YBJOM-4351; No. of Pages 5
ARTICLE IN PRESS Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment Branislav V. Bajkin a,∗ , Ivana M. Urosevic b , Karmen M. Stankov b , Bojan B. Petrovic a , Ivana A. Bajkin b a b
Dental Clinic of Vojvodina, Faculty of Medicine Novi Sad, University of Novi Sad, Hajduk Veljkova 12, 21000 Novi Sad, Serbia Clinical Center of Vojvodina, Faculty of Medicine Novi Sad, University of Novi Sad, Hajduk Veljkova 1, 21000 Novi Sad, Serbia
Accepted 11 September 2014
Abstract Our aim was to evaluate the effects of single and dual antiplatelet treatment on postoperative bleeding in patients having dental extractions. The prospective clinical study included 160 patients who were taking antiplatelet drugs. The first group (n = 43) were taking 2 drugs, mostly aspirin and clopidogrel, and the second group (n = 117) were taking a single antiplatelet drug in the form of aspirin (n = 84), clopidogrel (n = 20), and ticlopidine (n = 13). All patients had simple dental extractions, and local haemostasis was with resorbable collagen sponges, without suturing of the wound. The control group comprised 105 healthy subjects with a similar number of dental extractions. Bleeding was an “event” if it continued for more than 12 h, made the patient call or return to the dental practice or emergency department, induced a large haematoma or ecchymosis within the oral soft tissues, or required blood transfusion. A total of 110 teeth were extracted on 59 occasions in the dual drug group, and 232 teeth on 128 occasions in the single drug group. Bleeding was recorded after extraction in only one patient on dual aspirin–clopidogrel treatment, which was mild and easily controlled by local haemostasis. The incidence of postoperative bleeding did not differ significantly among the three groups (χ2 = 4.3, p = 0.11). However, the wound was sutured to achieve effective initial local haemostasis in 4/59 (6.8%) and 2/128 (1.6%) occasions of tooth extractions in the dual and single drug groups, respectively, and none in the control group (χ2 = 10.02, p = 0.007). Patients taking single or dual antiplatelet drugs may have teeth extracted safely without interruption of treatment using only local haemostatic measures. © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Aspirin; Thienopyridines; Antiplatelet therapy; Bleeding; Oral surgery; Tooth extraction
Introduction Antiplatelet agents are widely used in the prevention and management of arterial thrombosis, and the common indications for their long-term use are ischaemic heart disease, previous myocardial infarction, coronary artery bypass and placement of a stent, non-haemorrhagic stroke, transient ischaemic attacks, and peripheral arterial disease. ∗
Corresponding author. Tel.: +381 62770665; fax: +381 21526120. E-mail address: [email protected] (B.V. Bajkin).
Low doses of aspirin, clopidogrel, ticlopidine, and dipyridamole are the most common antiplatelet drugs, and they inhibit platelet function by different mechanisms. Aspirin irreversibly inactivates the enzyme cyclo-oxygenase and thereby prevents synthesis of thromboxane A2 , which has an important role in platelet aggregation. Aspirin affects the activity of platelets during their lifetime (7–10 days). Clopidogrel, ticlopidine, and prasugrel (thienopyridines) inhibit adenosine-diphosphate receptors and are also effective during the lifetime of a platelet. Dipyridamole inhibits the reuptake of adenosine and increases cAMP.1
http://dx.doi.org/10.1016/j.bjoms.2014.09.009 0266-4356/© 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Bajkin BV, et al. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.009
YBJOM-4351; No. of Pages 5
2
ARTICLE IN PRESS B.V. Bajkin et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
These drugs are sometimes combined, because they work in different ways. The combination of low-dose aspirin and clopidogrel is mainly used to prevent thrombotic complications after percutaneous insertion of a coronary stent.2,3 Despite the benefits of antiplatelet drugs they are not without risk in that they can increase the risk of bleeding, particularly gastrointestinal bleeding, haemorrhagic stroke, and postoperative bleeding. In patients who take combinations of antiplatelet drugs, the risk is higher because of their synergistic effect.2 Because of the fear of excessive bleeding, physicians often recommend discontinuation of antiplatelet drugs several days before oral operations,4,5 but this can expose patients to the risk of thromboembolism.6–9 Several studies have shown that there is no need to discontinue aspirin before dentoalveolar surgery.10–17 Nevertheless, there is a lack of published evidence about perioperative dental management of the patients on dual and non-aspirin antiplatelet drugs.4,5,13,18 Our aim was to evaluate the effect of single and dual antiplatelet drugs on postoperative bleeding in patients who had teeth extracted.
Patients and methods The prospective clinical study took place from September 2010 to December 2013. All patients provided written informed consent, and the study was approved by the local Ethics Committee. The dual group comprised 43 patients who were taking two antiplatelet drugs (asprin + clopidogrel, aspirin + ticlopidine and aspirin + prasugrel) and the single group 117 who were taking aspirin, clopidogrel, or ticlopidine alone. All participants were told to continue to take their antiplatelet drugs regularly. The control group comprised 105 healthy patients who were not taking any drugs. All patients required a simple extraction of one or more teeth under local anaesthesia with no need for a mucoperiosteal flap. Patients with liver disease, alcoholism, those taking anticoagulant therapy or non-steroidal antiinflammatory drugs that could interact with aspirin, those who had had a serious haemorrhage after dental extractions before starting the antiplatelet drugs, those who discontinued their drugs for whatever reason, and minors, were excluded from the study. All dental extractions were done in the outpatient clinic by one surgeon with minimal trauma. The local anaesthesia was achieved using 2% lignocaine with 1/80 000 adrenaline. The same local haemostatic measures were used for all patients. Extraction sockets were packed with a collagen sponge without primary suture of the wound. Afterwards patients were asked to hold the sterile gauze in a firm bite for 30 min. The patients were then observed for 2 h. If there was any bleeding after extraction a gauze pressure pad was applied to the wound for 10 min. This was repeated, if needed, twice, after
Table 1 Indications for antiplatelet medication. Indication
Dual antiplatelet treatment (n = 43)
Single antiplatelet treatment (n = 117)
Coronary artery stents After myocardial infarction After coronary artery bypass Angina pectoris Ischaemic heart disease and thrombophlebitis Ischaemic heart disease and cerebrovascular disease Ischaemic cerebrovascular disease After peripheral vascular surgery Thrombophlebitis Valvar heart disease Thrombophilia Primary prevention
28 7 3 3 1
14 21 25 30 0
1
5
0 0 0 0 0 0
10 4 4 1 1 2
which the wound was sutured with a non-resorbable 3/0 black silk suture. All patients were given a list of postoperative instructions and the telephone number of a surgeon who could be contacted in case of postoperative bleeding. Paracetamol was recommended for relief of pain. All participants were examined after 30 min and 2 h, and then on the first, second, and fifth days later. Patients who were unable to come for a regular check-up were contacted by telephone to find out if they had had any bleeding. They were also instructed to call the surgeon if any bleeding occurred. Any sutures were removed on the fifth day. Bleeding was identified as an “event” using criteria recommended by Lockhart et al.19 if it continued for more than 12 h; was enough to make the patient call or return to the dental practice or emergency department; resulted in the development of a large haematoma or ecchymosis within the oral soft tissues; or required a blood transfusion. We recorded all the cases where the wound required a suture for successful local haemostasis before discharge (two hours after the procedure), but we did not consider it a bleeding event. We used the χ2 test to evaluate the significance of differences in postoperative bleeding between the groups. The significance of differences between parametric variables was assessed using the analysis of variance. Probabilities of less than 0.05 were accepted as significant.
Results We initially studied 192 patients who were taking antiplatelet drugs. Nineteen patients who discontinued their antiplatelet dugs several days previously, for whatever reason, were excluded from the study. Thirteen patients who required a more complex extraction were also excluded. A total of 160 patients therefore met the study inclusion criteria 43 in the dual group and 117 in the single group. The indications for treatment are shown in Table 1. The control group consisted of 105 healthy subjects.
Please cite this article in press as: Bajkin BV, et al. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.009
ARTICLE IN PRESS
YBJOM-4351; No. of Pages 5
B.V. Bajkin et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
3
Table 2 Characteristics of the three groups of patients. Data are number (%) of patients unless otherwise stated. Variable Sex Male Female Mean (SD) age (years) Treatment Aspirin + clopidogrel Aspirin + ticlopidine Aspirin + prasugrel Aspirin Clopidogrel Ticlopidine No. of extractions (occasions) No. of teeth extracted Total Mean (SD) (/occasion) Range Single/multiple extractions Reasons for extraction Periodontal disease Deep caries Suturing for local haemostasis No. with postoperative bleeding
Dual aniplatelet treatment (n = 43)
Single antiplatelet treatment (n = 117)
Controls (n = 105)
32 11 61.1 (10.2)
66 51 63.4 (10.8)
61 44 61.2 (11.3)
39 2 2 – – – 59
– – – 84 20 13 128
127
110 1.9 (0.8) 1–4 23/36
232 1.8 (1) 1–5 62/66
246 1.9 (0.9) 1–5 49/78
53 57 4 (6.8%) 1 (1.7%)
108 124 2 (1.6%) None
113 13 None None
There were no significant differences among the three groups in sex (p = 0.13) or age (p = 0.26). Aspirin was the most commonly prescribed antiplatelet agent in both groups; all these patients took a dose of 100 mg, except 1 in the dual group and 2 in the single group who took 300 mg. Details are shown in Table 2. One patient in the dual group (aspirin–clopidogrel) developed postoperative bleeding (Table 2). This patient returned to the clinic the same day with prolonged bleeding after the extraction of 3 upper molars. The bleeding was easily controlled by suturing and compression of the wound. None of the patients in the single group developed postoperative bleeding, but one (taking aspirin) developed a minor haematoma on the cheek the day after extraction of two upper molars and suturing of the wound, which absorbed spontaneously within a few days. There was no significant difference in the incidence of postoperative bleeding among the 3 groups (χ2 = 4.34, p = 0.11). However, the wound required suturing to achieve effective initial haemostasis in 4/59 (6.8%) occasions of tooth extractions in the dual group, in 2/128 (1.6%) occasions in the single group, and in none of the control patients (χ2 = 10.02, p = 0.007).
Discussion Antiplatelet agents are widely used for the prevention and treatment of various ischaemic cardiovascular and cerebrovascular conditions. The Antithrombotic Trialists’ Collaboration confirmed in a meta-analysis that antiplatelet drugs had a protective effect in acute myocardial infarction or ischaemic stroke, both stable and unstable angina, previous
myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, and atrial fibrillation.20,21 Those studies confirmed that antiplatelet agents had a substantial benefit in the secondary prevention of occlusive vascular events, but for primary prevention their use should be weighed against the increased risk of bleeding.21 Each antiplatelet agent has its own mechanism of action that affects platelet aggregation differently. Because of these different mechanisms and their synergistic effects, combinations of two antiplatelet drugs are possible and are sometimes used. For example, clopidogrel together with lowdose aspirin is recommended in patients with stents,2,3 and this combination is increasingly used.1 The perioperative management of patients taking antiplatelet drugs includes balancing the risk of bleeding if they are continued, and the risk of thromboembolism if they are not.6–9 The risk of thrombosis of a stent after premature discontinuation of dual antiplatelet treatment is well recognised,3 and is the main cause of late thrombosis with serious consequences: reported mortality from presumed or documented thrombosis ranges from 20% to 45%.3 The American College of Chest Physicians recommends continuing the antiplatelet drugs perioperatively in patients who require operation within 6 weeks of placement of a metal stent or within 6 months of placement of a drug-eluting stent.22 Several recently published studies have reported that minor oral procedures can be safely (without a risk of bleeding) done in patients taking low doses of aspirin.10–16 Recommendations based on these results advocate continuation of the low-dose aspirin during dental extractions.3,22–25 However, the number of patients included in these studies was small, and the authors therefore suggested that further
Please cite this article in press as: Bajkin BV, et al. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.009
YBJOM-4351; No. of Pages 5
4
ARTICLE IN PRESS B.V. Bajkin et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
research is necessary. There has also been insufficient evidence so far about the risk of bleeding during oral procedures in patients taking thienopyridine alone or together with aspirin.1,3–5,22,25 Another recent study stated that there was no need to discontinue either the anticoagulant or aspirin in the patients taking the combined oral anticoagulant-aspirin regimen who required dental extraction.10 Several recent studies have also included patients on dual antiplatelet treatment who required oral surgery. The authors of these studies concluded that the continuation of dual antiplatelet drugs is relatively safe, but emphasised the need of further research because sample sizes were small.5,12,18 We recorded only 1/43 patients (59 occasions of tooth extractions) who developed mild postoperative bleeding) when taking dual antiplatelet drugs after extractions of 3 upper molars. None of the 117 patients (128 occasions of tooth extractions) in the single drug group (including 20 patients taking clopidogrel and 13 taking ticlopidine), developed a postoperative haemorrhage. However, suturing of the wound to achieve effective initial local haemostasis was needed in 4 and 2 patients taking dual and single antiplatelet drugs, respectively, but not in healthy subjects. We did not measure bleeding time in any of our patients. Those taking antiplatelet drugs may have prolonged bleeding time, but the test is not reliable enough to predict the risk of bleeding after dental surgery.1,25 Indeed, some recent reports about dental extractions in patients taking antiplatelet drugs have reported that the bleeding time was almost always within the normal range.14,16 The platelet aggregation test is more sensitive, but it is not in use in everyday practice.25 We know of only one small sample study in which the platelet aggregation test was used before dental extractions,13 and this suggests that this and other platelet function tests may be important for further research. The point of discussion can also be the definition of a bleeding event. There is no standard approach to defining bleeding after oral surgical procedures in patients taking antithrombotic drugs. Different authors have used different criteria for bleeding, making the results of these studies hard to compare. In our study, we used the criteria given by Lockhart et al.19 which are in our opinion good for defining a clinically important bleed.10 This study has some potential limitations—first, its relatively small sample size, and second that we studied only procedures with a low risk of bleeding (simple single and multiple extractions). It is also worth noting that an appreciable number of patients – 19 of 192 (10%) – who were not included in the study discontinued their antiplatelet drugs, usually aspirin, several days before the procedure for whatever reason. It seems that it takes time to educate our patients that teeth may be extracted safely without the discontinuation of antiplatelet drugs. An interdisciplinary discussion of this topic would be exceptionally useful.
Conflict of interest statement There is no conflict of interest.
Ethical approval/confirmation of patients’ permission The study was approved by the local Ethics Committee. All patients provided written informed consent to take part in the study.
References 1. North West Medicines Information Centre. Surgical management of the primary care dental patient on antiplatelet medication. North West Medicines Information Centre; 2010. Available at: http://ukmi.nhs.uk/activities/specialistServices/ (accessed 10 September 2014). 2. Eikelboom JW, Hirsh J, Spencer FA, Baglin TP, Weitz JI. Antiplatelet drugs: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 suppl.):e89S–119S. 3. Grines CL, Bonow RO, Casey Jr DE, et al. 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. Circulation 2007;115:813–8. 4. Nape˜nas JJ, Oost FC, DeGroot A, et al. Review of postoperative bleeding risk in dental patients on antiplatelet therapy. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:491–9. 5. Park MW, Her SH, Kwon JB, et al. Safety of dental extractions in coronary drug-eluting stenting patients without stopping multiple antiplatelet agents. Clin Cardiol 2012;35:225–30. 6. Biondi-Zoccai GG, Lotrionte M, Agostoni P, et al. A systematic review and metaanalysis on the hazards of discontinuing or not adhering to aspirin among 50 279 patients at risk for coronary artery disease. Eur Heart J 2006;27:2667–74. 7. Burger W, Chemnitius JM, Kneissl GD, Rücker G. Low-dose aspirin for secondary cardiovascular prevention – cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation – review and meta-analysis. J Intern Med 2005;257:399–414. 8. Maulaz AB, Bezerra DC, Michel P, Bogousslavsky J. Effect of discontinuing aspirin therapy on the risk of brain ischaemic stroke. Arch Neurol 2005;62:1217–20. 9. Ferrari E, Benhamou M, Cerboni P, Marcel B. Coronary syndromes following aspirin withdrawal: a special risk for late stent thrombosis. J Am Coll Cardiol 2005;45:456–9. 10. Bajkin BV, Bajkin IA, Petrovic BB. The effects of combined oral anticoagulant-aspirin therapy in patients undergoing tooth extractions: a prospective study. J Am Dent Assoc 2012;143:771–6. 11. Morimoto Y, Niwa H, Minematsu K. Risk factors affecting postoperative hemorrhage after tooth extraction in patients receiving oral antithrombotic therapy. J Oral Maxillofac Surg 2011;69:1550–6. 12. Nape˜nas JJ, Hong CHL, Brennan MT, Furney SL, Fox PC, Lockhart PB. The frequency of bleeding complications after invasive dental treatment in patients receiving single and dual antiplatelet therapy. J Am Dent Assoc 2009;140:690–5. 13. Brennan MT, Valerin MA, Noll JL, et al. Aspirin use and post-operative bleeding from dental extractions. J Dent Res 2008;87:740–4. 14. Krishnan B, Shenoy NA, Alexander M. Exodontia and antiplatelet therapy. J Oral Maxillofac Surg 2008;66:2063–6.
Please cite this article in press as: Bajkin BV, et al. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.009
YBJOM-4351; No. of Pages 5
ARTICLE IN PRESS B.V. Bajkin et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
15. Partridge CG, Campbell JH, Alvarado F. The effect of platelet-altering medications on bleeding from minor oral surgery procedures. J Oral Maxillofac Surg 2008;66:93–7. 16. 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;63:1262–5. 17. Brennan MT, Shariff G, Kent ML, Fox PC, Lockhart PB. Relationship between bleeding time test and postextraction bleeding in a healthy control population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:439–43. 18. 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;108:964–7. 19. 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;195:439–45. 20. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71–86.
5
21. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative metaanalysis of individual participant data from randomised trials. Lancet 2009;373:1849–60. 22. Douketis JD, Spyropoulos AC, Spencer FA, et al. 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):e326S–50S. 23. Aframian DJ, Lalla RV, Peterson DE. Management of dental patients taking common hemostasis-altering medications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103(Suppl: S45):e1–11. 24. Van Diermen DE, van der Waal I, Hoogstraten J. Management recommendations for invasive dental treatment in patients using oral antithrombotic medication, including novel oral anticoagulants. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2013;116:709–16. 25. Brennan MT, Wynn RL, Miller CS. Aspirin and bleeding in dentistry: an update and recommendations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:316–23.
Please cite this article in press as: Bajkin BV, et al. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.009
ARTICLE IN PRESS Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment Branislav V. Bajkin a,∗ , Ivana M. Urosevic b , Karmen M. Stankov b , Bojan B. Petrovic a , Ivana A. Bajkin b a b
Dental Clinic of Vojvodina, Faculty of Medicine Novi Sad, University of Novi Sad, Hajduk Veljkova 12, 21000 Novi Sad, Serbia Clinical Center of Vojvodina, Faculty of Medicine Novi Sad, University of Novi Sad, Hajduk Veljkova 1, 21000 Novi Sad, Serbia
Accepted 11 September 2014
Abstract Our aim was to evaluate the effects of single and dual antiplatelet treatment on postoperative bleeding in patients having dental extractions. The prospective clinical study included 160 patients who were taking antiplatelet drugs. The first group (n = 43) were taking 2 drugs, mostly aspirin and clopidogrel, and the second group (n = 117) were taking a single antiplatelet drug in the form of aspirin (n = 84), clopidogrel (n = 20), and ticlopidine (n = 13). All patients had simple dental extractions, and local haemostasis was with resorbable collagen sponges, without suturing of the wound. The control group comprised 105 healthy subjects with a similar number of dental extractions. Bleeding was an “event” if it continued for more than 12 h, made the patient call or return to the dental practice or emergency department, induced a large haematoma or ecchymosis within the oral soft tissues, or required blood transfusion. A total of 110 teeth were extracted on 59 occasions in the dual drug group, and 232 teeth on 128 occasions in the single drug group. Bleeding was recorded after extraction in only one patient on dual aspirin–clopidogrel treatment, which was mild and easily controlled by local haemostasis. The incidence of postoperative bleeding did not differ significantly among the three groups (χ2 = 4.3, p = 0.11). However, the wound was sutured to achieve effective initial local haemostasis in 4/59 (6.8%) and 2/128 (1.6%) occasions of tooth extractions in the dual and single drug groups, respectively, and none in the control group (χ2 = 10.02, p = 0.007). Patients taking single or dual antiplatelet drugs may have teeth extracted safely without interruption of treatment using only local haemostatic measures. © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Aspirin; Thienopyridines; Antiplatelet therapy; Bleeding; Oral surgery; Tooth extraction
Introduction Antiplatelet agents are widely used in the prevention and management of arterial thrombosis, and the common indications for their long-term use are ischaemic heart disease, previous myocardial infarction, coronary artery bypass and placement of a stent, non-haemorrhagic stroke, transient ischaemic attacks, and peripheral arterial disease. ∗
Corresponding author. Tel.: +381 62770665; fax: +381 21526120. E-mail address: [email protected] (B.V. Bajkin).
Low doses of aspirin, clopidogrel, ticlopidine, and dipyridamole are the most common antiplatelet drugs, and they inhibit platelet function by different mechanisms. Aspirin irreversibly inactivates the enzyme cyclo-oxygenase and thereby prevents synthesis of thromboxane A2 , which has an important role in platelet aggregation. Aspirin affects the activity of platelets during their lifetime (7–10 days). Clopidogrel, ticlopidine, and prasugrel (thienopyridines) inhibit adenosine-diphosphate receptors and are also effective during the lifetime of a platelet. Dipyridamole inhibits the reuptake of adenosine and increases cAMP.1
http://dx.doi.org/10.1016/j.bjoms.2014.09.009 0266-4356/© 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Bajkin BV, et al. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.009
YBJOM-4351; No. of Pages 5
2
ARTICLE IN PRESS B.V. Bajkin et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
These drugs are sometimes combined, because they work in different ways. The combination of low-dose aspirin and clopidogrel is mainly used to prevent thrombotic complications after percutaneous insertion of a coronary stent.2,3 Despite the benefits of antiplatelet drugs they are not without risk in that they can increase the risk of bleeding, particularly gastrointestinal bleeding, haemorrhagic stroke, and postoperative bleeding. In patients who take combinations of antiplatelet drugs, the risk is higher because of their synergistic effect.2 Because of the fear of excessive bleeding, physicians often recommend discontinuation of antiplatelet drugs several days before oral operations,4,5 but this can expose patients to the risk of thromboembolism.6–9 Several studies have shown that there is no need to discontinue aspirin before dentoalveolar surgery.10–17 Nevertheless, there is a lack of published evidence about perioperative dental management of the patients on dual and non-aspirin antiplatelet drugs.4,5,13,18 Our aim was to evaluate the effect of single and dual antiplatelet drugs on postoperative bleeding in patients who had teeth extracted.
Patients and methods The prospective clinical study took place from September 2010 to December 2013. All patients provided written informed consent, and the study was approved by the local Ethics Committee. The dual group comprised 43 patients who were taking two antiplatelet drugs (asprin + clopidogrel, aspirin + ticlopidine and aspirin + prasugrel) and the single group 117 who were taking aspirin, clopidogrel, or ticlopidine alone. All participants were told to continue to take their antiplatelet drugs regularly. The control group comprised 105 healthy patients who were not taking any drugs. All patients required a simple extraction of one or more teeth under local anaesthesia with no need for a mucoperiosteal flap. Patients with liver disease, alcoholism, those taking anticoagulant therapy or non-steroidal antiinflammatory drugs that could interact with aspirin, those who had had a serious haemorrhage after dental extractions before starting the antiplatelet drugs, those who discontinued their drugs for whatever reason, and minors, were excluded from the study. All dental extractions were done in the outpatient clinic by one surgeon with minimal trauma. The local anaesthesia was achieved using 2% lignocaine with 1/80 000 adrenaline. The same local haemostatic measures were used for all patients. Extraction sockets were packed with a collagen sponge without primary suture of the wound. Afterwards patients were asked to hold the sterile gauze in a firm bite for 30 min. The patients were then observed for 2 h. If there was any bleeding after extraction a gauze pressure pad was applied to the wound for 10 min. This was repeated, if needed, twice, after
Table 1 Indications for antiplatelet medication. Indication
Dual antiplatelet treatment (n = 43)
Single antiplatelet treatment (n = 117)
Coronary artery stents After myocardial infarction After coronary artery bypass Angina pectoris Ischaemic heart disease and thrombophlebitis Ischaemic heart disease and cerebrovascular disease Ischaemic cerebrovascular disease After peripheral vascular surgery Thrombophlebitis Valvar heart disease Thrombophilia Primary prevention
28 7 3 3 1
14 21 25 30 0
1
5
0 0 0 0 0 0
10 4 4 1 1 2
which the wound was sutured with a non-resorbable 3/0 black silk suture. All patients were given a list of postoperative instructions and the telephone number of a surgeon who could be contacted in case of postoperative bleeding. Paracetamol was recommended for relief of pain. All participants were examined after 30 min and 2 h, and then on the first, second, and fifth days later. Patients who were unable to come for a regular check-up were contacted by telephone to find out if they had had any bleeding. They were also instructed to call the surgeon if any bleeding occurred. Any sutures were removed on the fifth day. Bleeding was identified as an “event” using criteria recommended by Lockhart et al.19 if it continued for more than 12 h; was enough to make the patient call or return to the dental practice or emergency department; resulted in the development of a large haematoma or ecchymosis within the oral soft tissues; or required a blood transfusion. We recorded all the cases where the wound required a suture for successful local haemostasis before discharge (two hours after the procedure), but we did not consider it a bleeding event. We used the χ2 test to evaluate the significance of differences in postoperative bleeding between the groups. The significance of differences between parametric variables was assessed using the analysis of variance. Probabilities of less than 0.05 were accepted as significant.
Results We initially studied 192 patients who were taking antiplatelet drugs. Nineteen patients who discontinued their antiplatelet dugs several days previously, for whatever reason, were excluded from the study. Thirteen patients who required a more complex extraction were also excluded. A total of 160 patients therefore met the study inclusion criteria 43 in the dual group and 117 in the single group. The indications for treatment are shown in Table 1. The control group consisted of 105 healthy subjects.
Please cite this article in press as: Bajkin BV, et al. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.009
ARTICLE IN PRESS
YBJOM-4351; No. of Pages 5
B.V. Bajkin et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
3
Table 2 Characteristics of the three groups of patients. Data are number (%) of patients unless otherwise stated. Variable Sex Male Female Mean (SD) age (years) Treatment Aspirin + clopidogrel Aspirin + ticlopidine Aspirin + prasugrel Aspirin Clopidogrel Ticlopidine No. of extractions (occasions) No. of teeth extracted Total Mean (SD) (/occasion) Range Single/multiple extractions Reasons for extraction Periodontal disease Deep caries Suturing for local haemostasis No. with postoperative bleeding
Dual aniplatelet treatment (n = 43)
Single antiplatelet treatment (n = 117)
Controls (n = 105)
32 11 61.1 (10.2)
66 51 63.4 (10.8)
61 44 61.2 (11.3)
39 2 2 – – – 59
– – – 84 20 13 128
127
110 1.9 (0.8) 1–4 23/36
232 1.8 (1) 1–5 62/66
246 1.9 (0.9) 1–5 49/78
53 57 4 (6.8%) 1 (1.7%)
108 124 2 (1.6%) None
113 13 None None
There were no significant differences among the three groups in sex (p = 0.13) or age (p = 0.26). Aspirin was the most commonly prescribed antiplatelet agent in both groups; all these patients took a dose of 100 mg, except 1 in the dual group and 2 in the single group who took 300 mg. Details are shown in Table 2. One patient in the dual group (aspirin–clopidogrel) developed postoperative bleeding (Table 2). This patient returned to the clinic the same day with prolonged bleeding after the extraction of 3 upper molars. The bleeding was easily controlled by suturing and compression of the wound. None of the patients in the single group developed postoperative bleeding, but one (taking aspirin) developed a minor haematoma on the cheek the day after extraction of two upper molars and suturing of the wound, which absorbed spontaneously within a few days. There was no significant difference in the incidence of postoperative bleeding among the 3 groups (χ2 = 4.34, p = 0.11). However, the wound required suturing to achieve effective initial haemostasis in 4/59 (6.8%) occasions of tooth extractions in the dual group, in 2/128 (1.6%) occasions in the single group, and in none of the control patients (χ2 = 10.02, p = 0.007).
Discussion Antiplatelet agents are widely used for the prevention and treatment of various ischaemic cardiovascular and cerebrovascular conditions. The Antithrombotic Trialists’ Collaboration confirmed in a meta-analysis that antiplatelet drugs had a protective effect in acute myocardial infarction or ischaemic stroke, both stable and unstable angina, previous
myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, and atrial fibrillation.20,21 Those studies confirmed that antiplatelet agents had a substantial benefit in the secondary prevention of occlusive vascular events, but for primary prevention their use should be weighed against the increased risk of bleeding.21 Each antiplatelet agent has its own mechanism of action that affects platelet aggregation differently. Because of these different mechanisms and their synergistic effects, combinations of two antiplatelet drugs are possible and are sometimes used. For example, clopidogrel together with lowdose aspirin is recommended in patients with stents,2,3 and this combination is increasingly used.1 The perioperative management of patients taking antiplatelet drugs includes balancing the risk of bleeding if they are continued, and the risk of thromboembolism if they are not.6–9 The risk of thrombosis of a stent after premature discontinuation of dual antiplatelet treatment is well recognised,3 and is the main cause of late thrombosis with serious consequences: reported mortality from presumed or documented thrombosis ranges from 20% to 45%.3 The American College of Chest Physicians recommends continuing the antiplatelet drugs perioperatively in patients who require operation within 6 weeks of placement of a metal stent or within 6 months of placement of a drug-eluting stent.22 Several recently published studies have reported that minor oral procedures can be safely (without a risk of bleeding) done in patients taking low doses of aspirin.10–16 Recommendations based on these results advocate continuation of the low-dose aspirin during dental extractions.3,22–25 However, the number of patients included in these studies was small, and the authors therefore suggested that further
Please cite this article in press as: Bajkin BV, et al. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.009
YBJOM-4351; No. of Pages 5
4
ARTICLE IN PRESS B.V. Bajkin et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
research is necessary. There has also been insufficient evidence so far about the risk of bleeding during oral procedures in patients taking thienopyridine alone or together with aspirin.1,3–5,22,25 Another recent study stated that there was no need to discontinue either the anticoagulant or aspirin in the patients taking the combined oral anticoagulant-aspirin regimen who required dental extraction.10 Several recent studies have also included patients on dual antiplatelet treatment who required oral surgery. The authors of these studies concluded that the continuation of dual antiplatelet drugs is relatively safe, but emphasised the need of further research because sample sizes were small.5,12,18 We recorded only 1/43 patients (59 occasions of tooth extractions) who developed mild postoperative bleeding) when taking dual antiplatelet drugs after extractions of 3 upper molars. None of the 117 patients (128 occasions of tooth extractions) in the single drug group (including 20 patients taking clopidogrel and 13 taking ticlopidine), developed a postoperative haemorrhage. However, suturing of the wound to achieve effective initial local haemostasis was needed in 4 and 2 patients taking dual and single antiplatelet drugs, respectively, but not in healthy subjects. We did not measure bleeding time in any of our patients. Those taking antiplatelet drugs may have prolonged bleeding time, but the test is not reliable enough to predict the risk of bleeding after dental surgery.1,25 Indeed, some recent reports about dental extractions in patients taking antiplatelet drugs have reported that the bleeding time was almost always within the normal range.14,16 The platelet aggregation test is more sensitive, but it is not in use in everyday practice.25 We know of only one small sample study in which the platelet aggregation test was used before dental extractions,13 and this suggests that this and other platelet function tests may be important for further research. The point of discussion can also be the definition of a bleeding event. There is no standard approach to defining bleeding after oral surgical procedures in patients taking antithrombotic drugs. Different authors have used different criteria for bleeding, making the results of these studies hard to compare. In our study, we used the criteria given by Lockhart et al.19 which are in our opinion good for defining a clinically important bleed.10 This study has some potential limitations—first, its relatively small sample size, and second that we studied only procedures with a low risk of bleeding (simple single and multiple extractions). It is also worth noting that an appreciable number of patients – 19 of 192 (10%) – who were not included in the study discontinued their antiplatelet drugs, usually aspirin, several days before the procedure for whatever reason. It seems that it takes time to educate our patients that teeth may be extracted safely without the discontinuation of antiplatelet drugs. An interdisciplinary discussion of this topic would be exceptionally useful.
Conflict of interest statement There is no conflict of interest.
Ethical approval/confirmation of patients’ permission The study was approved by the local Ethics Committee. All patients provided written informed consent to take part in the study.
References 1. North West Medicines Information Centre. Surgical management of the primary care dental patient on antiplatelet medication. North West Medicines Information Centre; 2010. Available at: http://ukmi.nhs.uk/activities/specialistServices/ (accessed 10 September 2014). 2. Eikelboom JW, Hirsh J, Spencer FA, Baglin TP, Weitz JI. Antiplatelet drugs: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 suppl.):e89S–119S. 3. Grines CL, Bonow RO, Casey Jr DE, et al. 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. Circulation 2007;115:813–8. 4. Nape˜nas JJ, Oost FC, DeGroot A, et al. Review of postoperative bleeding risk in dental patients on antiplatelet therapy. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:491–9. 5. Park MW, Her SH, Kwon JB, et al. Safety of dental extractions in coronary drug-eluting stenting patients without stopping multiple antiplatelet agents. Clin Cardiol 2012;35:225–30. 6. Biondi-Zoccai GG, Lotrionte M, Agostoni P, et al. A systematic review and metaanalysis on the hazards of discontinuing or not adhering to aspirin among 50 279 patients at risk for coronary artery disease. Eur Heart J 2006;27:2667–74. 7. Burger W, Chemnitius JM, Kneissl GD, Rücker G. Low-dose aspirin for secondary cardiovascular prevention – cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation – review and meta-analysis. J Intern Med 2005;257:399–414. 8. Maulaz AB, Bezerra DC, Michel P, Bogousslavsky J. Effect of discontinuing aspirin therapy on the risk of brain ischaemic stroke. Arch Neurol 2005;62:1217–20. 9. Ferrari E, Benhamou M, Cerboni P, Marcel B. Coronary syndromes following aspirin withdrawal: a special risk for late stent thrombosis. J Am Coll Cardiol 2005;45:456–9. 10. Bajkin BV, Bajkin IA, Petrovic BB. The effects of combined oral anticoagulant-aspirin therapy in patients undergoing tooth extractions: a prospective study. J Am Dent Assoc 2012;143:771–6. 11. Morimoto Y, Niwa H, Minematsu K. Risk factors affecting postoperative hemorrhage after tooth extraction in patients receiving oral antithrombotic therapy. J Oral Maxillofac Surg 2011;69:1550–6. 12. Nape˜nas JJ, Hong CHL, Brennan MT, Furney SL, Fox PC, Lockhart PB. The frequency of bleeding complications after invasive dental treatment in patients receiving single and dual antiplatelet therapy. J Am Dent Assoc 2009;140:690–5. 13. Brennan MT, Valerin MA, Noll JL, et al. Aspirin use and post-operative bleeding from dental extractions. J Dent Res 2008;87:740–4. 14. Krishnan B, Shenoy NA, Alexander M. Exodontia and antiplatelet therapy. J Oral Maxillofac Surg 2008;66:2063–6.
Please cite this article in press as: Bajkin BV, et al. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.009
YBJOM-4351; No. of Pages 5
ARTICLE IN PRESS B.V. Bajkin et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
15. Partridge CG, Campbell JH, Alvarado F. The effect of platelet-altering medications on bleeding from minor oral surgery procedures. J Oral Maxillofac Surg 2008;66:93–7. 16. 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;63:1262–5. 17. Brennan MT, Shariff G, Kent ML, Fox PC, Lockhart PB. Relationship between bleeding time test and postextraction bleeding in a healthy control population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:439–43. 18. 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;108:964–7. 19. 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;195:439–45. 20. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71–86.
5
21. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative metaanalysis of individual participant data from randomised trials. Lancet 2009;373:1849–60. 22. Douketis JD, Spyropoulos AC, Spencer FA, et al. 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):e326S–50S. 23. Aframian DJ, Lalla RV, Peterson DE. Management of dental patients taking common hemostasis-altering medications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103(Suppl: S45):e1–11. 24. Van Diermen DE, van der Waal I, Hoogstraten J. Management recommendations for invasive dental treatment in patients using oral antithrombotic medication, including novel oral anticoagulants. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2013;116:709–16. 25. Brennan MT, Wynn RL, Miller CS. Aspirin and bleeding in dentistry: an update and recommendations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:316–23.
Please cite this article in press as: Bajkin BV, et al. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.009
