Unfractionated heparin (UFH) and the vitamin K antagonists (VKA), have been standard anticoagulants for the
last 70 years. They have a widespread effect on many coagulation factors, the serine proteases for UFH and the vitamin K
dependent factors for the VKAs. Refinements in the heparin molecule have occurred with the development of low molecular
weight heparins and eventually, fondaparinux, the latter of which, has only indirect anti-Xa activity. In the last two
decades, more target-specific drugs such as the parenteral direct thrombin inhibitors have been introduced into clinical
practice (lepirudin, bivalirudin, argatroban, and desirudin) and are widely used for selected indications in hospitalized patients.
More recently, the trend in anticoagulant development continues to target a specific factor either directly or indirectly.
Of great interest is the recent development of many oral direct factor inhibitors, the first new agents poised to replace
the VKAs. Of these, the oral direct Xa and IIa inhibitors are most promising and are far along in development.
However, other coagulation factors have been considered suitable targets for drug development. The following paper discusses
these agents and their selected targets, heparin.