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Evaluation of the DOAC-Stop Procedure by LC-MS/MS Assays for Determining the Residual Activity of Dabigatran, Rivaroxaban, and Apixaban.
Clin Appl Thromb Hemost. 2019 Jan-Dec; 25:1076029619872556.CA

Abstract

The effect of direct oral anticoagulants (DOACs) on laboratory tests dependent on the production of their targets, factor IIa and factor Xa (FXa), is a well-known problem and can cause both false positive and negative results. Therefore, the correct interpretation of tests performed in patients receiving DOACs is necessary to avoid misclassification and subsequent clinical consequences. However, even with significant experience, there are situations where it is not possible to assess the influence of some methods. Particularly important is the situation in the diagnosis of lupus anticoagulants using the dilute Russell viper venom timetest, which is based on direct FXa activation. A very promising solution to this situation is offered by the DOAC laboratory balancing procedure DOAC-Stop. For evaluating the effectiveness of this procedure, 60 (20 apixaban, 20 dabigatran, and 20 rivaroxaban) patients treated with DOACs were enrolled. All patient samples were analyzed for the presence of individual DOAC types and subsequently subjected to the DOAC-Stop procedure.We evaluated its effectiveness by our own high-performance liquid chromatography-coupled tandem mass spectrometrymethod, which simultaneously sets all high-sensitivity DOACs. Unlike coagulation tests based on the determination of the residual effects of DOACs on target enzymes, which is complicated by extensive interindividual variation, this methodology is highly specific and sensitive.The DOAC-Stop procedure eliminated dabigatran from 99.5%, rivaroxaban from 97.9%, and apixaban from 97.1% of participants in our group. Residual amounts did not exceed 2.7 ng/mL for dabigatran, 10.9 ng/mL for rivaroxaban, or 13.03 ng/mL for apixaban, which are safe values that do not affect either screening or special coagulation tests.

Authors+Show Affiliations

Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Czech Republic.Department of Clinical Biochemistry, Palacký University Olomouc and University Hospital Olomouc, Czech Republic.Department of Clinical Biochemistry, Palacký University Olomouc and University Hospital Olomouc, Czech Republic.Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Czech Republic.Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic.Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Czech Republic.Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Czech Republic.Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Czech Republic.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31523979

Citation

Slavik, L, et al. "Evaluation of the DOAC-Stop Procedure By LC-MS/MS Assays for Determining the Residual Activity of Dabigatran, Rivaroxaban, and Apixaban." Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, vol. 25, 2019, p. 1076029619872556.
Slavik L, Jacova J, Friedecky D, et al. Evaluation of the DOAC-Stop Procedure by LC-MS/MS Assays for Determining the Residual Activity of Dabigatran, Rivaroxaban, and Apixaban. Clin Appl Thromb Hemost. 2019;25:1076029619872556.
Slavik, L., Jacova, J., Friedecky, D., Ulehlova, J., Tauber, Z., Prochazkova, J., Hlusi, A., & Palova, M. (2019). Evaluation of the DOAC-Stop Procedure by LC-MS/MS Assays for Determining the Residual Activity of Dabigatran, Rivaroxaban, and Apixaban. Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 25, 1076029619872556. https://doi.org/10.1177/1076029619872556
Slavik L, et al. Evaluation of the DOAC-Stop Procedure By LC-MS/MS Assays for Determining the Residual Activity of Dabigatran, Rivaroxaban, and Apixaban. Clin Appl Thromb Hemost. 2019 Jan-Dec;25:1076029619872556. PubMed PMID: 31523979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of the DOAC-Stop Procedure by LC-MS/MS Assays for Determining the Residual Activity of Dabigatran, Rivaroxaban, and Apixaban. AU - Slavik,L, AU - Jacova,J, AU - Friedecky,D, AU - Ulehlova,J, AU - Tauber,Z, AU - Prochazkova,J, AU - Hlusi,A, AU - Palova,M, PY - 2019/9/17/entrez PY - 2019/9/17/pubmed PY - 2020/3/11/medline KW - DOAC-Stop KW - HPLC MS/MS KW - anticoagulants KW - apixaban KW - dabigatran KW - factor Xa inhibitors KW - lupus inhibitor KW - rivaroxaban SP - 1076029619872556 EP - 1076029619872556 JF - Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis JO - Clin. Appl. Thromb. Hemost. VL - 25 N2 - The effect of direct oral anticoagulants (DOACs) on laboratory tests dependent on the production of their targets, factor IIa and factor Xa (FXa), is a well-known problem and can cause both false positive and negative results. Therefore, the correct interpretation of tests performed in patients receiving DOACs is necessary to avoid misclassification and subsequent clinical consequences. However, even with significant experience, there are situations where it is not possible to assess the influence of some methods. Particularly important is the situation in the diagnosis of lupus anticoagulants using the dilute Russell viper venom timetest, which is based on direct FXa activation. A very promising solution to this situation is offered by the DOAC laboratory balancing procedure DOAC-Stop. For evaluating the effectiveness of this procedure, 60 (20 apixaban, 20 dabigatran, and 20 rivaroxaban) patients treated with DOACs were enrolled. All patient samples were analyzed for the presence of individual DOAC types and subsequently subjected to the DOAC-Stop procedure.We evaluated its effectiveness by our own high-performance liquid chromatography-coupled tandem mass spectrometrymethod, which simultaneously sets all high-sensitivity DOACs. Unlike coagulation tests based on the determination of the residual effects of DOACs on target enzymes, which is complicated by extensive interindividual variation, this methodology is highly specific and sensitive.The DOAC-Stop procedure eliminated dabigatran from 99.5%, rivaroxaban from 97.9%, and apixaban from 97.1% of participants in our group. Residual amounts did not exceed 2.7 ng/mL for dabigatran, 10.9 ng/mL for rivaroxaban, or 13.03 ng/mL for apixaban, which are safe values that do not affect either screening or special coagulation tests. SN - 1938-2723 UR - https://www.unboundmedicine.com/medline/citation/31523979/Evaluation_of_the_DOAC_Stop_Procedure_by_LC_MS/MS_Assays_for_Determining_the_Residual_Activity_of_Dabigatran_Rivaroxaban_and_Apixaban_ L2 - https://journals.sagepub.com/doi/10.1177/1076029619872556?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=www.ncbi.nlm.nih.gov DB - PRIME DP - Unbound Medicine ER -