The effect of a long-acting recombinant hirudin (PEG-hirudin) on experimental disseminated intravascular coagulation (DIC) in rabbits.
Reproducible disseminated intravascular coagulation in rabbits was provoked by two intravenous injections 24 hours apart of endotoxin from Salmonella enteritidis. There were mild symptoms of DIC before the second injection which considerably increased thereafter. In detail there was a sharp drop of the platelet count and a considerable diminution of Antithrombin III, of Protein C, Plasminogen and Antiplasmin as well as an appearance of fibrin monomer complexes and an increase of the aPTT. When PEG-hirudin in a single dose of 1 mg/kg BW was given simultaneously with the second injection of endotoxin the following alterations were observed: The drop of the platelet count and of the activities of Antithrombin III, Protein C, Plasminogen and Antiplasmin was significantly less pronounced. The fibrin monomer complexes were lower and the aPTT was less prolonged. The thrombin time, however, as a sign of a direct action of hirudin on thrombin was considerably more prolonged than in the controls. The combined effect of these alterations strongly points in the direction of a favourable influence of PEG-hirudin on the course of DIC. It is of special interest that 6 h after the intravenous injection of PEG-hirudin its full effect on the thrombin time was still detectable. This is apparently due to a longer half-life in circulation of PEG-hirudin than of natural hirudin.
Zawilska
K
K
Department of Haematology, Academy of Medicine, Poznan, Poland.
Zozulinska
M
M
Turowiecka
Z
Z
Blahut
M
M
Drobnik
L
L
Vinazzer
H
H
D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity; D001779:Blood Coagulation Factors / Q000032:analysis; D003692:Delayed-Action Preparations; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004731:Endotoxins / Q000633:toxicity; D006207:Half-Life; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage / Q000493:pharmacokinetics; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D012772:Shock, Septic / Q000188:drug therapy / Q000473:pathology
D001427:Bacterial Toxins; D001779:Blood Coagulation Factors; D003692:Delayed-Action Preparations; D004731:Endotoxins; D006629:Hirudins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C027952:salmonella toxin; D011092:Polyethylene Glycols