title: Monitoring of anticoagulant effects of direct thrombin inhibitors.
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.
authors.affiliation: 4th Department of Medicine, University Hospital, Mannheim, Germany.
authors.forename: Tivadar
authors.initials: T
authors.lastname: Fenyvesi
authors.forename: Ingrid
authors.initials: I
authors.lastname: Jörg
authors.forename: Job
authors.initials: J
authors.lastname: Harenberg
mesh_terms: D000925:Anticoagulants / Q000097:blood*; D001120:Arginine / Q000031:analogs & derivatives; D001384:Azetidines; D001596:Benzylamines; D001780:Blood Coagulation Tests / Q000379:methods / Q000592:standards; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D005998:Glycine / Q000031:analogs & derivatives* / Q000097:blood; D006493:Heparin / Q000097:blood; D006629:Hirudins / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D010875:Pipecolic Acids / Q000097:blood; D011994:Recombinant Proteins / Q000097:blood; D012680:Sensitivity and Specificity; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D006629:Hirudins; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; C109573:melagatran; D006493:Heparin; D001120:Arginine; D013917:Thrombin; C031942:argatroban; D005998:Glycine; C083544:lepirudin