Kinetics of hematoma expansion in murine warfarin-associated intracerebral hemorrhage
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Illanes Diez, Sergio
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Kinetics of hematoma expansion in murine warfarin-associated intracerebral hemorrhage
Abstract
Background and purpose: The burden of intracerebral hemorrhage associated with oral
anticoagulants (OAC-ICH) is growing. However, little is known about the pathophysiology of
W-ICH. Herein,we refine amousemodel of OAC-ICH using repetitive T2*MRI to describe kinetics
of hematoma enlargement, and establish a benchside point of care INR assay (PoC) for
assessment of anticoagulation. Methods: C57/BL6 mice drank warfarin (0.4 mg/kg/24 h) in their
water. ICH was induced by stereotactic injection of collagenase type VII (0.045U) into the left
striatum. Hemorrhagic blood volume was quantified byMRI T2* images and on cryosections 48 h
after ICH induction. Kinetics of hematoma expansion were compared in strongly,moderately,
and non-anticoagulated mice using repeated MRI T2* imaging. The PoC INR technique was
validated against standard laboratory INR, and tail vein bleeding time (TVBT). Results: PoC INR
correlated with central laboratory measurements (r=0.989; p<0.0001) andwith TVBT (r=0.982;
p<0.0001). Hematoma volume was 21.2±6.7mm3 in heavily (PoC INR 4−5), 12.3±4.8 in
moderately (INR 2−3), and 8.6±3.3 in non-anticoagulated mice (INR<1.2). Hematoma volume
determined from cryosections and T2* MRI correlated well (r=0.922). Strength of
anticoagulation was associated with neurologic outcome. Hematoma enlargement occurred
mainly during the first 3 h in anticoagulated mice. Conclusions: PoC allows repeated benchside
INR measurements in individual mice which reflect the level of anticoagulation. Stronger
anticoagulation results in larger hematoma volumes. As hematoma enlargement occurs
mainly during the first hours, potential hemostatic therapies should be tested early in this
OAC-ICH model.
Patrocinador
Sergio Illanes is supported by a DAAD-CONICYT Scholarship.
Roland Veltkamp is supported by an Else-Kröner-Memorial
Scholarship.
Identifier
URI: https://repositorio.uchile.cl/handle/2250/128605
DOI: doi:10.1016/j.brainres.2010.01.015
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BRAIN RESEARCH 1320 (2010), 135–142
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