title: Presence of direct thrombin inhibitors can affect the results and interpretation of lupus anticoagulant testing.
abstract: In vitro experiments were conducted to determine whether the direct thrombin inhibitors argatroban and lepirudin can interfere with the results of lupus anticoagulant (LA) testing. Concentration-response curves were generated to calculate the concentration of anticoagulant that prolongs the activated partial thromboplastin time (aPTT) to 75 seconds (2.5 times the baseline average). Corresponding concentrations of anticoagulant were added to plasma samples before running dilute Russell viper venom tests (DRVVTs) and LA-sensitive aPTTs (PTT-LAs). Because the DRVVT test system contains an antiheparin agent, DRVVT results were not prolonged in the presence of heparin. With argatroban added to normal plasma samples, neither the DRVVT percent correction of ratio nor the DRVVT test/confirm ratio were elevated, but when added to LA-positive plasma, some false-negative results were observed. Lepirudin increased the DRVVT percent correction of ratio and the DRVVT test/confirm ratio into a range that could lead to false-positive identifications of LAs. In sharp contrast to the DRVVT test system, distinction between LA-positive and LA-negative plasma samples was maintained and possibly even enhanced in the platelet neutralization procedure correction phase of the PTT-LA test system.
authors.affiliation: Department of Pathology, Pritzker School of Medicine, the University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Genzen
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Miller
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D010314:Partial Thromboplastin Time; D010446:Peptide Fragments / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology*; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013449:Sulfonamides; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D016682:Lupus Coagulation Inhibitor; D010446:Peptide Fragments; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; D014757:Viper Venoms; D006493:Heparin; D001120:Arginine; C031942:argatroban; C074619:bivalirudin