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Association Between Neutrophil–Lymphocyte Ratio and 30-Day Infection and Thrombotic Outcomes After Intraventricular Hemorrhage: A CLEAR III Analysis

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Abstract

Background

Serum neutrophil–lymphocyte ratio (NLR) is a surrogate marker for the inflammatory response after intracerebral hemorrhage (ICH) and is associated with perihematomal edema and long-term functional outcomes. Whether NLR is associated with short-term ICH complications is poorly understood. We hypothesized that NLR is associated with 30-day infection and thrombotic events after ICH.

Methods

We performed a post hoc exploratory analysis of the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial. The study exposure was the serum NLR obtained at baseline and on days 3 and 5. The coprimary outcomes, ascertained at 30 days, were any infection and a thrombotic event, defined as composite of cerebral infarction, myocardial infarction, or venous thromboembolism; both infection and thrombotic event were determined through adjudicated adverse event reporting. Binary logistic regression was used to study the relationship between NLR and outcomes, after adjustment for demographics, ICH severity and location, and treatment randomization.

Results

Among the 500 patients enrolled in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial, we included 303 (60.6%) without missing data on differential white blood cell counts at baseline. There were no differences in demographics, comorbidities, or ICH severity between patients with and without data on NLR. In adjusted logistic regression models, NLR ascertained at baseline (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.01–1.07, p = 0.03) and NLR ascertained at day 3 were associated with infection (OR 1.15; 95% CI 1.05–1.20, p = 0.001) but not with thrombotic events. Conversely, NLR at day 5 was associated with thrombotic events (OR 1.07, 95% CI 1.01–1.13, p = 0.03) but not with infection (OR 1.13; 95% CI 0.76–1.70, p = 0.56). NLR at baseline was not associated with either outcome.

Conclusions

Serum NLR ascertained at baseline and on day 3 after randomization was associated with 30-day infection, whereas NLR obtained on day 5 was associated with thrombotic events after ICH, suggesting that NLR could be a potential early biomarker for ICH-related complications.

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Funding

This study was supported by the National Institutes of Health through the following grants: National Institutes of Health 5U01NS062851 (Drs. Hanley, Awad, and Ziai) and K23NS105948 (Dr. Murthy). The funding agency had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Author notes

  1. Wendy C. Ziai and Santosh B. Murthy have contributed equally to this work.

Authors and Affiliations

  1. Clinical and Translational Neuroscience Unit, Department of Neurology, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA

    Safa Kaleem, Cenai Zhang, Stephanie Oh, Alexander E. Merkler, Hooman Kamel & Santosh B. Murthy

  2. Department of Neurological Surgery, University of Texas Health Science Center, Houston, TX, USA

    Aaron M. Gusdon

  3. Brain Injury Outcomes Division, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Radhika Avadhani, Daniel F. Hanley & Wendy C. Ziai

  4. Department of Neurological Surgery, University of Chicago School of Medicine, Chicago, IL, USA

    Isaam Awad & Wendy C. Ziai

  5. Division of Neurosciences Critical Care, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Santosh B. Murthy

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Contributions

Dr. SBM had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: SK, SBM. Acquisition, analysis, or interpretation of data: SBM, CZ. Drafting of the manuscript: SK, WCZ, SBM. Critical revision of the manuscript for important intellectual content: SK, CZ, AMG, SO, AEM, IA, DFH, HK, WCZ, SBM. Statistical analysis: SBM. Administrative, technical, or material support: SBM. Study supervision: WCZ, SBM. The final manuscript was approved by all authors.

Corresponding author

Correspondence to Santosh B. Murthy.

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Conflict of interest

Dr. Merkler reports personal fees for medicolegal consulting in stroke and neurological disorders. Dr. Awad is supported by the National Institutes of Health (NIH) (1U01NS080824 and U01NS106513). Dr. Hanley is supported by the NIH (U01NS080824 and U24TR001609), and reports personal fees from Op2Lysis, personal fees from BrainScope and Neurotrope, and nonfinancial support from Genentech outside the submitted work. Dr. Kamel has received grant support from the NIH, serves as Co-principal investigator (co-PI) for the NIH-funded AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA) trial (National Institute of Neurological Disorders and Stroke U01NS095869) which receives in-kind study drug from the Bristol Myers Squibb BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics, serves as Deputy Editor for JAMA Neurology, serves as a steering committee member of Medtronic’s Stroke atrial fibrillation (AF) trial (uncompensated), serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim, and has served on an advisory board for Roivant Sciences related to Factor XI inhibition. Dr. Ziai is supported by the NIH (1U01NS080824, R01NS102583, and U01NS106513), and receives consulting fees from C.R. Bard, Inc. outside of the area of work commented on here. Dr. Murthy is supported by the NIH (K23NS105948) and has received personal fees for medicolegal consulting on neurological disorders. The other authors have nothing to disclose.

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The article adheres to ethical guidelines and indicates ethical approvals (institutional review board). The study was approved by the Weill Cornell Medicine Institutional Review Board.

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Kaleem, S., Zhang, C., Gusdon, A.M. et al. Association Between Neutrophil–Lymphocyte Ratio and 30-Day Infection and Thrombotic Outcomes After Intraventricular Hemorrhage: A CLEAR III Analysis. Neurocrit Care 40, 529–537 (2024). https://doi.org/10.1007/s12028-023-01774-6

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