Monitoring of Argatroban and Lepirudin: What is the Input of Laboratory Values in "Real Life"?

Abstract

Monitoring of direct thrombin inhibitors (DTIs) in patients with heparin-induced thrombocytopenia (HIT) is primarily performed using the activated partial thromboplastin time (aPTT). This assay is poorly standardized, reagent dependent, and not DTI specific. We compared aPTT, thrombin time (TT), and prothrombin time (PT) to drug levels obtained by the ecarin chromogenic assay (ECA). We analyzed 495 samples of patients with confirmed or suspected HIT on treatment with either argatroban (n = 37) or lepirudin (n = 80). Mean DTI levels ± standard deviation (SD) were 0.41 ± 0.36 µg/mL for argatroban and 0.20 ± 0.21 µg/mL for lepirudin. Results of aPTT were highly variable: 67 ± 22 seconds for argatroban and 55 ± 20 seconds for lepirudin. Significant correlations ( P < .01) were found between ECA-based DTI level and TT (argatroban, r = .820 and lepirudin, r = .830), PT (argatroban, r = -.544), and aPTT (lepirudin, r = .572). However, there was no correlation of aPTT with argatroban or PT with lepirudin concentration. Multiple regression analyses revealed that the TT predicted 54% of argatroban and 42% of lepirudin levels, but no significant impact was seen for PT or aPTT. The aPTT-guided monitoring of DTI therapy leads to a high percentage of patients with inaccurate plasma levels, hence resulting to either undertreatment or overtreatment. Knowledge of baseline values prior to DTI therapy and inclusion of clinical settings are essential for dosing DTIs when using aPTT. However, due to several limitations of aPTT, monitoring according to exact plasma concentrations as obtained by specific tests such as ECA may be more appropriate.