CC BY 4.0 · TH Open 2018; 02(02): e202-e209
DOI: 10.1055/s-0038-1657785
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Evaluation of the DOAC-Stop® Procedure to Overcome the Effect of DOACs on Several Thrombophilia Screening Tests

Julien Favresse
1   Université Catholique de Louvain, CHU UCL Namur, Hematology Laboratory, Namur Thrombosis and Hemostasis Center, NARILIS, Yvoir, Belgium
,
Benjamin Lardinois
1   Université Catholique de Louvain, CHU UCL Namur, Hematology Laboratory, Namur Thrombosis and Hemostasis Center, NARILIS, Yvoir, Belgium
,
Lina Sabor
1   Université Catholique de Louvain, CHU UCL Namur, Hematology Laboratory, Namur Thrombosis and Hemostasis Center, NARILIS, Yvoir, Belgium
,
Bérangère Devalet
2   Department of Hematology, CHU UCL Namur, Namur Thrombosis and Hemostasis Center, Université Catholique de Louvain, Yvoir, Belgium
,
Julie Vandepapeliere
2   Department of Hematology, CHU UCL Namur, Namur Thrombosis and Hemostasis Center, Université Catholique de Louvain, Yvoir, Belgium
,
Maximilien Braibant
3   Department of Pharmacy, CHU UCL Namur, Namur Thrombosis and Hemostasis Center, Université Catholique de Louvain, Yvoir, Belgium
,
Sarah Lessire
4   Department of Anesthesiology, CHU UCL Namur, Namur Thrombosis and Hemostasis Center, Université Catholique de Louvain, Yvoir, Belgium
,
Bernard Chatelain
1   Université Catholique de Louvain, CHU UCL Namur, Hematology Laboratory, Namur Thrombosis and Hemostasis Center, NARILIS, Yvoir, Belgium
,
Hugues Jacqmin
1   Université Catholique de Louvain, CHU UCL Namur, Hematology Laboratory, Namur Thrombosis and Hemostasis Center, NARILIS, Yvoir, Belgium
,
Jonathan Douxfils
5   Department of Pharmacy, Namur Thrombosis and Hemostasis Center, Université de Namur, Yvoir, Belgium
6   QUALIblood SA, Namur, Belgium
,
François Mullier
1   Université Catholique de Louvain, CHU UCL Namur, Hematology Laboratory, Namur Thrombosis and Hemostasis Center, NARILIS, Yvoir, Belgium
› Institutsangaben
Weitere Informationen

Publikationsverlauf

16. Januar 2018

21. April 2018

Publikationsdatum:
01. Juni 2018 (online)

Abstract

The impact of direct oral anticoagulants (DOACs) on laboratory assays used for thrombophilia testing (e.g., antithrombin, protein S, protein C, lupus anticoagulant and activated protein-C resistance) is a well-known issue and may cause false-positive and -negative results. Therefore, the correct interpretation of tests that are performed in patients taking DOACs is mandatory to prevent misclassification and the subsequent clinical consequences. We aimed at evaluating the efficiency of a new and simple procedure (DOAC-Stop®; Haematex Research, Hornsby, Australia) to overcome the effect of all DOACs in real-life settings and to assess the percentage of erroneous results due to the presence of DOACs on thrombophilia screening tests. For this purpose, 135 DOAC-treated patients (38 apixaban, 40 dabigatran, 15 edoxaban, and 42 rivaroxaban) and 20 control patients were enrolled. A significant drop in apixaban, dabigatran, edoxaban, and rivaroxaban plasma concentrations following the DOAC-Stop® treatment was observed (74.8–8.2 ng/mL [p < 0.0001], 95.9–4.7 ng/mL [p < 0.0001], 102.1–8.8 ng/mL [p = 0.001], and 111.3–7.0 ng/mL [p < 0.0001], respectively). The DOAC-Stop® treatment was mostly effective to overcome the effect of DOACs on PTT-LA, dilute Russell's viper venom time (dRVVT) screen, and dRVVT confirm tests. Using our procedures, false-positive results due to DOACs were observed only with lupus anticoagulant tests (up to 75%) and fell to zero after the DOAC-Stop® procedure, regardless of the DOAC considered. In conclusion, the DOAC-Stop® adsorbent procedure appeared to be an effective and simple way to overcome the interference of DOAC on coagulation tests and should facilitate the interpretation of thrombophilia screening tests in patients taking DOACs.

 
  • References

  • 1 European Medicines Agency. Xarelto - Summary of Product Characteristics. 2017. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000944/WC500057108.pdf . Accessed May 18, 2018
  • 2 European Medicines Agency. Pradaxa - Summary of Product Characteristics. 2017. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf . Accessed May 18, 2018
  • 3 European Medicines Agency. Eliquis - Summary of Product Characteristics. 2017. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf . Accessed May 18, 2018
  • 4 European Medicines Agency. Lixiana - Summary of Product Characteristics. 2017. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002629/WC500189045.pdf . Accessed May 18, 2018
  • 5 Adcock DM, Gosselin R. Direct oral anticoagulants (DOACs) in the laboratory: 2015 review. Thromb Res 2015; 136 (01) 7-12
  • 6 Douxfils J, Ageno W, Samama CM. , et al. Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians. J Thromb Haemost 2018; 16 (02) 209-219
  • 7 Hoxha A, Banzato A, Ruffatti A, Pengo V. Detection of lupus anticoagulant in the era of direct oral anticoagulants. Autoimmun Rev 2017; 16 (02) 173-178
  • 8 Lippi G, Mattiuzzi C, Favaloro EJ. Thrombophilia testing in patients taking direct oral anticoagulants. Handle with care. Diagnosis (Berl) 2014; 1 (04) 311-312
  • 9 Goodwin AJ, Adcock DM. Thrombophilia testing and venous thrombosis. N Engl J Med 2017; 377 (23) 2297-2298
  • 10 Jacquemin M, Toelen J, Schoeters J. , et al. The addition of idarucizumab to plasma samples containing dabigatran allows the use of routine coagulation assays for the diagnosis of hemostasis disorders. J Thromb Haemost 2015; 13 (11) 2087-2092
  • 11 Exner T, Michalopoulos N, Pearce J, Xavier R, Ahuja M. Simple method for removing DOACs from plasma samples. Thromb Res 2018; 163: 117-122
  • 12 Pengo V, Bison E, Banzato A, Zoppellaro G, Jose SP, Denas G. Lupus anticoagulant testing: diluted Russell Viper Venom Time (dRVVT). Methods Mol Biol 2017; 1646: 169-176
  • 13 Pengo V, Tripodi A, Reber G. , et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009; 7 (10) 1737-1740
  • 14 Samama MCJ, Horellou MH, Lecompte T. Physiologie et Exploration de l'hémostase. Paris: Doin; 1990: 169-170
  • 15 Kadauke S, Khor B, Van Cott EM. Activated protein C resistance testing for factor V Leiden. Am J Hematol 2014; 89 (12) 1147-1150
  • 16 Herve T, Beaufils S, Kochan J, He L, Depasse F. Development of a new automated assay for measurement of the oral direct factor Xa inhibitor edoxaban plasma concentration. Blood 2014; 124: 2870
  • 17 Gouin-Thibault I, Flaujac C, Delavenne X. , et al. Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays. A multicentre French GEHT study. Thromb Haemost 2014; 111 (02) 240-248
  • 18 Rathbun S, Tafur A, Grant R, Esmon N, Mauer K, Marlar RA. Comparison of methods to determine rivaroxaban anti-factor Xa activity. Thromb Res 2015; 135 (02) 394-397
  • 19 Cini M, Legnani C, Cosmi B. , et al; START-Laboratory Register. Comparison of five specific assays for determination of dabigatran plasma concentrations in patients enrolled in the START-Laboratory Register. Int J Lab Hematol 2018; 40 (02) 229-236
  • 20 Jacquemin M, Toelen J, Feyen L. , et al. The adsorption of dabigatran is as efficient as addition of idarucizumab to neutralize the drug in routine coagulation assays. Int J Lab Hematol 2018
  • 21 Fraser CG. Biological Variation: From Principles to Practice. Washington, DC: AACC Press; 2001
  • 22 Shou W, Chen Q, Wu W, Cui W. Biological variations of lupus anticoagulant, antithrombin, protein C, protein S, and von Willebrand factor assays. Semin Thromb Hemost 2016; 42 (01) 87-92
  • 23 de Maat MP, van Schie M, Kluft C, Leebeek FW, Meijer P. Biological variation of hemostasis variables in thrombosis and bleeding: consequences for performance specifications. Clin Chem 2016; 62 (12) 1639-1646
  • 24 Gosselin R, Grant RP, Adcock DM. Comparison of the effect of the anti-Xa direct oral anticoagulants apixaban, edoxaban, and rivaroxaban on coagulation assays. Int J Lab Hematol 2016; 38 (05) 505-513
  • 25 Antovic A, Norberg EM, Berndtsson M. , et al. Effects of direct oral anticoagulants on lupus anticoagulant assays in a real-life setting. Thromb Haemost 2017; 117 (09) 1700-1704
  • 26 Connors JM. Thrombophilia testing and venous thrombosis. N Engl J Med 2017; 377 (12) 1177-1187
  • 27 Testa S, Tripodi A, Legnani C. , et al; START-Laboratory Register. Plasma levels of direct oral anticoagulants in real life patients with atrial fibrillation: results observed in four anticoagulation clinics. Thromb Res 2016; 137: 178-183
  • 28 Pouplard C, Vayne C, Berthomet C, Guery EA, Delahousse B, Gruel Y. The Taipan snake venom time can be used to detect lupus anticoagulant in patients treated by rivaroxaban. Int J Lab Hematol 2017; 39 (03) e60-e63
  • 29 van Os GM, de Laat B, Kamphuisen PW, Meijers JC, de Groot PG. Detection of lupus anticoagulant in the presence of rivaroxaban using Taipan snake venom time. J Thromb Haemost 2011; 9 (08) 1657-1659
  • 30 Arachchillage DR, Mackie IJ, Efthymiou M, Isenberg DA, Machin SJ, Cohen H. Interactions between rivaroxaban and antiphospholipid antibodies in thrombotic antiphospholipid syndrome. J Thromb Haemost 2015; 13 (07) 1264-1273
  • 31 Wilmer M, Stocker C, Bühler B, Conell B, Calatzis A. Improved distinction of factor V wild-type and factor V Leiden using a novel prothrombin-based activated protein C resistance assay. Am J Clin Pathol 2004; 122 (06) 836-842
  • 32 Gessoni G, Valverde S, Valle L, Gessoni F, Caruso P, Valle R. Lack of rivaroxaban influence on a prothrombinase-based assay for the detection of activated C protein resistance: an Italian ex vivo and in vitro study in normal subjects and factor V Leiden carriers. Int J Lab Hematol 2017; 39 (04) 418-422
  • 33 Hillarp A, Baghaei F, Fagerberg Blixter I. , et al. Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays. J Thromb Haemost 2011; 9 (01) 133-139
  • 34 Gessoni G, Valverde S, Valle L, Caruso P, Gessoni F, Valle R. Effect of dabigatran on a prothrombinase-based assay for detecting activated protein C resistance: an ex vivo and in vitro study in normal subjects and factor V Leiden carriers. Blood Transfus 2017; 15 (06) 562-567
  • 35 Douxfils J, Chatelain B, Chatelain C, Dogné JM, Mullier F. Edoxaban: impact on routine and specific coagulation assays. A practical laboratory guide. Thromb Haemost 2016; 115 (02) 368-381
  • 36 Van Blerk M, Bailleul E, Chatelain B. , et al. Influence of apixaban on commonly used coagulation assays: results from the Belgian national External Quality Assessment Scheme. Int J Lab Hematol 2017; 39 (04) 402-408
  • 37 Douxfils J, Mullier F, Robert S, Chatelain C, Chatelain B, Dogné JM. Impact of dabigatran on a large panel of routine or specific coagulation assays. Laboratory recommendations for monitoring of dabigatran etexilate. Thromb Haemost 2012; 107 (05) 985-997
  • 38 Betancur JF, Bonilla-Abadía F, Hormaza AA, Jaramillo FJ, Cañas CA, Tobón GJ. Direct oral anticoagulants in antiphospholipid syndrome: a real life case series. Lupus 2016; 25 (06) 658-662
  • 39 Dufrost V, Risse J, Zuily S, Wahl D. Direct oral anticoagulants use in antiphospholipid syndrome: are these drugs an effective and safe alternative to warfarin? A systematic review of the literature. Curr Rheumatol Rep 2016; 18 (12) 74
  • 40 Kunk PR, Brown J, McShane M, Palkimas S, Gail Macik B. Direct oral anticoagulants in hypercoagulable states. J Thromb Thrombolysis 2017; 43 (01) 79-85
  • 41 Malec K, Góralczyk T, Undas A. The use of direct oral anticoagulants in 56 patients with antiphospholipid syndrome. Thromb Res 2017; 152: 93-97