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 deflbrotide 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.

Defibrotide appears to have a number of effects on mediators of the coagulation and fibrinolytic systems. The drug selectively stimulates prostaglandin I₂ and E₂ production and, therefore, increases blood levels of these prostanoids. This appears to be a selective action, as thromboxane A₂ levels are unaffected. Defibrotide also increases the function of tissue plasminogen activator while decreasing that of plasminogen activator inhibitor, thus increasing fibrinolytic activity. Recent data indicate that defibrotide has some affinity for adenosine receptors, an action which may be responsible for the drug’s ability to increase prostaglandin I₂ levels and prevent leucocyte activation and subsequent release of oxygen free radicals. Furthermore, a specific binding site for defibrotide on the vascular endothelium has recently been identified, although the clinical relevance of this has yet to be clarified.

Defibrotide appears to be largely devoid of anticoagulant properties as determined by a lack of clinically significant effects on coagulation parameters, including partial and activated thromboplastin times and prothrombin time. Data concerning the influence of defibrotide on specific clotting factors are incomplete, but the drug appears to have no effect on von Willebrand factor, factor VIII, factor Xa and prekallikrein, while its effects on antithrombin-III, fibrinogen and Protein C require further clarification. Defibrotide has been reported to have little effect on platelet numbers, but may inhibit platelet function, possibly by stimulating the …