Effects of Oritavancin on Coagulation Tests in the Clinical Laboratory

Abstract

Previous studies have shown that some lipoglycopeptide and lipopeptide antimicrobial agents may cause falsely elevated values for some phospholipid-dependent coagulation tests. The effect of oritavancin, a lipoglycopeptide antibiotic, on coagulation test results was explored using pooled human plasma samples spiked with drug and in a clinical study after an infusion of a single 1,200-mg intravenous dose of oritavancin in normal healthy volunteers. Pooled plasma with oritavancin added ex vivo showed concentration-dependent prolongation of prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and dilute Russell viper venom time (DRVVT) test results. In contrast, oritavancin had no effect on the activated protein C resistance assay, chromogenic anti-factor Xa assay (anti-FXa), thrombin time, and an immunoassay for the laboratory diagnosis of heparin-induced thrombocytopenia. In participants that received a single dose of oritavancin, elevations in PT/INR result, aPTT, DRVVT, activated clotting time, and silica clotting time occurred, with the maximum times to resolution of test interference determined to be 12, 120, 72, 24, and 18 h, respectively. The anti-FXa assay was unaffected, whereas transient elevations in D dimer levels were observed in 30% of participants, with a maximum time to resolution of 72 h. Although oritavancin has no impact on the coagulation system in vivo, a single dose of oritavancin can produce falsely elevated values of some coagulation tests used to monitor hemostasis. The interference of oritavancin on affected tests is transient, and the test results revert to normal ranges within specified times after dosing.

Keywords: ABSSSI; antibiotic; coagulation; hemostasis; lipoglycopeptide; oritavancin.

FIG 1

Mean (±standard deviation [SD]) plasma oritavancin concentration-time profile observed in participants administered a single 1,200-mg dose of oritavancin. The individual blue dots represent the observed oritavancin concentrations in plasma samples from participants administered a 3-h infusion of a single 1,200-mg dose of oritavancin, whereas the dashed line represents the mean (±SD) of those values. The solid black line and gray band represent the median oritavancin concentration-time profile and the 90% confidence interval, respectively, from the simulated distribution of concentrations using the population PK model from the SOLO studies (13).

FIG 2

Relationship between oritavancin plasma concentrations and PT (using the Dade Innovin reagent) in participants (n = 20). The individual dots represent PT determinations observed at the corresponding oritavancin concentrations in subject plasma samples. The horizontal red line represents the upper limit of normal (ULN; 14 s) determined for the assay.

FIG 3

Relationship between oritavancin plasma concentrations and aPTT (using the STA-PTTa reagent) in participants (n = 20). The individual dots represent aPTT determinations observed at the corresponding oritavancin concentrations in subject plasma samples. The horizontal red line represents the upper limit of normal (ULN; 39 s) determined for the assay.