• Wulf Dietrich, Raimund Busley, Michael Spannagl, Siegmund Braun, Tibor Schuster, and Susanne Lison.
• Department of Anaesthesiology, Working Group of Perioperative Hemostasis, University of Munich, Winthirstrasse 4, Munich, Germany. wulf.dietrich@t-online.de
• Anesth. Analg.. 2013 Jun 1;116(6):1223-30.

BackgroundCardiopulmonary bypass is associated with a high degree of hemostatic system activation. Supplementation of antithrombin (AT) may attenuate this activation and increase a patient's susceptibility to heparin. However, the appropriate dosage of AT has not been defined. We sought to determine the dosage of AT concentrate necessary to achieve >100% AT activity at the end of cardiac surgery and the influence of AT on heparin sensitivity.MethodsForty-one patients were included. Thirty consecutive patients undergoing primary coronary artery bypass graft surgery with cardiopulmonary bypass were assigned to 3 groups of increasing dosages of AT concentrate. Eleven additional patients served as controls. AT activity and molecular markers of thrombin generation were determined, and heparin sensitivity was calculated.ResultsA median amount of 36.5 U (19.0; 42.8), 47.0 U (41.3; 61.6), and 50.0 U (47.4; 66.6) AT concentrate/kilogram body weight in the low, medium, and high AT group, respectively, was administered. At the end of surgery, AT activity with substitution was 84% (77; 111), 110% (92; 120), and 104% (97; 120) (median [25th; 75th percentile]), respectively, compared with 63% (49; 79) in controls (P < 0.05 all substitution groups versus control). Heparin sensitivity increased from 1.29 (1.17; 1.66) s/U heparin/kg in the control group to 2.02 (1.43; 3.65), 2.56 (1.52; 3.64), 1.72 (1.24; 2.66) s/U heparin/kg in the groups with substitution (P < 0.05 all substitution groups versus control). Compared with preoperative values, AT activity decreased during the postoperative period in all patients with a nadir on postoperative day 3 (P < 0.05 compared with baseline except for the medium AT group). Corresponding to this decrease, an increase in prothrombin fragment 1+2 and d-dimer could be observed postoperatively.DiscussionHigh dosages of AT were required to preserve physiologic AT activity during coronary artery bypass graft surgery and to significantly enhance heparin sensitivity, respectively. However, a significant decrease in AT activity, accompanied by high levels of thrombin generation, was encountered up to 5 days postoperatively.

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