Studies of Adsorption, Activation, and Inhibition of Factor XII on Immobilized Heparin

• Published in: Thrombosis research 1998, Vol.89 (1), p.41-50
• Main Authors: Sanchez, Javier, Elgue, Graciela, Riesenfeld, Johan, Olsson, Per
• Format: Article
• Language: English
• Subjects: Adsorption; Anticoagulants - therapeutic use; Antithrombin; Antithrombin III - pharmacology; Biological and medical sciences; Blood coagulation. Blood cells; C1 esterase inhibitor; Coagulation factors; Complement C1 Inactivator Proteins - pharmacology; Factor XII - drug effects; Factor XIIa - drug effects; Fundamental and applied biological sciences. Psychology; FXII, FXI; Heparin - therapeutic use; Humans; Immobilized heparin; Molecular and cellular biology; Reference Values
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(97)00310-1

The aim of the present investigation was to clarify whether immobilized heparin does, as previously suggested, prevent triggering of the plasma contact activation system. Purified FXII in the absence or presence of antithrombin and/or C1 esterase inhibitor as well as plasma was exposed for 1 to 600 seconds to a surface modified by end-point immobilization of heparin. With purified reagents, a process including surface adsorption and activation of FXII occurred within 1 second. In the presence of antithrombin, the resulting surface-bound α-FXIIa was inhibited within that time. Likewise, the adsorption of native FXII from plasma was a rapid process. However, the inhibition of surface-bound α-FXIIa was slightly slower than with purified components. Nevertheless, neither β-FXIIa nor FXIa were found in the plasma phase. Exposure of a surface prepared from heparin molecules, lacking antithrombin binding properties, to plasma resulted in surface-bound α-FXIIa within 1 second. In the liquid phase, β-FXIIa was detected after 2.5 seconds and, 12 seconds later, FXIIa and FXIa in complex with the C1 esterase inhibitor appeared. Addition of heparin to plasma prior to surface exposure did not prevent activation of surface-bound FXII, nor did it increase the β-FXIIa inhibition rate and prevent FXI activation in plasma, although β-FXIIa and FXIa-AT complex formation occurred. It is concluded that surface-immobilized heparin, unlike heparin in solution, effectively inhibits the initial contact activation enzymes by an antithrombin-mediated mechanism, thereby suppressing the triggering of the intrinsic plasma coagulation pathway.