Predicting the pharmacodynamics of heparin: a clinical evaluation of the hepcon system 4

The magnitude of the anticoagulation response to heparin (heparin responsiveness) varies substantially from patient to patient. Identifying extremes of sensitivity and resistance prior to intravenous administration of heparin would facilitate anticoagulation for cardiopulmonary bypass (CPB). The performance of the Hepcon System 4 (HemoTec, Inc. Englewood, CO), an instrument designed for that purpose, was tested. Using nonheparinized blood samples from 157 patients scheduled for surgery requiring CPB, this device performed activated coagulation times (ACT) with three different concentrations of in vitro heparin. After determining each patient's in vitro heparin response, the heparin dose predicted to produce ACT values of 480 seconds (group 1, N = 77) or 600 seconds (group 2, N = 80) was administered. Five minutes later each patient's ACT was determined with the Hemochron method (International Technidyne, Inc. Edison, NJ). Simultaneously, several other variables that might predict heparin responsiveness were investigated. When compared with the observed ACT, the Hepcon System 4 inadequately predicted the response. There was considerable scatter in this comparison, but most frequently the in vitro method substantially underestimated the in vivo heparin dose requirement. Heparin responsiveness decreased significantly with high platelet counts and advanced age, but was unaffected by the initial hematocrit, ACT, partial thromboplastin time, or preoperative heparin therapy. Previous investigations have not identified a relationship between advanced age and reduced heparin responsiveness. Combining the Hepcon heparin dose-response in vitro method with the other parameters evaluated, stepwise regression could only account for 39% of the observed variability in heparin responsiveness. Comparing the two groups, it appears that the ACT dose-response to heparin may not remain strictly linear in the ACT range of 350 to 500 seconds. This suggests saturation of the heparin receptors on antithrombin III. A mathematical equation that would predict heparin responsiveness well enough to warrant clinical application could not be constructed. Clinicians should expect older patients and thrombocytotic patients to frequently require higher initial heparin doses. Since heparin's response remains unpredictable, continued clinical application of the ACT to determine adequate anticoagulation is recommended.