title: A functional clotting assay to monitor the hirudin dosage.
abstract: Hirudin, a direct thrombin inhibitor, has potential advantages over indirect thrombin inhibitors and is increasingly used in clinical settings. There are, however, large variations in individual responses to this drug and no recognized clinical laboratory tests used to monitor its anticoagulant effects. We evaluated the use of the thromboelastograph, a common clinical coagulation instrument, to monitor the effects of hirudin in vitro. We developed a novel, whole blood clotting assay that utilizes the tissue factor stimulating properties of mercuric ion to measure the anticoagulant potential of therapeutic doses of hirudin. At doses equivalent to those found in the therapeutic range, the thromboelastograph was capable of showing significant changes when compared with control and different concentrations of hirudin (P < 0.05). A linear relationship was observed between increasing concentrations of recombinant hirudin and clotting times. In conclusion, the use of this test system warrants further investigation for monitoring hirudin.
authors.affiliation: Department of Medicine, New Jersey Medical School, Newark, New Jersey 07103, USA.
authors.forename: Ramzan M
authors.initials: RM
authors.lastname: Zakir
authors.forename: William
authors.initials: W
authors.lastname: Hoffman
authors.forename: Biren A
authors.initials: BA
authors.lastname: Bhatt
authors.forename: Charles R
authors.initials: CR
authors.lastname: Spillert
mesh_terms: D001780:Blood Coagulation Tests / Q000379:methods* / Q000592:standards; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D008628:Mercury / Q000494:pharmacology; D013916:Thrombelastography / Q000379:methods / Q000592:standards; D013925:Thromboplastin / Q000187:drug effects; D014914:Whole Blood Coagulation Time / Q000379:methods / Q000592:standards
chemical_list: D006629:Hirudins; D013925:Thromboplastin; D008628:Mercury