Methoden zur Bestimmung von Thrombininhibitoren / Methods for the determination of thrombin inhibitors

Direct thrombin inhibitors are licensed for anticoagulant therapy in several indications. The results of studies comparing these drugs with other antithrombotics also indicate a benefit in patients with myocardial infarction, unstable angina, deep venous thrombosis, disseminated intravascular coagulation, and during extracorporeal circulation. It has been shown that the various indications for this agent require a monitoring of blood levels. Activated partial thromboplastin time (APTT) and modifications of activated clotting time (ACT) have been used for this purpose. However, it could be demonstrated that these methods cannot be adapted to the monitoring of thrombin inhibitors because they are not sensitive enough to measure relevant blood levels in the therapeutic or toxic range and individual values vary too much. The correlation with the results of ecarin clotting time (ECT) and enzyme immunological and chromogenic substrate assays is poor. Direct measurement of thrombin inhibitor plasma levels using chromogenic substrates can be performed with automated analyzers and with small photometers as a bedside method. These tests are very precise, offer a wide measuring range and are not disturbed by heparin and antithrombin. Chromogenic substrate assays show a good correlation with the ECT. Depending on whether mechanical or optical measurement of clotting time is used, the ECT can be performed in whole blood or plasma. The performance of ECT measurement also allows bedside monitoring. Test characteristics like imprecision and measuring range are comparable to the results of chromogenic substrate assays. Limitations of ECT monitoring are not known. In conclusion, the use of chromogenic substrate or ECT measurement is the best approach for monitoring thrombin inhibitor levels. APTT should be determined if other methods are not available.