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Semin Thromb Hemost 2018; 44(05): 427-438
DOI: 10.1055/s-0036-1597902
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Direct Oral Anticoagulants for Thromboprophylaxis in Patients with Antiphospholipid Syndrome

Hannah Cohen
1   Haemostasis Research Unit, Department of Haematology, University College London, London, United Kingdom
2   Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
,
Maria Efthymiou
1   Haemostasis Research Unit, Department of Haematology, University College London, London, United Kingdom
,
Carolyn Gates
3   Department of Pharmacy, University College London Hospitals NHS Foundation Trust, London, United Kingdom
,
David Isenberg
4   Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom
5   Department of Rheumatology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
14 February 2017 (online)

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Abstract

The current mainstay of the treatment and secondary thromboprophylaxis of thrombotic antiphospholipid syndrome (APS) is anticoagulation with warfarin or other vitamin K antagonists (VKAs). In addition to their well-known limitations, VKAs are often problematic in APS patients because of the variable sensitivity of thromboplastins to lupus anticoagulant. As a result, the international normalized ratio may not accurately reflect the intensity of anticoagulation. Direct oral anticoagulants (DOACs) are established as therapeutic alternatives to VKAs for a wide range of indications, including the treatment and secondary prevention of venous thromboembolism. Definition of the role of DOACs in the treatment of thrombotic APS is emerging with the results of recent and ongoing clinical studies. This review focuses on the current situation with regard to DOACs for secondary thromboprophylaxis in APS and issues pertinent to DOAC use in APS patients, as well as potential future directions.

Keywords

direct oral anticoagulants - thromboprophylaxis - antiphospholipid syndrome - venous thromboembolism - ischemic stroke
 

  • References

  • 1 Erkan D, Aguiar CL, Andrade D. , et al. 14th International Congress on Antiphospholipid Antibodies: task force report on antiphospholipid syndrome treatment trends. Autoimmun Rev 2014; 13 (06) 685-696
    CrossrefPubMedGoogle Scholar
  • 2 Pradaxa (dabigatran) 150 mg and 110 mg hard capsules: summary of product characteristics (SPC), EU. Boehringer Ingelheim International GmBH. Available at: https://www.medicines.org.uk/emc/medicine/24839 . Accessed June 2016
    PubMedGoogle Scholar
  • 3 Eliquis (apixaban) 2.5 mg and 5 mg film-coated tablets film-coated tablets Summary of Product Characteristics (SPC). Bristol-Myers Squibb-Pfizer. Available at: http://www.medicines.org.uk/emc/medicine/24988 . Accessed June 2016
    PubMedGoogle Scholar
  • 4 Lixiana (edoxaban) 30 mg and 60 mg film-coated Tablets - Summary of Product Characteristics. Daiichi Sankyo UK Limited. Available at: https://www.medicines.org.uk/emc/medicine/30506 . Accessed June 2016
    PubMedGoogle Scholar
  • 5 Xarelto (rivaroxaban) 15 mg and 20 mg film-coated tablets. Summary of Product Characteristics. Bayer Pharma AG. Available at: https://www.medicines.org.uk/emc/medicine/25586 . Accessed June 2016
    PubMedGoogle Scholar
  • 6 Miyakis S, Lockshin MD, Atsumi T. , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (02) 295-306
    CrossrefPubMedGoogle Scholar
  • 7 Cervera R, Serrano R, Pons-Estel GJ. , et al; Euro-Phospholipid Project Group (European Forum on Antiphospholipid Antibodies). Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2015; 74 (06) 1011-1018
    Google Scholar
  • 8 Antiphospholipid syndrome. Available at: https://rarediseases.info.nih.gov/gard/5824/antiphospholipid-syndrome/resources/1 2016 . Accessed January 20, 2017
    PubMedGoogle Scholar
  • 9 Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, Ramire de Jesus G, Erkan D. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res (Hoboken) 2013; 65 (11) 1869-1873
    CrossrefPubMedGoogle Scholar
  • 10 Know VTE. International Society on Thrombosis and Haemostasis. Available at: http://www.worldthrombosisday.org/issue/vte/ Accessed June 2016
    PubMedGoogle Scholar
  • 11 Stroke Association. State of the Nation – Stroke Statistics. Available at: https://www.stroke.org.uk/sites/default/files/stroke_statistics_2015.pdf . Accessed June 2016
    PubMedGoogle Scholar
  • 12 Ruiz-Irastorza G, Egurbide MV, Ugalde J, Aguirre C. High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus. Arch Intern Med 2004; 164 (01) 77-82
    CrossrefPubMedGoogle Scholar
  • 13 Krnic-Barrie S, O'Connor CR, Looney SW, Pierangeli SS, Harris EN. A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis. Arch Intern Med 1997; 157 (18) 2101-2108
    CrossrefPubMedGoogle Scholar
  • 14 Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992; 117 (04) 303-308
    CrossrefPubMedGoogle Scholar
  • 15 Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GR. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995; 332 (15) 993-997
    CrossrefPubMedGoogle Scholar
  • 16 Schulman S, Svenungsson E, Granqvist S. ; Duration of Anticoagulation Study Group. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Am J Med 1998; 104 (04) 332-338
    CrossrefPubMedGoogle Scholar
  • 17 Kearon C, Akl EA. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood 2014; 123 (12) 1794-1801
    CrossrefPubMedGoogle Scholar
  • 18 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
    CrossrefPubMedGoogle Scholar
  • 19 Pengo V, Ruffatti A, Legnani C. , et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost 2010; 8 (02) 237-242
    CrossrefPubMedGoogle Scholar
  • 20 Ruiz-Irastorza G, Hunt BJ, Khamashta MA. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum 2007; 57 (08) 1487-1495
    CrossrefPubMedGoogle Scholar
  • 21 Muñoz-Rodriguez FJ, Font J, Cervera R. , et al. Clinical study and follow-up of 100 patients with the antiphospholipid syndrome. Semin Arthritis Rheum 1999; 29 (03) 182-190
    CrossrefPubMedGoogle Scholar
  • 22 Ruiz-Irastorza G, Khamashta MA, Hunt BJ, Escudero A, Cuadrado MJ, Hughes GR. Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5. Arch Intern Med 2002; 162 (10) 1164-1169
    CrossrefPubMedGoogle Scholar
  • 23 Crowther MA, Ginsberg JS, Julian J. , et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003; 349 (12) 1133-1138
    CrossrefPubMedGoogle Scholar
  • 24 Ames PR, Ciampa A, Margaglione M, Scenna G, Iannaccone L, Brancaccio V. Bleeding and re-thrombosis in primary antiphospholipid syndrome on oral anticoagulation: an 8-year longitudinal comparison with mitral valve replacement and inherited thrombophilia. Thromb Haemost 2005; 93 (04) 694-699
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Prandoni P, Simioni P, Girolami A. Antiphospholipid antibodies, recurrent thromboembolism, and intensity of warfarin anticoagulation. Thromb Haemost 1996; 75 (05) 859
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Girón-González JA, García del Río E, Rodríguez C, Rodríguez-Martorell J, Serrano A. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol 2004; 31 (08) 1560-1567
    PubMedGoogle Scholar
  • 27 Derksen RH, de Groot PG, Kater L, Nieuwenhuis HK. Patients with antiphospholipid antibodies and venous thrombosis should receive long term anticoagulant treatment. Ann Rheum Dis 1993; 52 (09) 689-692
    CrossrefPubMedGoogle Scholar
  • 28 Rance A, Emmerich J, Fiessinger JN. Anticardiolipin antibodies and recurrent thromboembolism. Thromb Haemost 1997; 77 (01) 221-222
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Ginsberg JS, Wells PS, Brill-Edwards P. , et al. Antiphospholipid antibodies and venous thromboembolism. Blood 1995; 86 (10) 3685-3691
    PubMedGoogle Scholar
  • 30 Finazzi G, Marchioli R, Brancaccio V. , et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS). J Thromb Haemost 2005; 3 (05) 848-853
    CrossrefPubMedGoogle Scholar
  • 31 Levine SR, Brey RL, Tilley BC. , et al; APASS Investigators. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA 2004; 291 (05) 576-584
    CrossrefPubMedGoogle Scholar
  • 32 Gardiner C, Hills J, Machin SJ, Cohen H. Diagnosis of antiphospholipid syndrome in routine clinical practice. Lupus 2013; 22 (01) 18-25
    CrossrefPubMedGoogle Scholar
  • 33 Keeling D, Mackie I, Moore GW, Greer IA, Greaves M. ; British Committee for Standards in Haematology. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol 2012; 157 (01) 47-58
    CrossrefPubMedGoogle Scholar
  • 34 Holbrook A, Schulman S, Witt DM. , et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e152S-e184S
    CrossrefPubMedGoogle Scholar
  • 35 Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I. , et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus 2011; 20 (02) 206-218
    CrossrefPubMedGoogle Scholar
  • 36 Tripodi A, Chantarangkul V, Clerici M, Negri B, Galli M, Mannucci PM. Laboratory control of oral anticoagulant treatment by the INR system in patients with the antiphospholipid syndrome and lupus anticoagulant. Results of a collaborative study involving nine commercial thromboplastins. Br J Haematol 2001; 115 (03) 672-678
    CrossrefPubMedGoogle Scholar
  • 37 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
    CrossrefPubMedGoogle Scholar
  • 38 Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14 (06) 1308-1313
    CrossrefPubMedGoogle Scholar
  • 39 Kubitza D, Becka M, Zuehlsdorf M, Mueck W. Body weight has limited influence on the safety, tolerability, pharmacokinetics, or pharmacodynamics of rivaroxaban (BAY 59-7939) in healthy subjects. J Clin Pharmacol 2007; 47 (02) 218-226
    CrossrefPubMedGoogle Scholar
  • 40 Heidbuchel H, Verhamme P, Alings M. , et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015; 17 (10) 1467-1507
    CrossrefPubMedGoogle Scholar
  • 41 Makris M, Van Veen JJ, Tait CR, Mumford AD, Laffan M. ; British Committee for Standards in Haematology. Guideline on the management of bleeding in patients on antithrombotic agents. Br J Haematol 2013; 160 (01) 35-46
    CrossrefPubMedGoogle Scholar
  • 42 Gulseth MP. Overview of direct oral anticoagulant therapy reversal. Am J Health Syst Pharm 2016; 73 (10, Suppl 2): S5-S13
    CrossrefPubMedGoogle Scholar
  • 43 Lanas A, García-Rodríguez LA, Polo-Tomás M. , et al. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice. Am J Gastroenterol 2009; 104 (07) 1633-1641
    CrossrefPubMedGoogle Scholar
  • 44 Connolly SJ, Ezekowitz MD, Yusuf S. , et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
    CrossrefPubMedGoogle Scholar
  • 45 Patel MR, Mahaffey KW, Garg J. , et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
    CrossrefPubMedGoogle Scholar
  • 46 Granger CB, Alexander JH, McMurray JJ. , et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
    CrossrefPubMedGoogle Scholar
  • 47 Giugliano RP, Ruff CT, Braunwald E. , et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369 (22) 2093-2104
    CrossrefPubMedGoogle Scholar
  • 48 Schulman S, Kearon C, Kakkar AK. , et al; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361 (24) 2342-2352
    CrossrefPubMedGoogle Scholar
  • 49 Bauersachs R, Berkowitz SD, Brenner B. , et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510
    CrossrefPubMedGoogle Scholar
  • 50 Büller HR, Prins MH, Lensin AW. , et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366 (14) 1287-1297
    CrossrefPubMedGoogle Scholar
  • 51 Büller HR, Décousus H, Grosso MA. , et al; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369 (15) 1406-1415
    CrossrefPubMedGoogle Scholar
  • 52 Agnelli G, Buller HR, Cohen A. , et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (09) 799-808
    CrossrefPubMedGoogle Scholar
  • 53 Cohen H, Arachchillage DR, Middeldorp S, Beyer-Westendorf J, Abdul-Kadir R. Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14 (08) 1673-1676
    CrossrefPubMedGoogle Scholar
  • 54 Beyer-Westendorf J, Michalski F, Tittl L. , et al. Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting. Thromb Haemost 2016; 116 (04) 651-658
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Schaefer JK, McBane RD, Black DF, Williams LN, Moder KG, Wysokinski WE. Failure of dabigatran and rivaroxaban to prevent thromboembolism in antiphospholipid syndrome: a case series of three patients. Thromb Haemost 2014; 112 (05) 947-950
    Article in Thieme ConnectPubMedGoogle Scholar
  • 56 Win K, Rodgers GM. New oral anticoagulants may not be effective to prevent venous thromboembolism in patients with antiphospholipid syndrome. Am J Hematol 2014; 89 (10) 1017
    CrossrefPubMedGoogle Scholar
  • 57 Son M, Wypasek E, Celinska-Lowenhoff M, Undas A. The use of rivaroxaban in patients with antiphospholipid syndrome: a series of 12 cases. Thromb Res 2015; 135 (05) 1035-1036
    CrossrefPubMedGoogle Scholar
  • 58 Noel N, Dutasta F, Costedoat-Chalumeau N. , et al. Safety and efficacy of oral direct inhibitors of thrombin and factor Xa in antiphospholipid syndrome. Autoimmun Rev 2015; 14 (08) 680-685
    CrossrefPubMedGoogle Scholar
  • 59 Signorelli F, Nogueira F, Domingues V, Mariz HA, Levy RA. Thrombotic events in patients with antiphospholipid syndrome treated with rivaroxaban: a series of eight cases. Clin Rheumatol 2016; 35 (03) 801-805
    CrossrefPubMedGoogle Scholar
  • 60 Unlu O, Cohen H, Cuadrado MJ. , et al; Antiphospholipid syndrome alliance for clinical trials & international networking registry analysis: direct oral anticoagulant use among antiphospholipid syndrome patients. [abstract]. Arthritis Rheumatol 2016;68:(Suppl 10) Available at: http://acrabstracts.org/abstract/antiphospholipid-syndrome-alliance-for-clinical-trials-international-networking-registry-analysis-direct-oral-anticoagulant-use-among-antiphospholipid-syndrome-patients/ . Accessed January 5, 2017
    PubMedGoogle Scholar
  • 61 Sciascia S, Breen K, Hunt BJ. Rivaroxaban use in patients with antiphospholipid syndrome and previous venous thromboembolism. Blood Coagul Fibrinolysis 2015; 26 (04) 476-477
    CrossrefPubMedGoogle Scholar
  • 62 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
    CrossrefPubMedGoogle Scholar
  • 63 Bachmeyer C, Elalamy I. Rivaroxaban as an effective treatment for recurrent superficial thrombophlebitis related to primary antiphospholipid syndrome. Clin Exp Dermatol 2014; 39 (07) 840-841
    CrossrefPubMedGoogle Scholar
  • 64 Cohen H, Hunt BJ, Efthymiou M. , et al; RAPS trial investigators. Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial. Lancet Haematol 2016; 3 (09) e426-e436
    CrossrefPubMedGoogle Scholar
  • 65 Cohen H, Doré CJ, Clawson S. , et al; RAPS Trial Protocol Collaborators. Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE. Lupus 2015; 24 (10) 1087-1094
    CrossrefPubMedGoogle Scholar
  • 66 Hemker HC, Al Dieri R, De Smedt E, Béguin S. Thrombin generation, a function test of the haemostatic-thrombotic system. Thromb Haemost 2006; 96 (05) 553-561
    Article in Thieme ConnectPubMedGoogle Scholar
  • 67 Hemker HC, Giesen P, Al Dieri R. , et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33 (01) 4-15
    CrossrefPubMedGoogle Scholar
  • 68 Al Dieri R, de Laat B, Hemker HC. Thrombin generation: what have we learned?. Blood Rev 2012; 26 (05) 197-203
    CrossrefPubMedGoogle Scholar
  • 69 Váradi K, Turecek PL, Schwarz HP. Thrombin generation assay and other universal tests for monitoring haemophilia therapy. Haemophilia 2004; 10 (Suppl 2): 17-21
    PubMedGoogle Scholar
  • 70 Mancuso ME, Chantarangkul V, Clerici M. , et al. The thrombin generation assay distinguishes inhibitor from non-inhibitor patients with severe haemophilia A. Haemophilia 2016; 22 (04) e286-e291
    CrossrefPubMedGoogle Scholar
  • 71 Besser M, Baglin C, Luddington R, van Hylckama Vlieg A, Baglin T. High rate of unprovoked recurrent venous thrombosis is associated with high thrombin-generating potential in a prospective cohort study. J Thromb Haemost 2008; 6 (10) 1720-1725
    CrossrefPubMedGoogle Scholar
  • 72 Tripodi A. The history of phenotypic testing in thrombosis and hemostasis. Semin Thromb Hemost 2008; 34 (07) 585-592
    Article in Thieme ConnectPubMedGoogle Scholar
  • 73 Dargaud Y, Trzeciak MC, Bordet JC, Ninet J, Negrier C. Use of calibrated automated thrombinography +/- thrombomodulin to recognise the prothrombotic phenotype. Thromb Haemost 2006; 96 (05) 562-567
    Article in Thieme ConnectPubMedGoogle Scholar
  • 74 Hron G, Kollars M, Binder BR, Eichinger S, Kyrle PA. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006; 296 (04) 397-402
    CrossrefPubMedGoogle Scholar
  • 75 Devreese K, Peerlinck K, Arnout J, Hoylaerts MF. Laboratory detection of the antiphospholipid syndrome via calibrated automated thrombography. Thromb Haemost 2009; 101 (01) 185-196
    Article in Thieme ConnectPubMedGoogle Scholar
  • 76 Devreese K, Peerlinck K, Hoylaerts MF. Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants. Blood 2010; 115 (04) 870-878
    CrossrefPubMedGoogle Scholar
  • 77 Efthymiou M, Lawrie AS, Mackie I. , et al. Thrombin generation and factor X assays for the assessment of warfarin anticoagulation in thrombotic antiphospholipid syndrome. Thromb Res 2015; 135 (06) 1191-1197
    CrossrefPubMedGoogle Scholar
  • 78 Arachchillage DR, Efthymiou M, Mackie IJ, Lawrie AS, Machin SJ, Cohen H. Rivaroxaban and warfarin achieve effective anticoagulation, as assessed by inhibition of TG and in-vivo markers of coagulation activation, in patients with venous thromboembolism. Thromb Res 2015; 135 (02) 388-393
    CrossrefPubMedGoogle Scholar
  • 79 Brodin E, Seljeflot I, Arnesen H, Hurlen M, Appelbom H, Hansen JB. Endogenous thrombin potential (ETP) in plasma from patients with AMI during antithrombotic treatment. Thromb Res 2009; 123 (04) 573-579
    CrossrefPubMedGoogle Scholar
  • 80 Gerotziafas GT, Dupont C, Spyropoulos AC. , et al. Differential inhibition of thrombin generation by vitamin K antagonists alone and associated with low-molecular-weight heparin. Thromb Haemost 2009; 102 (01) 42-48
    Article in Thieme ConnectPubMedGoogle Scholar
  • 81 Graff J, von Hentig N, Misselwitz F. , et al. Effects of the oral, direct factor Xa inhibitor rivaroxaban on platelet-induced thrombin generation and prothrombinase activity. J Clin Pharmacol 2007; 47 (11) 1398-1407
    CrossrefPubMedGoogle Scholar
  • 82 Perzborn E, Strassburger J, Wilmen A. , et al. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939--an oral, direct Factor Xa inhibitor. J Thromb Haemost 2005; 3 (03) 514-521
    CrossrefPubMedGoogle Scholar
  • 83 Samama MM, Mendell J, Guinet C, Le Flem L, Kunitada S. In vitro study of the anticoagulant effects of edoxaban and its effect on thrombin generation in comparison to fondaparinux. Thromb Res 2012; 129 (04) e77-e82
    CrossrefPubMedGoogle Scholar
  • 84 Herrmann R, Thom J, Wood A, Phillips M, Muhammad S, Baker R. Thrombin generation using the calibrated automated thrombinoscope to assess reversibility of dabigatran and rivaroxaban. Thromb Haemost 2014; 111 (05) 989-995
    Article in Thieme ConnectPubMedGoogle Scholar
  • 85 Green L, Lawrie AS, Patel S. , et al. The impact of elective knee/hip replacement surgery and thromboprophylaxis with rivaroxaban or dalteparin on thrombin generation. Br J Haematol 2010; 151 (05) 469-476
    CrossrefPubMedGoogle Scholar
  • 86 Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011; 124 (14) 1573-1579
    CrossrefPubMedGoogle Scholar
  • 87 Gerotziafas GT, Elalamy I, Depasse F, Perzborn E, Samama MM. In vitro inhibition of thrombin generation, after tissue factor pathway activation, by the oral, direct factor Xa inhibitor rivaroxaban. J Thromb Haemost 2007; 5 (04) 886-888
    CrossrefPubMedGoogle Scholar
  • 88 Wan H, Yang Y, Zhu J. , et al. An in-vitro evaluation of direct thrombin inhibitor and factor Xa inhibitor on tissue factor-induced thrombin generation and platelet aggregation: a comparison of dabigatran and rivaroxaban. Blood Coagul Fibrinolysis 2016; 27 (08) 882-885
    CrossrefPubMedGoogle Scholar
  • 89 Serebruany V, Sani Y, Lynch D. , et al. Effects of dabigatran in vitro on thrombin biomarkers by Calibrated Automated Thrombography in patients after ischemic stroke. J Thromb Thrombolysis 2012; 33 (01) 22-27
    CrossrefPubMedGoogle Scholar
  • 90 Kamisato C, Furugohri T, Morishima Y. A direct thrombin inhibitor suppresses protein C activation and factor Va degradation in human plasma: Possible mechanisms of paradoxical enhancement of thrombin generation. Thromb Res 2016; 141: 77-83
    CrossrefPubMedGoogle Scholar
  • 91 Tripodi A, Padovan L, Veena C, Scalambrino E, Testa S, Peyvandi F. How the direct oral anticoagulant apixaban affects thrombin generation parameters. Thromb Res 2015; 135 (06) 1186-1190
    CrossrefPubMedGoogle Scholar
  • 92 Kubitza D, Becka M, Voith B, Zuehlsdorf M, Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther 2005; 78 (04) 412-421
    CrossrefPubMedGoogle Scholar
  • 93 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
    CrossrefPubMedGoogle Scholar
  • 94 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
    CrossrefPubMedGoogle Scholar
  • 95 Merriman E, Kaplan Z, Butler J, Malan E, Gan E, Tran H. Rivaroxaban and false positive lupus anticoagulant testing. Thromb Haemost 2011; 105 (02) 385-386
    Article in Thieme ConnectPubMedGoogle Scholar
  • 96 Martinuzzo ME, Barrera LH, D'adamo MA, Otaso JC, Gimenez MI, Oyhamburu J. Frequent false-positive results of lupus anticoagulant tests in plasmas of patients receiving the new oral anticoagulants and enoxaparin. Int J Lab Hematol 2014; 36 (02) 144-150
    CrossrefPubMedGoogle Scholar
  • 97 Eby C. Novel anticoagulants and laboratory testing. Int J Lab Hematol 2013; 35 (03) 262-268
    CrossrefPubMedGoogle Scholar
  • 98 Halbmayer WM, Weigel G, Quehenberger P. , et al. Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests. Clin Chem Lab Med 2012; 50 (09) 1601-1605
    PubMedGoogle Scholar
  • 99 Arachchillage DR, Mackie IJ, Efthymiou M. , et al. Rivaroxaban limits complement activation compared with warfarin in antiphospholipid syndrome patients with venous thromboembolism. J Thromb Haemost 2016; 14 (11) 2177-2186
    CrossrefPubMedGoogle Scholar