Isabelle Gouin-Thibault1, Geneviève Freyburger2, Emmanuel de Maistre3, Sophie Susen4, Xavier Delavenne5, Jean-Louis Golmard6, Yves Gruel7, Pierre Sié8. 1. INSERM UMR_S1140, Faculté de Pharmacie, Paris, France; Laboratoire d'Hématologie, Centre Hospitalier Universitaire, Rennes, France. Electronic address: isabelle.gouin@chu-rennes.fr. 2. Laboratoire d'Hématologie, Centre Hospitalier Universitaire, Bordeaux, France. 3. Unité d'Hémostase, Centre Hospitalier Universitaire, Dijon, France. 4. Hémostase et transfusion, Centre Hospitalier Universitaire, Lille, France; UMR_S1011, Faculté de Médecine Pôle Recherche, Université de Lille Nord de France, Lille, France. 5. Laboratoire de Pharmacologie -Toxicologie, Centre Hospitalier Universitaire, Saint-Etienne, France; Groupe de Recherche sur la Thrombose, Université Jean Monnet, Saint-Etienne, France. 6. Biostatistics, AP-HP, Pitié-Salpêtriere University Hospital, Paris, France. 7. Hematologie-Hemostase, Centre Hospitalier Universitaire, Tours, France. 8. Hematology Laboratory, Toulouse University Hospital, Toulouse, France.
Abstract
Dabigatran etexilate, rivaroxaban and apixaban (DOACs) are widely used and measurement of their concentration is desirable in certain clinical situations. Target-specific assays are available but limited information exists on their performance especially in their ability to accurately measure low and high concentrations. AIMS: To define, in a multicenter study, the precision and accuracy of DOAC measurements in daily practice. METHODS: 15 plasma samples (kindly provided by Hyphen-Biomed) spiked with 5 blinded concentrations of dabigatran, rivaroxaban or apixaban (targeted 0-40-100-250-500ng/mL, actual concentrations measured by HPLC-MS/MS), were sent to 30 haemostasis laboratories. DOAC concentration, PT and aPTT were measured once in each sample using local reagents. Interlaboratory precision was determined by its coefficient of variation (CV) and accuracy by its bias. RESULTS: 464 DOAC measurements were performed in the 30 laboratories using 4 dabigatran and 5 rivaroxaban/apixaban calibrated assays on 3 analysers. Inter-laboratory CVs were below 18% for concentrations ≥100ng/mL, and higher for concentrations ~40ng/mL; biases were below 8% for all drugs and concentrations. In DOAC-free samples, concentrations were all below the lower limit of quantification except for one value (dabigatran: 35ng/mL). Depending on the concentrations, significant differences were found between reagents in rivaroxaban and apixaban concentration values. PT and aPTT ratios displayed a low sensitivity to apixaban. CONCLUSION: Our results suggest that calibrated DOAC assays allow the reliable measurement of a wide range of drug concentrations, even though improvement of their performances is necessary, especially for measuring low concentrations.
Dabigatran etexilate, rivaroxaban and apixaban (DOACs) are widely used and measurement of their concentration is desirable in certain clinical situations. Target-specific assays are available but limited information exists on their performance especially in their ability to accurately measure low and high concentrations. AIMS: To define, in a multicenter study, the precision and accuracy of DOAC measurements in daily practice. METHODS: 15 plasma samples (kindly provided by Hyphen-Biomed) spiked with 5 blinded concentrations of dabigatran, rivaroxaban or apixaban (targeted 0-40-100-250-500ng/mL, actual concentrations measured by HPLC-MS/MS), were sent to 30 haemostasis laboratories. DOAC concentration, PT and aPTT were measured once in each sample using local reagents. Interlaboratory precision was determined by its coefficient of variation (CV) and accuracy by its bias. RESULTS: 464 DOAC measurements were performed in the 30 laboratories using 4 dabigatran and 5 rivaroxaban/apixaban calibrated assays on 3 analysers. Inter-laboratory CVs were below 18% for concentrations ≥100ng/mL, and higher for concentrations ~40ng/mL; biases were below 8% for all drugs and concentrations. In DOAC-free samples, concentrations were all below the lower limit of quantification except for one value (dabigatran: 35ng/mL). Depending on the concentrations, significant differences were found between reagents in rivaroxaban and apixaban concentration values. PT and aPTT ratios displayed a low sensitivity to apixaban. CONCLUSION: Our results suggest that calibrated DOAC assays allow the reliable measurement of a wide range of drug concentrations, even though improvement of their performances is necessary, especially for measuring low concentrations.
Authors: Anne-Laure Sennesael; Anne-Sophie Larock; Jonathan Douxfils; Laure Elens; Gabriel Stillemans; Martin Wiesen; Max Taubert; Jean-Michel Dogné; Anne Spinewine; François Mullier Journal: Thromb J Date: 2018-11-12