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Prothrombotic effect of Rofecoxib in a murine venous thrombosis model.

Nagai N, Hoylaerts MF, Gallacher DJ, Lu HR, Lijnen HR

Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium.

The potential prothrombotic effect of the cyclooxygenase-2 (COX-2) inhibitor Rofecoxib (Vioxx) was investigated using murine thrombosis models. In a jugular vein thrombosis model (photochemically induced injury) in lean wild-type mice, Rofecoxib treatment for 4 weeks induced a mild prothrombotic tendency, as indicated by a shorter occlusion time as compared to placebo (median of 12 min versus 36 min; p<0.05). Thrombus size was somewhat, but not significantly, enhanced after Rofecoxib treatment. In a femoral artery thrombosis model (FeCl(3) induced injury) Rofecoxib did not cause an enhanced thrombotic tendency in mice with nutritionally induced or genetically determined (ob/ob) obesity. The occlusion time was comparable for obese wild-type mice with (8.8+/-0.7 min) or without (7.8+/-2.1 min) Rofecoxib treatment, as well as for ob/ob mice (8.5+/-0.7 min versus 6.8+/-3.0 min). Thus, an enhanced prothrombotic effect of Rofecoxib was detected when using a venous thrombosis model in lean mice, but not when using an arterial thrombosis model in obese mice.

Published 23 June 2008 in Thromb Res.
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