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Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions.
Stroke. 2017 09; 48(9):2457-2463.S

Abstract

BACKGROUND AND PURPOSE

In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation.

METHODS

Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations <30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values.

RESULTS

Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations <30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided >95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established.

CONCLUSIONS

Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients.

CLINICAL TRIAL REGISTRATION

URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070.

Authors+Show Affiliations

From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany.From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany.From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany.From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany.From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany.From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany.From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany.From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany.From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany.From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany. sven.poli@uni-tuebingen.de.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

28775134

Citation

Ebner, Matthias, et al. "Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions." Stroke, vol. 48, no. 9, 2017, pp. 2457-2463.
Ebner M, Birschmann I, Peter A, et al. Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions. Stroke. 2017;48(9):2457-2463.
Ebner, M., Birschmann, I., Peter, A., Härtig, F., Spencer, C., Kuhn, J., Blumenstock, G., Zuern, C. S., Ziemann, U., & Poli, S. (2017). Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions. Stroke, 48(9), 2457-2463. https://doi.org/10.1161/STROKEAHA.117.017981
Ebner M, et al. Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions. Stroke. 2017;48(9):2457-2463. PubMed PMID: 28775134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions. AU - Ebner,Matthias, AU - Birschmann,Ingvild, AU - Peter,Andreas, AU - Härtig,Florian, AU - Spencer,Charlotte, AU - Kuhn,Joachim, AU - Blumenstock,Gunnar, AU - Zuern,Christine S, AU - Ziemann,Ulf, AU - Poli,Sven, Y1 - 2017/08/03/ PY - 2017/05/08/received PY - 2017/07/11/revised PY - 2017/07/12/accepted PY - 2017/8/5/pubmed PY - 2017/9/28/medline PY - 2017/8/5/entrez KW - anticoagulants KW - blood coagulation tests KW - dabigatran KW - emergency medicine KW - emergency treatment KW - rivaroxaban KW - stroke SP - 2457 EP - 2463 JF - Stroke JO - Stroke VL - 48 IS - 9 N2 - BACKGROUND AND PURPOSE: In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation. METHODS: Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations <30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values. RESULTS: Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations <30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided >95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established. CONCLUSIONS: Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070. SN - 1524-4628 UR - https://www.unboundmedicine.com/medline/citation/28775134/Emergency_Coagulation_Assessment_During_Treatment_With_Direct_Oral_Anticoagulants:_Limitations_and_Solutions_ L2 - http://www.ahajournals.org/doi/full/10.1161/STROKEAHA.117.017981?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -