Background: There is limited data on ultra-early hematoma growth dynamics and its clinical relevance in primary intracerebral hemorrhage (ICH). We aimed to estimate the incidence of hematoma expansion (HE) within the hyperacute period of ICH, describe hematoma dynamics over time, investigate the associations between ultra-early HE and clinical outcomes after ICH, and assess the effect of tranexamic acid on ultra-early HE.

Methods: We performed a planned secondary analysis of the STOP-MSU international multicenter randomized controlled trial. Repeat CT imaging ~1 hour after treatment commencement was encouraged. Patients who underwent re-imaging up to 3 hours from baseline imaging were included in this descriptive study. Hematoma expansion was defined as either a ≥33% or ≥6 ml increase from baseline hematoma volume.

Results: We included 105 patients who had 1-hour imaging (median age 66years, 40% female, 53% tranexamic acid). Median time from onset to baseline imaging was 74min (IQR 56-87min), and between baseline and 1-hour imaging was 95min (IQR 74-132min). Forty-one patients (39%) had ultra-early HE. These patients had larger baseline hematoma volumes (15.9ml vs 9.1ml, p=0.03) compared to those with no early HE. Hematoma growth rate significantly reduced over time compared to the onset-to-baseline imaging period (clustered median regression p<0.01). In 92 patients with both 1-hour and 24-hour re-imaging, further HE between the 1-hour and 24-hour imaging was more common in those with ultra-early HE (29%) compared to those without (29% vs 6.6%, p<0.01). Ultra-early HE was associated with poor functional outcomes (mRS 3-6; aOR3.87 [1.21-12.40], p=0.02) and mortality (aOR6.16 [95% CI 2.15-17.68], p<0.01), adjusted for treatment group. There was no observed effect of tranexamic acid treatment on ultra-early hematoma expansion (41% vs. 37%, p=0.65).

Conclusion: Most hematoma growth occurs in the ultra-early period. The presence of hyperacute hematoma expansion is associated with ongoing hematoma growth, and poor clinical outcomes, and represents a target for therapeutic intervention.