AUTHOR=Barow Ewgenia , Quandt Fanny , Cheng Bastian , Gelderblom Mathias , Jensen Märit , Königsberg Alina , Boutitie Florent , Nighoghossian Norbert , Ebinger Martin , Endres Matthias , Fiebach Jochen B. , Thijs Vincent , Lemmens Robin , Muir Keith W. , Pedraza Salvador , Simonsen Claus Z. , Gerloff Christian , Thomalla Götz TITLE=Association of White Blood Cell Count With Clinical Outcome Independent of Treatment With Alteplase in Acute Ischemic Stroke JOURNAL=Frontiers in Neurology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.877367 DOI=10.3389/fneur.2022.877367 ISSN=1664-2295 ABSTRACT=Introduction

Higher white blood cell (WBC) count is associated with poor functional outcome in acute ischemic stroke (AIS). However, little is known about whether the association is modified by treatment with intravenous alteplase.

Methods

WAKE-UP was a randomized controlled trial of the efficacy and safety of magnetic resonance imaging [MRI]-based thrombolysis in unknown onset stroke. WBC count was measured on admission and again at 22–36 h after randomization to treatment (follow-up). Favorable outcome was defined by a score of 0 or 1 on the modified Rankin scale (mRS) 90 days after stroke. Further outcome were stroke volume and any hemorrhagic transformation (HT) that were assessed on follow-up CT or MRI. Multiple logistic regression analysis was used to assess the association between outcome and WBC count and treatment group.

Results

Of 503 randomized patients, WBC count and baseline parameters were available in 437 patients (μ = 64.7 years, 35.2% women) on admission and 355 patients (μ = 65.1 years, 34.1% women) on follow-up. Median WBC count on admission was 7.6 × 109/L (interquartile range, IQR, 6.1–9.4 × 109/L) and 8.2 × 109/L (IQR, 6.7–9.7 × 109/L) on follow-up. Higher WBC count both on admission and follow-up was associated with lower odds of favorable outcome, adjusted for age, National Institutes of Health (NIH) Stroke Scale Score, temperature, and treatment (alteplase vs. placebo, adjusted odds ratio, aOR 0.85, 95% confidence interval [CI] 0.78–0.94 and aOR 0.88, 95% CI 0.79–0.97). No interaction between WBC count and treatment group was observed (p = 0.11). Furthermore, WBC count on admission and follow-up was significantly associated with HT (aOR 1.14, 95% CI 1.05–1.24 and aOR 1.13, 95% CI 1.00–1.26). Finally, WBC count on follow-up was associated with larger stroke volume (aOR 2.57, 95% CI 1.08–6.07).

Conclusion

Higher WBC count is associated with unfavorable outcome, an increased risk of HT, and larger stroke volume, independent of treatment with alteplase. Whether immunomodulatory manipulation of WBC count improves stroke outcome needs to be tested.

Trial Registration

ClinicalTrials.gov Identifier: NCT01525290.