Studies of adsorption, activation, and inhibition of factor XII on immobilized heparin.
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 alpha-FXIIa was inhibited within that time. Likewise, the adsorption of native FXII from plasma was a rapid process. However, the inhibition of surface-bound alpha-FXIIa was slightly slower than with purified components. Nevertheless, neither beta-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 alpha-FXIIa within 1 second. In the liquid phase, beta-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 beta-FXIIa inhibition rate and prevent FXI activation in plasma, although beta-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.
Sanchez
J
J
Department of Surgical Sciences, Thoracic Clinics, Karolinska Hospital, Stockholm, Sweden. jass@expkir.ks.se
Elgue
G
G
Riesenfeld
J
J
Olsson
P
P
D000327:Adsorption; D000925:Anticoagulants / Q000627:therapeutic use*; D000990:Antithrombin III / Q000494:pharmacology*; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D005174:Factor XII / Q000187:drug effects*; D015956:Factor XIIa / Q000187:drug effects*; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D012016:Reference Values
D000925:Anticoagulants; D003174:Complement C1 Inactivator Proteins; D000990:Antithrombin III; D005174:Factor XII; D006493:Heparin; D015956:Factor XIIa