Key result
Poly(GEMA)-sulfate demonstrates anticoagulant activity distinct from heparin by inhibiting fibrin network formation.
Poly(GEMA)-sulfate acts as an anticoagulant through a novel mechanism involving the inhibition of fibrin network formation via an insoluble ion complex with fibrinogen.
May represent novel fibrinogen-targeted anticoagulant class; leaves open human translation and safety from animal data alone.
In our previous study on glycoside polymer, it was discovered that sulfated poly(glucosyloxyethyl methacrylate) [poly(GEMA)-sulfate], which bears sulfated D-(+)-glucose, exhibited anticoagulant activity. The anticoagulant activity of poly(GEMA)-sulfate in solution was prolonged by increasing the dose or degree of sulfation of the polymer. In this study, to recognize the mechanism of anticoagulant activity of poly(GEMA)-sulfate, we estimated the binding capacity of antithrombin III to thrombin and some in vitro clotting tests in the presence of poly(GEMA)-sulfate. These results revealed that poly(GEMA)-sulfate had an anticoagulant mechanism which differed to that of heparin. We concluded that the anticoagulant activity of poly(GEMA)-sulfate is responsible for inhibiting fibrin network formation by the insoluble ion complex between fibrinogen and poly(GEMA)-sulfate.
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Sakamoto et al. (1997) studied this question. poly(GEMA)-sulfate vs. heparin was evaluated on mechanism of anticoagulant activity. Poly(GEMA)-sulfate exhibits anticoagulant activity by inhibiting fibrin network formation through an insoluble ion complex with fibrinogen, a mechanism distinct from heparin.
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