Inhibition of the generation of thrombin and factor Xa by a fucoidan from the brown seaweed Ecklonia kurome

The effects of a fucoidan (C-II),which was purified from the brown seaweed Ecklonia kurome, on the generation of thrombin and factor Xa have been inve stigated by measuring the amidolytic activities by using the respective spe cific chromogenic substrates in both plasma and purified systems. C-II inhi bited significantly the generation of thrombin in both the intrinsic and th e extrinsic pathways, although the intrinsic inhibitory effect by C-II was more remarkable than the extrinsic one. On the other hand, C-II was a good inhibitor of the factor Xa generation in the intrinsic pathway, while it wa s a poor one in the extrinsic pathway. In the purified systems C-II also in hibited the formation of prothrombin-activating complex (i.e., prothrombina se), but not its activity. The concentration of C-II required for 50% inhib ition of thrombin generation was about one-tenth to one-seventh of that of the activity of the generated thrombin in plasma. These results indicate th at C-II has an inhibitory effect on the generation of thrombin by blocking the formation of prothrombinase and by preventing the generation of intrins ic factor Xa in addition to its antithrombin activity, and also that the ge neration-inhibitory effect is more remarkable than C-II's enhancement effec t on the antithrombin activity by heparin cofactor II in plasma. (C) 1999 E lsevier Science Ltd. All rights reserved.