Antithrombin agent

Fondaparinux sodium is the first of a new class of direct-acting antithrombin agents. The anticoagulant activity of heparin depends on the binding of ATIII to a critical pentasaccharide sequence within the heparin molecule. This results in a change in the conformation of AITII. This leads to the inhibitory effect of ATIII on factor Xa, which activates the conversion of prothrombin to thrombin. Fondaparinux is a synthetic pentasaccharide identical to the ATIII-binding site of heparin. 

Alexander KP Chen AY Roe MT et al, Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes, JAMA 2005 294 3108-31 16. 

In the meta-analysis with I I randomized studies, anticoagulant effects in ACS and PCI were compared between a direct antithrombin agent and UFH, The direct thrombin inhibitor showed better outcome in death or myocardial infarction than UFH (19). DTIs are expected to be an alternative to UFH for PCI. 

Sinnaeve PR, Van de Werf FJ, Will oral antithrombin agents replace warfarin Heart 2004 90 827-828. 

Figure 6. Structural heterogeneity in antithrombin agents. Besides the synthetic antithrombin agents, plasma derived antithrmnbin III and its recombinant equivaloit and various recombinant equivalents of naturally occurring antithrombin agents and conjugates have also become available...

Ikoma H. Development of argatroban as an anticoagulant and antithrombin agent in Japan. Pathophysiol Haemost Thromb 2002 32(Suppl 3) 23-8. 

Callas D, Fareed J (1995). Comparative pharmacology of site directed antithrombin agents. Implication in drug development. Thromb. Haemostasis. 74 473-781. Hursting M J, Alford K L, Becker J P, et al. (1997). Novastan A small-molecule, direct thrombin inhibitor. Sem. Thromb. Hemostasis. 23 503-516. 

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