Effect of warfarin on the risk of postoperative bleeding complications after tooth extractions: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LI Jie , WANG Zhangang ,  CHEN Gang

Stomatological Hospital of Tianjin Medical University, Tianjin, 300070, P.R.China;

Corresponding author：

CHEN Gang, Email: doctorchen@live.cn

Keywords：

Warfarin; Tooth extraction; Bleeding; Meta-analysis

DOI：

10.7507/1672-2531.201604045

Video：

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Objective To systematically review the effect of discontinuous warfarin on the risk of postoperative bleeding complications after tooth extractions. Methods PubMed, EMbase, The Cochrane Library (Issue 9, 2016), CNKI, VIP, WanFang Data, China Food and Drug Administration and the ADR supervision system of FDA were electronically searched to collect randomized controlled trials (RCTs) and cohort studies about the effect of discontinuous warfarin on risk of postoperative bleeding complications after tooth extractions in patients until September 30^th, 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. Results A total of 8 studies were included, involving 3 RCTs and 5 cohort studies. The results of meta-analysis showed that: there was no significant difference between the discontinuous or reduced warfarin group and the continuous warfarin group (RCTs: RR=0.86, 95%CI 0.49 to 1.51,P=0.60; cohort studies: RR=0.67, 95%CI 0.45 to 1.01,P=0.06). Conclusions Current evidence indicates that there is no statistically significant correlation between whether discontinuous warfarin and the risk of postoperative bleeding complications after tooth extractions. Due to the limited quantity and quality of included studies, the above conclusions are needed to be further verified by more high quality studies.

Citation： LI Jie, WANG Zhangang, CHEN Gang. Effect of warfarin on the risk of postoperative bleeding complications after tooth extractions: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(5): 573-579. doi: 10.7507/1672-2531.201604045 Copy

1.	Hirsh J, Dalen JE, Deykin D, et al. Oral anticoagulants. Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest, 1992, 102(4 Suppl): 312-326.
2.	Hirsh J, Dalen J, Anderson DR, et al. Oral anticoagulants: Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest, 2001, 119(Suppl 1): 8-21.
3.	Ziffer AM, Scopp IW, Beck J, et al. Profound bleeding after dental extractions during dicumarol therapy. N Engl J Med, 1957, 256(8): 351-353.
4.	Cannon PD, Dharmar VT. Minor oral surgical procedures in patients on oral anticoagulants-a controlled study. Aust Dent J, 2003, 48(2): 115-118.
5.	Herman WW, Konzelman JL Jr., Sutley SH. Current perspectives on dental patients receiving coumarin anticoagulant therapy. J Am Dent Assoc, 1997, 128(3): 327-335.
6.	Devani P, Lavery KM, Howell CJT. Dental extractions in patients on warfarin: Is alteration of anticoagulant regime necessary? Brit J Oral Max Surg, 1998, 36(2): 107-111.
7.	Katholi RE, Nolan SP, McGuire LB. The management of anticoagulation during noncardiac operations in patients with prosthetic heart valves. A prospective study. Am Heart J, 1978, 96(2): 163-165.
8.	Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorporated into the acc/aha 2006 guidelines 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 (writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the society of cardiovascular anesthesiologists, society for cardiovascular angiography and interventions, and society of thoracic surgeons. J Am Coll Cardiol, 2008, 52(13): 1-142.
9.	Vahanian A, Alfieri O, Andreotti F, et al. guidelines on the management of valvular heart disease (version 2012). The joint task force on the management of valvular heart disease of the european society of cardiology (esc) and the european association for cardio-thoracic surgery (eacts). G Ital Cardiol (Rome), 2013, 14(3): 167-214.
10.	Wilson SJA, Morgan J, Gray L, et al. A model for perioperative outpatient management of anticoagulation in high-risk patients: An evaluation of effectiveness and safety. Can J Hos Pharm, 2001, 54(4): 269-277.
11.	Zanon E, Martinelli F, Bacci C, et al. Safety of dental extraction among consecutive patients on oral anticoagulant treatment managed using a specific dental management protocol. Blood Coagul Fibrin, 2003, 14(1): 27-30.
12.	Bacci C, Maglione M, Favero L, et al. Management of dental extraction in patients undergoing anticoagulant treatment. Thromb Haemostasis, 2010, 104(5): 972-975.
13.	王文英, 崔念晖, 王恩博, 等. 华法林对老年人拔牙术后出血影响的临床观察. 中华口腔医学杂志, 2013, 48(7): 385-387.
14.	Broekema FI, van Minnen B, Jansma J, et al. Risk of bleeding after dentoalveolar surgery in patients taking anticoagulants. Brit J Oral Max Surg, 2014, 52(3): 15-19.
15.	Bajkin BV, Vujkov SB, Milekic BR, et al. Risk factors for bleeding after oral surgery in patients who continued using oral anticoagulant therapy. J Am Dent Assoc, 2015, 146(6): 375-381.
16.	毛琛. 华法林对老年人拔牙术后出血影响的临床观察. 医学美学美容, 中旬刊, 2015, 12(4): 27.
17.	Karsli ED, Erdogan O, Esen E, et al. Comparison of the effects of warfarin and heparin on bleeding caused by dental extraction: a clinical study. J Oral Maxil Surg, 2011, 69(10): 2500-2507.
18.	Souto JC, Oliver A, Zuazu-Jausoro I, et al. Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: A prospective randomized study. J Oral Maxil Surg, 1996, 54(1): 27-32.
19.	Cochrane handbook for systematic reviews of interventions version 5. 3. Available at: .
20.	Newcastle-ottawa quality assessment scale-cohort studies. Available at: .
21.	Borea G, Montebugnoli L, Capuzzi P, et al. Tranexamic acid as a mouthwash in anticoagulant-treated patients undergoing oral surgery. An alternative method to discontinuing anticoagulant therapy. Oral Surg Oral Med Oral Pathol, 1993, 75(1): 29-31.
22.	Evans IL, Sayers MS, Gibbons AJ, et al. Can warfarin be continued during dental extraction? Results of a randomized controlled trial. Brit J Oral Max Surg, 2002, 40(3): 248-252.
23.	Sacco R, Sacco M, Carpenedo M, et al. Oral surgery in patients on oral anticoagulant therapy: A randomized comparison of different intensity targets. Oral Surg Oral Med Oral Pathol, 2007, 104(1): 18-21.
24.	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. Brit Dent J, 2007, 203(7): 14, 410-411.
25.	Blinder D, Manor Y, Martinowitz U, et al. Dental extractions in patients maintained on oral anticoagulant therapy: Comparison of inr value with occurrence of postoperative bleeding. Int J Oral Maxillofac Surg, 2001, 30(6): 518-521.
26.	White RH, McKittrick T, Hutchinson R, et al. Temporary discontinuation of warfarin therapy: Changes in the international normalized ratio. Ann Intern Med, 1995, 122(1): 40-42.
27.	Perry DJ, Noakes TJC, Helliwell PS. Guidelines for the management of patients on oral anticoagulants requiring dental surgery. Brit Dent J, 2007, 203(7): 389-393.
28.	Wahl MJ. Myths of dental surgery in patients receiving anticoagulant therapy. J Am Dent Assoc, 2000, 131(1): 77-81.
29.	Armstrong MJ, Gronseth G, Anderson DC, et al. Summary of evidence-based guideline: Periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease report of the guideline development subcommittee of the american academy of neurology. Neurology, 2013, 80(22): 2065-2069.
30.	Powless RA, Omar HR, Mangar D, et al. Management of antithrombotic therapy before full-mouth extraction. J Am Dent Assoc, 2013, 41(6): 417-420.
31.	Scully C, Wolff A. Oral surgery in patients on anticoagulant therapy. Oral Surg Oral Med Oral Pathol, 2002, 94(1): 57-64.
32.	Czembirek C, Poeschl WP, Eder-Czembirek C, et al. Causes and timing of delayed bleeding after oral surgery. Clini Oral Invest, 2014, 18(6): 1655-1661.
33.	Sindet-Pedersen S, Ramstrom G, Bernvil S, et al. Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med, 1989, 320(13): 840-843.
34.	Ramstrom G, Sindet-Pedersen S, Hall G, et al. Prevention of postsurgical bleeding in oral surgery using tranexamic acid without dose modification of oral anticoagulants. J Oral Maxil Surg, 1993, 51(11): 1211-1216.
35.	Wood GD, Deeble T. Warfarin: Dangers with antibiotics. Dent Update, 1993, 20(8): 350, 352-353.

1. Hirsh J, Dalen JE, Deykin D, et al. Oral anticoagulants. Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest, 1992, 102(4 Suppl): 312-326.
2. Hirsh J, Dalen J, Anderson DR, et al. Oral anticoagulants: Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest, 2001, 119(Suppl 1): 8-21.
3. Ziffer AM, Scopp IW, Beck J, et al. Profound bleeding after dental extractions during dicumarol therapy. N Engl J Med, 1957, 256(8): 351-353.
4. Cannon PD, Dharmar VT. Minor oral surgical procedures in patients on oral anticoagulants-a controlled study. Aust Dent J, 2003, 48(2): 115-118.
5. Herman WW, Konzelman JL Jr., Sutley SH. Current perspectives on dental patients receiving coumarin anticoagulant therapy. J Am Dent Assoc, 1997, 128(3): 327-335.
6. Devani P, Lavery KM, Howell CJT. Dental extractions in patients on warfarin: Is alteration of anticoagulant regime necessary? Brit J Oral Max Surg, 1998, 36(2): 107-111.
7. Katholi RE, Nolan SP, McGuire LB. The management of anticoagulation during noncardiac operations in patients with prosthetic heart valves. A prospective study. Am Heart J, 1978, 96(2): 163-165.
8. Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorporated into the acc/aha 2006 guidelines 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 (writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the society of cardiovascular anesthesiologists, society for cardiovascular angiography and interventions, and society of thoracic surgeons. J Am Coll Cardiol, 2008, 52(13): 1-142.
9. Vahanian A, Alfieri O, Andreotti F, et al. guidelines on the management of valvular heart disease (version 2012). The joint task force on the management of valvular heart disease of the european society of cardiology (esc) and the european association for cardio-thoracic surgery (eacts). G Ital Cardiol (Rome), 2013, 14(3): 167-214.
10. Wilson SJA, Morgan J, Gray L, et al. A model for perioperative outpatient management of anticoagulation in high-risk patients: An evaluation of effectiveness and safety. Can J Hos Pharm, 2001, 54(4): 269-277.
11. Zanon E, Martinelli F, Bacci C, et al. Safety of dental extraction among consecutive patients on oral anticoagulant treatment managed using a specific dental management protocol. Blood Coagul Fibrin, 2003, 14(1): 27-30.
12. Bacci C, Maglione M, Favero L, et al. Management of dental extraction in patients undergoing anticoagulant treatment. Thromb Haemostasis, 2010, 104(5): 972-975.
13. 王文英, 崔念晖, 王恩博, 等. 华法林对老年人拔牙术后出血影响的临床观察. 中华口腔医学杂志, 2013, 48(7): 385-387.
14. Broekema FI, van Minnen B, Jansma J, et al. Risk of bleeding after dentoalveolar surgery in patients taking anticoagulants. Brit J Oral Max Surg, 2014, 52(3): 15-19.
15. Bajkin BV, Vujkov SB, Milekic BR, et al. Risk factors for bleeding after oral surgery in patients who continued using oral anticoagulant therapy. J Am Dent Assoc, 2015, 146(6): 375-381.
16. 毛琛. 华法林对老年人拔牙术后出血影响的临床观察. 医学美学美容, 中旬刊, 2015, 12(4): 27.
17. Karsli ED, Erdogan O, Esen E, et al. Comparison of the effects of warfarin and heparin on bleeding caused by dental extraction: a clinical study. J Oral Maxil Surg, 2011, 69(10): 2500-2507.
18. Souto JC, Oliver A, Zuazu-Jausoro I, et al. Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: A prospective randomized study. J Oral Maxil Surg, 1996, 54(1): 27-32.
19. Cochrane handbook for systematic reviews of interventions version 5. 3. Available at: .
20. Newcastle-ottawa quality assessment scale-cohort studies. Available at: .
21. Borea G, Montebugnoli L, Capuzzi P, et al. Tranexamic acid as a mouthwash in anticoagulant-treated patients undergoing oral surgery. An alternative method to discontinuing anticoagulant therapy. Oral Surg Oral Med Oral Pathol, 1993, 75(1): 29-31.
22. Evans IL, Sayers MS, Gibbons AJ, et al. Can warfarin be continued during dental extraction? Results of a randomized controlled trial. Brit J Oral Max Surg, 2002, 40(3): 248-252.
23. Sacco R, Sacco M, Carpenedo M, et al. Oral surgery in patients on oral anticoagulant therapy: A randomized comparison of different intensity targets. Oral Surg Oral Med Oral Pathol, 2007, 104(1): 18-21.
24. 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. Brit Dent J, 2007, 203(7): 14, 410-411.
25. Blinder D, Manor Y, Martinowitz U, et al. Dental extractions in patients maintained on oral anticoagulant therapy: Comparison of inr value with occurrence of postoperative bleeding. Int J Oral Maxillofac Surg, 2001, 30(6): 518-521.
26. White RH, McKittrick T, Hutchinson R, et al. Temporary discontinuation of warfarin therapy: Changes in the international normalized ratio. Ann Intern Med, 1995, 122(1): 40-42.
27. Perry DJ, Noakes TJC, Helliwell PS. Guidelines for the management of patients on oral anticoagulants requiring dental surgery. Brit Dent J, 2007, 203(7): 389-393.
28. Wahl MJ. Myths of dental surgery in patients receiving anticoagulant therapy. J Am Dent Assoc, 2000, 131(1): 77-81.
29. Armstrong MJ, Gronseth G, Anderson DC, et al. Summary of evidence-based guideline: Periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease report of the guideline development subcommittee of the american academy of neurology. Neurology, 2013, 80(22): 2065-2069.
30. Powless RA, Omar HR, Mangar D, et al. Management of antithrombotic therapy before full-mouth extraction. J Am Dent Assoc, 2013, 41(6): 417-420.
31. Scully C, Wolff A. Oral surgery in patients on anticoagulant therapy. Oral Surg Oral Med Oral Pathol, 2002, 94(1): 57-64.
32. Czembirek C, Poeschl WP, Eder-Czembirek C, et al. Causes and timing of delayed bleeding after oral surgery. Clini Oral Invest, 2014, 18(6): 1655-1661.
33. Sindet-Pedersen S, Ramstrom G, Bernvil S, et al. Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med, 1989, 320(13): 840-843.
34. Ramstrom G, Sindet-Pedersen S, Hall G, et al. Prevention of postsurgical bleeding in oral surgery using tranexamic acid without dose modification of oral anticoagulants. J Oral Maxil Surg, 1993, 51(11): 1211-1216.
35. Wood GD, Deeble T. Warfarin: Dangers with antibiotics. Dent Update, 1993, 20(8): 350, 352-353.

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