Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Defibrotide is a deoxyribonucleic acid derivative extracted from mammalian organs, which has been developed for the treatment of a number of vascular disorders. It appears to increase fibrinolysis and may possess antithrombotic, antiatherosclerotic and anti-ischaemic actions, probably due to its ability to selectively increase prostaglandin I2 and E2 levels and to increase tissue plasminogen activator and decrease plasminogen activator inhibitor function. Defibrotide is available as an intravenous and intramuscular preparation, and also as an oral formulation for long term use. Trials performed to date have provided initial evidence that defibrotide is effective in the treatment of peripheral obliterative arterial disease and acute thrombophlebitis, while preliminary data suggest possible use in preventing fibrin deposition in the circuitry of renal haemodialysis equipment. Efficacy in preventing deep vein thrombosis after surgery has been demonstrated but defibrotide does not appear to offer any therapeutic advantage over heparin. Further clinical experience is required in other disorders, including acute myocardial infarction, Raynaud's phenomenon, renal thrombotic microangiopathy and renal transplant rejection, before adequate assessment of efficacy in these areas can be made. Defibrotide is well tolerated, as assessed in trials of up to 6 months duration, with a low global incidence of adverse events (< 1 to 9%). Mild allergic reactions and gastrointestinal disturbances have occasionally been described, and a hypotensive effect has also infrequently been observed. Thus, available data suggest that defibrotide is a well tolerated agent with little or no anticoagulant activity, which is conveniently available in both parenteral and oral formulations. Initial data indicate that the drug may be a useful alternative in the treatment of peripheral obliterative arterial disease and thrombophlebitis, while its therapeutic potential in other vascular disorders and efficacy relative to established agents remains to be fully determined.
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PMID:Defibrotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in vascular disorders. 768 75

Defibrotide, a polydeoxyribonucleotide, has been found to modulate endothelial cell function, causing an increase in tissue plasminogen activator (t-PA) levels, a decrease in plasminogen activator inhibitor (PAI) levels, and an increase in prostaglandin I2 (PGI2) formation in humans. Defibrotide has no direct anticoagulant effect but has a synergistic action with heparin. A strong antithrombotic effect has been observed in animal models. Thus, defibrotide has a beneficial effect in cases of deep venous thrombosis (DVT), peripheral obliterative vascular disorder (POVD), stroke, vasculitis, and thromboembolism. Defibrotide also inhibits platelet function and activation. A significant decrease in platelet aggregate formation on the suture line in microarterial anastomosis in rats is one way defibrotide can inhibit platelet function and activation. In humans, a slight prolongation' of the lag period in collagen-induced aggregation has been observed. In addition, a slight decrease in the maximum amplitude of the secondary wave of ADP and adrenalin-induced aggregations was also found. Platelet adhesion is diminished, the platelet differential count on formvar membrane is altered, and platelet aggregate formation is significantly inhibited. With an increase in platelet cyclic AMP (cAMP) content and a decrease in malonyl dialdehyde (MDA) and thromboxane B2 (TXB2) formation, the levels of platelet secretion products such as PF-4 and beta-thromboglobulin (beta-TG) in plasma decreased progressively. It was also demonstrated that the 14C-glucose transport defect of the platelet membrane of atherosclerotic patients was partially corrected with defibrotide treatment.
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PMID:Effect of defibrotide on platelet function. 880 24