title: Differential effects of DX-9065a, argatroban, and synthetic pentasaccharide on tissue thromboplastin inhibition test and dilute Russell's viper venom test.
abstract: New synthetic direct and indirect factor Xa or factor IIa inhibitors are increasingly used for the prevention and treatment of thrombotic disorders, including patients suffering from antiphospholipid syndrome. In this study, the effects of the synthetic direct factor Xa inhibitor DX-9065a, the indirect synthetic heparinomimetic pentasaccharide, and the direct factor IIa inhibitor Argatroban were studied. These two widely used assays for the detection of lupus anticoagulant, namely the tissue thromboplastin inhibition (TTIT) and the dilute Russell viper venom tests (DRWT) proved useful. The drugs were added to a normal human plasma pool ranging in concentration from 0.04 to 10 microg/mL. Using the two tests named above, DX-9065a and Argatroban showed a dose-related prolongation of TTIT and DRWT in the concentration range from 0.04 to 5 micromol/mL, but the pentasaccharide only slightly prolonged the clotting times of these assays even at high concentrations. Argatroban had the more pronounced effect on both tests when compared with DX-9065a (p < 0.001). The most responsive assay for DX-9065a up to a concentration of 2.5 micromol/mL was the DRWT. For Argatroban both TTIT and DRWT were equally responsive. Patients whose plasma was tested for suspected lupus anticoagulant and who have been given DX-9065a or Argatroban may have false-positive results with the TTIT tests and DRWT. This effect should be considered during patient management. These results indicate that these assays could be used for the effective quantitation of the direct factor Xa or factor IIa inhibitors when suitable controls are used.
authors.affiliation: Kaunas Medical University, Department of Hematology and Department of Drug Technology, Kaunas, Lithuania.
authors.forename: Rolandas
authors.initials: R
authors.lastname: Gerbutavicius
authors.forename: Omer
authors.initials: O
authors.lastname: Iqbal
authors.forename: Harry L
authors.initials: HL
authors.lastname: Messmore
authors.forename: William H
authors.initials: WH
authors.lastname: Wehrmacher
authors.forename: Debra A
authors.initials: DA
authors.lastname: Hoppensteadt
authors.forename: Rima
authors.initials: R
authors.lastname: Gerbutaviciene
authors.forename: Rasa
authors.initials: R
authors.lastname: Griniute
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D009844:Oligosaccharides / Q000494:pharmacology; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011517:Prothrombin Time; D013449:Sulfonamides
chemical_list: C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000925:Anticoagulants; D009281:Naphthalenes; D009844:Oligosaccharides; D010875:Pipecolic Acids; D011422:Propionates; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban