Ultra-Early Hematoma Expansion Is Associated With Ongoing Hematoma Growth and Poor Functional Outcome
Chloe A. Mutimer, Teddy Y. Wu, Henry Zhao, Leonid Churilov, Bruce Campbell, Andrew Cheung, Atte Meretoja, Timothy Kleinig, Philip Choi, Henry Ma, Geoffrey Cloud, Rohan Grimley, Darshan Shah, Annemarei Ranta, Karim Mahawish, Vignan Yogendrakumar, Gagan Sharma, Geoffrey A. Donnan, Stephen M. Davis, Nawaf Yassi, Nguyen Thai My Phuong, Nguyen Thi Huong, Barry Snow, Richard Macdonell, John Macdonell, John King, Richard Stark, Neil Anderson, John Attia, Monique Kilkenny, John Kolbe
Abstract
BACKGROUND: There are limited data on ultra-early hematoma growth dynamics and their clinical impact in primary intracerebral hemorrhage (ICH). We aimed to estimate the incidence of hematoma expansion within the hyperacute period of ICH, describe hematoma dynamics over time, investigate the associations between ultra-early hematoma expansion and clinical outcomes after ICH, and assess the effect of tranexamic acid on ultra-early hematoma expansion. METHODS: We performed a preplanned secondary analysis of the STOP-MSU trial (Stopping Intracerebral Hemorrhage With Tranexamic Acid for Hyperacute Onset Presentation Including Mobile Stroke Units), which compared tranexamic acid with placebo in 201 patients with primary ICH presenting within 2 hours of symptom onset. Repeat computed tomography imaging ≈1 hour after treatment commencement was encouraged (ultra-early reimaging), and patients with this imaging were included in this descriptive study. Imaging analyses were separated into the following time epochs: baseline—the period from onset-to-baseline imaging; ultra-early—the period from baseline imaging to ultra-early reimaging; and interval—the period from ultra-early reimaging to 24-hour reimaging. Hematoma expansion was defined as a ≥33% or ≥6 mL increase from baseline, and functional outcomes were assessed at 90 days (poor functional outcome defined as modified Rankin Scale score of 3–6) using unadjusted logistic regression models. RESULTS: We included 105 patients who had ultra-early reimaging (median age, 66 years; 40% female). Median onset-to-baseline imaging time was 74 minutes (interquartile range, 56–87 minutes), and baseline-to-ultra-early reimaging time was 95 minutes (interquartile range, 74–132 minutes). Forty-one patients (39%) had ultra-early hematoma expansion. These patients had larger baseline hematomas (15.9 mL versus 9.1 mL, P =0.03) compared with those with no early hematoma expansion. Hematoma growth rate declined over time (clustered median regression P <0.01). In 92 patients with imaging at all 3 time points, patients with ultra-early hematoma expansion were more likely to have further interval expansion (9/31 [29%] versus 4/61 [6.6%], P <0.01). Of the 61 patients without ultra-early hematoma expansion, there were 10 (16.4%) whose total growth from baseline to 24-hour imaging fulfilled the expansion definition. Ultra-early hematoma expansion was associated with poor functional outcomes (unadjusted odds ratio, 3.91 [1.22–12.49]; P <0.01) and mortality (unadjusted odds ratio, 6.19 [2.17–17.66]; P <0.01). There was no observed effect of tranexamic acid treatment on ultra-early hematoma expansion ( P =0.65). CONCLUSIONS: In patients with ICH presenting within 2 hours of symptom onset, most hematoma growth occurs in the ultra-early period. The presence of ultra-early hematoma expansion is associated with ongoing hematoma growth, poor functional outcomes, and mortality and represents a target for therapeutic intervention.