British Columbia Drug and Poison Information Centre (BC DPIC)

Belief that warfarin should be discontinued before dental procedures, such as tooth extraction, existed as recently as eight years ago - despite evidence to the contrary.¹ More than half of all hematologists, oral surgeons, and maxillofacial surgeons surveyed in Ontario in 2005 routinely interrupted anticoagulation therapy for tooth extractions.² Surveys from other countries report that many dental professionals are unaware of their patients' coagulation status, and still discontinue antiplatelet therapy unnecessarily.³ However, current literature and consensus indicate that anticoagulation with warfarin can be continued with many primary care dental procedures.^4-9 There is also growing evidence that antiplatelet agents such as ASA and clopidogrel can be safely continued. Dental recommendations for the new oral anticoagulants, dabigatran and rivaroxaban, are not available, but based on a comparison of their pharmacodynamic properties and bleeding risks with warfarin or low-molecular-weight heparins, these too can likely be continued.

 

Balancing bleeding risks and thromboembolic risks

The gums and their supporting structures are highly vascular and prone to bleeding when damaged.⁶ While visible bleeding in the mouth is not considered as dangerous as "silent" bleeding that occurs internally or at non-compressible sites, oral bleeding can be distressing for the patient and potentially life threatening.⁵ However, many primary care dental procedures are unlikely to cause bleeding that cannot be managed with local measures. These include minimally invasive procedures such as periodontal probing, scaling above the gumline, polishing, and orthodontic procedures. Invasive procedures such as local infiltration, scaling below the gums, root planning, biopsies, tooth extractions, minor periodontal surgery, cavity filling, endodontic procedures (root canals), and prosthodontic procedures (crowns, bridges, and implants) are also unlikely to cause significant bleeding. Significiant bleeding is more likely to occur with more invasive procedures such as extraction of impacted teeth and use of periodontal flaps.^5,6,10,11,12 Patients with liver disease, kidney disease, hypertension, and gingival disease also have an increased risk of bleeding. The skill and experience of the dental practitioner and availability of hemostatic measures must also be considered when deciding whether to stop anticoagulants or antiplatelet agents.^7,11,13

 

One of the most frequently cited studies regarding thromboembolic risks in dentistry is Wahl's literature review in which 5/493 patients who stopped anticoagulants for a dental procedure had serious embolic complications, including 4 deaths.¹⁴ This report has been criticised because the patients had stopped anticoagulation for longer than usually recommended and the relationship to coagulation status was unclear.¹³ However, considering that recurrent venous thromboembolism is fatal in ~6% of patients and arterial thromboembolism is fatal in ~20%, many consider the risks of thromboembolism outweigh the risks from bleeding from oral procedures.¹³ Thromboembolic risks vary with the reason for anticoagulation or antiplatelet therapy. The American College of Chest Physicians has published a stratification of thromboemobolic risk.⁸ Dabigatran and rivaroxaban are not included, but risks would likely be similar to warfarin for similar indications.

 

Warfarin
Evidence that it is safe to continue warfarin with dental procedures began surfacing in the early 1980's.⁹ Numerous studies and thousands of patients later this has been confirmed, although high-quality evidence is sparse and inconclusive,⁶ and the relative utility of continuing versus interrupting warfarin continues to be debated.¹⁶

 

Nonetheless, literature and guidelines from North America, the UK, and Australia all recommend that anticoagulated patients undergoing minor invasive dental procedures continue their oral anticoagulants, provided their INR is therapeutic (2-3 for most indications; 2.5-3.5 for certain mechanical heart valves).^{4-9,12,13,17,19} Most of the studies considered here involve tooth extraction and, to a lesser degree, implants, so caution is needed when extrapolating to other dental procedures.

 

The INR should be checked 1 day prior to the procedure to ensure that the INR is within range,¹³ although some suggest 3 days prior to the procedure if the INR is stable⁷ or to allow time for corrective measures if the INR is too high.¹⁸ In various reviews, problematic bleeding not responding to local measures occurred in 0.5 to 3.5% of patients.^13,14,19 Bleeding does not correlate with an INR less than 4, and stopping warfarin does not guarantee that bleeding will not occur.¹⁷

 

Antiplatelet agents
Most of the available data on antiplatelet agents in dental procedures comes from studies of tooth extractions where ASA was being taken (2 controlled trials and one oberservational study, total exposed to ASA =89 at doses ranging from 75-325 mg/d). ASA did not significantly increase "excessive bleeding" (blood loss of > 30 to 50 mL) or in intra- and post-operative bleeding complications.^20-22 Data on clopidogrel or clopidogrel+ASA is limited. In one retrospective review of 43 patients (total of 88 invasive procedures totalling 213 tooth extractions), there was no evidence of bleeding requiring phone calls or visits to the dental clinic or emergency department. Most patients were on clopidogrel monotherapy (n=13) or dual antiplatelet therapy (n=26).²³

 

Dabigatran (Pradax^®) and rivaroxaban (Xarelto^®)
Dabigatran is a direct thrombin inhibitor approved for the prevention of VTE after hip or knee replacement and for the prevention of stroke or systemic embolism in atrial fibrillation where warfarin is inappropriate. The risk of severe bleeding was similar to those of patients using low-molecular-weight heparin (LMWH) in orthopaedic surgery, and the same as or lower than patients with atrial fibrillation well controlled on warfarin.²⁴

 

Rivaroxaban is a factor Xa inhibitor that is approved for prevention of VTE after total hip or knee replacement. It is likely to be approved for use in atrial fibrillation based on the results of the ROCKET-AF trial.²⁵ Clinical trials of orthopaedic patients report the risk of major bleeding is higher using rivaroxaban than LMWH, but not statistically higher;²⁴ data on bleeding risks in atrial fibrillation has not been published.

 

Coagulation monitoring is usually not required for rivaroxaban or dabigatran and reliable tests are not available. There are no evidence-based guidelines for the dental management of patients receiving these agents. However, because of their predictable and stable anticoagulant effects, comparable bleeding risks, and lower risk of drug interaction, dental management may be safer and easier with these drugs. However, more scientific evidence, time, and experience is needed.²⁶

 

Bridging anticoagulant therapy with low-molecular weight heparins (LMWH)
"Bridging therapy" means that short-acting anticoagulants are used to reduce the time a patient requiring anticoagulation is not anticoagulated, thus reducing their thromboembolic risk.²⁷ Bridging therapy may be appropriate for some dental patients if there are substantial bleeding risks involved. If bridging therapy is deemed necessary after a careful and detailed assessment of both the bleeding risks and thromboembolic risks, the LMWH dose should be based on the thromboembolic risk. Consider consulting an anticoagulation clinic or clinical hematologist.²⁸

 

NSAID Analgesics
The use of non-steroidal anti-inflammatory drugs (NSAIDs) with warfarin, ASA, and clopidogrel should be based on previously established advice and experience. Data on NSAID use with dabigatran and rivaroxaban is available from the orthopaedic surgery literature. For dabigatran the safety with NSAIDs appears to be similar to enoxaparin (the standard of care) with NSAIDs, and the risk of bleeding was not increased with concomitant NSAID use compared to dabigatran alone in patients undergoing major orthopaedic surgery.^30,31 The rate of major and clinically-relevant non-major bleeding among orthopaedic surgery patients in the RECORD study receiving rivaroxaban and an NSAID was slightly higher than with no NSAID use, but not statistically significantly.³¹ The UK recommends that if an NSAID is necessary, choose one with a shorter half-life and lower gastrointestinal and cardiovascular side effect profile, e.g. ibuprofen.³¹

 

Management of bleeding
Bleeding from dental procedures can usually be managed with local measures including gauze compression, absorbable sponge packing, suturing, and extemporaneously prepared tranexamic acid 4.8% mouthrinse.^19,32,33 However, suturing may cause more soft tissue damage and increase bleeding,³⁴ and some believe that when added to compression and suturing the benefits of tranexamic acid are small.¹⁷ Note that bleeding complications may be delayed 1-5 days after dental procedures.¹¹

 

Other practical advice for anticoagulated dental patients
Schedule dental procedures early in the day and early in the week to allow more time to deal with bleeding if it occurs. If anticoagulation is only temporary (e.g. VTE prophylaxis post-hip or knee replacement), consider postponing elective dental procedures until anticoagulation is no longer needed.^11,13

 

Written by Raymond Li, BSc(Pharm). Reviewed by Laird Birmingham, MD, MHSc, FRCPC.

 

References:

1. Jeske AH, Suchko GD. Lack of a scientific basis for routine discontinuation of oral anticoagulation therapy before dental treatment. J Am Dent Assoc. 2003; 134: 1492-7.
2. Lim W, Wang M, Crowther M, et al. The management of anticoagulated patients requiring dental extraction: a cross-sectional survey of oral and maxillofacial surgeons and hematologists. J Thromb Haemost. 2007;5:2157-9.
3. Murphy J, Twohig E, McWilliams SR. Dentists' approach to patients on anti-platelet agents and warfarin: a survey of practice. J Ir Dent Assoc. 2010;56:28-31.
4. Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):299S-339S.
5. Sandor G. Do patients taking oral anticoagulants need to discontinue their medication before surgical procedures? J Can Dental Assoc. 2004; 70: 482-3.
6. Nematullah A, Alabousi A, Blanas N, et al. Dental surgery for patients on anticoagulant therapy with warfarin: a systematic review and meta-analysis. J Can Dent Assoc. 2009; 75: 41a-i. (Available from URL:www.cda-adc.ca/jcda/vol-75/issue-1/41.html).
7. Perry DJ, et al. Guidelines for the management of patients on oral anticoagulants requiring dental surgery. Br Dent J. 2007; 203: 389-93.
8. Baker RI, et al. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. Med J Aust. 2004; 181: 492-7.
9. Kamien M. Remove the tooth but don't stop the warfarin. Aust Fam Phys. 2006; 35: 233-5.
10. Gupta A, et al. Bleeding disorders of importance in dental care and related patient management. Can Dent Assoc J. 2007; 73: 77-83.
11. Hermann WW, Konzelman JL Jr, Sutley SH. Current perspectives on dental patients receiving anticoaguilant therapy. J Am Dental Assoc. 1997; 128: 327-35.
12. Bacci C, Maglione M, Favero L,et al. Management of dental extraction in patients undergoing anticoagulant treatment. Results from a large, multicentre, prospective, case-control study. Thromb Haemost. 2010;104:972-5.
13. Pototski M, Amenabar JM. Dental management of patients receiving anticoagulation or antiplatelet treatment. J Oral Sci. 2007;49:253-8.
14. Wahl MJ. Myths of dental surgery in patients receiving anticoagulant therapy. J Am Dent Assoc. 2000;131:77-81.
15. Guidelines & Protocols Advisory Committee. Warfarin therapy management. October 2010. Available from URL:http://www.bcguidelines.ca/gpac/pdf/warfarin_management.pdf. Accessed 17/01/11.
16. Balevi B. Should warfarin be discontinued before a dental extraction? A decision-tree analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 110:691-7.
17. North West Medicines Information (UKMi). Surgical management of the primary care dental patient on warfarin (rev. March 2007). Available from http://www.dundee.ac.uk/tuith/Static/info/antiplatelet.pdf. Accessed 01/2011.
18. Hancocks S. Managing patient on warfarin. Br Dent J. 2007; 203: 373.
19. Rodríguez-Cabrera MA, Barona-Dorado C, Leco-Berrocal I, et al. Extractions without eliminating anticoagulant treatment: a literature review. Med Oral Patol Oral Cir Bucal. 2011. [Epub ahead of print]. Available from URL: http://www.medicinaoral.com/indexi.htm.
20. Ardekian L, Gaspar R, Peled M, et al. Does low-dose aspirin therapy complicate oral surgical procedures? J Am Dent Assoc. 2000;131:331-5.
21. Madan GA, Madan SG, Madan G, et al. Minor oral surgery without stopping daily low-dose aspirin therapy: a study of 51 patients. J Oral Maxillofac Surg. 2005; 63: 1262-5.
22. Brennan MT, et al. Aspirin use and post-operative bleeding from dental extractions. J Dent Res. 2008; 87: 740-4.
23. Napenas JJ, et al. The frequency of bleeding complications after invasive dental treatment in patients receiving single and dual antiplatelet therapy. J Am Dental Assoc. 2009; 140: 690-5.
24. Garcia D, Libby E, Crowther MA. The new oral anticoagulants. Blood. 2010; 115: 15-20.
25. Mitka M. New alternative to warfarin may help reduce stroke risk in patients with AF. JAMA. 2011; 305: 25-6.
26. Gomez-Moreno G, et al. Dabigatran and rivaroxaban, new oral anticoagulants, new approaches in dentistry. J Clin Exper Dent. 2010; 2:e1-5.
27. Douketis JD, Johnson JA, Turpie AG. Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med. 2004; 164: 1319-26.
28. Leong WA. Case studies in anticoagulation management. J Thromb Thrombolysis. 2008; 25: 78-84.
29. Eriksson BI, et al. risk of bleeding with dabigatran etexilate in patients undergoing major orthopaedic surgery is not increased by concomitant use of non-steroidal anti-inflammatory drugs or acetylsalicylic acid. [abstract PP-MO-167]. J Thrombo Haemostasis. 2009; 7(Suppl 2): 374.
30. Levy JH, Key NS, Azran MS. Novel oral anticoagulants: implications in the perioperative setting. Anesthesiology. 2010; 113: 726-45.
31. NHS Q&A 327. Is it safe to prescribe NSAIDs with dabigatran etexilate and rivaroxaban? April 2010. Available fromURL: www.nelm.nhs.uk. Accessed 01/2011.
32. Aldridge E, Cunningham LL. Current thoughts on treatment of patients receiving anticoagulation therapy. J Oral Maxillofac Surg. 2010; 68: 2879-87.
33. Patatanian E, Fugate SE. Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Ann Pharmacother. 2006;40:2205-10.
34. Al-Mubarak S, Al-Ali N, Abou-Rass M, et al. Evaluation of dental extractions, suturing and INR on postoperative bleeding of patients maintained on oral anticoagulant therapy. Br Dent J. 2007;203:E15.

 

©2011 B.C. Drug and Poison Information Centre

A version of this document was published in BCPhA's The Tablet. 2011; 19(7): 22-23.