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 int eresting challenges for coagulation laboratory parameter testing in the pre sence of argatroban. These issues are reported here. Regarding the monitoring of argatroban, the aPTT and ACT were effectively u sed clinically for low (0-2.5 mu g/mL) or high (1-15 mu g/mL) doses of arga troban. 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 an d high drug levels with less interference from other drugs or coagulation d efects. Also identified were the chromogenic antithrombin assay that could directly quantify argatroban and an HPLC based assay that could specificall y quantify argatroban and its metabolites. With regard to assay interference by argatroban, several important effects were observed. The presence of argatroban synergistically interfered with t he INR for those patients treated with oral anticoagulants. However, a chro mogenic based method was able to determine factor X levels as a monitor of the oral anticoagulation without effect from argatroban. A similar synergis tic response on the aPTT with heparin and argatroban was observed. Patients receiving argatroban evaluated for potential coagulation abnormalities cou ld not be tested with the routine functional (clot based) assays for fibrin ogen, factor levels or protein C. Argatroban acted as an inhibitor in these assays, causing a dose-dependent false decrease of fibrinogen and factor l evels, and a false increase of protein C. Using a chromogenic assay for pro tein C, values equal to those obtained by an immunologic assay were achieve d. These issues will most likely hold true for all thrombin inhibitors.