Effects of a defibrotide-heparin combination on some measures of haemostasis in healthy volunteers.
In an open-study design five healthy volunteers were first given 2500 IU sodium heparin intravenously and then, after 72 h, another injection of the same dosage of sodium heparin followed immediately by 400 mg defibrotide intravenously. In two separate experiments, prothrombin time, activated partial prothrombin time, antithrombin III, tissue plasminogen activator, its inhibitor and plasma heparin levels were measured at baseline and after 15 min in one experiment, and at baseline and after 2 h in the other experiment. The most important finding was that an interaction exists between heparin and defibrotide on haemostatic activity: activated partial prothrombin time was increased three-fold in volunteers given the defibrotide--heparin combination compared with volunteers given heparin alone. This statistically and clinically significant effect was evident 15 min after administration of defibrotide--heparin and was still present after 2 h. Possible explanations for this effect are discussed briefly.
Pogliani
E M
EM
Department of Internal Medicine, Hospital S. Gerardo, Monza, Italy.
Salvatore
M
M
Fowst
C
C
Girardello
R
R
Marelli
C
C
D000328:Adult; D004347:Drug Interactions; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D012016:Reference Values
D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; C036901:defibrotide; D006493:Heparin