The effects of danaparoid, dalteparin and heparin on tissue factor-induced experimental disseminated intravascular coagulation and bleeding time in the rat.
Danaparoid and heparin, on the basis of anti-activated factor X (anti-FXa) activity, were equipotent in accelerating the rate of interaction of FXa and antithrombin III. In rat tissue factor-induced disseminated intravascular coagulation (DIC) models, an intravenous administration of danaparoid inhibited the decrease in plasma fibrinogen and platelet counts and the increase in serum fibrinogen degradation products. Expressed on the basis of anti-FXa activity, these effects were comparable with those of dalteparin and heparin. In rat mesenteric small artery and vein, less bleeding was observed after intravenous administration of danaparoid than after dalteparin or heparin. Danaparoid did not affect adenosine diphosphate- or collagen-induced platelet aggregation, and showed weaker inhibitory effects on aggregation induced by thrombin, or collagen + thrombin, than did dalteparin or heparin. These findings suggest that danaparoid may be useful for the prevention of DIC and has less tendency to cause bleeding than dalteparin or heparin, probably as a result of its weaker ability to inhibit platelet aggregation.
Miyake
Y
Y
Pharmacology Group, Research & Development Division, Nippon Organon K. K., Osaka, Japan.
Yokota
K
K
Fujishima
Y
Y
Sukamoto
T
T
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D000990:Antithrombin III / Q000494:pharmacology; D001760:Bleeding Time; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000494:pharmacology; D017985:Dalteparin / Q000008:administration & dosage / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D006497:Heparan Sulfate / Q000008:administration & dosage / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment; D013925:Thromboplastin / Q000494:pharmacology*
D000925:Anticoagulants; D000990:Antithrombin III; D002809:Chondroitin Sulfates; D017985:Dalteparin; D003871:Dermatan Sulfate; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D015951:Factor Xa; D065427:Factor Xa Inhibitors; D006493:Heparin; D006497:Heparan Sulfate; D013925:Thromboplastin; C035838:danaparoid