Biotech Values

[DewDiligence]

A Rationally-Designed Heparin, M118, Has Anticoagulant Activity
Similar to Unfractionated Heparin and Different from Lovenox in
a Cell-Based Model of Thrombin Generation

[See #msg-26900300 and #msg-26897124 for related material.]

http://www.ncbi.nlm.nih.gov/pubmed/19543696

›Journal of Thrombosis and Thrombolysis. 2009 Jun 19.

Volovyk Z, Monroe DM, Qi Y, Becker R, Hoffman M.

Duke University Medical Center, Box 3712, Durham, NC, 27710, USA.

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 [i.e. they have weak inhibition of IIa]. M118 is a LMWH produced from UFH and retains its ability to promote both FXa and IIa inhibition [see graphic depiction in #msg-26898084].

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.‹