References

Davie EW. A brief historical review of the waterfall/cascade of blood coagulation. J Biol Chem. 2003; 278:(51)50819-50832
Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971; 231:(25)232-235
Boehringer Ingelheim Limited. http://www.emc.medicines.org.uk (Accessed November/30, 2013)
SANOFI. http://www.emc.medicines.org.uk (Accessed November 30, 2013)
Scully C., 6th edn. Oxford: Elsevier; 2010
Baglin T, Barrowcliffe TW, Cohen A, Greaves M. Guidelines on the use and monitoring of heparin. Br J Haematol. 2006; 133:(1)19-34
Napenas JJ, Oost FC, DeGroot A, Loven B, Hong CH, Brennan MT Review of postoperative bleeding risk in dental patients on antiplatelet therapy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013; 115:(4)491-499
Grines CL, Bonow RO, Casey DE, Gardner TJ, Lockhart PB, Moliterno DJ Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. A Science Advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Cathet Cardiovasc Interv. 2007; 69:(3)334-340
Hennekens C, Dalen J. Aspirin in the treatment and prevention of cardiovascular disease: past and current perspectives and future directions. Am J Med. 2013; 126:(5)373-378
A randomised, blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). The Lancet. 1996; 348:(9038)1329-1339
National Institute for Health and Care Excellence (NICE). Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events: TA210 Guidance, 2012. 2013. http://publications.nice.org.uk/clopidogrel-and-modified-release-dipyridamole-for-the-prevention-of-occlusive-vascular-events-ta210 (Accessed 12/11/2013)
Lockhart PB, Gibson J, Pond SH, Leitch J. Dental management considerations for the patient with an acquired coagulopathy. Part 2: Coagulopathies from drugs. Br Dent J. 2003; 195:(9)405-501
Quader M, Stump L, Sumpio B. Low molecular weight heparins: current use and indications. J Am Coll Surg. 1998; 187:(6)641-658
Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007; 357:(20)2001-2015
Lin PJ. Reviewing the reality: why we need to change. Eur Heart J. 2005; 7:15-20
Capodanno D, Ferreiro JL, Angiolillo DJ. Antiplatelet therapy: new pharmacological agents and changing paradigms. J Thromb Haem. 2013; 11:316-329
Roe MT, Armstrong PW, Fox KA, White HD, Prabhakaran D, Goodman SG Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012; 367:(14)1297-1309
Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361:(11)1045-1057
National Institute for Health and Care Excellence (NICE). Prasugrel for the treatment of acute coronary syndromes with percutaneous coronary intervention: TA182 Guidance, 2012. 2013. http://publications.nice.org.uk/prasugrel-for-the-treatment-of-acute-coronary-syndromes-with-percutaneous-coronary-intervention-ta182 (Accessed 12/11/2013)
National Institute for Health and Care Excellence (NICE). Ticagrelor for the treatment of acute coronary syndromes: TA236 Guidance, 2011. 2013. http://publications.nice.org.uk/ticagrelor-for-the-treatment-of-acute-coronary-syndromes-ta236 (Accessed 12/11/2013)
National Institute for Health and Care Excellence (NICE). Dabigatran etexilate for the prevention of venous thromboembolism: TA157 Guidance, 2008. 2013. http://publications.nice.org.uk/dabigatran-etexilate-for-the-prevention-of-venous-thromboembolism-after-hip-or-knee-replacement-ta157 (Accessed 11/30/2013)
National Institute for Health and Care Excellence (NICE). Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: TA249 Guidance, 2012. 2013. http://publications.nice.org.uk/dabigatran-etexilate-for-the-prevention-of-stroke-and-systemic-embolism-in-atrial-fibrillation-ta249 (Accessed 11/30/2013)
National Institute for Health and Care Excellence (NICE). Rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism: TA287 Guidance, 2013. 2013. http://publications.nice.org.uk/rivaroxaban-for-treating-pulmonary-embolism-and-preventing-recurrent-venous-thromboembolism-ta287 (Accessed 12/6/2013)
National Institute for Health and Care Excellence (NICE). Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults: TA170 Guidance, 2012. 2013. http://publications.nice.org.uk/rivaroxaban-for-the-prevention-of-venous-thromboembolism-after-total-hip-or-total-knee-replacement-ta170 (Accessed 12/6/2013)
National Institute for Health and Care Excellence (NICE). Rivaroxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation: TA256 Guidance, 2012. 2013. http://publications.nice.org.uk/rivaroxaban-for-the-prevention-of-stroke-and-systemic-embolism-in-people-with-atrial-fibrillation-ta256 (Accessed 12/6/2013)
National Institute for Health and Care Excellence (NICE). Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism: TA261 Guidance, 2012. 2013. http://publications.nice.org.uk/rivaroxaban-for-the-treatment-of-deep-vein-thrombosis-and-prevention-of-recurrent-deep-vein-ta261 (Accessed 12/6/2013)
National Institute for Health and Care Excellence (NICE). Apixaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation: TA275 Guidance, 2013. 2013. http://publications.nice.org.uk/apixaban-for-preventing-stroke-and-systemic-embolism-in-people-with-nonvalvular-atrial-fibrillation-ta275 (Accessed 12/6/2013)
National Institute for Health and Care Excellence (NICE). Apixaban for the prevention of venous thromboembolism after total hip or total knee replacement: TA245 Guidance, 2012. 2013. http://publications.nice.org.uk/apixaban-for-the-prevention-of-venous-thromboembolism-after-total-hip-or-knee-replacement-in-adults-ta245 (Accessed 12/6/2013)
Kaatz S, Kouides P, Garcia D, Spyropolous A, Crowther M, Douketis J Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012; 87:(S1)S141-145
Davis C, Robertson C, Shivakumar S, Lee M. Implications of dabigatran, a direct thrombin inhibitor, for oral surgery practice. J Can Dent Assoc. 2013; 79
Firriolo FJ, Hupp WS. Beyond warfarin: the new generation of oral anticoagulants and their implications for the management of dental patients. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012; 113:(4)431-441
Wallentin L, Yusuf S, Ezekowitz M, Alings M, Flather M, Franzosi M Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. The Lancet. 2010; 376:(9745)975-983
Burness CB, McKeage K. Dabigatran etexilate: a review of its use for the prevention of venous thromboembolism after total hip or knee replacement surgery. Drugs. 2012; 72:(7)963-986
Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008; 47:(5)285-295
Sorensen SV, Peng S, Monz BU, Bradley-Kennedy C, Kansal AR. A comparative analysis of models used to evaluate the cost-effectiveness of dabigatran versus warfarin for the prevention of stroke in atrial fibrillation. Pharmacoeconomics. 2013; 31:(7)589-604
Harrington AR, Armstrong EP, Nolan PE, Malone DC. Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke. 2013; 44:(6)1676-1681
Chang AM, Ho JC, Yan BP, Yu CM, Lam YY, Lee VW. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in patients with atrial fibrillation – a real patient data analysis in a Hong Kong teaching hospital. Clin Cardiol. 2013; 36:(5)280-285
Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral thrombin. inhibitor. Circulation. 2011; 123:(13)1436-1450
Connolly S, Ezekowitz M, Yusuf S, Eikelboom J, Oldgren J, Parekh A Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009; 361:(12)1139-1151
Salazar C, Malaga G, Malasquez G. Direct thrombin inhibitors versus vitamin K antagonists or low molecular weight heparins for prevention of venous thromboembolism following total hip or knee replacement. Cochrane Database Syst Rev. 2010; 4
van Ryn J, Stangier J, Haertter S, Liesenfeld K-, Wienen W, Feuring M Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010; 103:(6)1116-1127
Thomas T, Ganetsky V, Spinler S. Rivaroxaban: an oral factor Xa inhibitor. Clin Ther. 2013; 35:(1)4-27
Mohammed I, Syed W. Oral anticoagulants to reduce the risk of stroke in atrial fibrillation: how should a clinician choose?. Clin Cardiol. 2013; 36:(11)663-670
Van de Werf F, Brueckmann M, Connolly S, Friedman J, Granger C, Härtter S A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: The Randomized, phase II study to Evaluate the sAfety and pharmacokinetics of oraL dabIGatran etexilate in patients after heart valve replacemeNt (RE-ALIGN). Am Heart J. 2012; 163:(6)931-937
Artang R, Rome E, Nielsen J, Vidaillet H. Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors. Am J Cardiol. 2013; 112:(12)1973-1979
Xarelto 10 mg film-coated tablets – Summary of Product Characteristics, 2013. 2013. http://medicines.org.uk/emc/medicine/21265/SPC/Xarelto+10+mg+film-coated+tablets/ (Accessed 12/8/2013)
Bristol-Myers Squibb-Pfizer. Eliquis 5 mg film-coated tablets – Summary of Product Characteristics (SPC) – (eMC) 2013. 2013. http://medicines.org.uk/emc/medicine/27220/SPC/Eliquis+5+mg+film-coated+tablets/ (Accessed 12/8/2013)
Becker R, Yang H, Barrett Y, Mohan P, Wang J, Wallentin L Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban – an oral, direct and selective factor Xa inhibitor. J Thromb Thrombolysis. 2011; 32:(2)183-187
Samama M, Guinet C, Flem L, Ninin E, Debue J. Measurement of dabigatran and rivaroxaban in primary prevention of venous thromboembolism in 106 patients, who have undergone major orthopedic surgery: an observational study. J Thromb Thrombolysis. 2013; 35:(2)140-146
Patel M, Mahaffey K, Garg J, Pan G, Singer D, Hacke W Rivaroxaban versus Warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011; 365:(10)883-891
Lassen M, Gallus A, Raskob G, Pineo G, Chen D, Ramirez L. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010; 363:(26)2487-2498
Lassen M, Raskob G, Gallus A, Pineo G, Chen D, Hornick P. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. The Lancet. 2010; 375:(9717)807-815
Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013; 369:(22)2093-2104
Rossini R, Capodanno D, Lettieri C, Musumeci G, Nijaradze T, Romano M Prevalence, predictors, and long-term prognosis of premature discontinuation of oral antiplatelet therapy after drug eluting stent implantation. Am J Cardiol. 2011; 107:(2)186-194
North West Medicines Information Centre. Surgical management of the primary care dental patient on antiplatelet medication, 2007. 2013. http://www.ukmi.nhs.uk/med_info/documents/Dental_Patient_on_Antiplatelet_Medication.pdf (Accessed November/30)
Madan GA, Madan SG, Madan G, Madan AD. Minor oral surgery without stopping daily low-dose aspirin therapy: a study of 51 patients. J Oral Maxillofac Surg. 2005; 63:(9)1262-1265
Dudek D, Helewski K, Wyrobiec G, Harabin-Slowinska M, Kowalczyk-Ziomek G, Zaba M Therapy with acetylsalicylic acid does not interfere with oral surgery. Cent Eur J Med. 2013; 8:(4)392-397
Cieslik-Bielewska A, Pelc R, Cieslik T. Oral surgery procedures in patients on anticoagulants. Preliminary report. Kardiol Pol. 2005; 63:(2)137-141
Dunn AS, Turpie AG. Perioperative management of patients receiving oral anticoagulants: a systematic review. Arch Intern Med. 2003; 163:(8)901-908
Seymour RA, Hawkesford JE, Sykes J, Stillings M, Hill CM. An investigation into the comparative efficacy of soluble aspirin and solid paracetamol in postoperative pain after third molar surgery. Br Dent J. 2003; 194:(3)153-157
Lillis T, Ziakas A, Koskinas K, Tsirlis A, Giannoglou G. Safety of dental extractions during uninterrupted single or dual antiplatelet treatment. Am J Cardiol. 2011; 108:(7)964-967
Scully C, Wolff A. Oral surgery in patients on anticoagulant therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont. 2002; 94:(1)57-64
Lockhart PB, Gibson J, Pond SH, Leitch J. Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease. Br Dent J. 2003; 195:(8)439-445
Wahl MJ. Dental surgery and antiplatelet agents: bleed or die. Am J Med. 2014; 127:(4)260-267
, 67th edn. : British National Formulary; 2014
Rider OJ, Rider EB. The changing face of oral anticoagulants. Br Dent J. 2013; 215:(1)17-20
Scully C. Haematology: anticoagulant treatment, 6th edn. Oxford: Elsevier; 2010
Blinder D, Manor Y, Martinowitz U, Taicher S. Dental extractions in patients maintained on continued oral anticoagulant: comparison of local hemostatic modalities. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont. 1999; 88:(2)137-140
, 67th edn. : BMJ Group and Pharmaceutical Press; 2014
North West Medicines Information Centre. Surgical management of the primary care dental patient on warfarin, 2007. http://www.ukmi.nhs.uk/med_info/documents/Dental_Patient_on_Warfarin.pdf (Accessed September/12, 2014)
Martinez-Lopez F, Onate-Sanchez R, Arrieta-Blanco J, Onate-Cabrerizo D, Cabrerizo-Merino M. Clinical diseases with thrombotic risk and their pharmacologycal treatment: how they change the therapeutic attitude in dental treatments. Med Oral Patol Oral Cir Bucal. 2013; 18:(6)e888-895
Lin L, Nizam SI, Fatahzadeh M. The impact of Prasugrel, a new anti-platelet agent, on dental care of patients. Quintessence Int. 2013; 44:(5)433-438
Eli Lilly and Company Ltd. Effient® (prasugrel) – official site – safety and side effects, 2013. 2013. http://www.effient.com/Pages/effient-side-effects.aspx (Accessed 12/11/2013)
AstraZeneca UK Limited. Safety and side effects of Brilique, 2013. 2013. http://www.brilique.com/about-brilique/safety-and-side-effects.html#question_and_answer11 (Accessed 12/11/2013)
Price M, Walder J, Baker B, Heiselman D, Jakubowski J, Logan D Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease. J Am Coll Cardiol. 2012; 59:(25)2338-2343
Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET Study. Circulation. 2009; 120:(25)2577-2585
Thiele T, Sumnig A, Hron G, Muller C, Althaus K, Schroeder HWS Platelet transfusion for reversal of dual antiplatelet therapy in patients requiring urgent surgery: a pilot study. J Thromb Haem. 2012; 10:(5)968-971
AstraZeneca UK Limited. Brilique 90 mg film coated tablets – summary of product characteristics, 2013. 2013. http://www.medicines.org.uk/emc/medicine/23935/SPC/Brilique+90+mg+film+coated+tablets/ (Accessed 12/11/2013)
Eli Lilly and Company Ltd Daiichi Sankyo UK Limited. Efient 5 mg and 10 mg film-coated tablets – summary of product characteristics, 2013. 2013. http://www.medicines.org.uk/emc/medicine/21504/SPC/Efient+5mg+&+10mg+film-coated+tablets+(Eli+Lilly+and+Company+Ltd+Daiichi+Sankyo+UK+Limited)/#CLINICAL_PRECAUTIONS (Accessed 12/11/2013)
Boehringer Ingelheim Limited. Pradaxa (dabigatran etexilate) prescriber guide for stroke prevention in atrial fibrillation, 2013. http://www.pradaxa.co.uk/downloads/spaf-prescriber-guide.pdf (Accessed November, 2013)
Romond K, Miller C, Henry R. Dental management considerations for a patient taking dabigatran etexilate: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013; 116:(3)191-195
Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S 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)343-348
Weitz JI, Quinlan DJ, Eikelboom JW. Periprocedural management and approach to bleeding in patients taking dabigatran. Circulation. 2012; 126:(20)2428-2432
Bayer Healthcare. XARELTO® (rivaroxaban): stroke risk reduction in NVAF, DVT and PE risk reduction and prophylaxis, 2013. 2013. http://www.xareltohcp.com/sites/default/ (Accessed 12/8/2013)
Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood. 2012; 120:(15)2954-2962
Little J. New oral anticoagulants: will they replace warfarin?. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012; 113:(5)575-580
: BMJ Group and Pharmaceutical Press; 2014
Schulman S, Bijsterveld NR. Anticoagulants and their reversal. Transfus Med Rev. 2007; 21:(1)37-48
Cotton B, McCarthy J, Holcomb J. Acutely injured patients on dabigatran. N Engl J Med. 2011; 365:(21)2039-2040
Food and Drug Administration (USA). FDA Drug Safety Communication: Update on the risk for serious bleeding events with the anticoagulant Pradaxa (dabigatran), 2012. 2013. http://www.fda.gov/Drugs/DrugSafety/ucm326580.htm (Accessed 12/1/2013)
Food and Drug Administration (USA). FDA Drug Safety Communication: Pradaxa (dabigatran etexilate mesylate) should not be used in patients with mechanical prosthetic heart valves, 2012. 2013. http://www.fda.gov/Drugs/DrugSafety/ucm332912.htm (Accessed 12/1/2013)
Dabigatran (Pradaxa): contraindicated in patients with prosthetic heart valve(s) requiring anti-coagulant treatment, because of the risk of thrombosis and haemorrhage. Drug Safety Update. 2013; 6:(8)

A new generation of antiplatelet and anticoagulant medication and the implications for the dental surgeon

From Volume 42, Issue 9, November 2015 | Pages 840-854

Authors

Steven Johnston

BDS, MSc, MFDS RCS(Ed)

Dental Officer, NHS Orkney

Articles by Steven Johnston

Abstract

The management of dental patients taking either antiplatelet medication, anticoagulant medication or both has been well established in the previous literature. Recently, new generations of drugs have emerged which are becoming increasingly common, including direct thrombin inhibitors, factor X inhibitors and a new class of oral thienopyridines. The implications of these drugs for the dental surgeon are not yet fully known. Awareness remains low and there is very little information available within the literature on safe use during surgery. This review paper aims to provide some guidance for dental practitioners performing invasive procedures.

CPD/Clinical Relevance: A new generation of anticoagulant and antiplatelet drugs have serious implications for patients undergoing surgery and their use is increasing.

Article

Invasive procedures in dentistry generally consist of relatively minor, non life-threatening surgery. One complication which leads to intra- and post-operative disturbance to patient care is haemorrhage. A patient's ability to achieve haemostasis can be disrupted by a wide variety of congenital or acquired disorders of blood vessels, platelet function and/or number and the coagulation system. This review will focus on the management of antiplatelet and anticoagulant drug-induced increased risk of bleeding intra- and post-operatively, briefly looking at the more commonly used drugs at present, followed by a more detailed outline of the new generation of drugs which have emerged in the last decade, exploring the implications of each for dental surgery.

The components of coagulation are present within the circulating blood and, in health, remain in an inactivated state until injury is incurred. When the endothelium of a blood vessel is breached, vasoconstriction (the vascular component of haemostasis) ensues in order to reduce blood loss and assist in platelet adhesion. This adhesion is reliant upon von Willebrand factor within the subendothelium and leads to platelet activation and changes in cell morphology. Platelet agonists, such as adenosine diphosphate (ADP) and thromboxane A2 are then released. Fibrinogen binds to receptors on the platelet membrane, cross-linking the platelets in a process called platelet aggregation, forming the primary platelet plug and thus completing primary haemostasis.1 Three common antiplatelet drugs used in the prevention of thrombo-embolic disease act by reducing platelet aggregation via different mechanisms of action:

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