Effect of low molecular weight fucoidan and low molecular weight heparin in a rabbit model of arterial thrombosis.
BACKGROUND
Therapeutic use of unfractionated heparin and low molecular weight heparins (LMWHs) is limited by hemorrhagic adverse effects. We compared the antithrombotic effect of LMW fucoidan (LMWF) and LMWH in an experimental model.


METHODS
Thrombosis was induced in femoral arteries of male New Zealand White rabbits by in situ induction of endothelial apoptosis with staurosporine (10(-5)M for 30 min). Starting the day before apoptosis induction, the animals received subcutaneous LMWF (15 mg/kg), LMWH (enoxaparin 2.5 mg/kg) or saline solution (control group) twice a day for 4 days.


RESULTS
The degrees of apoptosis and endothelial denudation were similar in the 3 groups. The thrombotic score was significantly lower in the LMWF group than in the LMWH and control groups (p = 0.01). Tissue factor expression was significantly lower in the LMWF group than in the control and LMWH groups (p = 0.01). The plasma concentration of tissue factor pathway inhibitor was significantly increased after LMWF injection (137 +/- 28 vs. 102 +/- 17; p = 0.01), whereas no change was observed after LMWH treatment. LMWF did not prolong the bleeding time or decrease platelet aggregation.


CONCLUSIONS
LMWF appeared to be more effective than LMWH for preventing arterial thrombosis in this experimental model. LMWF also had a lower hemorrhagic risk than LMWH.
Durand
Eric
E
Faculté de Médecine, Université Paris Descartes, Paris, France. eric.durand@egp.aphp.fr
Helley
Dominique
D
Al Haj Zen
Ayman
A
Dujols
Céline
C
Bruneval
Patrick
P
Colliec-Jouault
Sylvia
S
Fischer
Anne-Marie
AM
Lafont
Antoine
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000494:pharmacology*; D006470:Hemorrhage / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000494:pharmacology*; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011134:Polysaccharides / Q000009:adverse effects / Q000494:pharmacology*; D011817:Rabbits; D019311:Staurosporine; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; D011134:Polysaccharides; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; C007789:fucoidan; D019311:Staurosporine