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 phospholipiddependent 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 antifactor 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.

Long‐Acting Lipoglycopeptides Can Interfere With Vancomycin Therapeutic Drug Monitoring

“…Oritavancin has also been shown to impact other coagulation tests such as a concentration-dependent prolongation of prothrombin time/international normalized ratio and dilute Russell viper venom time for detecting lupus anticoagulants. 24 Previous studies have highlighted the potential for false vancomycin concentrations in vancomycin TDM, 25,26 including one study in which a patient had an elevated vancomycin concentration before initiation of therapy. 27 Other studies have highlighted the impact of renal function on accumulation of the metabolite, CDP-1, that can also falsely increase vancomycin concentrations.…”

New Antimicrobials for Gram-Positive Sustained Infections: A Comprehensive Guide for Clinicians

“…Upon administration, Dalbavancin tightly binds to the D-ala-D-ala portion of peptidoglycan chains, a site different from that of penicillins and cephalosporins, preventing peptidoglycan elongation and interfering with bacterial cell wall synthesis. This fact leads to bacterial cell death [ 85 ].…”

Activated Partial Thromboplastin Time and Prothrombin Time Mixing Studies: Current State of the Art

“…Some lipoglycopeptide antibiotics active against methicillinresistant Staphylococcus aureus (MRSA) such as daptomycin, telavancin, or other lipoglycopeptides may cause prolongation of the aPTT and/or PT and concentration-dependent lack of correction upon mixing with NPP. [17][18][19] In addition, certain PEGylated drugs may cause prolongation of the aPTT depending on the type of PEG and the aPTT reagent used. 20,21 C-reactive protein, a protein produced in the liver and elevated in inflammatory conditions, has also been reported to factitiously prolong the aPTT in certain reagents.…”

“…Exogenous inhibitors include some anticoagulant drugs and certain antibiotics effective against MRSA. 14,15,[17][18][19] The anticoagulant agents that have in vivo inhibitor effects often have a corresponding in vitro effect resulting in prolonged clotting times and include heparins, hirudin-based anticoagulants, parenteral DTIs, and direct oral anticoagulants. 14,15 These typically yield noncorrection in mixing tests, but there should be no need for a mixing test if the history of drug administration is known.…”