A randomized trial of antithrombin concentrate for treatment of heparin resistance

Background. Heparin resistance is an important clinical problem traditionally treated with additional heparin or fresh frozen plasma. We undertook a randomized clinical trial to determine if treatment with antithrombin (AT) concentrate is effective for treating this condition. Methods. Patients requiring cardiopulmonary bypass who were considered to be heparin resistant (activated clotting time < 480 seconds after > 450 IU/kg heparin) were randomized to receive either 1000 U AT or additional heparin. Results. AT concentrate was effective in 42 of 44 patients (96%) for immediately obtaining a therapeutic activated clotting time. This compared favorably to 28 of 41 patients (68%) treated with additional heparin (p = 0.001). All patients who failed heparin therapy were successfully treated with AT. The patients receiving AT required less time to obtain an adequate ACT but there was no difference in clinical outcomes among the groups. Study patients had deficient AT activity at baseline (56% ± 25%), which improved in those given AT concentrate (75% ± 31% versus 50% ± 23%, p< 0.0005). Conclusions. Heparin resistance is frequently associated with AT deficiency. Treating this deficiency with AT concentrate is more effective and faster for obtaining adequate anticoagulation than using additional heparin.