Coagulation laboratory testing in patients treated with argatroban.
During clinical trials with the thrombin inhibitor argatroban, appropriate methods for drug monitoring were identified. Treated patients presented interesting challenges for coagulation laboratory parameter testing in the presence of argatroban. These issues are reported here. Regarding the monitoring of argatroban, the aPTT and ACT were effectively used clinically for low (0-2.5 microg/mL) or high (1-15 microg/mL) doses of argatroban. However, system (reagent and instrument) differences were noted in the time-to-clot values. A clot-based assay using Ecarin as the activator (ECT, Ecarin clotting time) appeared to be useful for monitoring both low and high drug levels with less interference from other drugs or coagulation defects. Also identified were the chromogenic antithrombin assay that could directly quantify argatroban and an HPLC based assay that could specifically quantify argatroban and its metabolites. With regard to assay interference by argatroban, several important effects were observed. The presence of argatroban synergistically interfered with the INR for those patients treated with oral anticoagulants. However, a chromogenic based method was able to determine factor X levels as a monitor of the oral anticoagulation without effect from argatroban. A similar synergistic response on the aPTT with heparin and argatroban was observed. Patients receiving argatroban evaluated for potential coagulation abnormalities could not be tested with the routine functional (clot based) assays for fibrinogen, factor levels or protein C. Argatroban acted as an inhibitor in these assays, causing a dose-dependent false decrease of fibrinogen and factor levels, and a false increase of protein C. Using a chromogenic assay for protein C, values equal to those obtained by an immunologic assay were achieved. These issues will most likely hold true for all thrombin inhibitors.
Walenga
J M
JM
Department of Thoracic & Cardiovascular Surgery, Loyola University Medical Center Maywood, Illinois 60153, USA.
Fasanella
A R
AR
Iqbal
O
O
Hoppensteadt
D A
DA
Ahmad
S
S
Wallis
D E
DE
Bakhos
M
M
D000991:Antithrombins / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D001681:Biological Assay / Q000379:methods; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000627:therapeutic use*; D011517:Prothrombin Time; D015203:Reproducibility of Results; D013449:Sulfonamides
D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban