Antithrombin, a serine protease inhibitor, plays an important role in the regulation of the coagulation cascade. It inhibits thrombin as well as factors Xa, IXa, XIa, and XIIa. Heparin markedly accelerates the rate at which antithrombin inhibits these enzymes. To prevent the formation of clots in the extracorporeal circuit, heparin is used during cardiopulmonary bypass surgery (CPB). However, in a small proportion of patients, adequate anticoagulation, defined as an activated clotting time (ACT) of >400 s after an intravenous bolus of heparin in a dose of 300 U/kg, is not achieved. Conventional treatment of heparin resistance includes fresh frozen plasma or large doses of heparin. Antithrombin concentrates were given to 12 patients who were considered to be heparin resistant at our institution. All patients had received >300 U/kg of heparin before antithrombin concentrates were infused. In all patients, the ACT prolonged to >400 s after concentrates were infused, and in nine of 12 cases to >600 s. Of these nine patients, six (67%) did not receive any allogeneic transfusions, whereas three (33%) required allogeneic blood transfusions. In nine of 12 patients, no more heparin was given after infusing antithrombin concentrate. It appears that antithrombin concentrate, which is a fractionated, pasteurized plasma product, is a possible safer alternative to excessive heparin doses or fresh frozen plasma for CPB patients who are heparin resistant.
