PMID- 28043992
OWN - NLM
STAT- MEDLINE
DCOM- 20171023
LR  - 20180308
IS  - 1873-734X (Electronic)
IS  - 1010-7940 (Linking)
VI  - 51
IP  - 4
DP  - 2017 Apr 1
TI  - Direct oral anticoagulants and heparins: laboratory values and pitfalls in 
      'bridging therapy'.
PG  - 624-632
LID - 10.1093/ejcts/ezw368 [doi]
AB  - OBJECTIVES: The three direct oral anticoagulants (DOACs) dabigatran, apixaban and 
      rivaroxaban are now widely used in clinical practice. For patients requiring 
      perioperative interruption of DOACs, heparin bridging is still under discussion. 
      Here we show, for the first time, the influence of concomitantly used DOACs and 
      heparins on laboratory assays. METHODS: For spiking experiments, 10 healthy 
      donors and nine patients treated with DOACs were investigated. The measurement of 
      DOACs and heparins was performed with routine methods on the ACL TOP [HEMOCLOT (R) 
      direct thrombin inhibitor (CoaChrom Diagnostica, Austria), COAMATIC (R) Heparin 
      (Chromogenix, USA) calibrated with rivaroxaban, apixaban, unfractionated heparin 
      (UFH) and low molecular weight heparin (LMWH), additionally PT reagent 
      RecombiPlasTin 2G and aPTT reagent SynthASil (Instrumentation Laboratory, 
      Germany)] and the DOACs were additionally quantified with liquid 
      chromatography-mass spectrometry. A linear regression model has been used to 
      estimate the effect of DOAC prestimulation. RESULTS: No influence of dabigatran 
      could be demonstrated in the anti-Xa testing methods for LMWH, UFH, rivaroxaban 
      or apixaban. All FXa-inhibiting drugs affected all the anti-Xa testing methods in 
      their own specific ways. Compared with heparin alone, measurement of heparins in 
      samples with a basic concentration of DOACs (200 ng/ml) displays a more dramatic 
      increase. Samples of patients with therapeutic intake of DOACs spiked with UFH 
      and LMWH showed the expected pharmacokinetic profiles, but increased 
      pharmacodynamic effects. CONCLUSIONS: Direct thrombin and FXa inhibitors exhibit 
      distinct effects on assay results when used concomitantly with heparins. These 
      interactions must be considered in the interpretation of assay results during 
      bridging therapy.
CI  - (c) The Author 2016. Published by Oxford University Press on behalf of the European 
      Association for Cardio-Thoracic Surgery. All rights reserved.
FAU - Eller, Thomas
AU  - Eller T
AD  - Labor Krone GbR, Siemensstrasse, Bad Salzuflen, Germany.
FAU - Flieder, Tobias
AU  - Flieder T
AD  - Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitatsklinik der 
      Ruhr-Universitat Bochum, Institut fur Laboratoriums- und Transfusionsmedizin, 
      Georgstrasse, Bad Oeynhausen, Germany.
FAU - Fox, Vanessa
AU  - Fox V
AD  - Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitatsklinik der 
      Ruhr-Universitat Bochum, Institut fur Laboratoriums- und Transfusionsmedizin, 
      Georgstrasse, Bad Oeynhausen, Germany.
FAU - Gripp, Tatjana
AU  - Gripp T
AD  - Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitatsklinik der 
      Ruhr-Universitat Bochum, Institut fur Laboratoriums- und Transfusionsmedizin, 
      Georgstrasse, Bad Oeynhausen, Germany.
FAU - Dittrich, Marcus
AU  - Dittrich M
AD  - Department of Bioinformatics, Biocenter, University of Wurzburg, Am Hubland, 
      Wurzburg, Germany.
FAU - Kuhn, Joachim
AU  - Kuhn J
AD  - Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitatsklinik der 
      Ruhr-Universitat Bochum, Institut fur Laboratoriums- und Transfusionsmedizin, 
      Georgstrasse, Bad Oeynhausen, Germany.
FAU - Alban, Susanne
AU  - Alban S
AD  - Pharmaceutical Institute, Christian-Albrechts University of Kiel, Gutenbergstr, 
      Kiel, Germany.
FAU - Knabbe, Cornelius
AU  - Knabbe C
AD  - Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitatsklinik der 
      Ruhr-Universitat Bochum, Institut fur Laboratoriums- und Transfusionsmedizin, 
      Georgstrasse, Bad Oeynhausen, Germany.
FAU - Birschmann, Ingvild
AU  - Birschmann I
AD  - Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitatsklinik der 
      Ruhr-Universitat Bochum, Institut fur Laboratoriums- und Transfusionsmedizin, 
      Georgstrasse, Bad Oeynhausen, Germany.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PL  - Germany
TA  - Eur J Cardiothorac Surg
JT  - European journal of cardio-thoracic surgery : official journal of the European 
      Association for Cardio-thoracic Surgery
JID - 8804069
RN  - 0 (Anticoagulants)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridones)
RN  - 3Z9Y7UWC1J (apixaban)
RN  - 9005-49-6 (Heparin)
RN  - 9NDF7JZ4M3 (Rivaroxaban)
RN  - I0VM4M70GC (Dabigatran)
SB  - IM
MH  - Administration, Oral
MH  - Anticoagulants/*administration & dosage/blood/pharmacology
MH  - Blood Coagulation/drug effects
MH  - Blood Coagulation Tests/methods
MH  - Dabigatran/administration & dosage/blood/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Drug Monitoring/methods
MH  - Factor Xa Inhibitors/administration & dosage/blood/pharmacology
MH  - Heparin/*administration & dosage/blood/pharmacology
MH  - Heparin, Low-Molecular-Weight/administration & dosage/blood/pharmacology
MH  - Humans
MH  - Perioperative Care/methods
MH  - Pyrazoles/administration & dosage/blood/pharmacology
MH  - Pyridones/administration & dosage/blood/pharmacology
MH  - Rivaroxaban/administration & dosage/blood/pharmacology
OTO - NOTNLM
OT  - Apixaban
OT  - Dabigatran
OT  - Heparin
OT  - Rivaroxaban
OT  - Surgery
EDAT- 2017/01/04 06:00
MHDA- 2017/10/24 06:00
CRDT- 2017/01/04 06:00
PHST- 2016/03/24 00:00 [received]
PHST- 2016/10/19 00:00 [accepted]
PHST- 2017/01/04 06:00 [pubmed]
PHST- 2017/10/24 06:00 [medline]
PHST- 2017/01/04 06:00 [entrez]
AID - ezw368 [pii]
AID - 10.1093/ejcts/ezw368 [doi]
PST - ppublish
SO  - Eur J Cardiothorac Surg. 2017 Apr 1;51(4):624-632. doi: 10.1093/ejcts/ezw368.