A rationally designed heparin, M118, has anticoagulant activity similar to unfractionated heparin and different from Lovenox in a cell-based model of thrombin generation

Abstract

Unfractionated heparin (UFH) enhances antithrombin (AT) inhibition of thrombin (IIa) and factor Xa (FXa). Low molecular weight heparins (LMWH) primarily enhance AT inhibition of FXa. M118 is a LMWH produced from UFH and retains its ability to promote both FXa and IIa inhibition. We tested the hypothesis that M118 has anticoagulant activities similar to UFH in an in vitro model of coagulation. Platelet IIa generation was assessed in a cell-based model that mimics aspects of coagulation in vivo. Inhibition of IIa generation as a function of concentration was steeper for UFH than Lovenox. The effect of M118 closely paralleled that of UFH. By contrast, M118 did not prolong the aPTT to as great a degree as UFH, though both prolonged the aPTT more than did Lovenox. Our data suggest that the ability to inhibit platelet surface IIa generation correlates with the therapeutic level of heparins and confirms similarities between the anticoagulant properties of M118 and UFH.