ABSTRACT
Monitoring of direct thrombin inhibitors with the activated partial thromboplastin
time (aPTT) is limited by poor linearity and reproducibility. Recently, direct prothrombin
activation methods have been developed for coagulation analysis: ecarin clotting time
(ECT) and prothrombinase-induced clotting time (PiCT). Laboratory monitoring of the
direct thrombin inhibitors lepirudin, argatroban, and melagatran was analyzed and
compared with monitoring unfractionated heparin (UFH).
Plasma samples of six healthy donors were spiked with lepirudin and argatroban extending
to 3000 ng/mL, melagatran extending to 1000 ng/mL, and UFH up to 0.48 IU/mL. Clotting
times of aPTT (two reagents), ECT, PiCT, and prothrombin time were determined in a
KC 10, a micro instrument.
At 3000 ng/mL ECT values were 339.1 ± 25.0 seconds with lepirudin and 457.5 ± 29.5
seconds with argatroban. ECT was 586.0 ± 38.2 seconds with 1000 ng/mL melagatran.
The PiCT method provided clotting times of 137.0 ± 8.4 seconds with UFH, 128.0 ± 23.4
seconds with lepirudin, and 151 ± 23.9 seconds with argatroban, and 153.5 ± 9.9 seconds
with melagatran, with the concentrations mentioned.
ECT is more sensitive to therapeutic drug concentration ranges than aPTT (prolongations
of 3-7 versus 2-3). PiCT yields comparable results with direct thrombin inhibitors
and UFH. This method could therefore be suitable for monitoring both drug groups.
KEYWORDS
Thrombin inhibitors - ecarin clotting time - prothrombinase-induced clotting time
- hirudin - argatroban - melagatran
