Effect of daptomycin on prothrombin time and the requirement for outlier exclusion in International Sensitivity Index calibration of thromboplastin

Besselaar, A. M. H. P. Van Den; Tripodi, Armando

doi:10.1111/j.1538-7836.2007.02679.x

Cited by 14 publications

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References 4 publications

(3 reference statements)

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“…Based on the linear regression results in warfarin users, the PT-INR at a daptomycin peak concentration of 70 μg/mL is predicted to be 1.15 times (Reagent 2) and 1.20 times (Reagent 3) higher than the PT-INR at a trough concentration of 20 μg/mL. These estimates are in the similar range of effects previously reported by in vitro studies (ranging from 1.15 to more than three times higher at 100 μg/mL than at 0 μg/mL) [3, 5, 6, 9]. These magnitudes of elevation are clinically relevant, especially considering that higher daptomycin dosing (>6 mg/kg) was recently suggested and used for certain clinical situations [10, 11].…”

Section: Discussionsupporting

confidence: 69%

Dose-dependent artificial prolongation of prothrombin time by interaction between daptomycin and test reagents in patients receiving warfarin: a prospective in vivo clinical study

Saito

Hatakeyama

Hashimoto

et al. 2017

Ann Clin Microbiol Antimicrob

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BackgroundDaptomycin has been reported to cause artificial prolongation of prothrombin time (PT) by interacting with some test reagents of PT. This prolongation was particularly prominent with high concentrations of daptomycin in vitro. However, whether this prolongation is important in clinical settings and the optimal timing to assess PT remain unclear.MethodsA prospective clinical study was conducted with patients who received daptomycin for confirmed or suspected drug-resistant, gram-positive bacterial infection at a university hospital in Japan. PT at the peak and trough of daptomycin was tested using nine PT reagents. Linear regression analyses were used to examine the difference in daptomycin concentration and the relative change of PT-international normalized ratios (PT-INR).ResultsThirty-five patients received daptomycin (6 mg/kg). The mean ± standard deviation of the trough and peak concentrations of daptomycin were 13.5 ± 6.3 and 55.1 ± 16.9 μg/mL, respectively. Twelve patients (34%) received warfarin. With five PT reagents, a significant proportion of participants experienced prolongation of PT-INR at the daptomycin peak concentration compared to the PT-INR at the trough, although the mean relative change was less than 10%. None of the participants clinically showed any signs of bleeding. A linear, dose-dependent prolongation of PT was observed for one reagent [unadjusted coefficient β 3.1 × 10−3/μg/mL; 95% confidence interval (CI) 2.3 × 10−5–6.3 × 10−3; p = 0.048]. When patients were stratified based on warfarin use, this significant linear relationship was observed in warfarin users for two PT reagents (adjusted coefficient β, 6.4 × 10−3/μg/mL; 95% CI 3.5 × 10−3–9.3 × 10−3; p < 0.001; and adjusted coefficient β, 8.3 × 10−3/μg/mL; 95% CI 4.4 × 10−3–1.2 × 10−2; p < 0.001). In non-warfarin users, this linear relationship was not observed for any PT reagents.ConclusionsWe found that a higher concentration of daptomycin could lead to artificial prolongation of PT-INR by interacting with some PT reagents. This change may not be clinically negligible, especially in warfarin users receiving a high dose of daptomycin. It may be better to measure PT at the trough rather than at the peak daptomycin concentration.

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Section: Discussionsupporting

confidence: 69%

Dose-dependent artificial prolongation of prothrombin time by interaction between daptomycin and test reagents in patients receiving warfarin: a prospective in vivo clinical study

Saito

Hatakeyama

Hashimoto

et al. 2017

Ann Clin Microbiol Antimicrob

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“…Since clinical bleeding related to oritavancin use has not been reported in clinical studies (The Medicines Company, data on file), the elevations in phospholipid-dependent coagulation test results indicate an ex vivo test interference. The prolongation of phospholipid-dependent coagulation test results by oritavancin occurred in a concentration-dependent manner, similar to that described for telavancin and daptomycin (4,5,7). In the phase 1 study, elevations in PT/INR results, aPTT, DRVVT, ACT, and SCT occurred in a transient manner following administration of a single 1,200-mg dose of oritavancin in participants.…”

Section: Discussionmentioning

confidence: 78%

“…Previous studies have shown that some lipoglycopeptide or lipopeptide antibiotics (e.g., telavancin and daptomycin) may artificially prolong phospholipid-dependent coagulation test results (4)(5)(6)(7). Although these agents do not interfere with the coagulation system in vivo, their interference with coagulation assays can confound monitoring of hemostasis in the clinical setting.…”

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confidence: 99%

Effects of Oritavancin on Coagulation Tests in the Clinical Laboratory

Belley

Robson

Francis³

et al. 2017

Antimicrob Agents Chemother

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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.

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“…(iv) The reason(s) that Neoplastin Plus (or RBT/05) and the plasmas used in the FCSA EQA survey interact with each other differently from the other thromboplastins used in the survey is presently unknown. Possible explanations could be: (i) the additives and/ or preservatives added to the plasmas before lyophilization; (ii) possible contamination with divalent ions such as magnesium or others [5]; (iii) the presence of drugs used by the donors of the plasmas, such as antibiotics, that have already been reported to affect the INR [6,7]; and (iii) the process of lyophilization itself, which could make the lyophilized material act differently from their fresh counterpart [8].…”

Section: (Ii) the Finding That The Inr Measured With Neoplastinmentioning

confidence: 99%

Discrepancy of the international normalized ratio observed in the external quality assessment survey: a cause for concern

Tripodi

Chantarangkul

Legnani

et al. 2012

Journal of Thrombosis and Haemostasis

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To cite this article: Tripodi A, Chantarangkul V, Legnani C, Frontoni R, Testa S. Discrepancy of the international normalized ratio observed in the external quality assessment survey: a cause for concern. J Thromb Haemost 2012; 10: 714-6.The External Quality Assessment (EQA) survey of the international normalized ratio (INR) organized and carried out by the FCSA (Italian Federation of Thrombosis Centers) enrols on average 240 participants across the country. Participants receive twice per year sets of lyophilized plasmas at increased levels of anticoagulation and are asked to determine the INR using their local methods (i.e. thromboplastin/ coagulometer combination). Participants also receive detailed instructions on how to handle lyophilized test plasmas (reconstitution and storage until analysis). Results are then centralized for statistical analyses that include the calculation for each test plasma of the following parameters. (i) The overall mean, after exclusion of outliers [1]; this value is taken as the ÔconsensusÕ value for further evaluation. (ii) The standard deviation (SD) and the coefficient of variation (CV). (iii) Results from each participant and plasma are compared with the ÔconsensusÕ value to calculate the deviation as percentage discrepancy ([participant value)consensus value]/consensus value) · 100 and z-score ([participant value)consensus value]/SD) · 100. Further analyses according to subgroups using the same thromboplastin in combination with coagulometers manufactured by the same company as the thromboplastins are performed whenever the numbers of participants in each subgroup are adequate. The lyophilized plasmas employed in the FCSA EQA survey and in this investigation were provided by Hart Biologicals (Hartlepool, UK). They were prepared from plasmas of patients stabilized on vitamin K antagonists (VKA). Factor V for these plasmas was higher than 70 IU dL (Table 1a) and most of the participants in this group had results that were far in excess of 20% from the ÔconsensusÕ value. Conversely, the mean INR obtained with the other thromboplastins used in the survey, whose number of participants exceeded 10, were in fair agreement with the INR ÔconsensusÕ value, with discrepancies that were 9% or less (i.e. )6% or )5% Recombiplastin [IL]; 8% or 7% Thromborel S [Siemens, Tarrytown, NY, USA]; 9% or 3% Innovin (Siemens); and 6% or 0% Thromboplastin S (Diagen, Oxford, UK) for plasmas B-1159-9 or B-1159-5, respectively). The discrepancy between the mean INR value obtained with Neoplastin Plus and the INR ÔconsensusÕ value sparked concern among participants in the survey and the thromboplastin manufacturer. Therefore, the organizers decided to carry out an independent investigation to seek explanations for the above discrepancy.To account for the possible inaccuracy of the international sensitivity index (ISI) determination declared by the manufacturer and used by participants in the survey, one lot of Neoplastin Plus (lot 624151), representative of the manufacturer production, was purchased and ...

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Effect of daptomycin on prothrombin time and the requirement for outlier exclusion in International Sensitivity Index calibration of thromboplastin

Cited by 14 publications

References 4 publications

Dose-dependent artificial prolongation of prothrombin time by interaction between daptomycin and test reagents in patients receiving warfarin: a prospective in vivo clinical study

Dose-dependent artificial prolongation of prothrombin time by interaction between daptomycin and test reagents in patients receiving warfarin: a prospective in vivo clinical study

Effects of Oritavancin on Coagulation Tests in the Clinical Laboratory

Discrepancy of the international normalized ratio observed in the external quality assessment survey: a cause for concern

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