Internal and Emergency Medicine

, Volume 12, Issue 3, pp 387–406 | Cite as

Italian intersociety consensus on DOAC use in internal medicine

  • Domenico Prisco
  • Walter Ageno
  • Cecilia Becattini
  • Armando D’Angelo
  • Giovanni Davì
  • Raimondo De Cristofaro
  • Francesco Dentali
  • Giovanni Di Minno
  • Anna Falanga
  • Gualberto Gussoni
  • Luca Masotti
  • Gualtiero Palareti
  • Pasquale Pignatelli
  • Roberto M. Santi
  • Francesca Santilli
  • Mauro Silingardi
  • Antonella Tufano
  • Francesco Violi
  • SIMI (Italian Society of Internal Medicine)
  • FADOI (Federation of Associations of Hospital Doctors on Internal Medicine)
  • SISET (Italian Society for the Study of Haemostasis and Thrombosis)


The direct oral anticoagulants (DOACs) are drugs used in clinical practice since 2009 for the prevention of stroke or systemic embolism in non-valvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism. The four DOACs, including the three factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and one direct thrombin inhibitor (dabigatran) provide oral anticoagulation therapy alternatives to Vitamin K antagonists (VKAs). Despite their clear advantages, the DOACs require on the part of the internist a thorough knowledge of their pharmacokinetic and pharmacodynamic characteristics to ensure their correct use, laboratory monitoring and the appropriate management of adverse events. This document represents a consensus paper on the use of DOACs by representatives of three Italian scientific societies: the Italian Society of Internal Medicine (SIMI), the Federation of the Associations of Hospital Managers (FADOI), and the Society for the Study of Haemostasis and Thrombosis (SISET). This document formulates expert opinion guidance for pragmatic managing, monitoring and reversing the anticoagulant effect of DOACs in both chronic and emergency settings. This practical guidance may help the internist to create adequate protocols for patients hospitalized ion internal medicine wards, where patients are often elderly subjects affected by poly-morbidities and renal insufficiency, and, thus, require particular attention to drug–drug interactions and peri-procedural protocols.


Atrial fibrillation Venous thromboembolism Pulmonary embolism Venous thrombosis Internist Drug interactions Elderly Direct oral anticoagulant Novel oral anticoagulant 



The assistance of Amanda Mannucci in the preparation of final draft is acknowledged. The authors thank the Presidents of the three Societies participating in this Consensus: Francesco Perticone, President of SIMI (Italian Society of Internal Medicine); Mauro Campanini, President of FADOI (Federation of Associations of Hospital Doctors on Internal Medicine); Anna Falanga, President of SISET (Italian Society for the Study of Haemostasis and Thrombosis).

Compliance with ethical standards

Conflict of interest

DP declares fees for participations in editorial boards and lectures by Bayer, Boehringer Ingelheim, BMS-Pfizer and Daiichi Sankyo given to his Institution. WA declares research support by Bayer and Boehringer Ingelheim; he also declare participation in advisory boards for Bayer, Boehringer Ingelheim, Daiichi Sankyo and BMS-Pfizer. CB declares speakers’ fees by Bayer, Bristol Meyer Squibb and Boehringer Ingelheim. AD declares speakers’ fees by Bayer, Boehringer Ingelheim, BMS-Pfizer and Daiichi Sankyo given to his Institution. FD declares a consultance activity for Bayer and Boehringer Ingelheim and participations in advisory boards of Boehringer Ingelheim, BMS-Pfizer. AF declare a role of speakers’ bureau for Pfizer, Aspen and Rovi. GP declares participation in advisory board or speakers’ fees by Alfa-Wassermann, Daiichi-Sankyo, Pfizer, Roche, Siemens and Werfen. PP declares speakers’ fees by Bayer, Boehringer Ingelheim, BMS-Pfizer and Daiichi Sankyo FS declares fesearch support by Bayer. GD, RD, GDM, GG, LM, RMS, MS, AT, FV declare that they have no conflict of interest.

Statement of human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent



  1. 1.
    Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P (2015) Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Europace 17:1467–1507CrossRefPubMedGoogle Scholar
  2. 2.
    van Es N, Coppens M, Schulman S, Middeldorp S, Buller HR (2014) Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 124(12):1968–1975CrossRefPubMedGoogle Scholar
  3. 3.
    Ruff CT, Giugliano RP, Braunwald E, Antman EM (2014) New oral anticoagulants in patients with atrial fibrillation—authors’reply. Lancet 384(9937):25–26CrossRefPubMedGoogle Scholar
  4. 4.
    Marcucci M, Iorio A, Nobili A, Tettamanti M, Pasina L, Marengoni A, Salerno F, Corrao S, Mannucci PM (2010) Factors affecting adherence to guidelines for antithrombotic therapy in elderly patients with atrial fibrillation admitted to internal medicine wards. Eur J Intern Med 21(6):516–523CrossRefPubMedGoogle Scholar
  5. 5.
    Di Pasquale G, Mathieu G, Maggioni AP, Fabbri G, Lucci D, Vescovo G, Pirelli S, Chiarella F, Scherillo M, Gulizia MM, Gussoni G, Colombo F, Panuccio D, Nozzoli C, Berisso MZ (2013) Current presentation and management of 7148 patients with atrial fibrillation in cardiology and internal medicine hospital centers: the ATA AF study. Int J Cardiol 167(6):2895–2903CrossRefPubMedGoogle Scholar
  6. 6.
    Gussoni G, Di Pasquale G, Vescovo G, Gulizia M, Mathieu G, Scherillo M, Panuccio D, Lucci D, Nozzoli C, Fabbri G, Colombo F, Riva L, Baldo CI, Maggioni AP, Mazzone A (2013) Decision making for oral anticoagulants in atrial fibrillation: the ATA-AF study. Eur J Intern Med 24(4):324–332CrossRefPubMedGoogle Scholar
  7. 7.
    Mannucci PM, Nobili A (2015) Appropriateness of antithrombotic prophylaxis in the oldest old with non-valvular atrial fibrillation: ARAPACIS and REPOSI. Eur J Intern Med 26(9):e47–e48CrossRefPubMedGoogle Scholar
  8. 8.
    Konstantinides SV (2014) 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 35(45):3145–3146CrossRefPubMedGoogle Scholar
  9. 9.
    Vedovati MC, Germini F, Agnelli G, Becattini C (2015) Direct oral anticoagulants in patients with VTE and cancer: a systematic review and meta-analysis. Chest 147(2):475–483CrossRefPubMedGoogle Scholar
  10. 10.
    Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ (2013) Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 368(8):709–718CrossRefPubMedGoogle Scholar
  11. 11.
    Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JR, Wells P, Woller SC, Moores L (2016) Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 149(2):315–352CrossRefPubMedGoogle Scholar
  12. 12.
    Hoffman R, Brenner B (2012) The promise of novel direct oral anticoagulants. Best Pract Res Clin Haematol 25(3):351–360CrossRefPubMedGoogle Scholar
  13. 13.
    Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P (2013) European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 15(5):625–651CrossRefPubMedGoogle Scholar
  14. 14.
    Mekaj YH, Mekaj AY, Duci SB, Miftari EI (2015) New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. Ther Clin Risk Manag 11:967–977CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Raccah BH, Perlman A, Danenberg HD, Pollak A, Muszkat M, Matok I (2016) Major bleeding and hemorrhagic stroke with direct oral anticoagulants in patients with renal failure: systematic review and meta-analysis of randomized trials. Chest 149(6):1516–1524CrossRefPubMedGoogle Scholar
  16. 16.
    Wang Y, Bajorek B (2014) New oral anticoagulants in practice: pharmacological and practical considerations. Am J Cardiovasc Drugs 14(3):175–189CrossRefPubMedGoogle Scholar
  17. 17.
    Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, Bhatt DL, Goodman S, Verheugt FW, Flather M, Huber K, Liaw D, Husted SE, Lopez-Sendon J, De Caterina R, Jansky P, Darius H, Vinereanu D, Cornel JH, Cools F, Atar D, Leiva-Pons JL, Keltai M, Ogawa H, Pais P, Parkhomenko A, Ruzyllo W, Diaz R, White H, Ruda M, Geraldes M, Lawrence J, Harrington RA, Wallentin L (2011) Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 365(8):699–708CrossRefPubMedGoogle Scholar
  18. 18.
    Short NJ, Connors JM (2014) New oral anticoagulants and the cancer patient. Oncologist 19(1):82–93CrossRefPubMedGoogle Scholar
  19. 19.
    Lippi G, Favaloro EJ, Mattiuzzi C (2014) Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring? Semin Thromb Hemost 40(7):756–765CrossRefPubMedGoogle Scholar
  20. 20.
    Gnoth MJ, Buetehorn U, Muenster U, Schwarz T, Sandmann S (2011) In vitro and in vivo P-glycoprotein transport characteristics of rivaroxaban. J Pharmacol Exp Ther 338(1):372–380CrossRefPubMedGoogle Scholar
  21. 21.
    Wang L, Zhang D, Raghavan N, Yao M, Ma L, Frost CE, Maxwell BD, Chen SY, He K, Goosen TC, Humphreys WG, Grossman SJ (2010) In vitro assessment of metabolic drug–drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos 38(3):448–458CrossRefPubMedGoogle Scholar
  22. 22.
    Mavrakanas TA, Samer C, Fontana P, Perrier A (2015) Direct oral anticoagulants: efficacy and safety in patient subgroups. Swiss Med Wkly 145:w14081PubMedGoogle Scholar
  23. 23.
    Cordeanu M, Gaertner S, Bensalah N, Mirea C, Hamade A, Stephan D (2016) Rivaroxaban induced liver injury: a cholestatic pattern. Int J Cardiol 216:97–98CrossRefPubMedGoogle Scholar
  24. 24.
    Kaatz S, Mahan CE (2014) Stroke prevention in patients with atrial fibrillation and renal dysfunction. Stroke 45(8):2497–2505CrossRefPubMedGoogle Scholar
  25. 25.
    Meguid El Nahas A, Bello AK (2005) Chronic kidney disease: the global challenge. Lancet 365(9456):331–340CrossRefPubMedGoogle Scholar
  26. 26.
    January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW (2014) 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 130(23):2071–2104CrossRefPubMedGoogle Scholar
  27. 27.
    Chan KE, Edelman ER, Wenger JB, Thadhani RI, Maddux FW (2015) Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis. Circulation 131(11):972–979CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Lakkireddy D, Reddy YM, Di Biase L, Vallakati A, Mansour MC, Santangeli P, Gangireddy S, Swarup V, Chalhoub F, Atkins D, Bommana S, Verma A, Sanchez JE, Burkhardt JD, Barrett CD, Baheiry S, Ruskin J, Reddy V, Natale A (2014) Feasibility and safety of uninterrupted rivaroxaban for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. J Am Coll Cardiol 63(10):982–988CrossRefPubMedGoogle Scholar
  29. 29.
    Garcia D, Alexander JH, Wallentin L, Wojdyla DM, Thomas L, Hanna M, Al-Khatib SM, Dorian P, Ansell J, Commerford P, Flaker G, Lanas F, Vinereanu D, Xavier D, Hylek EM, Held C, Verheugt FW, Granger CB, Lopes RD (2014) Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures. Blood 124(25):3692–3698CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Bin Abdulhak AA, Khan AR, Tleyjeh IM, Spertus JA, Sanders SU, Steigerwalt KE, Garbati MA, Bahmaid RA, Wimmer AP (2013) Safety and efficacy of interrupted dabigatran for peri-procedural anticoagulation in catheter ablation of atrial fibrillation: a systematic review and meta-analysis. Europace 15(10):1412–1420CrossRefPubMedGoogle Scholar
  31. 31.
    Beyer-Westendorf J, Gelbricht V, Forster K, Ebertz F, Kohler C, Werth S, Kuhlisch E, Stange T, Thieme C, Daschkow K, Weiss N (2014) Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry. Eur Heart J 35(28):1888–1896CrossRefPubMedGoogle Scholar
  32. 32.
    Schulman S, Carrier M, Lee AY, Shivakumar S, Blostein M, Spencer FA, Solymoss S, Barty R, Wang G, Heddle N, Douketis JD (2015) Perioperative management of dabigatran: a prospective cohort study. Circulation 132(3):167–173CrossRefPubMedGoogle Scholar
  33. 33.
    Pernod G, Albaladejo P, Godier A, Samama CM, Susen S, Gruel Y, Blais N, Fontana P, Cohen A, Llau JV, Rosencher N, Schved JF, de Maistre E, Samama MM, Mismetti P, Sie P (2013) Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP)—March 2013. Arch Cardiovasc Dis 106(6–7):382–393CrossRefPubMedGoogle Scholar
  34. 34.
    Alikhan R, Rayment R, Keeling D, Baglin T, Benson G, Green L, Marshall S, Patel R, Pavord S, Rose P, Tait C (2014) The acute management of haemorrhage, surgery and overdose in patients receiving dabigatran. Emerg Med J 31(2):163–168CrossRefPubMedGoogle Scholar
  35. 35.
    Ferrandis R, Castillo J, de Andres J, Gomar C, Gomez-Luque A, Hidalgo F, Llau JV, Sierra P, Torres LM (2013) The perioperative management of new direct oral anticoagulants: a question without answers. Thromb Haemost 110(3):515–522CrossRefPubMedGoogle Scholar
  36. 36.
    Tran H, Joseph J, Young L, McRae S, Curnow J, Nandurkar H, Wood P, McLintock C (2014) New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/bleeding management. Australasian Society of Thrombosis and Haemostasis. Intern Med J 44(6):525–536CrossRefPubMedGoogle Scholar
  37. 37.
    Douketis JD, Spyropoulos AC, Spencer FA, Mayr M, Jaffer AK, Eckman MH, Dunn AS, Kunz R (2012) Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl):e326S–e350SCrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Daniels PR (2015) Peri-procedural management of patients taking oral anticoagulants. BMJ 351:h2391CrossRefPubMedGoogle Scholar
  39. 39.
    Baglin T, Hillarp A, Tripodi A, Elalamy I, Buller H, Ageno W (2013) Measuring oral direct inhibitors (ODIs) of thrombin and factor Xa: a recommendation from the Subcommittee on Control of Anticoagulation of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 11:756–760Google Scholar
  40. 40.
    Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, Themeles E, Heidbuchel H, Avezum A, Reilly P, Connolly SJ, Yusuf S, Ezekowitz M (2012) Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the randomized evaluation of long-term anticoagulation therapy (RE-LY) randomized trial. Circulation 126(3):343–348CrossRefPubMedGoogle Scholar
  41. 41.
    Philippart R, Brunet-Bernard A, Clementy N, Bourguignon T, Mirza A, Angoulvant D, Babuty D, Lip GY, Fauchier L (2016) Oral anticoagulation, stroke and thromboembolism in patients with atrial fibrillation and valve bioprosthesis. The Loire Valley Atrial Fibrillation Project. Thromb Haemost 115(5):1056–1063CrossRefPubMedGoogle Scholar
  42. 42.
    Spyropoulos AC, Douketis JD (2012) How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood 120(15):2954–2962CrossRefPubMedGoogle Scholar
  43. 43.
    De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A, Leone G (2006) The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. Haematologica 91(5):695–698PubMedGoogle Scholar
  44. 44.
    Eichinger S, Stumpflen A, Hirschl M, Bialonczyk C, Herkner K, Stain M, Schneider B, Pabinger I, Lechner K, Kyrle PA (1998) Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism. Thromb Haemost 80(4):566–569PubMedGoogle Scholar
  45. 45.
    Kyrle PA, Minar E, Hirschl M, Bialonczyk C, Stain M, Schneider B, Weltermann A, Speiser W, Lechner K, Eichinger S (2000) High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 343(7):457–462CrossRefPubMedGoogle Scholar
  46. 46.
    Eischer L, Gartner V, Schulman S, Kyrle PA, Eichinger S (2009) 6 versus 30 months anticoagulation for recurrent venous thrombosis in patients with high factor VIII. Ann Hematol 88(5):485–490CrossRefPubMedGoogle Scholar
  47. 47.
    Segal JB, Brotman DJ, Necochea AJ, Emadi A, Samal L, Wilson LM, Crim MT, Bass EB (2009) Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA 301(23):2472–2485CrossRefPubMedGoogle Scholar
  48. 48.
    Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M (2011) Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 124(14):1573–1579CrossRefPubMedGoogle Scholar
  49. 49.
    Dzik WH (2015) Reversal of oral factor Xa inhibitors by prothrombin complex concentrates: a re-appraisal. J Thromb Haemost 13(Suppl 1):S187–S194CrossRefPubMedGoogle Scholar
  50. 50.
    Dickneite G, Hoffman M (2014) Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence? Thromb Haemost 111(2):189–198CrossRefPubMedGoogle Scholar
  51. 51.
    Zahir H, Brown KS, Vandell AG, Desai M, Maa JF, Dishy V, Lomeli B, Feussner A, Feng W, He L, Grosso MA, Lanz HJ, Antman EM (2015) Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation 131(1):82–90CrossRefPubMedGoogle Scholar
  52. 52.
    Levi M, Moore KT, Castillejos CF, Kubitza D, Berkowitz SD, Goldhaber SZ, Raghoebar M, Patel MR, Weitz JI, Levy JH (2014) Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers. J Thromb Haemost 12(9):1428–1436CrossRefPubMedGoogle Scholar
  53. 53.
    Lauw MN, Coppens M, Eikelboom JW (2014) Recent advances in antidotes for direct oral anticoagulants: their arrival is imminent. Can J Cardiol 30(4):381–384CrossRefPubMedGoogle Scholar
  54. 54.
    Pollack CV, Jr., Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, Weitz JI (2015) Idarucizumab for dabigatran reversal. N Engl J Med 373(6):511–520Google Scholar
  55. 55.
    Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, Crowther M (2015) Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 375(12):1131–1141CrossRefGoogle Scholar
  56. 56.
    Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso M, Brown K, Dishy V, Noveck RJ, Costin JC (2014) Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 371(22):2141–2142CrossRefPubMedGoogle Scholar
  57. 57.
    Levy JH, Ageno W, Chan NC, Crowther M, Verhamme P, Weitz JI (2016) When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb Haemost 14(3):623–627CrossRefPubMedGoogle Scholar
  58. 58.
    Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC, Klein WW, Alonso-Garcia A, Blomstrom-Lundqvist C, De Backer G, Flather M, Hradec J, Oto A, Parkhomenko A, Silber S, Torbicki A (2001) ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation): developed in Collaboration With the North American Society of Pacing and Electrophysiology. J Am Coll Cardiol 38(4):1231–1266CrossRefPubMedGoogle Scholar
  59. 59.
    Francart SJ, Hawes EM, Deal AM, Adcock DM, Gosselin R, Jeanneret C, Friedman KD, Moll S (2014) Performance of coagulation tests in patients on therapeutic doses of rivaroxaban. A cross-sectional pharmacodynamic study based on peak and trough plasma levels. Thromb Haemost 111(6):1133–1140CrossRefPubMedGoogle Scholar
  60. 60.
    Chan NC, Hirsh J, Ginsberg JS, Eikelboom JW (2015) Real-world variability in dabigatran levels in patients with atrial fibrillation: reply. J Thromb Haemost 13(6):1168–1169CrossRefPubMedGoogle Scholar
  61. 61.
    Siguret V, Gouin-Thibault I, Gaussem P, Pautas E (2013) Optimizing the use of anticoagulants (heparins and oral anticoagulants) in the elderly. Drugs Aging 30(9):687–699CrossRefPubMedGoogle Scholar
  62. 62.
    Tripodi A (2013) The laboratory and the direct oral anticoagulants. Blood 121(20):4032–4035CrossRefPubMedGoogle Scholar
  63. 63.
    Pengo V, Crippa L, Falanga A, Finazzi G, Marongiu F, Palareti G, Poli D, Testa S, Tiraferri E, Tosetto A, Tripodi A, Manotti C (2011) Questions and answers on the use of dabigatran and perspectives on the use of other new oral anticoagulants in patients with atrial fibrillation. A consensus document of the Italian Federation of Thrombosis Centers (FCSA). Thromb Haemost 106(5):868–876CrossRefPubMedGoogle Scholar
  64. 64.
    Tripodi A, Chantarangkul V, Guinet C, Samama MM (2011) The International Normalized Ratio calibrated for rivaroxaban has the potential to normalize prothrombin time results for rivaroxaban-treated patients: results of an in vitro study. J Thromb Haemost 9(1):226–228CrossRefPubMedGoogle Scholar
  65. 65.
    Barrett YC, Wang Z, Frost C, Shenker A (2010) Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay. Thromb Haemost 104(6):1263–1271CrossRefPubMedGoogle Scholar
  66. 66.
    Becker RC, Alexander JH, Newby LK, Yang H, Barrett Y, Mohan P, Wang J, Harrington RA, Wallentin LC (2010) Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation activity biomarkers following acute coronary syndrome. Thromb Haemost 104(5):976–983CrossRefPubMedGoogle Scholar
  67. 67.
    Becker RC, Yang H, Barrett Y, Mohan P, Wang J, Wallentin L, Alexander JH (2011) Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban—an oral, direct and selective factor Xa inhibitor. J Thromb Thrombolysis 32(2):183–187CrossRefPubMedGoogle Scholar
  68. 68.
    Ogata K, Mendell-Harary J, Tachibana M, Masumoto H, Oguma T, Kojima M, Kunitada S (2010) Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J Clin Pharmacol 50(7):743–753CrossRefPubMedGoogle Scholar
  69. 69.
    Wolzt M, Samama MM, Kapiotis S, Ogata K, Mendell J, Kunitada S (2011) Effect of edoxaban on markers of coagulation in venous and shed blood compared with fondaparinux. Thromb Haemost 105(6):1080–1090CrossRefPubMedGoogle Scholar
  70. 70.
    Cuker A, Husseinzadeh H (2015) Laboratory measurement of the anticoagulant activity of edoxaban: a systematic review. J Thromb Thrombolysis 39(3):288–294CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© SIMI 2017

Authors and Affiliations

  • Domenico Prisco
    • 1
  • Walter Ageno
    • 2
  • Cecilia Becattini
    • 3
  • Armando D’Angelo
    • 4
  • Giovanni Davì
    • 5
  • Raimondo De Cristofaro
    • 6
  • Francesco Dentali
    • 2
  • Giovanni Di Minno
    • 7
  • Anna Falanga
    • 8
  • Gualberto Gussoni
    • 9
  • Luca Masotti
    • 10
  • Gualtiero Palareti
    • 11
  • Pasquale Pignatelli
    • 12
  • Roberto M. Santi
    • 13
  • Francesca Santilli
    • 5
  • Mauro Silingardi
    • 14
  • Antonella Tufano
    • 7
  • Francesco Violi
    • 12
  • SIMI (Italian Society of Internal Medicine)
  • FADOI (Federation of Associations of Hospital Doctors on Internal Medicine)
  • SISET (Italian Society for the Study of Haemostasis and Thrombosis)
  1. 1.Department of Experimental and Clinical MedicineUniversity of FlorenceFlorenceItaly
  2. 2.Department of Clinical and Experimental MedicineInsubria UniversityVareseItaly
  3. 3.Internal and Cardiovascular Medicine-Stroke UnitUniversity of PerugiaPerugiaItaly
  4. 4.Coagulation Service and Thrombosis Research UnitScientific Institute San RaffaeleMilanItaly
  5. 5.Clinica Medica, Department of Medicine and Aging SciencesUniversity of Chieti G.D’AnnunzioChietiItaly
  6. 6.Institute of Internal Medicine and Geriatrics, Center for Haemorrhagic and Thrombotic Diseases, Haematology, Foundation Policlinico universitario “Agostino Gemelli”Catholic University of the Sacred HeartRomeItaly
  7. 7.Clinica Medica, Department of Clinical Medicine and SurgeryAOU Policlinico Federico IINaplesItaly
  8. 8.Department of Immunohematology and Transfusion Medicine, and the Thrombosis and Hemostasis CenterHospital Papa Giovanni XXIIIBergamoItaly
  9. 9.Department of Clinical ResearchFADOIMilanItaly
  10. 10.Internal MedicineSanta Maria Nuova HospitalFlorenceItaly
  11. 11.Cardiovascular DiseasesUniversity of BolognaBolognaItaly
  12. 12.Department of Internal Medicine and Medical Specialties“La Sapienza” University of RomeRomeItaly
  13. 13.Haemostasis and Thrombosis Unit, HaematologyAz. Osp. “SS.Antonio e Biagio e C. Arrigo”AlessandriaItaly
  14. 14.Internal Medicine Unit A - Ospedale MaggioreAUSL BolognaBolognaItaly

Personalised recommendations