Intracerebral Hemorrhage Volume Reduction and Timing of Intervention Versus Functional Benefit and Survival in the MISTIE III and STICH Trials

To date, only limited data are available on the effects of pretreatment with novel oral anticoagulants in the event of traumatic brain injury (TBI). We determined intracerebral hemorrhage volume and functional outcome in a standardized TBI model in mice treated with warfarin or dabigatran. Additionally, we investigated whether excess concentrations of dabigatran could increase bleeding and whether this was preventable by using prothrombin complex concentrate (PCC). C57 mice were treated orally with warfarin or dabigatran; sham-treated mice served as controls. Effective anticoagulation was verified by measurement of international normalized ratio and diluted thrombin time, and TBI was induced by controlled cortical impact (CCI). Twenty-four hours after CCI, intracerebral hemorrhage volume was larger in warfarin-pretreated mice than in controls (10.1 ± 4.9 vs 4.1 ± 1.7 μL; analysis of variance post hoc P = 0.001), but no difference was found between controls and dabigatran-pretreated mice (5.3 ± 1.5 μL). PCC applied 30 minutes after CCI did not reliably reduce intracerebral hemorrhage induced by excess dabigatran concentration compared with saline (10.4 ± 11.2 vs 8.7 ± 7.1 μL). Our data suggest pathophysiological differences in TBI occurring during warfarin and dabigatran anticoagulation. The reduced hemorrhage formation under dabigatran therapy could present a safety advantage compared with warfarin. An excess dabigatran concentration, however, can increase hemorrhage.

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Blood Pressure Lowering Decreases Intracerebral Hemorrhage Volume and Improves Behavioral Outcomes in Experimental Animals

Journal of Stroke ◽

10.5853/jos.2020.02390 ◽

2020 ◽

Vol 22 (3) ◽

pp. 416-418

Author(s):

Ferdinand O. Bohmann ◽

Alexander Seiler ◽

Sarah Gelhard ◽

Leonie Stolz ◽

Boris Brill ◽

...

Keyword(s):

Blood Pressure ◽

Intracerebral Hemorrhage ◽

Behavioral Outcomes ◽

Blood Pressure Lowering ◽

Experimental Animals ◽

Pressure Lowering ◽

Hemorrhage Volume

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Diagnostic and prognostic value of serum hepcidin concentration in patients with acute spontaneous supratentorial intracerebral hemorrhage

Zaporozhye Medical Journal ◽

10.14739/2310-1210.2021.2.228593 ◽

2021 ◽

Vol 23 (2) ◽

pp. 168-174

Author(s):

O. А. Koziolkin ◽

A. A. Kuznietsov

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Intracerebral Hemorrhage ◽

Logistic Regression Analysis ◽

Prognostic Value ◽

Cerebral Lesions ◽

Acute Period ◽

Serum Hepcidin ◽

Hemorrhage Volume ◽

Diagnostic And Prognostic Value

The aim of the study was to evaluate the diagnostic and prognostic value of serum hepcidin concentration in patients with acute spontaneous supratentorial intracerebral hemorrhage (SSICH). Materials and methods. Prospective cohort study of 88 patients with acute SSICH receiving the conservative therapy was conducted. Level of neurological deficit was evaluated using the Full Outline of UnResponsiveness Scale, the Glasgow Coma Scale and the National Institute of Health Stroke Scale. Computed tomography was performed to detect an intracerebral hemorrhage volume (ICHV), secondary intraventricular hemorrhage volume (SIVHV) and total volume of intracranial hemorrhage (TVICH). Laboratory blood samples were taken within 24 hours of hospitalization. Hepcidin levels, serum iron concentrations and total iron-binding capacity were determined, followed by calculations of transferrin saturation coefficient. Early neurological deterioration (END) and unfavorable variants of the acute period of SSICH (lethal outcome, modified Rankin score 4-5 on the 21st day of the disease) were considered as endpoints. Statistical processing of the obtained results included a correlation analysis, logistic regression analysis and ROC-analysis. Results. It was identified, that serum hepcidin level in the patients with SSICH was correlated with ICHV (R = 0.44, P ˂ 0.01), SIVHV (R = 0.45, P ˂ 0.01) and TVICH (R = 0.57, P ˂ 0.01). Hepcidin serum concentrations in the patients with ICHV >30 ml exceeded the value of those in cases of ICHV ≤30 ml by 69.0 % (P ˂ 0.0001). Serum levels of hepcidin were significantly higher in the patients with an unfavorable course and outcome of the disease in the acute period on the 1st day of admission (P ˂ 0.0001). Informative multipredictor models were developed via multiple logistic regression analysis, which include hepcidin values coupled with clinical and neurovisualization findings and are predictive of lethal and unfavorable acute period functional outcomes (AUC = 0,93, P ˂ 0.0001). Conclusions. The level of serum hepcidin in patients with acute SSICH is associated with the severity of cerebral lesions. The integration of serum hepcidin concentration with clinical and neuroimaging findings in the structure of multipredictor logistic regression models allows to determine the vital and functional prognosis of the acute period of SSICH with an accuracy of >85 %

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Commentary on Associations of Radiographic Small Vessel Disease with Acute Intracerebral Hemorrhage Volume, Hematoma Expansion, and Intraventricular Hemorrhage

Neurocritical Care ◽

10.1007/s12028-019-00884-4 ◽

2019 ◽

Vol 32 (2) ◽

pp. 361-362

Author(s):

Sarah E. Nelson

Keyword(s):

Intracerebral Hemorrhage ◽

Intraventricular Hemorrhage ◽

Small Vessel Disease ◽

Small Vessel ◽

Hematoma Expansion ◽

Vessel Disease ◽

Acute Intracerebral Hemorrhage ◽

Hemorrhage Volume

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Evaluation of Volumetric Change of Intracerebral Hemorrhage in Patients Treated with Thrombolysis for Intraventricular Hemorrhage

Neurocritical Care ◽

10.1007/s12028-020-01054-7 ◽

2020 ◽

Author(s):

Franziska Staub-Bartelt ◽

Jasper Hans van Lieshout ◽

Thomas Beez ◽

Rainer Kram ◽

Daniel Hänggi ◽

...

Keyword(s):

Basal Ganglia ◽

Intracerebral Hemorrhage ◽

Ct Scan ◽

Intraventricular Hemorrhage ◽

Volume Reduction ◽

Percentage Reduction ◽

Hematoma Volume ◽

Group A ◽

Group B ◽

Lysis Therapy

Abstract Background Intraventricular hemorrhage (IVH) is often caused by irruption of intracerebral hemorrhage (ICH) of basal ganglia or thalamus into the ventricular system. Instillation of recombinant tissue plasminogen activator (rtPA) via an external ventricular drainage (EVD) has been shown to effectively decrease IVH volumes while the impact of rtPA instillation on ICH volumes remains unclear. In this series, we analyzed volumetric changes of ICH in patients with and without intrathecal lysis therapy. Methods Between 01/2013 and 01/2019, 36 patients with IVH caused by hemorrhage of basal ganglia, thalamus or brain stem were treated with rtPA via an EVD (Group A). Initial volumes were determined in the first available computed tomography (CT) scan, final volumes in the last CT scan before discharge. During the same period, 41 patients with ICH without relevant IVH were treated without intrathecal lysis therapy at our neurocritical care unit (Group B). Serial CT scans were evaluated separately for changes in ICH volumes for both cohorts using OsiriX DICOM viewer. The Wilcoxon signed-rank test was performed for statistical analysis in not normally distributed variables. Results Median initial volume of ICH for treatment Group A was 6.5 ml and was reduced to 5.0 ml after first instillation of rtPA (p < 0.01). Twenty-six patients received a second treatment with rtPA (ICH volume reduction 4.5 to 3.3 ml, p < 0.01) and of this cohort further 16 patients underwent a third treatment (ICH volume reduction 3.0 ml to 1.5 ml, p < 0.01). Comparison of first and last CT scan in Group A confirmed an overall median percentage reduction of 91.7% (n = 36, p < 0.01) of ICH volumes and hematoma resolution in Group A was significantly more effective compared to non-rtPA group, Group B (percentage reduction = 68%) independent of initial hematoma volume in the regression analysis (p = 0.07, mean 11.1, 95%CI 7.7–14.5). There were no adverse events in Group A related to rtPA instillation. Conclusion Intrathecal lysis therapy leads to a significant reduction in the intraparenchymal hematoma volume with faster clot resolution compared to the spontaneous hematoma resorption. Furthermore, intrathecal rtPA application had no adverse effect on ICH volume.

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Tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign trial: Rationale and design

International Journal of Stroke ◽

10.1177/1747493017694394 ◽

2017 ◽

Vol 12 (3) ◽

pp. 326-331 ◽

Cited By ~ 10

Author(s):

Liping Liu ◽

Yilong Wang ◽

Xia Meng ◽

Na Li ◽

Ying Tan ◽

...

Keyword(s):

High Risk ◽

Intracerebral Hemorrhage ◽

Tranexamic Acid ◽

Primary Outcome Measure ◽

Hematoma Expansion ◽

Spot Sign ◽

Double Blind ◽

Risk Patients ◽

Acute Intracerebral Hemorrhage ◽

Hemorrhage Volume

Rationale Acute intracerebral hemorrhage inflicts a high-economic and -health burden. Computed tomography angiography spot sign is a predictor of hematoma expansion, is associated with poor clinical outcome and is an important stratifying variable for patients treated with haemostatic therapy. Aims We aim to compare the effect of treatment with tranexamic acid to placebo for the prevention of hemorrhage growth in patients with high-risk acute intracerebral hemorrhage with a positive spot sign. Design The tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign (TRAIGE) is a prospective, multicenter, placebo-controlled, double-blind, investigator-led, randomized clinical trial that will include an estimated 240 participants. Patients with intracerebral hemorrhage demonstrating symptom onset within 8 h and with the spot sign as a biomarker for ongoing hemorrhage, and no contraindications for antifibrinolytic therapy, will be enrolled to receive either tranexamic acid or placebo. The primary outcome measure is the presence of hemorrhage growth defined as an increase in intracerebral hemorrhage volume >33% or >6 ml from baseline to 24 ± 2 h. The secondary outcomes include safety and clinical outcomes. Conclusion The TRAIGE trial evaluates the efficacy of haemostatic therapy with tranexamic acid in the prevention of hemorrhage growth among high-risk patients with acute intracerebral hemorrhage.

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Abilities of a Densitometric Analysis of Computed Tomography Images and Hemorrhagic Parameters to Predict Outcome Favorability in Patients With Intracerebral Hemorrhage

Neurosurgery ◽

10.1093/neuros/nyx379 ◽

2017 ◽

Vol 83 (2) ◽

pp. 226-236 ◽

Cited By ~ 4

Author(s):

Hakseung Kim ◽

Xiaoke Yang ◽

Young Hun Choi ◽

Byung C Yoon ◽

Keewon Kim ◽

...

Keyword(s):

Computed Tomography ◽

Intracerebral Hemorrhage ◽

Rapid Assessment ◽

Ct Images ◽

Interquartile Range ◽

Densitometric Analysis ◽

Computed Tomography Images ◽

Outcome Favorability ◽

Actual Volume ◽

Hemorrhage Volume

Abstract BACKGROUND Intracerebral hemorrhage (ICH) is one of the most devastating subtypes of stroke. A rapid assessment of ICH severity involves the use of computed tomography (CT) and derivation of the hemorrhage volume, which is often estimated using the ABC/2 method. However, these estimates are highly inaccurate and may not be feasible for anticipating outcome favorability. OBJECTIVE To predict patient outcomes via a quantitative, densitometric analysis of CT images, and to compare the predictive power of these densitometric parameters with the conventional ABC/2 volumetric parameter and segmented hemorrhage volumes. METHODS Noncontrast CT images of 87 adult patients with ICH (favorable outcomes = 69, unfavorable outcomes = 12, and deceased = 6) were analyzed. In-house software was used to calculate the segmented hemorrhage volumes, ABC/2 and densitometric parameters, including the skewness and kurtosis of the density distribution, interquartile ranges, and proportions of specific pixels in sets of CT images. Nonparametric statistical analyses were conducted. RESULTS The densitometric parameter interquartile range exhibited greatest accuracy (82.7%) in predicting favorable outcomes. The combination of skewness and the interquartile range effectively predicted mortality (accuracy = 83.3%). The actual volume of the ICH exhibited good coherence with ABC/2 (R = 0.79). Both parameters predicted mortality with moderate accuracy (<78%) but were less effective in predicting unfavorable outcomes. CONCLUSION Hemorrhage volume was rapidly estimated and effectively predicted mortality in patients with ICH; however, this value may not be useful for predicting favorable outcomes. The densitometric analysis exhibited significantly higher power in predicting mortality and favorable outcomes in patients with ICH.

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