Abstract Body: Background: Direct oral anticoagulants (DOAC) are associated with an increased risk of
hematoma expansion (HE) in spontaneous intracerebral hemorrhage (ICH). However, the
critical DOAC level influencing this risk remains unclear. This study investigates the impact of DOAC levels on the risk of HE in patients with DOAC-associated ICH.
Methods: We conducted a retrospective analysis of patients with DOAC-associated ICH who had DOAC-calibrated anti-Xa or -IIa activity levels measured upon admission. Patients were categorized based on a clinically established cutoff for subtherapeutic DOAC levels (<30 ng/ml). Hematoma expansion was defined as a ≥35% increase in hematoma volume between admission and 24-72 hour follow-up CT scans, with symptomatic HE defined as a concurrent ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS). Multivariable logistic regression models were used to assess the association between DOAC levels and HE, adjusting for baseline ICH volume, onset-to-imaging time, systolic blood pressure, and the use of reversal agents.
Results: Among 2147 ICH patients admitted between January 2012 and November 2023, 88 had DOAC-associated ICH with available DOAC levels (apixaban, n=36; rivaroxaban, n=30; edoxaban, n=17; dabigatran, n=4). No significant differences were observed in baseline (24.3±27.5 vs. 19.5±16.6 ml; p=0.6) or follow-up ICH volumes (30.6±36.4 vs. 36.4±14.6 ml; p=0.6) between patients with high versus low DOAC levels. Rates of HE (15.4% vs. 22.2%; p=0.6) and symptomatic HE (7.7% vs. 11.1%; p=0.5) were also similar across groups. DOAC levels below the cutoff did not predict HE (adjusted OR 0.7, 95% CI 0.1-4.5; p=0.7). These findings remained consistent when applying a <50 ng/ml DOAC cutoff and in the subgroup of patients not receiving reversal therapy.
Conclusions: Our study suggests that DOAC levels, as defined by the current cutoffs, do not significantly predict hematoma expansion in patients with DOAC-associated ICH. Further research in multicenter cohorts is necessary to better delineate the relationship between specific DOAC levels and the risk of HE.