False prolongation of International Normalized Ratio associated with daptomycin

Persistent elevation of prothrombin time (PT) and International Normalized Ratio (INR) values in a patient receiving daptomycin is reported.

A morbidly obese 51-year-old man was hospitalized for evaluation for surgical intervention for gallstone pancreatitis and biliary obstruction. Previously prescribed warfarin therapy was withheld due to suspected coagulopathy and an elevated INR (5.1), and warfarin reversal was initiated. After undergoing partial cholecystectomy on hospital day 6, the patient developed sepsis and was treated with i.v. meropenem and daptomycin for vancomycin-resistant Enterococcus infection. Warfarin therapy, which had been resumed after cholecystectomy, was again discontinued on hospital day 12. On the eighth day of daptomycin therapy, the INR remained elevated (2.6) even though the patient had no warfarin exposure for 9 days. On hospital day 21, thromboelastography (TEG) indicated normal whole blood coagulation. Other anticoagulation markers normalized, but the INR remained elevated until daptomycin was discontinued. Daptomycin has been shown to falsely prolong the INR when specific laboratory reagents are used for PT and INR testing, but the specific reagent used in this case has not been previously implicated.

Daptomycin therapy appeared to cause a false and substantial INR elevation in a patient who had been receiving warfarin. Results of TEG suggested that the INR elevation was an artifact of a drug-laboratory interaction and did not represent an anticoagulated state. The patient's INR normalized after linezolid was substituted for daptomycin.