Clinical monitoring of hirudin and direct thrombin inhibitors.
In addition to heparin, the standard medication for prophylaxis and therapy of thromboembolism, several other substances have been developed and tested for clinical use with the aim of decreasing or eliminating side effects. Most of all, hirudin, a direct antithrombin (AT), has proved to be effective. To define the therapeutic range and to avoid underdosage or overdosage, clinical monitoring is necessary. For monitoring of hirudin, thrombin time (TT) is not suited because of the missing linearity of the standard curve. Activated partial thromboplastin time (aPTT) can be used only in the lower hirudin level range, where the standard curve is quite linear. However, high and toxic hirudin levels cannot be determined using aPTT. Another drawback is a high variation in single measurements and in the normal value of patients. Methods using chromogenic substrates are suited for determination of hirudin in plasma but cannot be used at bedside. Especially for monitoring of hirudin, the ecarin clotting time (ECT) was developed. The standard curve is linear over the entire concentration range. There are no influences by other coagulation parameters or anticoagulants. For both acute clinical situations and long-term monitoring, this method capable of point-of-care therapy (POCT) will be the method of choice.
Nowak
G
G
Medical Faculty, Friedrich Schiller University Jena, Research Group Pharmacological Haemostaseology, Jena, Germany. ine@bug.mpg.uni-jena.de
D000991:Antithrombins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001780:Blood Coagulation Tests / Q000592:standards; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D010450:Endopeptidases / Q000494:pharmacology; D024764:Hirudin Therapy; D006629:Hirudins / Q000493:pharmacokinetics*; D006801:Humans; D013917:Thrombin / Q000037:antagonists & inhibitors
D000991:Antithrombins; D006629:Hirudins; D010450:Endopeptidases; D013917:Thrombin; C020097:ecarin