Defibrotide Shown to Prevent and Dissolve Blood Clots in Rabbits

Niada and colleagues, writing in Haemostasis in 1986, report that defibrotide, a polydeoxyribonucleotide of mammalian origin, can both prevent and break down blood clots in rabbits, without acting as a conventional blood thinner.

The researchers worked in an animal model, inducing venous thrombosis (clot formation in a vein) in rabbits using collagen. Given orally at doses of 12.5, 25 or 50 mg per kg before clot induction, defibrotide blocked clot growth during the first two hours, with the dose linked to both peak effect and total inhibition over time. When infused intravenously at 20, 31.7 or 50 mg per kg per hour into rabbits with clots that were already 24 hours old, defibrotide dissolved the clots in a dose-related way, and the degree of clot dissolution tracked with the drug's plasma levels. This thrombolytic effect matched that of urokinase, a standard clot-dissolving drug, given at 750 to 3,000 IU per kg per hour. Heparin, a common anticoagulant, had no effect in this model, and prostacyclin (PGI2) showed only modest activity.

The authors suggest defibrotide works partly by prompting blood vessel tissue to release substances involved in clot breakdown, including plasminogen activator factor and prostacyclin.

As an animal study of a specific drug compound, this paper cannot show whether these effects occur in humans or extend to other uses of polydeoxyribonucleotides.