Perioperative Management of Patients Receiving New Anticoagulants

Author(s): Massimo Lamperti*, Andrey Khozenko, Arun Kumar

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 19 , 2019

Become EABM
Become Reviewer
Call for Editor


There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

Keywords: New oral anticoagulants, reversals, management, arterial thrombosis, cardiac surgery, activated charcoal, intracranial bleedings.

Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation 2012; 125(1): e2-e220.
[PMID: 22179539]
Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the american college of cardiology/american heart association task force on practice guidelines. J Am Coll Cardiol 2014; 63(22): e57-e185.
[] [PMID: 24603191]
Ageno W, Gallus AS, Wittkowsky A, et al. American College of Chest Physicians: Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines.Chest. 2012; 143: pp. 44S-68S.
Raval AN, Cigarroa JE, Chung MK, et al. Management of patients on non-vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: a scientific statement from the American Heart Association. Circulation 2017; 135(10): e604-33.
[] [PMID: 28167634]
Untereiner O, Seince PF, Chterev V, et al. Management of direct oral anticoagulants in the perioperative setting. J Cardiothorac Vasc Anesth 2015; 29(3): 741-8.
[] [PMID: 26009288]
Kocabas U, Kaya E, Avcı G. Novel oral anticoagulants in non-valvular atrial fibrillation: pharmacological properties, clinical trials, guideline recommendations, new antidote drugs and real-world data. Int J Cardiovasc Academy 2016; 2: 167-73.
McIlmoyle K, Tran H. Perioperative management of oral anticoagulation. BJA Educ 2018; 18: 259-64.
Lessire S, Douxfils J, Baudar J, et al. Is Thrombin Time useful for the assessment of dabigatran concentrations? An in vitro and ex vivo study. Thromb Res 2015; 136(3): 693-6.
[] [PMID: 26251077]
Bluecher A, Meyer Dos Santos S, Ferreirós N, et al. Microfluidic coagulation assay for monitoring anticoagulant therapy in acute stroke patients. Thromb Haemost 2017; 117(3): 519-28.
[] [PMID: 28124061]
Bliden KP, Chaudhary R, Mohammed N, et al. Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system. J Thromb Thrombolysis 2017; 43(4): 437-45.
[] [PMID: 28247290]
Dias JD, Norem K, Doorneweerd DD, Thurer RL, Popovsky MA, Omert LA. Use of thromboelastography (TEG) for detection of new oral anticoagulants. Arch Pathol Lab Med 2015; 139(5): 665-73.
[] [PMID: 25927150]
Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015; 373(6): 511-20.
[] [PMID: 26095746]
Ruff CT, Giugliano RP, Antman EM. Management of bleeding with non-vitamin K antagonist oral anticoagulants in the era of specific reversal agents. Circulation 2016; 134(3): 248-61.
[] [PMID: 27436881]
Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med 2015; 373(25): 2413-24.
[] [PMID: 26559317]
Connolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 2016; 375(12): 1131-41.
[] [PMID: 27573206]
Ansell JE, Bakhru SH, Laulicht BE, et al. Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban. Thromb Haemost 2017; 117(2): 238-45.
[] [PMID: 27853809]
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): 1573-9.
[] [PMID: 21900088]
Perzborn E, Heitmeier S, Laux V, Buchmüller A. Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitro. Thromb Res 2014; 133(4): 671-81.
[] [PMID: 24529498]
Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137(2): 263-72.
[] [PMID: 19762550]
Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37(38): 2893-962.
[] [PMID: 27567408]
Beyer-Westendorf J, Forster K, Pannach S, et al. Rates, management and outcome of bleeding complications during rivaroxaban therapy in daily care: results from the Dresden NOAC registry. Blood 2014; 124: 955-62.
[] [PMID: 24859362]
Healey JS, Eikelboom J, Douketis J, et al. 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 2012; 126(3): 343-8.
[] [PMID: 22700854]
Faraoni D, Samama CM, Ranucci M, et al. Perioperative management of new oral anticoagulants: an international survey. Clin Lab Med 2014; 34: 637-54.
[] [PMID: 25168948]
Gogarten W, Vandermeulen E, Van Aken H, Kozek S, Llau JV, Samama CM. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol 2010; 27(12): 999-1015.
[] [PMID: 20890208]
Sié P, Samama CM, Godier A, et al. Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Haemostasis and the French Study Group on Thrombosis and Haemostasis. Arch Cardiovasc Dis 2011; 104(12): 669-76.
[] [PMID: 22152517]
Heidbuchel H, Verhamme P, Alings M, et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013; 34(27): 2094-106.
[] [PMID: 23625209]
Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 2015; 373(9): 823-33.
[] [PMID: 26095867]
Douketis JD, Healey JS, Brueckmann M, et al. Perioperative bridging anticoagulation during dabigatran or warfarin interruption among patients who had an elective surgery or procedure. Substudy of the RE-LY trial. Thromb Haemost 2015; 113(3): 625-32.
[] [PMID: 25472710]
Essebag V, Healey JS, Ayala-Paredes F, et al. Strategy of continued vs interrupted novel oral anticoagulant at time of device surgery in patients with moderate to high risk of arterial thromboembolic events: The BRUISE CONTROL-2 trial. Am Heart J 2016; 173: 102-7.
[] [PMID: 26920602]
Sousa-Uva M, Head SJ, Milojevic M, et al. 2017 EACTS Guidelines on perioperative medication in adult cardiac surgery. Eur J Cardiothorac Surg 2018; 53(1): 5-33.
[] [PMID: 29029110]
Steffel J, Verhamme P, Potpara TS, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39(16): 1330-93.
[] [PMID: 29562325]
Albaladejo P, Bonhomme F, Blais N, et al. Management of direct oral anticoagulants in patients undergoing elective surgeries and invasive procedures: Updated guidelines from the French Working Group on Perioperative Hemostasis (GIHP) - September 2015. Anaesth Crit Care Pain Med 2017; 36(1): 73-6.
[] [PMID: 27659969]
Hassan K, Bayer N, Schlingloff F, et al. Bleeding complications after use of novel oral anticoagulants in patients undergoing cardiac surgery. Ann Thorac Surg 2018; 105(3): 702-8.
[] [PMID: 29305143]
Teddy P, Nair G. Anti-stroke prophylaxis--the ethics of collateral damage. J Clin Neurosci 2012; 19(6): 792-4.
[] [PMID: 22459182]
Toyoda K, Arihiro S, Todo K, et al. Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: the SAMURAI-NVAF study. Int J Stroke 2015; 10(6): 836-42.
[] [PMID: 25581108]
Komotar RJ, Starke RM, Connolly ES Jr. Orally administered factor xa inhibitor, rivaroxaban: a novel thromboembolic prophylaxis agent. Neurosurgery 2008; 63(4): N10-1.
[] [PMID: 18981864]
Ho CW, Ho MH, Chan PH, et al. Ischemic stroke and intracranial hemorrhage with aspirin, dabigatran, and warfarin: impact of quality of anticoagulation control. Stroke 2015; 46(1): 23-30.
[] [PMID: 25406148]
Takahashi H, Jimbo Y, Takano H, et al. Intracerebral hematoma occurring during warfarin versus non-vitamin K antagonist oral anticoagulant therapy. Am J Cardiol 2016; 118(2): 222-5.
[] [PMID: 27289294]
Adachi T, Hoshino H, Takagi M, Fujioka S. Volume and characteristics of intracerebral hemorrhage with direct oral anticoagulants in comparison with warfarin. Cerebrovasc Dis Extra 2017; 7(1): 62-71.
[] [PMID: 28376486]
Kawabori M, Niiya Y, Iwasaki M, et al. Characteristics of symptomatic intracerebral hemorrhage in patient receiving direct oral anticoagulants: Comparison with warfarin. J Stroke Cerebrovasc Dis 2018; 27(5): 1338-42.
[] [PMID: 29397310]
Beynon C, Potzy A, Sakowitz OW, Unterberg AW. Rivaroxaban and intracranial haemorrhage after mild traumatic brain injury: A dangerous combination? Clin Neurol Neurosurg 2015; 136: 73-8.
[] [PMID: 26070116]
Senger S, Keiner D, Hendrix P, Oertel J. New target-specific oral anticoagulants and intracranial bleeding: management and outcome in a single-center case series. World Neurosurg 2016; 88: 132-9.
[] [PMID: 26732970]
Castillo JM, Afanador HF, Manjarrez E, Morales XA. Non-traumatic spontaneous spinal subdural hematoma in a patient with non-valvular atrial fibrillation during treatment with rivaroxaban. Am J Case Rep 2015; 16: 377-81.
[] [PMID: 26090890]
Dargazanli C, Lonjon N, Gras-Combe G. Nontraumatic spinal subdural hematoma complicating direct factor Xa inhibitor treatment (rivaroxaban): a challenging management. Eur Spine J 2016; 25(Suppl. 1): 100-3.
[] [PMID: 26228186]
Zaarour M, Hassan S, Thumallapally N, Dai Q. Rivaroxaban-induced nontraumatic spinal subdural hematoma: An uncommon yet life-threatening complication. Case Rep Hematol 2015; 2015275380
[] [PMID: 26543654]
Colell A, Arboix A, Caiazzo F, Grivé E. Iatrogenic spinal subdural hematoma due to apixaban: A case report and review of the literature. Case Rep Hematol 2018; 20184507638
[] [PMID: 29670777]
Wolfe AR, Faroqui RM, Visvikis GA, Mantello MT, Perel AB, Tewari SO. Spinal subarachnoid and subdural hematoma presenting as a Brown-Séquard-like myelopathy following minor trauma in a patient on dabigatran etexilate. Radiol Case Rep 2017; 12(2): 257-60.
[] [PMID: 28491164]
Mathais Q, Esnault P, Cruc M, Bernard C, Prunet B, Gaillard PE. Spontaneous cervical spinal epidural hematoma associated with dabigatran. World Neurosurg 2018; 112: 264-6.
[] [PMID: 29425981]
Bamps S, Decramer T, Vandenbussche N, et al. Dabigatran-associated spontaneous acute cervical epidural hematoma. World Neurosurg 2015; 83: 257-8.
Kimura S, Ogata T, Fukae J, et al. Revascularization for acute ischemic stroke is safe for rivaroxaban users. J Stroke Cerebrovasc Dis 2014; 23(9): e427-31.
[] [PMID: 25149204]
Korya D, Dababneh H, Moussavi M, Panezai S, Noor E, Kirmani JF. Intravenous thrombolysis in a patient using factor Xa inhibitor. J Vasc Interv Neurol 2014; 7(3): 1-4.
[PMID: 25298850]
Ishihara H, Torii H, Imoto H, Oka F, Sadahiro H, Suzuki M. Intravenous thrombolysis with recombinant tissue plasminogen activator in a stroke patient treated with rivaroxaban. J Stroke Cerebrovasc Dis 2014; 23(10): e457-9.
[] [PMID: 25280819]
Shahjouei S, Tsivgoulis G, Bavarsad Shahripour R, Jones GM, Alexandrov AV, Zand R. Safety of intravenous thrombolysis among stroke patients taking new oral anticoagulants--case series and systematic review of reported cases. J Stroke Cerebrovasc Dis 2015; 24(12): 2685-93.
[] [PMID: 26542821]
Kurowski D, Jonczak K, Shah Q, et al. Safety of endovascular intervention for stroke on therapeutic anticoagulation: multicenter cohort study and meta-analysis. J Stroke Cerebrovasc Dis 2017; 26(5): 1104-9.
[] [PMID: 28110890]
Kermer P, Eschenfelder CC, Diener HC, et al. Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany - A national case collection. Int J Stroke 2017; 12(4): 383-91.
[] [PMID: 28494694]
Edwards G, Roman C, Jithoo R, Mitra B. Use of idarucizumab for dabigatran reversal: Emergency department experience in two cases with subdural haematoma. Trauma Case Rep 2017; 13: 46-9.
[] [PMID: 29644298]
Vosko MR, Bocksrucker C, Drwiła R, et al. Real-life experience with the specific reversal agent idarucizumab for the management of emergency situations in dabigatran-treated patients: a series of 11 cases. J Thromb Thrombolysis 2017; 43(3): 306-17.
[] [PMID: 28210988]
De Vlieger J, Dietvorst S, Demaerel R, et al. Neurosurgery in a patient at peak levels of rivaroxaban: taking into account all factors. Res Pract Thromb Haemost 2017; 1: 296-300.
Fugate JE, Rabinstein AA, McBane RD, Lanzino G. Dabigatran: a primer for neurosurgeons. World Neurosurg 2013; 79(1): 154-8.
[] [PMID: 22722043]
Dwyer CM, Damodaran O, Heckelmann M, Sheridan MM. What neurosurgeons need to know about dabigatran etexilate (pradax(®)/pradaxa(®)/prazaxa(®)). Asian J Neurosurg 2015; 10(2): 66-8.
[] [PMID: 25972932]
Culkin DJ, Exaire EJ, Green D, et al. Anticoagulation and antiplatelet therapy in urological practice: ICUD/AUA review paper. J Urol 2014; 192(4): 1026-34.
[] [PMID: 24859439]
Ellis G, John Camm A, Datta SN. Novel anticoagulants and antiplatelet agents; a guide for the urologist. BJU Int 2015; 116(5): 687-96.
[] [PMID: 25808010]
Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood 2012; 120(15): 2954-62.
[] [PMID: 22932800]
Veitch AM, Vanbiervliet G, Gershlick AH, et al. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Gut 2016; 65(3): 374-89.
[] [PMID: 26873868]
McCormack P, Simcock PR, Tullo AB. Management of the anticoagulated patient for ophthalmic surgery. Eye (Lond) 1993; 7(Pt 6): 749-50.
[] [PMID: 8119424]
Jeganathan VSE, Agarwal PK. The implications of novel oral anticoagulation in ocular surgery. New Front Ophthalmol 2015; 1: 24-8.
Chelly JE, Metais B, Schilling D, Luke C, Taormina D. Combination of Superficial and Deep Blocks with Rivaroxaban. Pain Med 2015; 16(10): 2024-30.
[] [PMID: 26177810]
Idestrup C, Sawhney M, Nix C, Kiss A. The incidence of hematoma formation in patients with continuous femoral catheters following total knee arthroplasty while receiving rivaroxaban as thromboprophylaxis: an observational study. Reg Anesth Pain Med 2014; 39(5): 414-7.
[] [PMID: 25102065]
Radcliff KE, Ong A, Parvizi J, Post Z, Orozco F. Rivaroxaban-induced epidural hematoma and cauda equina syndrome after total knee arthroplasty: A case report. Orthop Surg 2014; 6(1): 69-71.
[] [PMID: 24590998]
Caputo AM, Gottfried ON, Nimjee SM, Brown CR, Michael KW, Richardson WJ. Spinal Epidural Hematoma Following Epidural Steroid Injection in a Patient Treated with Dabigatran: A Case Report. JBJS Case Connect 2013; 3(2)(Suppl. 9).e64
[] [PMID: 29252220]
Rosencher N, Llau JV, Mueck W, Loewe A, Berkowitz SD, Homering M. Incidence of neuraxial haematoma after total hip or knee surgery: RECORD programme (rivaroxaban vs. enoxaparin). Acta Anaesthesiol Scand 2013; 57(5): 565-72.
[] [PMID: 23336294]
Llau JV, Kamphuisen P, Albaladejo P. European guidelines on perioperative venous thromboembolism prophylaxis: Chronic treatments with antiplatelet agents. Eur J Anaesthesiol 2018; 35(2): 139-41.
[PMID: 29112547]
Horlocker TT, Vandermeuelen E, Kopp SL, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: american society of regional anesthesia and pain medicine evidence-based guidelines (Fourth Edition) Reg Anesth Pain Med 2018; 43: 263-309.
Hylek EM. Therapeutic potential of oral factor Xa inhibitors. N Engl J Med 2010; 363(26): 2559-61.
[] [PMID: 21175319]
Rosencher N, Bonnet M-P, Sessler DI. Selected new antithrombotic agents and neuraxial anaesthesia for major orthopaedic surgery: management strategies. Anaesthesia 2007; 62(11): 1154-60.
[] [PMID: 17924897]
Narouze S, Benzon HT, Provenzano DA, et al. Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications: guidelines from the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain. Reg Anesth Pain Med 2015; 40(3): 182-212.
[] [PMID: 25899949]
Gogarten W, Vandermeulen E, Van Aken H, Kozek S, Llau JV, Samama CM. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol 2010; 27(12): 999-1015.
[] [PMID: 20890208]
Horlocker TT, Vandermeuelen E, Kopp SL, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American society of regional anesthesia and pain medicine evidence-based guidelines (Fourth Edition).Regional Anesthesia Pain Med. 2018; 43: pp. 263-309.
Burjorjee JE, Rooney R, Jaeger M. Epidural hematoma following cessation of a direct oral anticoagulant: A case report. Reg Anesth Pain Med 2018; 43(3): 313-6.
[] [PMID: 29369958]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 13 September, 2019
Page: [2149 - 2157]
Pages: 9
DOI: 10.2174/1381612825666190709220449
Price: $65

Article Metrics

PDF: 43
HTML: 11
PRC: 1