute ischemic stroke (AIS). Intravenous tissue plasminogen activator (IV tPA) is a thrombolytic and is the only FDA-approved treatment for AIS. The effects of FVIII elevation on outcomes in AIS patients treated with IV tPA are unknown. Methods: This is a retrospective case-control study using a prospectively collected dataset at a single high-volume stroke center. AIS patients from 2008 to 2015 who were over 18 years old, received IV tPA, and had FVIII levels drawn during their acute hospitalization were included. After adjusting for key covariates, we analyzed whether patients with elevated FVIII (eFVIII), defined as FVIII greater than 150%, experienced significant differences in outcomes compared to those with normal FVIII (nFVIII). Primary outcomes of interest were neuroworsening, defined as an increase in NIHSS score of 2 or more points in a 24-hour period, and poor functional outcome, defined as a modified Rankin Scale score (mRS) greater than 2 at discharge. Results: Of 155 patients included, 100 patients (64.52%) had eFVIII. Patients in the eFVIII group had a higher median age (53 vs. 50, p=0.047), were more frequently black (71% vs. 49%, p=0.007), and had higher median NIHSS scores upon admission (8 vs. 6, p=0.028). In adjusted models, patients with eFVIII were 3.19 times more likely to experience a neuroworsening event (OR = 3.19, 95% CI 1.11-9.12) and 4.64 times more likely to have poor functional outcome at discharge (OR 4.64, 95% CI 1.85-11.57) compared to those with nFVIII. Discussion: FVIII elevation mitigates the effects of IV tPA on short-term outcomes among patients with acute ischemic stroke. The results of this study support the potential clinical utility of FVIII as a stroke biomarker in the development of patient risk profiles on admission.