Abstract WP126: Predictors Of Intracranial Hemorrhage Volume Expansion In Patients Receiving Factor Xa Inhibitors In The Annexa-4 Trial

Introduction: Andexanet, a specific reversal agent for FXa inhibitors, showed an effective hemostasis in 82% of patients with major bleeding in the ANNEXA-4 trial. However, little is known about the predictors associated with hematoma expansion in patients with FXa inhibitor-associated intracranial hemorrhage (ICrH) receiving andexanet. Methods: ANNEXA-4 was a prospective, single-arm, open-label study of andexanet in patients with acute major bleeding within 18h after taking a FXa inhibitor. Hematoma volumes at baseline and 12h after andexanet treatment were measured utilizing a computerized-assisted volumetric method. Univariate and multivariate logistic regression analyses of baseline clinical and non-clinical parameters were performed to identify factors predictive of different volumes of hematoma expansion. Results: A total of 305 patients with both baseline and follow-up imaging were included (mean age 80 years; 60.2% with intracerebral hemorrhage; 55.4% taking apixaban; 32.5% taking rivaroxaban). Overall median baseline hematoma volume was 10.4 mls (IQR 2.7-28.1) and time from symptom onset to baseline CT was 3.3h (1.5-6.8). Mean baseline anti-FXa activity levels were 148 ng/mL (SD 107.5). In follow up scans, 48 cases (15.7%) showed evidence of ICrH expansion ≥6 mls. Utilizing a four category ICrH Expansion Scale as the dependent variable, ordinal logistic regression identified Glasgow Coma Scale (GCS) score (OR 0.79; 95% CI 0.64-0.97), baseline ICrH volume (OR 1.02; 95% CI 1.01-1.04) and time from symptom onset to CT (OR 0.73 (0.53-0.99) as significant predictors of ICrH expansion. Baseline anti-FXA activity (OR 1.54; 95% CI 0.95-2.51; p value 0.08) and multiple compartment ICrH (OR 2.32; 95% CI 0.98-5.51; p value 0.06) showed trend as predictors of ICrH expansion. ICrH expansion dichotomized by ≥6 mls or <6 mls as dependent variable, identified similar predictors of ICrH expansion. Conclusions: Shorter time from onset of symptoms to CT, lower GCS score and larger hematoma volumes at presentation increased the probability of ICrH expansion in FXa-associated ICrH treated with andexanet. These findings can inform the eligibility criteria of clinical trials targeting hemostatic efficacy in patients with FXa-associated ICrH.