Ultra-early hematoma expansion is associated with ongoing hematoma growth and poor functional outcome

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Abstract INTRODUCTION There are limited data on ultra-early hematoma growth dynamics and their clinical impact in primary intracerebral hemorrhage (ICH). We aimed to (a) estimate the incidence of hematoma expansion within the hyperacute period of ICH, (b) describe hematoma dynamics over time, (c) investigate the associations between ultra-early hematoma expansion and clinical outcomes after ICH, and (d) assess the effect of tranexamic acid on ultra-early hematoma expansion. METHODS We performed a planned secondary analysis of the STOP-MSU international multicenter randomized controlled trial. The trial compared tranexamic acid with placebo in 201 patients with primary ICH presenting within 2 hours of symptom onset. 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 of the 201 patients who had 1-hour imaging (median age 66 years, 40% female, 53% tranexamic acid). Median time from onset to baseline imaging was 74min (IQR 56-87 min), and between baseline and 1-hour imaging was 95 min (IQR 74-132 min). Forty-one patients (39%) had ultra-early hematoma expansion. These patients had larger baseline hematoma volumes (15.9 ml vs 9.1 ml, p=0.03) compared to those with no early hematoma expansion. Hematoma growth rate declined 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, 9/31 (29%) of those with ultra-early hematoma expansion had further expansion between the 1-hour and 24-hour scan, compared to only 4/61(6.6%) without ultra-early expansion (p<0.01). Of those 61 patients, there were 10 (16.4%) who fulfilled the expansion definition by 24 hours. Ultra-early hematoma expansion was associated with poor functional outcomes (mRS 3-6; aOR 3.87 [1.21-12.40], p=0.02) and mortality (aOR 6.16 [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). CONCLUSIONS Most hematoma growth occurs in the ultra-early period. The presence of hyperacute hematoma expansion is associated with ongoing hematoma growth, poor functional outcomes and mortality, and represents a target for therapeutic intervention.

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