open access

Vol 52, No 4 (2021)
Original research article
Published online: 2021-06-07
Submitted: 2021-06-07
Accepted: 2021-06-07
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Therapeutic monitoring of direct oral anticoagulants — an 8-year observational study

Grzegorz Grześk1
DOI: 10.5603/AHP.a2021.0039
·
Acta Haematol Pol 2021;52(4):446-452.
Affiliations
  1. Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland

open access

Vol 52, No 4 (2021)
ORIGINAL RESEARCH ARTICLE
Published online: 2021-06-07
Submitted: 2021-06-07
Accepted: 2021-06-07

Abstract

Introduction: For years, anticoagulants have been the basic group of drugs that slow down, inhibit or prevent blood clotting by inhibiting thrombin formation or reducing its activity. Treatment with DOACs does not require routine anticoagulation monitoring due to their wide therapeutic index. However, there are circumstances where it may be necessary to know the drug levels to manage the risk of side effects or to confirm laboratory efficacy. In such a situation, an indication for DOAC laboratory testing could be the suspicion of excessively high or low DOAC levels. The aim of this article was to determine trends in concentrations of DOACs in a real life population of patients. 

Material and methods: Consultations in clinical pharmacology extended with DOAC level assessments were performer in the Department of Cardiology and Clinical Pharmacology. The trial was designed as a retrospective analysis of laboratory analyses and included 480 laboratory tests performed in 236 patients.

Results: Mean CHA2DS2-VASc scoring 3.91 ±1.92 and HAS-BLED scoring 3.57 ±1.75 indicated high risks of both thrombosis and bleeding. Geometric mean of trough concentrations for dabigatran, rivaroxaban and apixaban were 91.53 ng/mL, 62.74 ng/mL and 124.81 ng/mL, whereas peak concentrations for all DOACs were significantly higher, at 220.80 ng/mL (p < 0.0001), 116.59 ng/mL (p < 0.0001) and 186.18 ng/mL (p =0.0354), respectively. Values for males and females did not differ significantly. Dose adjustment, performed according to rules described for every drug in registered drug characteristics, did not change significantly concentrations. Trough concentrations higher than 20 ng/mL were found at the 10th percentile for all DOACs, but higher at 40 ng/mL at the 5th percentile was found only for apixaban. Peak concentration lower than 400 ng/mL were for the 95th percentile for apixaban and for the 90th percentile for dabigatran and rivaroxaban.

Conclusion: Monitoring-based pharmacotherapy with DOACs should be restricted only to specific clinical settings; in the general population, it is not necessary. Recently, in many experienced centers, therapeutic drug monitoring of DOACs has gained great importance in selected clinical settings and it very likely will soon become commonplace in clinical practice.  

Abstract

Introduction: For years, anticoagulants have been the basic group of drugs that slow down, inhibit or prevent blood clotting by inhibiting thrombin formation or reducing its activity. Treatment with DOACs does not require routine anticoagulation monitoring due to their wide therapeutic index. However, there are circumstances where it may be necessary to know the drug levels to manage the risk of side effects or to confirm laboratory efficacy. In such a situation, an indication for DOAC laboratory testing could be the suspicion of excessively high or low DOAC levels. The aim of this article was to determine trends in concentrations of DOACs in a real life population of patients. 

Material and methods: Consultations in clinical pharmacology extended with DOAC level assessments were performer in the Department of Cardiology and Clinical Pharmacology. The trial was designed as a retrospective analysis of laboratory analyses and included 480 laboratory tests performed in 236 patients.

Results: Mean CHA2DS2-VASc scoring 3.91 ±1.92 and HAS-BLED scoring 3.57 ±1.75 indicated high risks of both thrombosis and bleeding. Geometric mean of trough concentrations for dabigatran, rivaroxaban and apixaban were 91.53 ng/mL, 62.74 ng/mL and 124.81 ng/mL, whereas peak concentrations for all DOACs were significantly higher, at 220.80 ng/mL (p < 0.0001), 116.59 ng/mL (p < 0.0001) and 186.18 ng/mL (p =0.0354), respectively. Values for males and females did not differ significantly. Dose adjustment, performed according to rules described for every drug in registered drug characteristics, did not change significantly concentrations. Trough concentrations higher than 20 ng/mL were found at the 10th percentile for all DOACs, but higher at 40 ng/mL at the 5th percentile was found only for apixaban. Peak concentration lower than 400 ng/mL were for the 95th percentile for apixaban and for the 90th percentile for dabigatran and rivaroxaban.

Conclusion: Monitoring-based pharmacotherapy with DOACs should be restricted only to specific clinical settings; in the general population, it is not necessary. Recently, in many experienced centers, therapeutic drug monitoring of DOACs has gained great importance in selected clinical settings and it very likely will soon become commonplace in clinical practice.  

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Keywords

therapeutic drug monitoring, TDM, dabigatran, rivaroxaban, apixaban, direct oral anticoagulant, DOAC

About this article
Title

Therapeutic monitoring of direct oral anticoagulants — an 8-year observational study

Journal

Acta Haematologica Polonica

Issue

Vol 52, No 4 (2021)

Article type

Original research article

Pages

446-452

Published online

2021-06-07

DOI

10.5603/AHP.a2021.0039

Bibliographic record

Acta Haematol Pol 2021;52(4):446-452.

Keywords

therapeutic drug monitoring
TDM
dabigatran
rivaroxaban
apixaban
direct oral anticoagulant
DOAC

Authors

Grzegorz Grześk

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