title: Effect of argatroban on the activated partial thromboplastin time: a comparison of 21 commercial reagents.
abstract: Argatroban is a direct thrombin inhibitor used for the treatment of heparin-induced thrombocytopenia. The drug is administered by continuous infusion, at a recommended initial dose of 2 microg/kg per min, to achieve activated partial thromboplastin times (aPTTs) 1.5-3.0 times baseline. We evaluated the effect of argatroban, at clinically relevant concentrations, on aPTTs using 21 commercially available reagents. The aPTTs of plasma containing argatroban at 0.125-8.0 microg/ml (final concentration) were assessed using each reagent and an ACL 3000+ coagulation analyzer. Argatroban increased aPTTs (and aPTT ratios relative to control) in a broadly comparable fashion among reagents. Concentration-aPTT ratio profiles linearized well using logarithmic-logarithmic transformation (r > 0.98), with the regression slope taken as the reagent's sensitivity to argatroban. Sensitivity ranged from 0.304 +/- 0.006 to 0.364 +/- 0.007. Only the least and two most sensitive reagents (all now unavailable in the United States) differed significantly in sensitivity from the other reagents (P < 0.05). aPTT ratios of 2.25 occurred for all reagents at 0.41-0.92 mug/ml argatroban, and for 14 (67%) reagents at 0.53-0.67 microg/ml. This corresponds to a approximately 0.5 microg/kg per min dose difference in healthy subjects. We conclude that most aPTT reagents are similarly sensitive to argatroban, and reagent choice is unlikely to significantly affect argatroban monitoring in patients with heparin-induced thrombocytopenia.
authors.affiliation: Florida Hospital Center for Thrombosis and Hemostasis, 2501 North Orange Avenue, Orlando, FL 32804, USA. John.Francis@flhosp.org
authors.forename: John L
authors.initials: JL
authors.lastname: Francis
authors.forename: Marcie J
authors.initials: MJ
authors.lastname: Hursting
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives; D001777:Blood Coagulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D010314:Partial Thromboplastin Time / Q000592:standards*; D010875:Pipecolic Acids / Q000097:blood / Q000494:pharmacology*; D011933:Reagent Kits, Diagnostic / Q000592:standards*; D012680:Sensitivity and Specificity; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D010875:Pipecolic Acids; D011933:Reagent Kits, Diagnostic; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban