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Publications

Journal Article Preprint Epublish

PubMed: 39229082 DOI: 10.1101/2024.08.15.608155

Low hemoglobin causes hematoma expansion and poor intracerebral hemorrhage outcomes.

bioRxiv

Authors: Azzurra Cottarelli, Rayan Mamoon, Robin Ji, Eric Mao, Amelia Boehme, Aditya Kumar, Sandy Song, Valentina Allegra, Sabrina V Sharma, Elisa Konofagou, Vadim Spektor, Jia Guo, E Sander Connolly, Padmini Sekar, Daniel Woo, David J Roh

Affiliations

  • Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.
  • Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.
  • Department of Biomedical Engineering, Columbia University, New York, NY.
  • Department of Radiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.
  • Department of Psychiatry, Columbia University, New York, NY.
  • Department of Neurological Surgery, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.
  • Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH.

Abstract

Objectives

Although lower hemoglobin levels associate with worse intracerebral hemorrhage (ICH) outcomes, causal drivers for this relationship remain unclear. We investigated the hypothesis that lower hemoglobin relates to increased hematoma expansion (HE) risk and poor outcomes using human observational data and assessed causal relationships using a translational murine model of anemia and ICH.

Methods

ICH patients with baseline hemoglobin measurements and serial CT neuroimaging enrolled between 2010-2016 to a multicenter, prospective observational cohort study were studied. Patients with systemic evidence of coagulopathy were excluded. Separate regression models assessed relationships of baseline hemoglobin with HE (≥33% and/or ≥6mL growth) and poor long-term neurological outcomes (modified Rankin Scale 4-6) after adjusting for relevant covariates. Using a murine collagenase ICH model with serial neuroimaging in anemic vs. non-anemic C57/BL6 mice, intergroup differences in ICH lesion volume, ICH volume changes, and early mortality were assessed.

Results

Among 1190 ICH patients analyzed, lower baseline hemoglobin levels associated with increased odds of HE (adjusted OR per -1g/dL hemoglobin decrement: 1.10 [1.02-1.19]) and poor 3-month clinical outcomes (adjusted OR per -1g/dL hemoglobin decrement: 1.11 [1.03-1.21]). Similar relationships were seen with poor 6 and 12-month outcomes. In our animal model, anemic mice had significantly greater ICH lesion expansion, final lesion volumes, and greater mortality, as compared to non-anemic mice.

Conclusions

These results, in a human cohort and a mouse model, provide novel evidence suggesting that anemia has causal roles in HE and poor ICH outcomes. Additional studies are required to clarify whether correcting anemia can improve these outcomes.

MeSH

Hemoglobins, Mortality, Cerebral Hemorrhage, Hemorrhage, Neuroimaging, Hematoma, Anemia