Abstract
The association between Factor V Leiden (FVL) and ischemic stroke in young adults remains uncertain. We compared the prevalence of FVL coding in ischemic stroke versus non-stroke hospitalizations and examined in-hospital outcomes among young adults with ischemic stroke in the United States.Using the 2016-2022 National Inpatient Sample, we identified hospitalizations for patients aged 18-49 years with a primary diagnosis of ischemic stroke and a secondary diagnosis of FVL. We compared survey-weighted FVL prevalence between stroke and non-stroke hospitalizations. Among stroke hospitalizations, we evaluated discharge disposition, length of stay, and inflation-adjusted costs with survey-weighted regression models adjusted for demographics and comorbidities. Among 67.8 million hospitalizations of adults aged 18-49 years, 297,905 (0.44%) were for ischemic stroke. FVL coding was more frequent in stroke than non-stroke hospitalizations (0.85% vs. 0.25%, p < .001). Among stroke admissions, FVL prevalence increased from 0.81% in 2016 to 0.95% in 2022 (relative increase 18.3%; p for trend = 0.14), while also rising among non-stroke hospitalizations. Stroke hospitalizations with FVL coding involved patients who were younger, more often female and White, and had fewer recorded traditional vascular risk factors. After adjustment, FVL coding was associated with longer length of stay (9.5% increase) and higher hospital costs (11.2% increase); discharge disposition did not differ meaningfully by FVL status. In this large, cross-sectional inpatient sample, FVL was more frequently coded among young adults hospitalized with ischemic stroke than among other hospitalizations and was associated with greater resource use. However, the design, reliance on ICD-10 codes, and likely differential thrombophilia testing limit causal inference and may partially explain the higher FVL prevalence in stroke admissions. These findings highlight the need for prospective, mechanistically focused studies with standardized thrombophilia testing and detailed stroke phenotyping to clarify the contribution of FVL to arterial ischemic stroke and to identify which patients, if any, might benefit from targeted FVL evaluation and tailored prevention strategies.