A New Antithrombotic Agent in the Treatment of Acute Renal Failure Due to Hemolytic-Uremic Syndrome and Thrombotic Thrombocytopenic Purpura

Hepatic Veno-Occlusive Disease following Hematopoietic Stem Cell Transplantation

“…DF inihibits fibrin deposition and may modulate vitronectin and fibronectin release, which as components of extracellular matrix are linked to collagen formation and fibrosis [106, 107, 108]. Clinical trials of DF have demonstrated activity in peripheral vascular disease, microvascular thrombotic states, ischemic organ injury and chemotherapy-related hemolytic uremic syndrome [103, 107, 109, 110]. Recent preclinical studies of human derived, LPS-exposed microvascular and macrovascular endothelium by Falanga et al [111, 112]have shown selective and protective effects of DF in LPS-mediated microvascular injury through enhanced fibrinolysis and modulation of soluble tissue factor and TFPI expression.…”

Pharmacologic Intervention to Prevent Hemodialysis Vascular Access Thrombosis

“…Initially, it was shown to reduce intimal hyperplasia after thrombi were electrically induced in dogs [131]. In humans, II it has reduced the incidence of intimal hyperplasia in renal transplant grafts [132] and prevented thrombosis of subcla vian catheter use for total parenteral nutrition [133] and reversed the acute renal failure associated with endothelial injury in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura [134]. More recently, cyclos porin-treated rats have been found to have an increase in PGL produced by defibrotide which was thought to confer a protective effect against cyclosporin-produced glomeru lar injury [135].…”

Morphometric and Ultrastructural Study of Experimental Venous Thrombosis

“…Defibrotide is an antithrombotic agent which has been proven to be effective in a number of venous and arterial thrombotic models as well as human thrombotic dis eases [1,2,[5][6][7][8][9], Its mechanism of action is through the inhibition of antiplasmin, in crease in plasminogen activator production and stimulation of synthesis and release of prostacyclin from endothelial cells. The pharmacological actions are dose-dependent and equally present after endovenous and oral administation [7,8], The venous thrombotic model used in this study is based on the ability of a colla gen-coated thread to activate fibrin deposi tion and platelet adhesion and aggregation; it has been reported that during the first 6 h the thrombus looks like a blood clot made up by red cells and by a loose fibrin network [11].…”

“…Defibrotide has been shown to be effec tive in a number of experimental arterial and venous thrombotic models as well as in hu man patients affected by vascular occlusive disorders [1,2], A protective effect in acute myocardial infarction has also been demon- strated [3,4], Defibrotide does not display anticoagulant or hemodynamic effects, but has powerful profibrinolytic activity which is due to the release of plasminogen-activat ing factor and inhibition of antiplasmin ac tivity [5][6][7] and to increased production of prostacyclin (PGD) from the vascular endo thelial tissue [8,9].…”