The number of patients who are on long-term anticoagulation
therapy while experiencing
traumatic brain injury (TBI) is rising. This experimental study evaluated whether
warfarin pre-treatment increases
brain hemorrhage and worsens functional outcome after TBI, and whether the rapid
reversal of anticoagulation after TBI prevents
warfarin-exacerbated brain damage. Normal CD-1 mice (C) and mice pre-treated with
warfarin (W) to an International Normalized Ratio of 3.5±0.9 underwent TBI using a controlled cortical impact model. Mean
hemorrhage volume 24 h after TBI was 1.2±0.4 μL in C mice and 10.9±6.9 μL in W mice (p=0.029, n=4 per group). In a second study, anticoagulated mice received either saline (W-S) or
prothrombin complex concentrate (W-PCC, 100 U/kg) intravenously 60 min after TBI.
Anticoagulation reversal using PCC (W-PCC mice) reduced
hemorrhage volumes as compared to W-S animals (7.3±6.0 versus 19.8±14.0 μL, p=0.045, n=8 per group). In a third study, we examined motor deficits and lesion volume in C, W-S, and W-PCC mice until 33 days after injury. Functional outcome and lesion volume were no different between groups (n=10 per group). In conclusion, we characterized an experimental model of TBI occurring during
warfarin anticoagulation. Anticoagulation led to higher intracerebral blood volumes, but did not significantly worsen functional outcome. The rapid
reversal of anticoagulation may be effective in preventing excess
bleeding.