The New Oral Anticoagulants and Anesthesia
The oral anticoagulant therapy (OAT), used for prevention and treatment of thromboembolic disease, has been performed in clinical practice, before 2011, using dicumarolic drugs only.
The INR control into the therapeutic range with warfarin is difficult to achieve and to maintain because of the pharmacodynamic and pharmacokinetic property. The patients need frequent INR tests and change of weekly dosage. The slow onset (3–6 days to reach the therapeutic range) and long half-life promoted research for development of new agents.
The new oral anticoagulants (NOACs) came into this context with the advantages to be oral drugs and having the advantages of low-molecular-weight heparin (LMWH) which do not require routine monitoring and dose adjustment as required with warfarin or heparin.
The NOACs show a high therapeutic index, rapid onset of anticoagulant effect, low half-life, low interaction with drug or food, and fixed daily dosage.
The management of patient in NOAC therapy for surgery or anaesthesiology treatments is increasing now. Very important is the knowledge about the new oral anticoagulants for the right management of the risk of bleeding or thrombosis complications during the periods of pre-intra-post scheduled or unscheduled surgery.
The new oral anticoagulants have great advantages in spite of the effects of the sanitary costs compared to previous and conventional anticoagulant therapy.
The therapeutic indications based on randomised clinical trials were approved by the European Medicines Agency (EMA) and in Italy by the Agenzia Italiana del Farmaco (AIFA) introducing the NOA into European and Italian clinical protocols.
The NOACs compared with vitamin K antagonist (VKA) such as warfarin, acenocumarol, and heparin (LMWH and unfractionated UFH) have the same efficiency and safety for thromboprophylaxis after major orthopaedic surgery and treatment of venous thromboembolism, pulmonary embolism, and thromboembolic events in non-valvular atrial fibrillation.
The results coming from trials from 2011 to 2013, contribute to introduce the NOACs in anticoagulant therapy in Italy and Europe with EMA and AIFA approbation.
An important help to clinicians came from the guidelines giving valuation of bleeding or thrombosis risk through the scores. The surgery interventions and regional anaesthesia have the same impact on risk: the anaesthesia neuraxial invasive procedure presents bleeding risk equal to major surgery.
Another concept focused is about the peridural haematoma which presents the same risk during the procedure of positioning and during catheter removing.
With regard to anaesthesiology and surgery procedures, the problem is discontinuation of NOAC therapy: the interval safety between stop and restarting and indication for bridge therapy, but there are not absolute indications to guarantee no risk of bleeding or thrombotic complications. So every patient with low or high risk of bleeding/thrombosis must be carefully monitored in their clinical condition during pre - and post-surgery and anaesthesia periods.
KeywordsAnticoagulants New oral anticoagulants (NOACs) Regional anaesthesia Bleeding risk Thrombosis risk
- 1.Brunton LL, Chabner BA, Knollmann BC. Goodman e Gilman: the pharmacological basis of therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011.Google Scholar
- 3.De Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H, Bachmann F, Baigent C, Huber K, Jespersen J, Kristensen SD, Lip GY, Morais J, Rasmussen LH, Siegbahn A, Verheugt FW, Weitz JI, Coordinating Committee. New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC Working Group on Thrombosis ‐ Task Force on Anticoagulants in Heart Disease position paper. J Am Coll Cardiol. 2012;59:1413–25.CrossRefGoogle Scholar
- 15.AIFA-Concept Paper su Nuovi Anticoagulanti Orali. Available from http://www.agenziafarmaco.gov.it/sites/default/files/version_2012_09_24_cp_noacs_1.pdf.
- 17.Toth J, Gan G, van Ryn J, et al. Reversal of dabigatran’s anticoagulant activity in the monkey by a specific antidote and pharmacokinetic and pharmacodynamic modeling [abstract]. Blood. 2012;120(21):Abstract 22.Google Scholar
- 23.Heidbuchell H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. EHRA Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J. 2013;34:2094. https://doi.org/10.1093/eurheartj/eht134.CrossRefGoogle Scholar
- 25.Levi M, Moore T, Castillejos C, et al. Effects of three-factor and four-factor prothrombin complex concentrates on the pharmacodynamics of rivaroxaban [abstract]. J Thromb Haemost. 2013;11(Suppl 2):167.Google Scholar
- 29.Llau JV, Ferrandis R, Castillo J, et al. en representación de los participantes en el Foro de Consenso de la ESRA-España de fármacos que alteran la hemostasia. Manejo de los anticoagulantes orales de acción directa en el periodo perioperatorio y técnicas invasivas. Rev Esp Anestesiol Reanim. 2012;59:321–30.CrossRefGoogle Scholar
- 30.Falk-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic therapy and prevention of thrombosis. 9th ed American College of chest Physicians evidence based clinical practice guidelines. Chest. 2012;141(2 Suppl):2785–3255.Google Scholar
- 36.Gomez-Outez A, Terleira-Fernandez AI, Suarez-Gea ML, Vargas-Castrillon E. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons. Br Med J. 2012;344:3675.CrossRefGoogle Scholar
- 37.Membership of the Working Party, Harrop-Griffiths W, Cook T, Gill H, Hill D, Ingram M, Makris M, Malhotra S, Nicholls B, Popat M, Swales H, Wood P. Regional anaesthesia and patients with abnormalities of coagulation: The Association of Anaesthetists of Great Britain & Ireland. The Obstetric Anaesthetists Association Regional Anaesthesia UK. Anaesthesia. 2013;68:966.CrossRefGoogle Scholar
- 39.Benzon HT, Avram MJ, Green D, Bonow RO. New oral anticoagulants and regional anaesthesia. Br J Anaesth. 2003 Dec;111(Suppl 1):i96–113.Google Scholar
- 41.Douketis JD, Spyropoulos AC, Spencer FA, et al. American College of Chest Physicians. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):326–50S.CrossRefGoogle Scholar