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

Tanoue, Shunsuke; Inamasu, Joji; Yamada, Masayuki; Toyama, Hiroshi; Hirose, Yuichi

doi:10.1016/j.jstrokecerebrovasdis.2014.09.010

Cited by 10 publications

(4 citation statements)

References 23 publications

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“…In another case, oral doses of 10 and 20 mg/kg of dabigatran also did not increase ICH using the same 0.2 unit dose of collagenase, but bleeding was quantified solely by MRI. 31 This last study corroborates our findings about the effect of NOACs on ICH using MRI. However, increased ICH was detected by MRI when dabigatran etexilate was administered intraperitoneally at doses of 2.25 to 9 mg/kg.…”

Section: Discussionsupporting

confidence: 90%

“…In another case, oral doses of 10 and 20 mg/kg of dabigatran also did not increase ICH using the same 0.2 unit dose of collagenase, but bleeding was quantified solely by MRI. 31 This last study corroborates Fig. 5 Evans blue extravasation from the brains of rats treated with saline or oral anticoagulants after 24 hours of collagenase-induced ICH.…”

Section: Discussionsupporting

confidence: 80%

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A Combination of Ex Vivo and In Vivo Strategies for Evaluating How Much New Oral Anticoagulants Exacerbate Experimental Intracerebral Bleeding

Mourāo

Fonseca

Ferreira

et al. 2023

TH Open

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Background Intracerebral hemorrhage is the most serious complication of anticoagulant therapy but the effects of different types of oral anticoagulants on the expansion of these hemorrhages are still unclear. Clinical studies have revealed controversial results; more robust and long-term clinical evaluations are necessary to define their outcomes. An alternative is to test the effect of these drugs in experimental models of intracerebral bleeding induced in animals. Aims To test new oral anticoagulants (dabigatran etexilate, rivaroxaban, and apixaban) in an experimental model of intracerebral hemorrhage induced by collagenase injection into the brain striatum of rats. Warfarin was used for comparison. Methods Ex vivo anticoagulant assays and an experimental model of venous thrombosis were employed to determine the doses and periods of time required for the anticoagulants to achieve their maximum effects. Subsequently, volumes of brain hematoma were evaluated after administration of the anticoagulants, using these same parameters. Volumes of brain hematoma were evaluated by magnetic resonance imaging, H&E (hematoxylin and eosin) staining, and Evans blue extravasation. Neuromotor function was assessed by the elevated body swing test. Results and Conclusions The new oral anticoagulants did not increase intracranial bleeding compared with control animals, while warfarin markedly favored expansion of the hematomas, as revealed by magnetic resonance imaging and H&E staining. Dabigatran etexilate caused a modest but statistically significant increase in Evans blue extravasation. We did not observe significant differences in elevated body swing tests among the experimental groups. The new oral anticoagulants may provide a better control over a brain hemorrhage than warfarin.

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Section: Discussionsupporting

confidence: 90%

“…In another case, oral doses of 10 and 20 mg/kg of dabigatran also did not increase ICH using the same 0.2 unit dose of collagenase, but bleeding was quantified solely by MRI. 31 This last study corroborates Fig. 5 Evans blue extravasation from the brains of rats treated with saline or oral anticoagulants after 24 hours of collagenase-induced ICH.…”

Section: Discussionsupporting

confidence: 80%

A Combination of Ex Vivo and In Vivo Strategies for Evaluating How Much New Oral Anticoagulants Exacerbate Experimental Intracerebral Bleeding

Mourāo

Fonseca

Ferreira

et al. 2023

TH Open

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“…After the hemorrhagic event, warfarin was replaced with dabigatran, a novel oral anti-coagulant approved for use in Japan in 2011. 18 Although hemorrhagic complications are less common in patients using dabigatran than in those using warfarin, 18,19 there is a lack of data on the frequency of dabigatran-associated hemorrhage in patients who have already sustained warfarin-associated hemorrhage, and careful follow-up is warranted.…”

Section: Discussionmentioning

confidence: 99%

Warfarin-associated Intraspinal Hematoma

et al. 2016

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Intracerebral hemorrhage is a well-known complication resulting from warfarin use; however, warfarin-associated intraspinal hematoma is very rare. Warfarin-associated intraspinal hematoma may exhibit delayed progression, and patients may present with atypical symptoms, occasionally resulting in delayed diagnosis. We report the case of a 65-year-old man who visited our emergency department (ED) with acute urinary retention. He had been previously diagnosed with non-valvular atrial fibrillation, arterial hypertension, and benign prostatic hyperplasia, and he used warfarin for the prevention of systemic embolism. The patient was initially diagnosed with worsening of the prostatic hyperplasia. After 2 days, he revisited the ED with painless paraparesis. Magnetic resonance imaging of the thoracic spine revealed an intraspinal hematoma at Th7-8, and blood coagulation tests indicated a prothrombin time-international normalized ratio of 3.33. Despite attempts to reverse the effects of warfarin with vitamin K administration, the paraparesis progressed to paraplegia, necessitating urgent surgical removal of the hematoma. Partial recovery of motor function was evident after surgery. From the present case, we learned that intraspinal hematoma should be included in the differential diagnosis of patients using warfarin who present with acute urinary retention. Although there are no evidence-based treatment guidelines for warfarin-associated intraspinal hematoma, surgical treatment may be warranted for those who exhibit neurological deterioration.

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“…Translational MRI (Magnetic resonance imaging) research with using rodent models are indispensable in many basic medical researches (Hansen et al, 1980) (Denic et al, 2011) (Tanoue et al, 2015), because it is a non-invasive monitoring device. Many MR-images of a small animal model's brain taken by MRI are generally examined with reference to the Atlas (Paxinos, G. and Watson, C., 2013), which describes functions and geometric positions of the brain tissue in a form of geography.…”

Section: Introductionmentioning

confidence: 99%

A novel design of rat's head positioner for MRI and its feasibility

Narita

Yamada

2018

JAMDSM

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A novel design of an animal bed, which is termed "head positioner", for fixing a rat is newly proposed in this research. The head positioner is used for a basic medical study to analyze brain activities for small animals with MRI (Magnetic resonance imaging). Various requests and specifications for it is described by investigations and our preliminary experiments in advance. A rat's head positioner is designed by a 3D CAD (Computer Aided Design) and also created by a 3D printer with using PLA (polylactic acid) resin. An MRI experiment is performed by the new head positioner and a lot of sharp images can be taken by reducing a rat's head motions. The images of the rat's brain data can be also taken with the same angle as a brain Atlas which combine geometric positions with brain functions in a form of geography. It enables us to analyze the rat's reaction from the viewpoints of the brain functions. A feasibility of the new design of rat's head positioner is demonstrated in this paper.

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

Cited by 10 publications

References 23 publications

A Combination of Ex Vivo and In Vivo Strategies for Evaluating How Much New Oral Anticoagulants Exacerbate Experimental Intracerebral Bleeding

A Combination of Ex Vivo and In Vivo Strategies for Evaluating How Much New Oral Anticoagulants Exacerbate Experimental Intracerebral Bleeding

Warfarin-associated Intraspinal Hematoma

A novel design of rat's head positioner for MRI and its feasibility

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