Traumatic Brain Injury during Warfarin Anticoagulation: An Experimental Study in Mice

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 mu L in C mice and 10.9 +/- 6.9 mu L 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 mu L, 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.