• Andreas Koster, Thomas Fischer, Marcus Gruendel, Andreas Mappes, Wolfgang M Kuebler, Matthias Bauer, and Herman Kuppe.
• Department of Anesthesia, Deutsches Herzzentrum Berlin, Germany. Koster@dhzb.de
• J. Cardiothorac. Vasc. Anesth. 2003 Apr 1; 17 (2): 171-5.

ObjectiveAttenuation of hemostatic activation is a central goal during CPB. However, this poses a problem in patients insensitive to heparin. The present investigation was performed to assess different strategies of managing patients with heparin resistance during CPB.DesignA randomized, prospective clinical investigation.SettingA major European heart center.ParticipantsFive groups with 20 patients each were investigated.InterventionsThe groups were handled as follows: (1). maintenance of a target ACT, (2). maintenance of the target unfractionated heparin (UFH) level and supplementation of a UFH level-based strategy with (3). AT III, (4). the direct thrombin inhibitor r-hirudin, or (5). the short-acting platelet glycoprotein (GP) IIb/IIIa antagonist tirofiban. Platelet count and generation of contact factor XIIa, thrombin, and soluble fibrin were assessed. Samples were obtained before CPB and after CPB before protamine infusion.Measurements And Main ResultsThere were no differences observed in the generation of factor XIIa. The UFH-based strategy and supplementation with AT III, r-hirudin, and tirofiban resulted in significantly reduced (p < 0.05) thrombin generation compared with ACT management. A significant reduction of fibrin formation was seen only in patients who received AT III, r-hirudin, or tirofiban supplementation to the UFH. The administration of tirofiban resulted in a significant preservation of the platelet count compared with the other groups. There were no significant differences in the postoperative blood loss.ConclusionsActivation of hemostasis during CPB in heparin-resistant patients most likely has to be attributed to stimulation of the tissue factor pathway. Even the sole use of high concentrations of UFH does not effectively inhibit this activation. Therefore, in these patients anticoagulation during CPB with UFH should be supplemented with either AT III, a short-acting direct thrombin inhibitor, or a short-acting platelet glycoprotein IIb/IIIa antagonist.Copyright 2003 Elsevier Inc. All rights reserved.

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