ABSTRACT
Direct thrombin inhibitors are available for prophylactic as well as therapeutic purposes.
Application of hirudin in therapeutic doses has been shown to require drug monitoring.
Currently, most experience is available for recombinant hirudin, but the principle
aspects of drug monitoring are the same for all direct thrombin inhibitors. Most frequently,
activated partial thromboplastin time (aPTT) and modifications of the activated clotting
time (ACT) have been used for the monitoring of hirudin therapy. However, these methods
are insensitive at plasma levels higher than 0.6 mg/L of hirudin, so that overdoses
may be missed despite monitoring. Correlations between ecarin clotting time (ECT),
enzyme immunoassays, and chromogenic substrate assays on one side and global tests
on the other side are poor. Fully automated chromogenic substrate-based assays, also
available as point-of-care tests (POCT), are more precise and sensitive and are not
disturbed by interferents such as heparin and antithrombin. Good correlations can
be observed between chromogenic assays and the ECT performed in plasma or whole blood
samples. ECT can also be determined with POCT systems. Test characteristics such as
imprecision and measuring range are comparable to those of the chromogenic assays.
In conclusion, therapy with direct thrombin inhibitors should be monitored with chromogenic
assays or ECT.
KEYWORDS
Hirudin - direct thrombin inhibitors - monitoring - ecarin clotting time - chromogenic
assay
