Back to Search
Start Over
Determination of dabigatran and rivaroxaban by ultra-performance liquid chromatography-tandem mass spectrometry and coagulation assays after major orthopaedic surgery
- Source :
- Thrombosis Research, 139, 128-134. Elsevier
- Publication Year :
- 2016
- Publisher :
- Elsevier, 2016.
-
Abstract
- Major orthopaedic surgery is associated with an increased risk of venous thromboembolism. Direct oral anticoagulants (DOACs) are recommended as thromboprophylactic agents after orthopaedic surgery. Although routine monitoring of DOACs in general is not required, measuring DOAC concentration may be necessary in clinical settings. The effects of DOACs on routine coagulation assays in spiked material are studied extensively, however, few data are available on DOAC concentration in patients after major orthopaedic surgery. We measured trough and peak DOAC concentrations with UPLC-MS/MS and routine coagulation tests in a prospective study including 40 patients receiving thromboprophylactic treatment with dabigatran 220 mg od and 40 patients receiving rivaroxaban 10 mg od after major orthopaedic surgery. For rivaroxaban, the median trough concentration with UPLC-MS/MS was 17.1 ng/mL and median peak concentration was 149 ng/mL. The anti-Xa assay displayed a good correlation, but a positive bias in comparison to the reference method. Furthermore, trough levels were mostly below the LOD of the anti-Xa assay. For dabigatran, the median trough concentration with UPLC-MS/MS was 12.1 ng/mL, and median peak level was 80.8 ng/mL. A positive bias was found when results from coagulation assays were compared to UPLC-MS/MS data. However, the addition of glucuronidated metabolites to dabigatran concentration UPLC-MS/MS data generally resolved most of this bias. Age was found to have a significant influence on dabigatran pharmacokinetics, irrespective of kidney function, whereas no effect of age was found during rivaroxaban treatment. In both treatment groups, female subjects displayed faster pharmacokinetics in comparison to male subjects, although not reaching significance. We conclude that UPLC-MS/MS is the method of choice to measure trough concentrations of DOACs in patients after orthopaedic surgery. Current coagulation assays are not suited for this purpose. We found large heterogeneity in both peak and trough concentrations of DOACs, and showed that pharmacokinetics of novel oral anticoagulants may be influenced by age and gender. Whether patients with high or low trough concentrations are at increased risk for bleeding or thromboembolic events respectively remains to be established.
- Subjects :
- Male
medicine.medical_specialty
Urology
Renal function
030204 cardiovascular system & hematology
Dabigatran
03 medical and health sciences
Direct oral anticoagulants ultra-performance liquid chromatography-tandem mass spectrometry coagulation assays orthopaedic surgery
0302 clinical medicine
Rivaroxaban
Pharmacokinetics
Tandem Mass Spectrometry
medicine
Coagulation testing
Humans
Orthopedic Procedures
Trough Concentration
Prospective cohort study
Blood Coagulation
Chromatography, High Pressure Liquid
Aged
Aged, 80 and over
business.industry
Anticoagulants
Venous Thromboembolism
Hematology
Middle Aged
030220 oncology & carcinogenesis
Anesthesia
Orthopedic surgery
Female
Drug Monitoring
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 18792472 and 00493848
- Volume :
- 139
- Database :
- OpenAIRE
- Journal :
- Thrombosis Research
- Accession number :
- edsair.doi.dedup.....489682c2c7f7b4d8414634bdcbb8450e