Monitoring of r-Hirudin Anticoagulation during Cardiopulmonary Bypass – Assessment of the Whole Blood Ecarin Clotting Time

Abstract

SummaryThe use of recombinant ® hirudin as an anticoagulant in performing extracorporeal circulation systems including cardiopulmonary bypass (CPB) devices requires a specific and easy to handle monitoring system. The usefulness of the celite-induced activated clotting time (ACT) and the activated partial thromboplastin time (APTT) for r-hirudin monitoring has been tested on ex vivo blood samples obtained from eight patients treated with r-hirudin during open heart surgery. The very poor relationship between the prolongation of the ACT and APTT values and the concentration of r-hirudin as measured using a chromogenic factor Ila assay indicates that both assays are not suitable to monitor r-hirudin anticoagulation. As an alternative approach a whole blood clotting assay based on the prothrombin-activating snake venom ecarin has been tested. In vitro experiments using r-hirudin- spiked whole blood samples showed a linear relationship between the concentration of hirudin added and the prolongation of the clotting times up to a concentration of r-hirudin of 4.0 µg/ml. Interassay coefficients (CV) of variation between 2.1% and 5.4% demonstrate the accuracy of the ecarin clotting time (ECT) assay. Differences in the interindividual responsiveness to r-hirudin were analyzed on r-hirudin- spiked blood samples obtained from 50 healthy blood donors. CV- values between 1.8% and 6% measured at r-hirudin concentrations between 0.5 and 4 µg/ml indicate remarkably slight differences in r-hirudin responsiveness. ECT assay results of the ex vivo blood samples linearily correlate (r = 0.79) to the concentration of r-hirudin. Moreover, assay results were not influenced by treatment with aprotinin or heparin. These findings together with the short measuring time with less than 120 seconds warrant the whole blood ECT to be a suitable assay for monitoring of r-hirudin anticoagulation in cardiac surgery.

Recombinant hirudin anticoagulation for aortic valve replacement in heparin-induced thrombocytopenia

“…Therefore, the use of ECT, despite limited experience, has been suggested for on-site monitoring of CPB anticoagulation with r-hirudin. 8 Anticoagulation with r-hirudin after cardiac surgery with r-hirudin-based CPB anticoagulation has been reported previously. 9 Based on that report, and because of the short half life of r-hirudin, we started the continuous r-hirudin infusion on the 2nd postoperative hour because chest tube blood loss was < 50 ml·hr -1 although aPTT was prolonged (Table III).…”

“…A good linear relationship was demonstrated between the hirudin concentration and the ECT but not the ACT values. 8 In addition, ECT values are not influenced by moderate hemodilution. Therefore, the use of ECT, despite limited experience, has been suggested for on-site monitoring of CPB anticoagulation with r-hirudin.…”

“…Anticoagulation was monitored with celite-based activated clotted time (ACT) (Hemochron®, International Technidyne Corp., Edison, N.Y., USA) and citrated whole blood ecarin clotting time (ECT) (Ecarin, Diagnostica Stago, Asnières, France) performed in the operation room. The ECT was performed with a KC 10 coagulometer (Amelung, Lengo, Germany) according to Pötzsch et al 8 Ecarin was reconstituted at a concentration of 16 U·ml -1 with HEPES buffer in saline containing 0.025 mol·1 -1 calcium chloride and was preincubated at 37. Whole blood ECT was performed in duplicate by addition of 5 0 µl ecarin solution to 100 µl citrated whole blood preincubated for one minute at 37°C.…”

Clinical Monitoring of Direct Thrombin Inhibitors Using the Ecarin Clotting Time

“…Investigators found a strong linear relationship between the ECT values and lepirudin concentrations that ranged from 0.35-5.88 µg/ml (r=0.94), whereas the aPTT demonstrated only weak correlation (r=0.61). Other studies also have found that the ECT correlated better with lepirudin levels and demonstrated less interpatient variability compared with the aPTT 20 or the activated clotting time (ACT). 20,21 In particular, the aPTT curve seems to flatten for lepirudin concentrations above 0.5 µg/ml.…”

“…Other studies also have found that the ECT correlated better with lepirudin levels and demonstrated less interpatient variability compared with the aPTT 20 or the activated clotting time (ACT). 20,21 In particular, the aPTT curve seems to flatten for lepirudin concentrations above 0.5 µg/ml. 18 Clinical applicability of the ECT tests used in these studies was limited by the fact that it required several manipulations to obtain final results.…”