Comparison of Celite and Kaolin Based Heparin and Protamine Dosing Assays During Cardiac Surgery: The In Vitro Effect of Aprotinin

Abstract

Both aprotinin and in vitro heparin and protamine dosing assays (RxDx System) have been shown to reduce postoperative bleeding in the cardiac surgery patient. While celite activated clotting time tests in the presence of heparin are artificially prolonged by aprotinin, the kaolin based ACT is not. In order to optimize heparin anticoagulation management during cardiac surgery when aprotinin is used, we have evaluated the utility of kaolin based heparin and protamine dosing assays in the presence of aprotinin. In vitro studies were performed using normal donor blood after the addition of heparin and/or aprotinin. Clinical evaluations compared anticoagulation management based upon the two activators (celite and kaolin) in 21 patients requiring cardiopulmonary bypass (CPB) who were not receiving aprotinin. The kaolin heparin and protamine assays were unaffected by aprotinin using in vitro aprotinin supplemented normal donor blood samples. The amounts of aprotinin used were equivalent to the calculated plasma concentration in an average size patient (6 liter blood volume) receiving either full (1 H) or half (1/2 H) Hammersmith doses. Heparin and protamine doses, based on the kaolin assays, were not significantly different between aprotinin (apr) treated and control samples (p>0.20). In a clinical evaluation of CPB patients, the C-ACT and K-ACT showed good correlation (r= 0.97, n = 213), as did the respective dose determination based on the celite and kaolin RxDx assays: heparin dose (r = 0.88, n = 69) and protamine dose (r = 0.88, n = 19). These studies illustrate comparable heparin and protamine dosing using either celite or kaolin based RxDx assays during cardiac surgery. These findings also suggest that the kaolin based ACT and dosing assays may be useful in monitoring heparin anticoagulation in cardiac surgery patients receiving aprotinin with the potential of combining these two blood conservation methods.