Endogenous Anticoagulation during Extracorporeal Perfusion in the Dog: Generation of a Heparin-Like Inhibitor

摘要

Studies were done to define the coagulation defect that develops in anesthetized dogs perfused with an arteriovenous extracorporeal perfusion system without added heparin. The development of whole blood clotting times (WBCT) greater than 24 hors is associated with the appearance of a plasma inhibitor of thrombin and Factor Xa clotting of bovine plasma. This inhibitor stimulated the inactivation of Factor Xa by antithrombin III (ATIII) but not by o-methyl-isourea modified ATIII. Thrombin inhibition by ATIII was also stimulated. Six perfused dogs developed an equivalent of 0.98 to 6.15 U/ml of heparin activity determined by inhibition of thrombin-induced clotting of normal canine plasma. This activity was heat stable, adsorbed by BaSO4 and neutralized by protamine. Infusion of protamine sulfate into two perfused dogs reversed the anticoagulant activity and brought the WBCT from greater than 24 hours to less than control. Five eviscerated dogs in which the hepatic artery was ligated developed peak plasma heparin activity of 3.2 + or - 1.0 U/Ml. We conclude that dogs perfused on our extracorporeal perfusion system without added heparin develop and endogenous heparin activity in their plasma which is major contributor to their autoanticoagulated state. In addition, this heparin activity may have an extra-hepatic origin. (Author)