Anticoagulant profile of low molecular weight heparinoids (KB-101) and its in vivo effects on the experimental DIC (disseminated intravascular coagulation) were investigated in comparison with unfractionated heparin (UFH). KB-101 displayed considerably less effects than UFH on the conventional laboratory tests as activated partial thromboplastin, prothrombin and thrombin time. Both of these agents catalyzed the inactivation of factor Xa by antithrombin III (AT III) and the inactivation of thrombin by AT III and heparin cofactor II (HC II). The potencies of KB-101 on the inactivation of these activated coagulation factors were far lesser than those of UFH. On the other hand, the anti-Xa to anti-thrombin activity ratio of KB-101 was about 28 times higher than that of UFH. Either KB-101 and UFH enhanced the antiplasmin activity in plasma, which was less prominent in KB-101 than UFH.
The in vivo effects of these heparin on the endotoxin-induced experimental DIC using rats, were assessed by coagulation and fibrinolytic parameters and the degree of fibrin deposition in the renal glomeruli. The inhibitory effects of KB-101 on DIC were proved to be as equivalent to those of UFH. From these results it was concluded that KB-101 showed a higher anti-Xa to anti-thrombin activity ratio than UFH and revealed a potent inhibitory effects on experimental DIC, which suggested its therapeutic efficacy for DIC.
