Neutrophil Extracellular Trap Biomarker Titers and Delayed Cerebral Ischemia in Patients With Aneurysmal Subarachnoid Hemorrhage

Abstract

Background: Myeloperoxidase (MPO)-DNA complexes have been associated with arterial and venous thrombosis. Their role in patients with aneurysmal subarachnoid hemorrhage (aSAH) is unknown. Here, we sought to explore whether serum MPO-DNA-complexes are present in patients with aSAH, and whether levels of serum MPO-DNA complexes are associated with delayed cerebral ischemia (DCI). Methods: We performed a post-hoc analysis of a prospective, blinded, observational single-center biomarker study that enrolled consecutive patients with spontaneous SAH between July 2018 and September 2020. Serum samples obtained on admission and on hospital day 4 were analyzed for concentrations of MPO-DNA complexes. The primary outcome was the occurrence of DCI defined as new infarction on brain CT-scan. The secondary outcome was clinical vasospasm, a composite of clinical and transcranial doppler parameters. We used Wilcoxon's signed-rank-test to assess for differences between paired measures. Results: Among 100 patients with spontaneous SAH, mean age 59 (SD+13) years, 55% women, 78 patients had an aneurysmal SAH and complete DCI information. Among these, 29 (37%) developed DCI. MPO-DNA complexes were detected in all serum samples. The median MPO-DNA level was 33 ng/ml (IQR, 18-43 ng/ml) on admission, and 22 ng/ml (IQR, 11-31 ng/ml) on day 4 (Mann-Whitney test: p=0.015). In the primary outcome analysis, we found a significant reduction in MPO-DNA levels from admission to day 4 in patients with DCI (paired test, p=0.036) but not in those without DCI (p=0.171). The secondary analysis showed a similar reduction in MPO-DNA levels between admission and day 4 in patients with (p=0.006), but not in those without clinical vasospasm (p=0.473). Conclusions: MPO-DNA-complexes are detectable in peripheral serum samples of patients with aSAH. A pronounced reduction in MPO-DNA levels over the first days after aSAH might herald DCI. The potential of MPO-DNA serum levels to serve as a biomarker of DCI requires further exploration.