Abstract
Low hemoglobin levels are known to be associated with hematoma expansion (HE) and poor functional outcome in patients with intracerebral hemorrhage (ICH). However, it is not yet known whether low hemoglobin itself causes HE directly or is merely a confounder. Thus, we investigated the mediation effect of the mean Hounsfield unit (HU) of hematoma on the relationship between low hemoglobin and expansion of ICH. Overall, 232 consecutive patients with ICH who underwent non-contrast computed tomography (NCCT) within 12 h since onset were included. The mean HU and hematoma volume on NCCT were investigated using semi-automated planimetry. HE was defined as an increase in hematoma volume > 33% or 6 mL. The respective associations among the hemoglobin level, mean HU, and HE were analyzed using multivariable regression analysis, adjusting for age, sex, and known HE predictors. Mediation analysis was performed to examine the potential causal association among the three. HE occurred in 34.5% of patients; hemoglobin levels were inversely associated with HE occurrence (adjusted odds ratio, 0.90; p = 0.03). The mean HU of the hematoma was lower in patients with HE than in patients without HE (58.5 ± 3.3 vs. 56.8 ± 3.0; p < 0.01). Hemoglobin levels on admission were linearly related to the mean HU (adjusted β, 0.33; p < 0.01) after adjusting for known HE predictors (time from onset to CT, antithrombotic use, hematoma volume). Causal mediation analysis showed a significant mediation effect of the mean HU on the association between hemoglobin levels and HE (p = 0.04). The proportion of indirect effect through the mean HU among the total effect was 19% (p = 0.05). The mediation effect became nonsignificant in the when the multivariable model was adjusted with additional covariates (baseline systolic blood pressure and hematoma location). The mean HU of the hematoma mediated the association between hemoglobin levels and HE occurrence. Therefore, the mean HU of the hematoma may be a potential marker of impaired hemostasis in patients with ICH.
Highlights
Hematoma expansion (HE) is the cause of early neurologic deterioration, leading to poor functional outcomes after intracerebral hemorrhage (ICH)
Among the predictive markers of hematoma expansion (HE) on non-contrast computed tomography (NCCT), the mean Hounsfield unit (HU) of hematoma may reflect the process of clot contraction and local hemostasis[6]
Patients with HE were older, had higher baseline National Institute of Health Stroke Scale score (NIHSS) scores, and were more likely to be on anticoagulants
Summary
Hematoma expansion (HE) is the cause of early neurologic deterioration, leading to poor functional outcomes after intracerebral hemorrhage (ICH). Various clinical and imaging predictors of HE have been identified Modification of these factors, including intensive blood pressure control and hemostatic therapies, showed potential in limiting HE but failed to improve clinical outcomes[1,2]. Patients with ICH having lower hemoglobin levels are known to have poor functional outcomes[3]. A. recent study has demonstrated that the effect of lower hemoglobin levels on functional outcomes is significantly mediated via the occurrence of H E4. Analyzing the relationship among hemoglobin levels, the mean HU of hematoma, and HE may help elucidate HE mechanisms in patients with low hemoglobin[6].
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