Edoxaban: Impact on routine and specific coagulation assays. A practical laboratory guide.
Assessment of plasma concentration/effect of edoxaban may be useful in some situations. Also, clinicians need to know how routine coagulation assays are influenced. It was our aim to determine coagulation tests useful for the assessment of edoxaban's pharmacodynamics and provide recommendations for the interpretation of haemostasis diagnostic tests. Edoxaban was spiked at concentrations ranging from 0 to 1,000 ng/ml in platelet-poor plasma which covers the on-therapy range (from ± 25 ng/ml at Ctrough to ± 170 ng/ml at Cmax). aPTT, PT, dRVVT, chromogenic anti-Xa assays, TGA and a large panel of haemostasis diagnostic tests were performed using several reagents. A concentration-dependent prolongation of aPTT, PT and dRVVT was observed. The effect was dependent on the reagents. FXa chromogenic assays showed high sensitivity and a linear correlation depending on the methodology. TGA may be useful to assess the pharmacodynamics of edoxaban but its turnaround time and the lack of standardisation are limitations. Edoxaban impairs the assessment of lupus anticoagulant, protein S (clotting method), APC-R, antithrombin (FXa-based assay) and measurement of clotting factor activity. Immunological assays and assays acting below the FXa are not influenced by edoxaban. In conclusion, some PT reagents could be used to estimate edoxaban activity. Chromogenic anti-Xa assays are required to assess the plasma concentration. TGA may be useful but requires standardisation. In case of thrombophilia or in the exploration of a haemorrhagic event, immunological assays should be recommended, when applicable. Standardisation of the time between the last intake and the sampling is mandatory to provide a proper assessment of the result.
Jonathan Douxfils, Department of Pharmacy, Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, B-5000, Belgium, E-mail: jonathan.douxfils@unamur.be.
Jonathan
J
Douxfils
Bernard
B
Chatelain
Christian
C
Chatelain
Jean-Michel
JM
Dogné
François
F
Mullier
D000991:Antithrombins / Q000737:chemistry; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000379:methods*; D001792:Blood Platelets / Q000166:cytology; D002138:Calibration; D004305:Dose-Response Relationship, Drug; D015951:Factor Xa / Q000737:chemistry; D065427:Factor Xa Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005340:Fibrinogen / Q000737:chemistry; D006487:Hemostasis; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000737:chemistry; D010314:Partial Thromboplastin Time; D010949:Plasma / Q000737:chemistry; D011486:Protein C / Q000737:chemistry; D017293:Protein S / Q000737:chemistry; D011517:Prothrombin Time; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013818:Thermogravimetry; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*; D013917:Thrombin / Q000737:chemistry; D019851:Thrombophilia / Q000097:blood
D000991:Antithrombins; D065427:Factor Xa Inhibitors; D016682:Lupus Coagulation Inhibitor; D011486:Protein C; D017293:Protein S; D011725:Pyridines; D013844:Thiazoles; D005340:Fibrinogen; D013917:Thrombin; D015951:Factor Xa; C552171:edoxaban
Edoxaban; coagulation tests; drug measurement; factor Xa inhibitors; guidelines