PMID- 30604921
OWN - NLM
STAT- MEDLINE
DCOM- 20190403
LR  - 20190403
IS  - 1751-553X (Electronic)
IS  - 1751-5521 (Linking)
VI  - 41
IP  - 2
DP  - 2019 Apr
TI  - Development of new methodologies for the chromogenic estimation of betrixaban 
      concentrations in plasma.
PG  - 250-261
LID - 10.1111/ijlh.12963 [doi]
AB  - INTRODUCTION: Chromogenic anti-Xa assays are the most appropriate tests to 
      estimate the amount of betrixaban in plasma but the sensitivity of available 
      tests is limited and improvements are needed to encompass the on-therapy range. 
      METHODS: Betrixaban was spiked at concentrations ranging from 0 to 500 ng/mL in 
      plasma from healthy donors. Three commercial tests were used (Biophen((R)) DiXaI((R)) 
      , STA((R)) Liquid Anti-Xa, and HemosIL((R)) Liquid Anti-Xa), and adaptation of their 
      sample dilution scheme was performed. These new methodologies were also tested on 
      plasma spiked with amounts of unfractionated heparin (UFH), low molecular weight 
      heparins (LMWH), or fondaparinux covering the on-therapy ranges to evaluate their 
      sensitivity to indirect factor Xa inhibitors. RESULTS: Results showed 
      concentration-dependent decreases in OD/min inversely proportional to the 
      dilutions. While modifications improve the sensitivity of these tests to 
      betrixaban (eg, (1/2)*OD/min of 502 ng/mL [95% CI: 495-508 ng/mL] for Biophen((R)) 
      DiXaI((R)) [1:50] is reduced to 51 ng/mL [95% CI: 50-52 ng/mL] for improved 
      Biophen((R)) DiXaI((R)) [1:5]), results also showed an increased sensitivity to 
      indirect factor Xa inhibitors, except for Biophen((R)) DiXaI((R)) which remains 
      insensitive to UFH and LMWH. CONCLUSIONS: Results showed that the improvement of 
      current chromogenic anti-Xa methodologies enhances the sensitivity of these 
      assays to betrixaban but also to indirect factor Xa inhibitors. This lack of 
      specificity may lead to overestimation of betrixaban concentrations in patients 
      bridged with heparins. To avoid this cross-interference, the use of the 
      Biophen((R)) DiXaI((R)) may be a solution except for fondaparinux which remains 
      active even in the presence of the Biophen((R)) DiXaI((R)) 's specific buffer. For 
      the other chromogenic assays, the conception and validation of specific buffer is 
      required.
CI  - (c) 2018 John Wiley & Sons Ltd.
FAU - Siriez, Romain
AU  - Siriez R
AUID- ORCID: 0000-0002-5003-6939
AD  - Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur 
      Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, 
      Belgium.
FAU - Evrard, Jonathan
AU  - Evrard J
AUID- ORCID: 0000-0003-4255-1591
AD  - Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur 
      Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, 
      Belgium.
FAU - Dogne, Jean-Michel
AU  - Dogne JM
AD  - Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur 
      Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, 
      Belgium.
FAU - Pochet, Lionel
AU  - Pochet L
AUID- ORCID: 0000-0002-2560-9555
AD  - Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur 
      Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, 
      Belgium.
FAU - Bouvy, Celine
AU  - Bouvy C
AD  - Qualiblood s.a, Namur, Belgium.
FAU - Lessire, Sarah
AU  - Lessire S
AUID- ORCID: 0000-0001-6689-6100
AD  - Department of Anesthesiology, Namur Thrombosis and Hemostasis Center (NTHC), 
      Namur Research Institute for Life Sciences (NARILIS), Universite Catholique de 
      Louvain, CHU UCL Namur, Yvoir, Belgium.
FAU - Mullier, Francois
AU  - Mullier F
AUID- ORCID: 0000-0001-6947-6099
AD  - Hematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur 
      Research Institute for Life Sciences (NARILIS), Universite Catholique de Louvain, 
      CHU UCL Namur, Yvoir, Belgium.
FAU - Douxfils, Jonathan
AU  - Douxfils J
AUID- ORCID: 0000-0002-7644-5298
AD  - Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur 
      Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, 
      Belgium.
AD  - Qualiblood s.a, Namur, Belgium.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
DEP - 20190103
PL  - England
TA  - Int J Lab Hematol
JT  - International journal of laboratory hematology
JID - 101300213
RN  - 0 (Benzamides)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Pyridines)
RN  - 74RWP7W0J9 (betrixaban)
SB  - IM
MH  - Benzamides/*pharmacokinetics
MH  - Blood Chemical Analysis/*methods
MH  - Factor Xa Inhibitors/*pharmacokinetics
MH  - Female
MH  - Humans
MH  - Male
MH  - Pyridines/*pharmacokinetics
OTO - NOTNLM
OT  - betrixaban
OT  - chromogenic anti-Xa assays
OT  - factor Xa inhibitors
OT  - fondaparinux
OT  - guidance
OT  - heparins
EDAT- 2019/01/04 06:00
MHDA- 2019/04/04 06:00
CRDT- 2019/01/04 06:00
PHST- 2018/09/28 00:00 [received]
PHST- 2018/11/16 00:00 [revised]
PHST- 2018/11/27 00:00 [accepted]
PHST- 2019/01/04 06:00 [pubmed]
PHST- 2019/04/04 06:00 [medline]
PHST- 2019/01/04 06:00 [entrez]
AID - 10.1111/ijlh.12963 [doi]
PST - ppublish
SO  - Int J Lab Hematol. 2019 Apr;41(2):250-261. doi: 10.1111/ijlh.12963. Epub 2019 Jan 
      3.