Premium
Effect of vascular injury on inhibition of venous thrombosis with ZK‐807834, a direct inhibitor of factor Xa
Author(s) -
Abendschein D. R.,
Baum P. K.,
Light D. R.,
Morser J.
Publication year - 2003
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1046/j.1538-7836.2003.00336.x
Subject(s) - thrombosis , ed50 , medicine , venous thrombosis , dose , balloon catheter , pharmacology , anesthesia , balloon , receptor
Summary. 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 2 h (total dosages of 0.0023–2.3 µmol kg −1 , n = 6/group) resulted in dose‐dependent reductions in clot weight compared with vehicle controls, but the ED 50 was 0.03 µmol kg −1 for non‐injured veins and 0.42 µmol 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.