ABSTRACT
Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are the anticoagulants of choice when parenteral anticoagulation is required. Both can be given subcutaneously or intravenously, and both are effective in a variety of clinical settings (Hirsh et aI., 2001). UFH in particular has several limitations. These include its poor bioavailability after subcutaneous injection as well as the marked variability in the anticoagulant response to UFH treatment in patients with acute thromboembolism (Hirsh, 1991; Young et aI., 1992). Another problem is the risk of inducing heparin-induced thrombocytopenia (HIT). These limitations are closely linked (Greinacher, 1995): the underlying cause is the high density of negative charges of the heparin molecule, leading to nonspecific binding of heparin to plasma proteins other than antithrombin (AT). This results in inhibition of the anticoagulant effects of heparin, as well as changes in the conformational structure of the proteins following binding to heparin, with the potential for exposure of neoepitopes, or cryptic epitopes, toward which an immune response can be induced.
