Early edema in warfarin-related intracerebral hemorrhage

Levine, Joshua M.; Snider, Ryan W.; Finkelstein, David; Gurol, M. Edip; Chanderraj, Rishi; Smith, Eric E.; Greenberg, Steven M.; Rosand, Jonathan

doi:10.1007/s12028-007-0039-3

Cited by 44 publications

(40 citation statements)

References 37 publications

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“…Potentially, TA may accelerate fibrin clot stabilization, which is a necessary step in the early phase of perihematomal edema formation after ICH. 32,33 This is a major limitation for TA use in ICH.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of Hemostatic Therapy in Experimental Warfarin-Associated Intracerebral Hemorrhage

Illanes

Zhou

Schwarting

et al. 2011

Stroke

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Background and Purpose— Intracerebral hemorrhage associated with oral anticoagulants has a poor prognosis. Current treatment guidelines are based on case series and plausibility only, and a common consensus on effective hemostatic therapy is missing. We compared the effectiveness of diverse hemostatic approaches in a mouse model of warfarin-associated intracerebral hemorrhage. Methods— Male C57BL/6 mice received anticoagulant treatment with warfarin (0.4 mg/kg for 3 days). Intracerebral hemorrhage was induced by striatal injection of collagenase, and 30 minutes later, mice received an intravenous injection of saline (200 μL n=15), prothrombin complex concentrate (100 U/kg, n=10), fresh-frozen plasma (200 μL, n=13), recombinant human Factor VII activated (3.5 mg/kg, n=8 and 10 mg/kg, n=8), or tranhexamic acid (400 mg/kg, n=12). Intracerebral hemorrhage volume was quantified on T2-weighted images after 24 hours. Results— Mean hematoma volumes were 7.4±1.8 mm 3 in the nonwarfarin controls and 21.9±5.0 mm 3 in the warfarin group receiving saline. Prothrombin complex concentrate (7.5±2.3 mm 3 ) and fresh-frozen plasma (8.7±2.1) treatment resulted in significantly smaller hematoma volume compared with saline. Recombinant human Factor VII activated (10 mg/kg: 14.7±3.4; 3.5 mg/kg: 15.0±6.8 mm 3 ) and tranexamic acid (16.2±4.1 mm 3 ) were less effective. Water content in the hemorrhagic hemisphere was similar in all groups except for tranexamic acid in which it was significantly increased. Conclusions— Prothrombin complex concentrate and fresh-frozen plasma effectively prevent hematoma growth in murine warfarin-associated intracerebral hemorrhage, whereas Factor VIIa was less effective. Tranexamic acid exacerbates perihematoma edema in this mouse warfarin-associated intracerebral hemorrhage model.

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Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of Hemostatic Therapy in Experimental Warfarin-Associated Intracerebral Hemorrhage

Illanes

Zhou

Schwarting

et al. 2011

Stroke

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“…These findings are supported by the work done by Gebel et al [87] who, in addition, noted that a larger baseline-relative edema volume (edema volume divided by hematoma volume) was associated with a significant decrease in poor 3-month outcome (OR 0.09 per 1-mL increase, p = 0.016). The etiology of this is likely multifactorial and includes blood-brain barrier damage, lysis of red blood cells, and white blood cell recruitment, in addition to release of plasma proteins, thrombin, hemoglobin, iron, matrix metalloproteinases, interleukins, and other inflammatory mediators [9,25,[89][90][91][92][93].…”

Section: Perihematomal Edemamentioning

confidence: 99%

Clinical and Radiographic Predictors of Intracerebral Hemorrhage Outcome

et al. 2018

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Background: Intracerebral hemorrhage (ICH) represents 10-15% of all stroke cases in the US annually. Fewer than 40% of these patients ever reach long-term functional independence, and mortality rate is roughly 40% at 1 month. Due to the high morbidity and mortality rates after ICH, early detection of high-risk patients would be beneficial in directing the management course and goals of care. This review aims to discuss relevant clinical and radiographic characteristics that can serve as predictors of poor prognosis and examine their efficacy in predicting patient outcomes after ICH. Summary: A literature review was conducted on various clinical and radiographic factors. They were examined for their predictive value in relation to ICH outcome. Studies that focused on each of these factors were included, and their results analyzed for trends with regard to incidence, patient outcome, and mortality rate. Key Message: In this review, we examined clinical and radiographic characteristics that have been found to be significantly associated to a varying degree with poor outcome. Clinical and radiographic predictors of poor patient outcome are invaluable when it comes to identifying high-risk patients and triaging accordingly as well as guiding decision-making.

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“…Of note, rebleeding is commoner in OAT-ICH compared with ICH in the setting of normal coagulation (Flibotte et al, 2004). Since coagulation cascade activation and thrombin production are important steps in cellular damage and disruption of the BBB following ICH, it seems logical that OAT-ICH will result in a different tissue response than spontaneous ICH as hematomas may contain noncoagulated blood (Levine et al, 2007;Xi et al, 2006). A new model of OAT-ICH incorporates water-soluble warfarin into mouse feeding bottles (Foerch et al, 2008).…”

Section: Multiple Models For Multiple Etiologiesmentioning

confidence: 99%

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

Kirkman

Allan

Parry‐Jones

2011

J Cereb Blood Flow Metab

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Intracerebral hemorrhage (ICH) has the highest mortality of all stroke subtypes, yet treatments are mainly limited to supportive management, and surgery remains controversial. Despite significant advances in our understanding of ICH pathophysiology, we still lack preclinical models that accurately replicate the underlying mechanisms of injury. Current experimental ICH models (including autologous blood and collagenase injection) simulate different aspects of ICH-mediated injury but lack some features of the clinical condition. Newly developed models, notably hypertension-and oral anticoagulant therapy-associated ICH models, offer added benefits but further study is needed to fully validate them. Here, we describe and discuss current approaches to experimental ICH, with suggestions for changes in how this condition is studied in the laboratory. Although advances in imaging over the past few decades have allowed greater insight into clinical ICH, there remains an important role for experimental models in furthering our understanding of the basic pathophysiologic processes underlying ICH, provided limitations of animal models are borne in mind. Owing to differences in existing models and the failed translation of benefits in experimental ICH to clinical practice, putative neuroprotectants should be trialed in multiple models using both histological and functional outcomes until a more accurate model of ICH is developed.

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Early edema in warfarin-related intracerebral hemorrhage

Abstract: Warfarin-related ICH is associated with less early relative edema than non-coagulopathic ICH. This is consistent with the theory that coagulation contributes to early edema. Early edema may be associated with improved functional outcome.

Cited by 44 publications

References 37 publications

Comparative Effectiveness of Hemostatic Therapy in Experimental Warfarin-Associated Intracerebral Hemorrhage

Comparative Effectiveness of Hemostatic Therapy in Experimental Warfarin-Associated Intracerebral Hemorrhage

Clinical and Radiographic Predictors of Intracerebral Hemorrhage Outcome

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

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