Non-Anticoagulant Actions of Glycosaminoglycans

Unfractionated heparin (UFH) remains the agent of choice for the prevention and treatment of venous thromboembolism (VTE).1 The anticoagulant activity of UFH is primarily mediated through its specific binding to antithrombin III (AT-III)2,3 resulting in a marked enhancement of its ability to inactivate thrombin, factor Xa, and other blood coagulation serine-proteases. UFH is known to bind to a number of plasma proteins including hystidine-rich glycoprotein,4 vitronectin,5 fibronectin,6 von Willebrand factor,7 and platelet factor-48. The binding of UFH to AT-III and HC-II is mediated by a specific saccharide sequence,1,3,9 that is present in approximately one-third of the molecules of commercial UFH,10,11 while the non-specific binding of UFH to the other plasma proteins appears to be related to heparin molecular size, the higher molecular weight chains showing a greater affinity binding than those of lower molecular weight12.