Journal article
Early Inflammatory Biomarkers Associated With Functional Outcomes in Acute Cerebral Venous Thrombosis: CLOT-VENUS Substudy
Stroke (1970)
04/22/2026
DOI: 10.1161/STROKEAHA.125.052774
PMID: 42017277
Abstract
BACKGROUND:
Inflammatory serum biomarkers, including neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), are associated with outcomes in acute cerebrovascular diseases. However, their prognostic role in cerebral venous thrombosis remains uncertain. We aimed to assess the prognostic value of these biomarkers in acute cerebral venous thrombosis by identifying optimal thresholds and internally validating their predictive performance.
METHODS:
This retrospective observational cohort study included adults diagnosed with acute cerebral venous thrombosis from the international CLOT-VENUS registry (Collaboration on Cerebral Venous Thrombosis Study; 2004–2024), including 2 comprehensive stroke centers in the United States and Mexico. Biomarkers of interest (neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, PLR, SII) were calculated from admission complete blood counts. The primary outcome was functional status at 6 months, measured by the modified Rankin Scale dichotomized as 0 to 2 versus 3 to 6. Secondary outcomes included modified Rankin Scale score at discharge and mortality. Associations were tested with multivariable logistic regression adjusted for clinically relevant covariates. Optimal biomarker cutoffs were identified using stratified bootstrap receiver operating characteristic analysis and internally validated with out-of-bag testing.
RESULTS:
Of 432 patients, 394 met the inclusion criteria, and complete data were available for 339 of those patients. Median age was 40 years [interquartile range, 27–45], and 65.2% were female. Elevated biomarkers at admission were associated with modified Rankin Scale score 3 to 6 at discharge and 6 months. At 6 months, optimal cutoff values for neutrophil-to-lymphocyte ratio >4.88 (adjusted odds ratio [aOR], 2.19; P=0.044), monocyte-to-lymphocyte ratio >0.54 (aOR, 2.32; P=0.027), PLR>161.04 (aOR, 3.33; P=0.003), and SII>1388.58 (aOR, 2.03; P=0.049). Similar associations occurred at discharge using the same thresholds. PLR and SII notably predicted mortality at discharge (PLR aOR, 6.33; P=0.008, and SII aOR, 3.93; P=0.031) and at 6 months (PLR aOR, 7.19; P=0.004, and SII aOR, 4.69; P=0.010).
CONCLUSIONS:
Elevated admission levels of neutrophil-to-lymphocyte ratio, PLR, monocyte-to-lymphocyte ratio, and SII are independently associated with poor discharge and 6-month outcomes in patients with acute cerebral venous thrombosis. These accessible biomarkers may aid early risk stratification. Further studies should validate and explore its usefulness in clinical models for personalized management.
Details
- Title: Subtitle
- Early Inflammatory Biomarkers Associated With Functional Outcomes in Acute Cerebral Venous Thrombosis: CLOT-VENUS Substudy
- Creators
- Leonardo Cruz-Criollo - University of Iowa Health CareMilagros Galecio-Castillo - University of Iowa Health CareAaron Rodriguez-Calienes - University of Iowa Health CarePiyush Kalakoti - University of Iowa Health CareVanessa Cano-Nigenda - Instituto Nacional de Neurología y NeurocirugíaAnderson Brito - University of Iowa Health CareMiguel Barboza - Rafael Advanced Defense Systems (Israel)Jason Gao - University of Iowa Health CareAndres Mercado - Instituto Nacional de Neurología y NeurocirugíaAdrian Pereda - Instituto Nacional de Neurología y NeurocirugíaJason Lefkowitz - University of Iowa Health CareJorge Cespedes - University of Iowa Health CareNashwa Abdelhakim - University of Iowa Health CareBinbin Zheng-Lin - Providence Portland Medical CenterAmir Shaban - University of Iowa Health CareBrian J Smith - University of Iowa Health CareNicholas M Mohr - University of IowaAntonio Arauz - Instituto Nacional de Neurología y NeurocirugíaSantiago Ortega-Gutierrez - University of Iowa Health Care
- Resource Type
- Journal article
- Publication Details
- Stroke (1970)
- DOI
- 10.1161/STROKEAHA.125.052774
- PMID
- 42017277
- ISSN
- 1524-4628
- eISSN
- 1524-4628
- Publisher
- American Heart Association
- Grant note
- R03 NS126804 / NINDS NIH HHS
- Language
- English
- Electronic publication date
- 04/22/2026
- Academic Unit
- Neurology; Radiology; Epidemiology; Emergency Medicine; Iowa Neuroscience Institute; Biostatistics; Anesthesia; Injury Prevention Research Center; Neurosurgery; Holden Comprehensive Cancer Center
- Record Identifier
- 9985157616002771