title: Effects of the oral, direct factor Xa inhibitor apixaban on routine coagulation assays and anti-FXa assays.
abstract: BACKGROUND
  Apixaban is an oral direct factor Xa inhibitor developed for the prophylaxis and treatment of thromboembolic disorders. Laboratory monitoring is not necessary, but the effects on common coagulation reagents and assays constitute clinically valuable information.
  
  
  OBJECTIVE
  To investigate the effects of apixaban on commonly used coagulation methods, and to evaluate anti-FXa assays for specific determination of the drug concentration.
  
  
  METHODS
  Apixaban was added to plasma from healthy subjects in the concentration range 0-1000 μg L(-1) , and analyses were performed with different reagents for activated partial thromboplastin time (APTT), prothrombin time (PT), antithrombin, protein C, and protein S. A lupus anticoagulant assay and an APTT assay with varying phospholipid concentrations were used to study the phospholipid dependence.
  
  
  RESULTS
  In general, apixaban showed fewer effects in vitro than have been shown for rivaroxaban, another direct FXa inhibitor. The concentration needed to double the APTT varied between 2200 and 4700 μg L(-1) , and the concentration needed to double the PT varied between 700 and 3900 μg L(-1) . The effects on antithrombin, protein C and protein S assays were dependent on the type of reagent. Apixaban did not cause false-positive lupus anticoagulant results. Chromogenic anti-FXa assays showed linear dose-response curves with apixaban.
  
  
  CONCLUSIONS
  Therapeutic concentrations of apixaban variably affect different assay groups, and even different reagents within an assay group. The effects were much smaller than with rivaroxaban. The use of APTT and/or PT assays to screen the anticoagulant activity of apixaban cannot be recommended. A chromogenic anti-FXa assay can be used for reliable measurements of apixaban concentration.
authors: Clinical Chemistry, University and Regional Laboratories Region Skåne, Malmö, Sweden.
authors: A
authors: A
authors: Hillarp
authors: K M
authors: KM
authors: Gustafsson
authors: L
authors: L
authors: Faxälv
authors: K
authors: K
authors: Strandberg
authors: F
authors: F
authors: Baghaei
authors: I
authors: I
authors: Fagerberg Blixter
authors: M
authors: M
authors: Berndtsson
authors: T L
authors: TL
authors: Lindahl
mesh_terms: D000284:Administration, Oral; D001777:Blood Coagulation / Q000187:drug effects*; D002138:Calibration; D015951:Factor Xa / Q000737:chemistry*; D065427:Factor Xa Inhibitors / Q000737:chemistry*; D005189:False Positive Reactions; D064368:Healthy Volunteers; D006801:Humans; D019934:International Normalized Ratio; D016682:Lupus Coagulation Inhibitor / Q000737:chemistry; D009025:Morpholines / Q000737:chemistry; D010314:Partial Thromboplastin Time; D010743:Phospholipids / Q000737:chemistry; D011486:Protein C / Q000737:chemistry; D017293:Protein S / Q000737:chemistry; D011517:Prothrombin Time; D011720:Pyrazoles / Q000737:chemistry*; D011728:Pyridones / Q000737:chemistry*; D015203:Reproducibility of Results; D000069552:Rivaroxaban; D013876:Thiophenes / Q000737:chemistry
chemical_list: D065427:Factor Xa Inhibitors; D016682:Lupus Coagulation Inhibitor; D009025:Morpholines; D010743:Phospholipids; D011486:Protein C; D017293:Protein S; D011720:Pyrazoles; D011728:Pyridones; D013876:Thiophenes; C522181:apixaban; D000069552:Rivaroxaban; D015951:Factor Xa
keywords: analysis; anticogaulants; apixaban; blood coagulation tests; factor Xa