Abstract | BACKGROUND AND PURPOSE: METHODS: In C57BL/6 mice receiving DE (4.5 or 9.0 mg/kg), in vivo and in vitro coagulation assays and dabigatran plasma levels were measured repeatedly. Thirty minutes after inducing ICH by striatal collagenase injection, mice received an intravenous injection of saline, prothrombin complex concentrate (PCC; 100 U/kg), murine fresh-frozen plasma (200 μL), or recombinant human factor VIIa (8.0 mg/kg). ICH volume was quantified on brain cryosections 24 hours later. RESULTS: DE substantially prolonged tail vein bleeding time and ecarin clotting time for 4 hours corresponding to dabigatran plasma levels. Intracerebral hematoma expansion was observed mainly during the first 3 hours on serial T2* MRI. Anticoagulation with high doses of DE increased the hematoma volume significantly. PCC and, less consistently, fresh-frozen plasma prevented excess hematoma expansion caused by DE, whereas recombinant human factor VIIa was ineffective. Prevention of hematoma growth and reversal of tail vein bleeding time by PCC were dose-dependent. CONCLUSIONS: The study provides strong evidence that PCC and, less consistently, fresh-frozen plasma prevent excess intracerebral hematoma expansion in a murine ICH model associated with dabigatran. The efficacy and safety of this strategy must be further evaluated in clinical studies.
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Authors | Wei Zhou, Sönke Schwarting, Sergio Illanes, Arthur Liesz, Moritz Middelhoff, Markus Zorn, Martin Bendszus, Sabine Heiland, Joanne van Ryn, Roland Veltkamp |
Journal | Stroke
(Stroke)
Vol. 42
Issue 12
Pg. 3594-9
(Dec 2011)
ISSN: 1524-4628 [Electronic] United States |
PMID | 21998060
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antithrombins
- Benzimidazoles
- beta-Alanine
- Dabigatran
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Topics |
- Animals
- Antithrombins
(administration & dosage, therapeutic use)
- Benzimidazoles
(administration & dosage, therapeutic use)
- Blood Coagulation
(drug effects)
- Brain
(drug effects, pathology)
- Cerebral Hemorrhage
(drug therapy, pathology)
- Dabigatran
- Dose-Response Relationship, Drug
- Mice
- beta-Alanine
(administration & dosage, analogs & derivatives, therapeutic use)
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