title: A single test to assay warfarin, dabigatran, rivaroxaban, apixaban, unfractionated heparin, and enoxaparin in plasma.
abstract: Essentials Simple and fast assaying of different anticoagulants (ACs) is useful in emergent situations. We used highly diluted prothrombin time (dPT) or highly diluted Fiix-PT (dFiix-PT) to assay ACs. Both tests could quantify target specific anticoagulants and warfarin anticoagulation. Improved results were consistently observed with the dFiix-PT compared with the dPT.
  
  
  
  Background Assaying anticoagulants is useful in emergency situations or before surgery. Different specific assays are currently needed depending on the anticoagulant. Objectives We hypothesized that levels of warfarin, dabigatran, rivaroxaban, apixaban, and heparins could be measured with use of the diluted prothrombin time (dPT) and diluted Fiix-PT (dFiix-PT), using highly diluted thromboplastin (TP). The latter test is affected only by reduced levels of active factors II and X but corrects test plasma for other deficiencies Methods Increasing TP dilutions were used to identify suitable dilutions to measure dabigatran, rivaroxaban, apixaban, unfractionated heparin (UFH), and enoxaparin. Calibrators containing known amounts of direct oral anticoagulants (DOACs) were used to make standard curves. Citrated plasma samples were obtained from patients taking warfarin or DOACs with known drug concentrations as determined by specific assays. Results The dFiix-PT at a TP dilution of 1:1156 could be used to measure all of the drugs tested at therapeutic concentrations except for fondaparinux. The dPT achieved the same but required two TP dilutions (1:750 and 1:300). The warfarin effect could be assessed by using dFiix-PT at 1:1156 with a PT ratio identical to the international normalized ratio. Six different TPs yielded similar results, but two were less sensitive. Dabigatran, rivaroxaban, and apixaban could be accurately measured in patient samples using both dilute PT assays, but a better correlation was consistently observed between the dFiix-PT and specific assays than with the dPT. Conclusion The dFiix-PT using a single dilution of TP may be suitable to assess the anticoagulant effects of warfarin, dabigatran, rivaroxaban, apixaban, heparin, and enoxaparin.
authors.affiliation: Landspitali The National University Hospital of Iceland, Reykjavik, Iceland.
authors.forename: L R
authors.initials: LR
authors.lastname: Letertre
authors.affiliation: Landspitali The National University Hospital of Iceland, Reykjavik, Iceland.
authors.forename: B R
authors.initials: BR
authors.lastname: Gudmundsdottir
authors.affiliation: University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Francis
authors.affiliation: University of California, Davis Medical Center, Sacramento, CA, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Gosselin
authors.affiliation: Danderyd Hospital and Department of Clinical Sciences & Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Skeppholm
authors.affiliation: Clinical Pharmacology, Karolinska University Hospital & Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: R E
authors.initials: RE
authors.lastname: Malmstrom
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Moll
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC, USA.|University of North Carolina Department of Pharmacy, Chapel Hill, NC, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hawes
authors.affiliation: University of North Carolina Department of Pharmacy, Chapel Hill, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Francart
authors.affiliation: Landspitali The National University Hospital of Iceland, Reykjavik, Iceland.|Faculty of Medicine, University of Iceland School of Health Sciences, Reykjavik, Iceland.
authors.forename: P T
authors.initials: PT
authors.lastname: Onundarson
mesh_terms: D000925:Anticoagulants / Q000737:chemistry; D001780:Blood Coagulation Tests / Q000379:methods*; D001782:Blood Donors; D002138:Calibration; D000069604:Dabigatran / Q000097:blood*; D017984:Enoxaparin / Q000097:blood*; D005170:Factor X / Q000737:chemistry; D005260:Female; D000077425:Fondaparinux; D006493:Heparin / Q000097:blood*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D011134:Polysaccharides / Q000097:blood; D011516:Prothrombin / Q000737:chemistry; D011517:Prothrombin Time; D011720:Pyrazoles / Q000097:blood*; D011728:Pyridones / Q000097:blood*; D015203:Reproducibility of Results; D000069552:Rivaroxaban / Q000097:blood*; D013925:Thromboplastin / Q000737:chemistry; D014859:Warfarin / Q000097:blood*
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D011134:Polysaccharides; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin; D011516:Prothrombin; D005170:Factor X; D006493:Heparin; D013925:Thromboplastin; D000069552:Rivaroxaban; D000069604:Dabigatran; D000077425:Fondaparinux
keywords: apixaban; assay; dabigatran; heparin; rivaroxaban