Extrinsic Pathway-Associated Activated Clotting Time for Anticoagulation Monitoring During Cardiopulmonary Bypass

To the Editor: In a recently published paper, Despotis et al. [1] confirmed that aprotinin prolonged whole blood activated partial thromboplastin time (APTT), a clotting test known to be triggered by the intrinsic clotting pathway. Furthermore, they demonstrated that whole blood prothrombin time (PT), a test triggered by the extrinsic clotting pathway, was not influenced by aprotinin. Based on these results, they suggested that, in patients receiving aprotinin during cardiopulmonary bypass (CPB), the value of postoperative whole blood activated partial thromboplastin time for controlling post-CPB microvascular bleeding must be interpreted with caution, and whole blood PT can be an alternative. We recently found similar results with another extrinsic pathway-associated test, activated clotting time (ACT), in the presence of aprotinin. In human whole blood containing a heparin concentration of 3 IU/mL and variable aprotinin concentrations of 0, 200, and 400 kallikrein inhibiting units (KIU)/mL, the conventional ACT, activated through the intrinsic pathway by celite, increased from 451 +/- 34 s at 0 KIU/mL aprotinin to 751 +/- 122 s at 400 KIU/mL aprotinin Table 1. In contrast, the extrinsic pathway-associated ACT, activated by thromboplastin in a final concentration of 4 mg/mL, was not influenced by aprotinin.Table 1: Effect of Aprotinin on Activated Clotting Time (Seconds)It thus seems that the extrinsic pathway-associated whole blood clotting test, whether it is based on a whole blood PT method to be used after CPB or on a Hemochron (Intl. Technidyne Co., Edison, NJ) ACT method to be used during CPB, has considerable value in monitoring heparin anticoagulation in the presence of aprotinin. Since aprotinin is being increasingly used during cardiac surgery, development of a reliable bedside test to exclude the artificial effect of aprotinin on anticoagulation monitoring is of great importance. Y. J. Gu, MD, PhD R. J. Huyzen, MD W. van Oeveren, PhD Departments of Cardiothoracic Surgery and Anesthesiology University Hospital Groningen, The Netherlands