Antithrombotic and anticoagulant activities of a low molecular weight fucoidan by the subcutaneous route

Fucoidans (high-molecular-weight sulfated polysaccharides extracted from br own seaweeds) have anticoagulant and antithrombotic effects, They inhibit t hrombin by catalyzing both serpins (antithrombin and heparin cofactor II) a ccording to their chemical structures and origins. In this study, a low-mol ecular-weight (LMW) fucoidan of 8 kDa was obtained by chemical degradation of a high-molecular-weight fraction. The antithrombotic and anticoagulant a ctivities of this new compound were compared to those of a low-molecular-we ight heparin (LMWH), dalteparin, following subcutaneous administration to r abbits. This LMW fucoidan exhibited dose-related venous antithrombotic acti vity, with an ED80 of about 20 mg/kg, 2 h after a single subcutaneous injec tion. Its activity was comparable to that of dalteparin (close to 200 anti- Xa IU/kg) and was maximal 30 min after a single subcutaneous injection. The activity remained stable (about 70%) from 1 to 4 h after injection, but di sappeared by 8 h. The antithrombotic activity was not associated with eithe r a prolongation of the thrombin clotting time (TCT) or an increase in anti -Xa activity, contrary to dalteparin. A slight prolongation of APTT occurre d with both compounds. This venous antithrombotic activity was associated w ith a decrease in ex vivo thrombin generation and with a significant increa se in the lag phase in a thrombin generation test. LMW fucoidan thus has po tent antithrombotic activity and a potentially weaker haemorrhagic effect ( i.e. a smaller effect on coagulation tests and a smaller prolongation of th e bleeding time) than dalteparin.