Non‐contrast CT Markers of Hematoma Expansion and Andexanet Response in Factor Xa Inhibitor‐Associated Intracerebral Hemorrhage: An Analysis from ANNEXa ‐I Trial
Koji TanakaUmberto PensatoMohamed AlshamraniAristeidis H. KatsanosPargol BalaliSucharita RayScott E. KasnerJan Beyer‐WestendorfDanilo ToniDavid SeiffgeCarlos MolinaDavid TannéAnna CzłonkowskaArne LindgrenDaniel BereczkiElse C. SandsetGeorgios TsivgoulisProf Hanne ChristensenJonathan M. CoutinhoPeter VerhammePierre AmarencoRobin LemmensRoland VeltkampSaskia MiddeldorpThompson RobinsonTruman J. MillingWilfried LangVitor Tedium‐CruzMark CrowtherLizhen XuMikael KnutssonPer LadenvallJohn W. EikelboomMukul SharmaAshkan ShoamaneshAndrew M. Demchuk
Key result
Non-contrast CT markers are linked to increased hematoma expansion in FXa inhibitor-associated ICH.
- n=434
Why the study?
Do non-contrast CT markers predict hematoma expansion and response to andexanet in patients with factor Xa inhibitor-associated intracerebral hemorrhage?
Key Points
- To evaluate whether non-contrast computed tomography (NCCT) markers predict hematoma expansion and influence the therapeutic efficacy of andexanet in factor Xa inhibitor-associated intracerebral hemorrhage.
- Conducted a post hoc analysis of the multicenter ANNEXa-I trial in patients with factor Xa inhibitor-associated intracerebral hemorrhage (n = 434).
- Evaluated baseline NCCT imaging markers and defined hematoma expansion as an absolute volume increase of ≥12.5 mL or a relative increase of ≥35%.
- At least one NCCT marker was present in 72.1% of patients at baseline, and hematoma expansion occurred in 31.8% of the cohort.
- Heterogeneous density, hypodensity, and the black hole sign were each independently associated with hematoma expansion.
- The therapeutic effect of andexanet on limiting hematoma expansion was generally consistent across all evaluated NCCT marker subgroups.
Study Design
Type
Observational (n=434)
Structured PICO
Do non-contrast CT markers predict hematoma expansion and response to andexanet in patients with factor Xa inhibitor-associated intracerebral hemorrhage?
P
Population
434 patients with factor Xa inhibitor-associated intracerebral hemorrhage analyzed for non-contrast CT markers of hematoma expansion.
E
Exposure
Andexanet
O
Outcome
Hematoma expansion (HE) (≥12.5 mL or ≥ 35% increase in hematoma volume)surrogate
Non-contrast CT markers such as heterogeneous density, hypodensity, and the black hole sign can identify patients at high risk of hematoma expansion in FXa inhibitor-associated ICH.
Limitations
- post hoc analysis
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Our findings show that hematoma growth rate is a strong predictor of expansion. The benefit of andexanet alfa is robust, but careful patient selection can further enhance outcomes.”
WSWade SmithProfessor of neurology, University of California San Francisco
“The ability to limit hematoma expansion soon after intracerebral hemorrhage occurs is intuitively important, but ultimately what matters is whether patients have better long-term functional outcomes.”
SCStuart ConnollyProfessor of medicine, McMaster University
“Andexanet can be considered for patients with ICH associated with factor Xa inhibitors but, as with many treatments, we will need to balance the benefits and risks and use careful risk stratification for patient selection.”
Implication
NCCT markers may aid expansion risk stratification in FXa-ICH; leaves open prediction of andexanet response.
Abstract
In this post hoc analysis of the ANNEXa-I trial (n = 434), we evaluated non-contrast computed tomography (NCCT) markers of hematoma expansion (HE) in factor Xa inhibitor (FXai) -associated intracerebral hemorrhage (ICH). At least one NCCT marker was present in 72.1%, and HE (≥12.5 mL or ≥ 35% increase in hematoma volume) occurred in 31.8%. Heterogeneous density, hypodensity, and the black hole sign were independently associated with HE. The effect of andexanet on HE was generally consistent across NCCT marker subgroups. These findings support the utility of NCCT markers for identifying patients at high risk of HE in FXai-associated ICH. ANN NEUROL 2026.
Discussion
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Cite This Study
Tanaka et al. (2026) conducted an observational in Factor Xa inhibitor-associated intracerebral hemorrhage (n=434). Non-contrast computed tomography (NCCT) markers was evaluated on Hematoma expansion (≥12.5 mL or ≥ 35% increase in hematoma volume). Non-contrast CT markers were present in 72.1% of patients and independently associated with hematoma expansion, which occurred in 31.8% of patients with FXa inhibitor-associated ICH.