Dose-dependent effect of daptomycin on the artificial prolongation of prothrombin time in coagulation abnormalities: In vitro verification

Abstract

Background: Several studies have reported that daptomycin induced artificial prolongation of prothrombin time (PT) in some test reagents, particularly in warfarin users. However, it remains unknown whether the artificial prolongation can be affected by coagulation abnormalities other than the use of warfarin. Thus, we investigated the effect of daptomycin on PT with two types of coagulation abnormalities. Methods: Plasma samples were pooled by four groups: healthy volunteers (Plasma A), warfarin users with a PT-international normalized ratio (INR) of approximately 2.0 (Plasma B) or 3.0 (Plasma C), and patients with liver cirrhosis with a PT-INR of approximately 2.0 (Plasma D). Plasma A was composed of plasma from two healthy individuals (9 mL from each individual). Plasma B, C, and D were composed of plasma from 36 patients (0.5 mL from each patient). Daptomycin was added to each sample to create solutions with several concentrations (0-150 μg/mL). The PT-INR for each solution was measured with three PT reagents. Linear regression analyses were used to determine the association between daptomycin concentration and PT-INR. The relative change in PT-INR due to daptomycin concentrations was calculated. Results: Strong linear correlations were observed between daptomycin concentrations and PT-INR for all the plasma groups and reagents (R2 > 0.7, P < 0.01). At a daptomycin concentration of 150 μg/mL, the relative increase of PT-INR was ≥10% in the majority of the plasma groups with an elevated baseline PT-INR in all reagents tested. Conclusions: Daptomycin induced the artificial prolongation of PT-INR in a concentration-dependent manner, particularly in plasma samples with an elevated baseline PT-INR. PT should be evaluated at the trough levels of daptomycin.