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Limitations of Specific Coagulation Tests for Direct Oral Anticoagulants: A Critical Analysis.
J Am Heart Assoc. 2018 10 02; 7(19):e009807.JA

Abstract

Background During treatment with direct oral anticoagulants (DOAC), coagulation assessment is required before thrombolysis, surgery, and if anticoagulation reversal is evaluated. Limited data support the accuracy of DOAC -specific coagulation assays around the current safe-for-treatment threshold of 30 ng/ mL . Methods and Results In 481 samples obtained from 96 patients enrolled at a single center, DOAC concentrations were measured using Hemoclot direct thrombin inhibitor assay, Biophen direct thrombin inhibitor assay or ecarin clotting time for dabigatran, chromogenic anti-Xa assay (AXA) for factor Xa inhibitors (rivaroxaban, apixaban) and ultraperformance liquid chromatography-tandem mass spectrometry as reference. All dabigatran-specific assays had high sensitivity to concentrations >30 ng/ mL , but specificity was lower for Hemoclot direct thrombin inhibitor assay (78.2%) than for Biophen direct thrombin inhibitor assay (98.9%) and ecarin clotting time (94.6%). AXA provided high sensitivity and specificity for rivaroxaban, but low sensitivity for apixaban (73.8%; concentrations up to 82 ng/ mL were misclassified as <30 ng/ mL). If no DOAC -specific calibration for AXA is available, results 2-fold above the upper limit of normal indicate relevant rivaroxaban concentrations. For apixaban, all elevated results should raise suspicion of relevant anticoagulation. Conclusions DOAC -specific tests differ considerably in diagnostic performance for concentrations close to the currently accepted safe-for-treatment threshold. Compared with Biophen direct thrombin inhibitor assay and ecarin clotting time, limited specificity of Hemoclot direct thrombin inhibitor assay poses a high risk of unnecessary anticoagulation reversal or treatment delays in patients on dabigatran. While AXA accurately detected rivaroxaban, the impact of low apixaban levels on the assay was weak. Hence, AXA results need to be interpreted with extreme caution when used to assess hemostatic function in patients on apixaban. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 02371044, NCT 02371070.

Authors+Show Affiliations

1 Department of Internal Medicine and Cardiology Charité University Medicine Berlin Campus Virchow Klinikum Berlin Germany. 2 Department of Neurology with Focus on Neurovascular Diseases and Neurooncology and Hertie Institute for Clinical Brain Research University Hospital Tübingen Germany.3 Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center Ruhr University Bad Oeynhausen Germany.4 Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry Department of Internal Medicine University Hospital Tübingen Germany. 5 Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich University of Tübingen Germany. 6 German Centre for Diabetes Research (DZD) Neuherberg Germany.2 Department of Neurology with Focus on Neurovascular Diseases and Neurooncology and Hertie Institute for Clinical Brain Research University Hospital Tübingen Germany.2 Department of Neurology with Focus on Neurovascular Diseases and Neurooncology and Hertie Institute for Clinical Brain Research University Hospital Tübingen Germany.3 Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center Ruhr University Bad Oeynhausen Germany.7 Department of Neurology University Hospital Heidelberg Heidelberg Germany.8 Department of Clinical Epidemiology and Applied Biometry University of Tübingen Germany.9 Department of Cardiology and Cardiovascular Medicine University Hospital Tübingen Germany. 10 Department of Cardiology and Cardiovascular Research Institute Basel (CRIB) University Hospital Basel Switzerland.2 Department of Neurology with Focus on Neurovascular Diseases and Neurooncology and Hertie Institute for Clinical Brain Research University Hospital Tübingen Germany.2 Department of Neurology with Focus on Neurovascular Diseases and Neurooncology and Hertie Institute for Clinical Brain Research University Hospital Tübingen Germany.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

30371316

Citation

Ebner, Matthias, et al. "Limitations of Specific Coagulation Tests for Direct Oral Anticoagulants: a Critical Analysis." Journal of the American Heart Association, vol. 7, no. 19, 2018, pp. e009807.
Ebner M, Birschmann I, Peter A, et al. Limitations of Specific Coagulation Tests for Direct Oral Anticoagulants: A Critical Analysis. J Am Heart Assoc. 2018;7(19):e009807.
Ebner, M., Birschmann, I., Peter, A., Härtig, F., Spencer, C., Kuhn, J., Rupp, A., Blumenstock, G., Zuern, C. S., Ziemann, U., & Poli, S. (2018). Limitations of Specific Coagulation Tests for Direct Oral Anticoagulants: A Critical Analysis. Journal of the American Heart Association, 7(19), e009807. https://doi.org/10.1161/JAHA.118.009807
Ebner M, et al. Limitations of Specific Coagulation Tests for Direct Oral Anticoagulants: a Critical Analysis. J Am Heart Assoc. 2018 10 2;7(19):e009807. PubMed PMID: 30371316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Limitations of Specific Coagulation Tests for Direct Oral Anticoagulants: A Critical Analysis. AU - Ebner,Matthias, AU - Birschmann,Ingvild, AU - Peter,Andreas, AU - Härtig,Florian, AU - Spencer,Charlotte, AU - Kuhn,Joachim, AU - Rupp,André, AU - Blumenstock,Gunnar, AU - Zuern,Christine S, AU - Ziemann,Ulf, AU - Poli,Sven, PY - 2018/10/30/entrez PY - 2018/10/30/pubmed PY - 2019/11/13/medline KW - anticoagulation reversal KW - coagulation testing KW - direct oral anticoagulants KW - emergency surgery KW - thrombolysis SP - e009807 EP - e009807 JF - Journal of the American Heart Association JO - J Am Heart Assoc VL - 7 IS - 19 N2 - Background During treatment with direct oral anticoagulants (DOAC), coagulation assessment is required before thrombolysis, surgery, and if anticoagulation reversal is evaluated. Limited data support the accuracy of DOAC -specific coagulation assays around the current safe-for-treatment threshold of 30 ng/ mL . Methods and Results In 481 samples obtained from 96 patients enrolled at a single center, DOAC concentrations were measured using Hemoclot direct thrombin inhibitor assay, Biophen direct thrombin inhibitor assay or ecarin clotting time for dabigatran, chromogenic anti-Xa assay (AXA) for factor Xa inhibitors (rivaroxaban, apixaban) and ultraperformance liquid chromatography-tandem mass spectrometry as reference. All dabigatran-specific assays had high sensitivity to concentrations >30 ng/ mL , but specificity was lower for Hemoclot direct thrombin inhibitor assay (78.2%) than for Biophen direct thrombin inhibitor assay (98.9%) and ecarin clotting time (94.6%). AXA provided high sensitivity and specificity for rivaroxaban, but low sensitivity for apixaban (73.8%; concentrations up to 82 ng/ mL were misclassified as <30 ng/ mL). If no DOAC -specific calibration for AXA is available, results 2-fold above the upper limit of normal indicate relevant rivaroxaban concentrations. For apixaban, all elevated results should raise suspicion of relevant anticoagulation. Conclusions DOAC -specific tests differ considerably in diagnostic performance for concentrations close to the currently accepted safe-for-treatment threshold. Compared with Biophen direct thrombin inhibitor assay and ecarin clotting time, limited specificity of Hemoclot direct thrombin inhibitor assay poses a high risk of unnecessary anticoagulation reversal or treatment delays in patients on dabigatran. While AXA accurately detected rivaroxaban, the impact of low apixaban levels on the assay was weak. Hence, AXA results need to be interpreted with extreme caution when used to assess hemostatic function in patients on apixaban. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 02371044, NCT 02371070. SN - 2047-9980 UR - https://www.unboundmedicine.com/medline/citation/30371316/Limitations_of_Specific_Coagulation_Tests_for_Direct_Oral_Anticoagulants:_A_Critical_Analysis_ L2 - http://www.ahajournals.org/doi/full/10.1161/JAHA.118.009807?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -