Interpreting the International Normalized Ratio (INR) in individuals receiving argatroban and warfarin.
The effects of argatroban, a direct thrombin inhibitor, on the International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) and functional factor X during warfarin co-administration were established to provide means to interpret INRs during argatroban/warfarin co-therapy. Twenty-four subjects receiving warfarin (7.5 mg, day 1; 3-6 mg/day, days 2-10) and argatroban (1-4 microg/kg/min over 5 h, days 1-11) were assessed daily for these coagulation parameters prior to argatroban infusion (warfarin "monotherapy") and at its conclusion ("co-therapy"). Argatroban increased aPTTs dose-dependently. Co-therapy INR increased linearly with monotherapy INR, with slope sensitive to argatroban dose and thromboplastin used. Prediction errors for monotherapy INRs were < or =+/- 0.4 for argatroban 1-2 microg/kg/min but > or = +/-1.0 for higher doses. Despite co-therapy INRs >7, no major bleeding occurred. Factor X remained > or =37% of normal. Therefore, the predictable effect of argatroban (< or =2 microg/kg/min only) [corrected] on INRs during warfarin co-therapy allows for reliable prediction of the level of oral anticoagulation.
Sheth
S B
SB
SmithKline Beecham Pharmaceuticals, Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia 19426-0989, USA. Sunita_Sheth-1@sbphrd.com
DiCicco
R A
RA
Hursting
M J
MJ
Montague
T
T
Jorkasky
D K
DK
D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D001120:Arginine / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005170:Factor X / Q000187:drug effects / Q000378:metabolism; D006490:Hemostatics / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D013449:Sulfonamides; D013925:Thromboplastin / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D014859:Warfarin / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity
D000925:Anticoagulants; D006490:Hemostatics; D010875:Pipecolic Acids; D013449:Sulfonamides; D014859:Warfarin; D005170:Factor X; D013925:Thromboplastin; D001120:Arginine; C031942:argatroban