Anticoagulant and antithrombotic effects of combinations of defibrotide with heparins and other antithrombotic agents in an animal thrombosis model.

Defibrotide, acetylsalicylic acid, low molecular weight heparin (CY 216), sodium heparin, Molsidomin and a thromboxane receptor antagonist have been investigated separately and in combinations in an animal thrombosis model in which rat mesenteric venules are damaged by defined laser energy. Furthermore, the ex vivo anticoagulant activity of Defibrotide and heparin were studied in rat plasma. All investigated agents showed a significant and dose-dependent antithrombotic effect when venules were damaged. A strong additive effect was observed when Defibrotide was administered together with heparins. The combinations of Defibrotide with other antithrombotic agents did not have significant additive effects. In the present study the combination of Defibrotide and heparins showed a prolongation of aPTT and Heptest in comparison with heparin given exclusively.