Review of the Current Issues Surrounding Monitoring of the Direct Thrombin Inhibitor Argatroban in the Laboratory

The direct thrombin inhibitor argatroban is licensed for use in Heparin-induced thrombocytopenia. Original trial data gave the recommendation of monitoring argatroban by Activated Partial Thromboplastin Time (APTT) stating a therapeutic target range of 1.5-3.0 times baseline APTT and not exceeding 100 s. APTT has limitations due to prolongation arising in factor deficiencies, lupus anticoagulants, liver disease, and high FVIII levels leading to potential overestimation of argatroban. Argatroban has demonstrated a plateau effect on APTT at higher concentrations; additionally, APTT reagents have different sensitivity to argatroban, potentially underestimating or overestimating the argatroban. Anti-IIa methods have been recommended as a suitable alternative to accurately quantify argatroban levels. However, there is a lack of consensus on what the target therapeutic range should be. This review will demonstrate how argatroban monitoring by APTT may not be the most suitable method to successfully dose argatroban based on the current state of knowledge and recent published guidelines and highlight the benefits of the anti-IIa methods.