title: 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.
authors.affiliation: The Medicines Company, Parsippany, New Jersey, USA adam.belley@themedco.com.
authors.forename: Adam
authors.initials: A
authors.lastname: Belley
authors.affiliation: Christchurch Clinical Studies Trust, Christchurch, New Zealand.
authors.forename: Richard
authors.initials: R
authors.lastname: Robson
authors.affiliation: Florida Hospital Center for Thrombosis Research, Winter Park, Florida, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Francis
authors.affiliation: Colorado Coagulation, Laboratory Corporation of America Holdings, Englewood, Colorado, USA.
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Adcock
authors.affiliation: Colorado Coagulation, Laboratory Corporation of America Holdings, Englewood, Colorado, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Tiefenbacher
authors.affiliation: Institute for Clinical Pharmacodynamics, Latham, New York, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Rubino
authors.affiliation: The Medicines Company, Parsippany, New Jersey, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Moeck
authors.affiliation: The Medicines Company, Parsippany, New Jersey, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sylvester
authors.affiliation: The Medicines Company, Parsippany, New Jersey, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Dudley
authors.affiliation: The Medicines Company, Parsippany, New Jersey, USA.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Loutit
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D005260:Female; D006020:Glycopeptides / Q000627:therapeutic use*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D000077427:Lipoglycopeptides; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D014640:Vancomycin / Q000031:analogs & derivatives
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D000077427:Lipoglycopeptides; C100708:oritavancin; D014640:Vancomycin
keywords: ABSSSI; antibiotic; coagulation; hemostasis; lipoglycopeptide; oritavancin