Interaction of daptomycin with two recombinant thromboplastin reagents leads to falsely prolonged patient prothrombin time/International Normalized Ratio results

Webster, Peggy S., Oleson, Frederick B. Jr, Paterson, David L., Arkin, Charles F., Mangili, Alexandra, Craven, Donald E., Adcock, Dorothy M., Lindfield, Kimberly C., Knapp, Andrew G. and Martone, William J. (2008) Interaction of daptomycin with two recombinant thromboplastin reagents leads to falsely prolonged patient prothrombin time/International Normalized Ratio results. Blood Coagulation and Fibrinolysis, 19 1: 32-38. doi:10.1097/MBC.0b013e3282f10275


Author Webster, Peggy S.
Oleson, Frederick B. Jr
Paterson, David L.
Arkin, Charles F.
Mangili, Alexandra
Craven, Donald E.
Adcock, Dorothy M.
Lindfield, Kimberly C.
Knapp, Andrew G.
Martone, William J.
Title Interaction of daptomycin with two recombinant thromboplastin reagents leads to falsely prolonged patient prothrombin time/International Normalized Ratio results
Journal name Blood Coagulation and Fibrinolysis   Check publisher's open access policy
ISSN 0957-5235
1473-5733
Publication date 2008-01-01
Sub-type Article (original research)
DOI 10.1097/MBC.0b013e3282f10275
Volume 19
Issue 1
Start page 32
End page 38
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Subject 1102 Cardiovascular Medicine and Haematology
1115 Pharmacology and Pharmaceutical Sciences
Abstract A cluster of patients experiencing elevations of International Normalized Ratio without clinical bleeding in temporal association with daptomycin therapy was identified during postmarketing safety surveillance. A common element was the thromboplastin reagent used for the laboratory assay. The present study evaluated the effect of daptomycin on measured prothrombin time using commercially available thromboplastin reagent kits commonly used in the United States. Thirty reagent kits were obtained. Daptomycin was added to pooled normal human plasma samples to achieve final concentrations of 0-200 μg/ml. Quality control ranges were established for each reagent kit using normal and abnormal control plasmas. Triplicate assays of the prothrombin time were performed on the daptomycin-spiked plasma samples using each of the 30 kits. The activated partial thromboplastin time and thrombin time were also assessed. Statistical comparisons of interest were performed using analysis of variance with the Bonferroni t-test for multiple comparisons; α = 0.05 was used. Addition of daptomycin to human plasma samples dose-dependently prolonged measured prothrombin times when two recombinant thromboplastin reagents were utilized. The findings were statistically and clinically significant. No clinically meaningful effect was observed with the other reagents. The activated partial thromboplastin time and thrombin time were not affected. Prolonged International Normalized Ratio patient values were an artifact caused by the interaction of daptomycin with the in-vitro prothrombin time test reagent; an in-vivo anticoagulant effect was not observed. Healthcare providers should consider a possible drug-laboratory test interaction if prolonged prothrombin time or elevated International Normalized Ratio values are observed in patients receiving daptomycin.
Keyword Daptomycin
Thromboplastin
Effect
Prothrombin
Thromboplastin reagent kits
Thrombin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Centre for Clinical Research Publications
 
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Created: Wed, 27 Jan 2010, 23:23:05 EST by Macushla Boyle on behalf of Royal Brisbane Clinical School