The effect of danaparoid sodium (danaparoid) on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats. 1998

Y Fujishima, and K Yokota, and T Sukamoto
Department of Pharmacology, Pharmaceutical Research Laboratories, Kanebo, Ltd., Osaka, Japan.

Danaparoid sodium (danaparoid) is a low molecular weight heparinoid with anticoagulation properties, which mainly consists of heparan sulfate. Compared with heparin sodium (heparin), danaparoid has a much higher anti-Xa/anti-thrombin ratio. We compared the effect of danaparoid on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats with heparin. A bolus injection of endotoxin (10 mg/kg) induced gradual decreases in the platelet count, and the plasma fibrinogen, antithrombin III (AT-III) and heparin cofactor II levels, as well as an increase in the fibrinogen/fibrin degradation products level from 1 to 6 hours after the injection, indicating that both coagulation and fibrinolysis were activated. The intravenous administration of danaparoid or heparin 3 hours after the endotoxin injection inhibited the endotoxin-induced decreases in the platelet count and plasma fibrinogen level and also inhibited the endotoxin-induced increase in glomerular fibrin deposition in the kidney. Differences between danaparoid and heparin were observed in their effects on the plasma AT-III level and clotting time. Danaparoid significantly inhibited both the decrease in the plasma AT-III level and the prolongation of the prothrombin time induced by endotoxin, where as heparin showed no effect on those responses. Moreover, danaparoid enhanced the prolongation of the activated partial thromboplast in time induced by endotoxin to a lesser degree than heparin. These findings suggest that the effects of danaparoid on the endotoxin-induced decrease of the plasma AT-III level and the prolongation of the clotting time are more advantageous than those of heparin. The results may have been due to a higher anti-Xa/anti-thrombin ratio of danaparoid than that of heparin, indicating that danaparoid may be useful in the treatment of DIC.

UI MeSH Term Description Entries
D008297 Male Males
D002809 Chondroitin Sulfates Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate. Chondroitin 4-Sulfate,Chondroitin 6-Sulfate,Chondroitin Sulfate A,Chondroitin Sulfate C,Blutal,Chondroitin 4-Sulfate, Aluminum Salt,Chondroitin 4-Sulfate, Potassium Salt,Chondroitin 6-Sulfate, Potassium Salt,Chondroitin 6-Sulfate, Sodium Salt,Chondroitin Sulfate,Chondroitin Sulfate 4-Sulfate, Sodium Salt,Chondroitin Sulfate, Calcium Salt,Chondroitin Sulfate, Iron (+3) Salt,Chondroitin Sulfate, Iron Salt,Chondroitin Sulfate, Potassium Salt,Chondroitin Sulfate, Sodium Salt,Chondroitin Sulfate, Zinc Salt,Chonsurid,Sodium Chondroitin Sulfate,Translagen,Chondroitin 4 Sulfate,Chondroitin 4 Sulfate, Aluminum Salt,Chondroitin 4 Sulfate, Potassium Salt,Chondroitin 6 Sulfate,Chondroitin 6 Sulfate, Potassium Salt,Chondroitin 6 Sulfate, Sodium Salt,Chondroitin Sulfate 4 Sulfate, Sodium Salt,Chondroitin Sulfate, Sodium,Sulfate, Chondroitin,Sulfate, Sodium Chondroitin,Sulfates, Chondroitin
D003871 Dermatan Sulfate A naturally occurring glycosaminoglycan found mostly in the skin and in connective tissue. It differs from CHONDROITIN SULFATE A (see CHONDROITIN SULFATES) by containing IDURONIC ACID in place of glucuronic acid, its epimer, at carbon atom 5. (from Merck, 12th ed) Chondroitin Sulfate B,beta-Heparin,Sulfate B, Chondroitin,Sulfate, Dermatan,beta Heparin
D004211 Disseminated Intravascular Coagulation A disorder characterized by procoagulant substances entering the general circulation causing a systemic thrombotic process. The activation of the clotting mechanism may arise from any of a number of disorders. A majority of the patients manifest skin lesions, sometimes leading to PURPURA FULMINANS. Consumption Coagulopathy,Coagulation, Disseminated Intravascular,Disseminated Coagulation, Intravascular,Intravascular Coagulation, Disseminated,Intravascular Disseminated Coagulation,Coagulation, Intravascular Disseminated,Coagulations, Disseminated Intravascular,Coagulations, Intravascular Disseminated,Coagulopathies, Consumption,Coagulopathy, Consumption,Consumption Coagulopathies,Disseminated Coagulations, Intravascular,Disseminated Intravascular Coagulations,Intravascular Coagulations, Disseminated,Intravascular Disseminated Coagulations
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D004731 Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Endotoxin
D006497 Heparitin Sulfate A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS. Heparan Sulfate,Sulfate, Heparan,Sulfate, Heparitin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000925 Anticoagulants Agents that prevent BLOOD CLOTTING. Anticoagulant Agent,Anticoagulant Drug,Anticoagulant,Anticoagulant Agents,Anticoagulant Drugs,Anticoagulation Agents,Indirect Thrombin Inhibitors,Agent, Anticoagulant,Agents, Anticoagulant,Agents, Anticoagulation,Drug, Anticoagulant,Drugs, Anticoagulant,Inhibitors, Indirect Thrombin,Thrombin Inhibitors, Indirect
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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