Effect of vascular injury on inhibition of venous thrombosis with ZK-807834, a direct inhibitor of factor Xa

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Abstract

Inhibition of factor Xa with the small molecule inhibitor ZK-807834 (Mr 527 Da, K i 0.11 nM) attenuates progression of thrombosis, but the ED 50 is substantially lower for venous compared with arterial thrombosis in experimental animals. To determine whether this reflects differences in the extent of vascular injury, we compared the dose-response of ZK-807834 for inhibition of venous thrombosis induced with a cotton thread and copper wire device in the presence and absence of balloon catheter-induced injury to the vena cava in rabbits. ZK-807834 administration over 2h (total dosages of 0.0023-2.3 (imol kg -1, n = 6/group) resulted in dose-dependent reductions in clot weight compared with vehicle controls, but the ED50 was 0.03 (imolkg -1 for non-injured veins and 0.42 (irnol kg -1 for injured veins. We conclude that vascular injury invokes a tissue factor-mediated response that increases the dose requirements for inhibition of venous thrombosis with ZK-807834. © 2003 International Society on Thrombosis and Haemostasis.

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Abendschein, D. R., Baum, P. K., Lightand, D. R., & Morser, J. (2003). Effect of vascular injury on inhibition of venous thrombosis with ZK-807834, a direct inhibitor of factor Xa. Journal of Thrombosis and Haemostasis, 1(9), 1955–1958. https://doi.org/10.1046/j.1538-7836.2003.00336.x

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