The Role of Antithrombin III in Heparin Resistance

Abstract

Resistance to the anticoagulation action of sodium heparin during cardiopulmonary bypass is a serious concern and a poorly understood phenomenon. In the majority of cases, the desired prolongation of the activated clotting time (ACT) is achieved by administration of additional heparin. A patient's previous exposure to heparin has been suggested as the cause of this clinical dilemma. The administration of fresh frozen plasma to patients who demonstrated a heparin resistance have been shown to produce a normalization of their heparin/ACT dose response curve and a decrease in total heparin requirements during cardiopulmonary bypass. These results could be an indication of a deficiency of a component in patient's plasma. This study was designed to compare antithrombin III (AT III) in two patient populations. Group A consisted of 15 patients receiving intravenous heparin therapy prior to cardiopulmonary bypass for greater than 24 hours. Population B included 15 patients who had not been exposed to heparin therapy preoperatively. All patients were candidates for coronary artery bypass grafting. The quantitative assay utilized the Loyal Rocket Immunoelectrophoresis Technique and the qualitative assay was determined by the AT III Anti-10A Activity Assay. Two sample t-test analyses of variance revealed no statistical significance (p<0.05) between the two populations in either quantitative assay (p=0.054) or the qualitative assay (p=0.06). A comparison of the ration (qualitative/quantitative) showed a statistical difference (p=0.016). It can be suggested from these results that the resistance to heparin demonstrated in heparin therapy patients is the result of a combination of factors associated with AT III. Administration of heparin decreases the available AT III and decreases its function. The combination of these two factors contributes to this resistance phenomenon.