Does Dabigatran Increase the Risk of Delayed Hematoma Expansion in a Rat Model of Collagenase-induced Intracerebral Hemorrhage?

Background and Purpose: The characteristics of direct oral anticoagulant (DOAC)-related intracerebral hemorrhage (ICH) have not been fully clarified. We planned to recruit patients prospectively and to investigate the characteristics and outcomes in patients with ICH receiving direct oral anticoagulant (DOAC) and warfarin treatment. Methods: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke patients receiving OAC. Patient enrollment started in April 2016 at 25 tertiary centers across Japan. We compared imaging, clinical characteristics, and discharge modified Rankin Scale (mRS) between DOAC- and warfarin-related ICH patients with atrial fibrillation (AF). Results: A total of 154 patients (51 women; median age 77 [quartiles 69-87] years) were analyzed. Of these, 111 patients (72%) received prior DOAC treatment and the remaining 43 (28%) received prior warfarin treatment (Fig. A, B and C). There were no relevant differences in clinical and hematoma characteristics between DOAC- and warfarin-related ICH regarding baseline hematoma volume (median [quartiles]: DOAC, 11 [5-23] mL vs. warfarin, 12 [5-30] mL; P =0.95), rate of hematoma expansion (DOAC, 12/111 [11%] vs. warfarin, 4/43 [9%]; P =0.80), rate of subcortical hemorrhage (DOAC, 15/111 [11%] vs. warfarin, 10/43 [9%]; P =0.80) and the proportion of patients with unfavorable outcome (mRS, 4-6: DOAC 76/108 [70%] vs. warfarin 23/38 [61%]; P =0.26). Cerebral microbleeds (CMBs) were detected more frequently in DOAC group than in warfarin (47/76 [62%] vs. 11/32 [34%]; P <0.01). Subgroup analyses showed that type of DOAC agent did not result in relevant differences in imaging characteristics or outcome (Fig. D and E). Conclusions: Our results showed that there were no significant differences in hematoma characteristics and functional outcome among AF patients with DOAC- or warfarin-related ICH.

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Abstract 3729: Delayed Hematoma Expansion Occurs After ICH: Observations from the Safety of Pioglitazone for Hematoma Resolution in INtraCerebral Hemorrhage (SHRINC) trial

Stroke ◽

10.1161/str.43.suppl_1.a3729 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Navdeep S Sangha ◽

Farhaan Vahidy ◽

Mallikarjunarao Kasam ◽

Mohammed Rahbar ◽

Bursaw Andrew ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Prospective Study ◽

Univariate Analysis ◽

Primary Objective ◽

Hematoma Expansion ◽

Hematoma Growth ◽

Secondary Objective ◽

Magnetic Resonance Imaging Mri ◽

Associated Risk Factors

Background and Purpose Early hematoma expansion (EHE) has been described in the first 48 hours. SHRINC is a phase 2 prospective safety trial whose primary objective is to assess the safety of pioglitazone (PIO) when administered to patients with spontaneous intracerebral hemorrhage (SICH) compared to standard care. A secondary objective is to characterize the changes in hematoma resolution and expansion over time. This prospective study addresses the natural history, clinical impact, and associated risk factors of late hematoma expansion (LEX) by serial magnetic resonance imaging (MRI) after SICH. Methods SHRINC aims to enroll 78 subjects between the ages of 18-80 with a SICH of ≥ 5 ml. This analysis includes the first 42 patients enrolled. Four subjects were excluded because they did not have an MRI after day 2. A baseline CTH was performed followed by an MRI within 24 hours of symptom onset. Hematoma volume (Hv) was measured on FLAIR sequences using a previously published semi-automated range of interest method. LEX was defined as an increase in Hv > 0.5 ml after the 48 hour MRI. Factors associated with LEX were evaluated with logistic regression. Longitudinal analyses were used for measurements taken over the follow up period. Results: Ten (26.3%) of 38 subjects displayed LEX. Eight subjects had LEX between day 2 to 14, and 4 between days 14 to 28. The median initial Hv was 16.1cc in LEX patients and 24.1cc in those without expansion (NEX) (p=0.23). Lower platelet counts (p=0.04) and BUN levels (p=0.03) were associated with LEX in univariate analysis. Multivariate analysis suggested that those with higher BUN levels were less likely to have LEX (OR=0.81; 95%CI 0.65-0.99). Blood pressure and EHE (13.2%) were not associated with LEX. There was no difference in neurological worsening (NIHSS increase ≥ 4), 6 month mRS or death between LEX and NEX. Conclusion: This is the first prospective study to address LEX with serial MRIs. LEX occurs between day 2 to 14 and day 14 to 28. Elevated BUN levels may decrease the likelihood of LEX. A limitation of our study is that the effect of PIO on LEX could not be evaluated because SHRINC is a blinded trial. Further studies will assess the pathophysiology of LEX and its potential implications in clinical trials evaluating hematoma growth and resolution.

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Abstract 3543: Imaging Correlates of Early Neurologic Deterioration among Patients with Intracerebral Hemorrhage

Stroke ◽

10.1161/str.43.suppl_1.a3543 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Nerses Sanossian ◽

Adrian M Burgos ◽

David S Liebeskind ◽

Sidney Starkman ◽

Pablo Villablanca ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Hematoma Expansion ◽

Hematoma Volume ◽

Phase 3 ◽

Neurologic Deterioration ◽

Irregular Border ◽

History Of ◽

Initial Imaging ◽

Fazekas Scale ◽

Frequent Presence

Background: Early neurologic deterioration (END) occurs commonly in intracerebral hemorrhage (ICH) patients being transported by EMS ambulances, but the imaging correlates of END have not been previously delineated. Methods: We analyzed consecutive ICH patients in the Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Trial, a phase 3, multicenter of paramedic-initiated magnesium sulfate vs. placebo for stroke patients presenting within 2 hours of symptom onset. END was defined as a 2-point or greater decrease in the Glasgow Coma Scale (GCS) from paramedic evaluation to ED evaluation. Baseline imaging studies were independently analyzed by 2 neurologists for ICH location, volume, presence of intraventricular hemorrhage (IVH), heterogeneity (defined as >20 point difference in Hounsfield units), irregular hematoma borders, multilobulated appearance, and substantial edema (defined as >0.5cm thickness). Leukoaraiosis was graded using the Fazekas scale for periventricular and deep white matter changes (0-3 for each). Results: Among 127 patients, mean age was 66 (SD 14) years, 34% were women, 35% were Hispanic ethnicity, 83% white, and 84% had a history of HTN. Patients were evaluated by paramedics a median of 23 (IQR 16, 39) minutes after last known well time (LKWT). At that time, the median GCS was 15 (IQR 15-15) and mean SBP/DBP was 177/95 (SD 34/22). Initial post-arrival brain imaging was performed a median of 94 (IQR 77, 117) min after LKWT. Post-arrival study GCS scores were obtained at a median of 108 (IQR 70, 144) min after LWKT. Early neurologic deterioration occurred in 37 (29%) patients. Among these patients, median first ED GCS was 3 (IQR 3-10). On first imaging, compared with neurologically stable patients, END patients had larger hematoma volume (33 cc v 16 cc, p<0.0001), and more frequent presence of intraventricular extension (45% v 20%, p=0.003), midline shift (58% v 22%), substantial edema (54% v 26%, p=0.038), heterogeneous density (50% v 22%, p=0.006), multilobulated appearance (44% v 18%, p=0.002), and irregular border (39% v 14%, p=0.010). Leukoaraiosis and cortical v subcortical location did not affect rates of END. In multivariate analysis, hematoma volume and presence of IVH were imaging findings independently associated with early neurologic deterioration. Conclusions: About 3 in 10 patients with hyperacute ICH neurologically deteriorate during the prehospital and early emergency department course, often before neuroimaging is obtained. Patients with early neurologic deterioration have larger hematoma volume and occurrence of IVH on initial imaging. These findings suggest hematoma expansion prior to ED arrival drives early neurologic deterioration in ICH and emphasize the need for prehospital interventions.

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Abstract TP291: Hematoma Retraction and Perihematoma Hypodensity in Neutral Brain Model of Intracerebral Hemorrhage

Stroke ◽

10.1161/str.44.suppl_1.atp291 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Shahram Majidi ◽

Basit Rahim ◽

Sarwat I Gilani ◽

Waqas I Gilani ◽

Malik M Adil ◽

...

Keyword(s):

Biological Activity ◽

Intracerebral Hemorrhage ◽

Ct Scan ◽

Early Period ◽

Ct Scans ◽

Hematoma Expansion ◽

Human Cadaver ◽

Fresh Blood ◽

The Right

Background: The temporal evolution of intracerebral hematomas and perihematoma edema in the ultra-early period on computed tomographic (CT) scans in patients with intracerebral hemorrhage (ICH) is not well understood. We aimed to investigate hematoma and perihematoma changes in “neutral brain” models of ICH. Methods: One human and 6 goat cadaveric heads were used as “neutral brains” to provide physical properties of the brain without any biological activity or new bleeding. ICH was induced by slow injection of 4 ml of fresh blood into the right basal ganglia of the goat brains. Similarly, 20 ml of fresh blood was injected deep into the white matter of the human cadaver head in each hemisphere. Serial CT scans of the heads were performed at 0, 1, 3, and 5 hours after inducing ICH. Analyze software (AnalyzeDirect, Overland Park, KS) was used to measure hematoma and perihematoma hypodensity volumes in the baseline and follow up CT scans. Results: The initial hematoma volumes of 11.6 ml and 10.5 ml in the right and the left hemispheres of the human cadaver brain gradually decreased to 6.6 ml and 5.4 ml at 5 hours, showing 43% and 48% retraction of hematoma, respectively. The volume of the perihematoma hypodensity in the right and left hemisphere increased from 2.6 ml and 2.2 ml in the 1 hour follow up CT scans to 4.9 ml and 4.4 ml in the 5 hour CT scan, respectively. Hematoma retraction was also observed in all six ICH models in the goat brains. The mean ICH volume in the goat heads was decreased from 1.49 ml in the baseline CT scan to 1.01 ml in the 5 hour follow up CT scan showing 29.6% hematoma retraction. Perihematoma hypodensity was visualized in 70% of ICH in goat brains, with an increasing mean hypodensity volume of 0.4 ml in the baseline CT scan to 0.8 ml in the 5 hour follow up CT scan. Conclusion: Our study demonstrated that substantial hematoma retraction and perihematoma hypodensity occurs in intracerebral hematomas in the absence of any new bleeding or biological activity of the surrounding brain. Such observations suggest that active bleeding is underestimated in patients with no or small hematoma expansion and our understanding of perihematoma hypodesity needs to be reconsidered.

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Response to “The NAG Scale: Noble Predictive Scale for Hematoma Expansion in Intracerebral Hemorrhage”

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2018.09.022 ◽

2018 ◽

Vol 27 (12) ◽

pp. 3673-3674

Author(s):

Ajay Hegde

Keyword(s):

Intracerebral Hemorrhage ◽

Hematoma Expansion

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