J Oral Maxillofac Surg 66:2063-2066, 2008 Exodontia and Antiplatelet Therapy Balasubramanian Krishnan, MDS, DNB, MOMS RCPS (Glasgow),* Nithin A. Shenoy, MDS,† and Mohan Alexander, MDS, MOMS RCPS (Glasgow)‡ Purpose: The fear of excessive bleeding often prompts the physician to stop long-term, low-dose antiplatelet therapy before any surgical procedure. This may put the patient at risk of an adverse thromboembolic event. We undertook an assessment of the incidence of prolonged postoperative bleeding after dental extractions among patients on uninterrupted antiplatelet therapy, and evaluated the need to stop such medications before dental extractions. Patients and Methods: Eighty-two patients requiring dental extractions were included in this study, of whom 57 were on antiplatelet therapy (aspirin). Patients were divided into 3 groups. Group 1 consisted of patients in whom antiplatelet therapy was interrupted (n ⫽ 25), group 2 consisted of those continuing their medication (n ⫽ 32), and group 3 comprised healthy patients not on antiplatelet therapy (n ⫽ 25). Preoperative bleeding time and clotting time were determined in all patients. The surgical procedure involved single or multiple teeth extractions under local anesthesia with a vasoconstrictor. All patient groups were similar regarding age, gender distribution, dosage of antiplatelet drug, and medical condition for which the drug was prescribed. Events of single or multiple teeth extractions were also comparable among the 3 groups. Pressure packing was performed in all cases as in routine dental extractions. One-way analysis of variance was performed to determine the significance of prolonged bleeding among groups. Results: The mean bleeding times in groups 1, 2, and 3 were 3 minutes, 2 minutes and 45 seconds, and 1 minute and 49 seconds, respectively. The mean clotting times in groups 1, 2, and 3 were 5 minutes and 4 seconds, 4 minutes and 52 seconds, and 3 minutes and 42 seconds, respectively. No patient in any group had any episode of prolonged or significant bleeding from the extraction sites. Local hemostasis had been satisfactorily obtained in all cases with the use of a pressure pack for 30 minutes. Conclusions: Routine dental extractions can be safely performed in patients on long-term antiplatelet medication, with no interruption or alteration of their medication. Such patients do not have an increased risk of prolonged or excessive postoperative bleeding. © 2008 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 66:2063-2066, 2008 Advances in medical science have ensured an increased lifespan for human beings. Unfortunately, this has come at the price of a greater incidence of medically compromising conditions in a large proportion Received from the Department of Oral and Maxillofacial Surgery, Mahatma Gandhi Postgraduate Institute of Dental Sciences, Indira Nagar, Pondicherry, India. *Lecturer. †Former Postgraduate Trainee. ‡Former Professor and Head. Address correspondence and reprint requests to Dr Alexander: Oral and Maxillofacial Surgery, D.J. Dental College, Niwari Road, Modinagar 201204, Uttar Pradesh, India; e-mail: mohanalexin@yahoo.com © 2008 American Association of Oral and Maxillofacial Surgeons 0278-2391/08/6610-0013$34.00/0 doi:10.1016/j.joms.2008.06.027 of such individuals. Of particular interest to the oral and maxillofacial surgeon are those patients who are maintained on oral antiplatelet agents. Although newer antiplatelet agents are available, aspirin continues to be favored because of its low cost and reliable efficacy. The fear of uncontrolled or excessive bleeding prompts medical practitioners to stop or alter these drugs before surgical procedures. However, considerable debate has been generated with regard to balancing the risk of a postsurgical hemorrhage with that of precipitating a thromboembolic event. Stopping or altering antiplatelet therapy may expose such patients to the risk of thromboembolism, myocardial infarction, or cerebrovascular accidents.1 We undertook an assessment of the incidence of prolonged postoperative bleeding after dental extractions among patients on uninterrupted antiplatelet 2063 2064 EXODONTIA AND ANTIPLATELET THERAPY therapy, and evaluated the need to stop such medications before dental extractions. Patients and Methods Our Ethics and Research Committee approved the study, conducted over a period of 25 months (from 2004 to 2006). Informed consent was obtained from all patients in this study. Eighty-two patients requiring dental extractions were included. Among these, 57 were on antiplatelet therapy (aspirin) for various cardiac ailments. All patients underwent estimations of bleeding time (BT; Duke’s method) and clotting time (CT; slide method) on the day of extractions. Those with a preoperative bleeding time of more than 20 minutes, a history of bleeding disorders, concomitant anticoagulant therapy, newer antiplatelet drugs along with aspirin, pregnancy, or alcoholism, and minors, were excluded from the study. The cardiac condition for which the drug was prescribed, and the duration and dose of medication, were recorded (Table 1). Potential complications while performing surgical procedures with uninterrupted or interrupted antiplatelet therapy were explained to all patients by a single investigator (B.K.) and were then divided into 2 groups, depending on their choice. Group 1 comprised patients in whom antiplatelet therapy would be stopped before dental extractions. Group 2 consisted of patients who would undergo dental extractions without any interruption or alteration of antiplatelet therapy. A third group included healthy patients who had never received any kind of antiplatelet therapy (control group). Before the procedure, all patients received a local anesthetic injection (2% lignocaine with vasoconstrictor). Extractions (single or multiple) were performed by the same operator (N.A.S.) in all cases, with as little trauma as possible. Patients were instructed to bite on a pressure pack for 30 minutes. Evidence of bleeding from the extraction site beyond this time period was considered to be prolonged postoperative bleeding. All patients were discharged only after ensuring that Table 1. CARDIAC AILMENTS FOR WHICH ANTIPLATELET MEDICATIONS WERE PRESCRIBED Cardiac Ailments Number of Patients Myocardial infarction Ischemic heart disease Coronary artery disease Post bypass Valvular surgery 12 15 10 12 8 Krishnan, Shenoy, and Alexander. Exodontia and Antiplatelet Therapy. J Oral Maxillofac Surg 2008. satisfactory hemostasis had been achieved at the extraction site. Patients were instructed to report back immediately in case of any complaint of postoperative bleeding. “Clinically significant bleeding”2 was defined as bleeding that: 1. Continued beyond 12 hours of the operative procedure; 2. Caused a patient to call or return to the dental office or emergency department; 3. Resulted in the development of a large hematoma within the soft tissues; and 4. Required a blood transfusion. Analysis of variance was used to evaluate results among the 3 groups and determine statistical significance, if any. Results Among the 57 patients on antiplatelet therapy included in the first 2 groups, 25 patients were in group 1, and 32 were in group 2. The control group comprised 25 patients. All patient groups were similar with regard to age and gender distribution. The 2 treatment groups were also comparable with regard to dosage of antiplatelet drug and the medical condition for which the drug had been prescribed. Events of single or multiple teeth extractions were also comparable among the 3 groups. Aspirin doses were 75 or 150 mg per day. Duration of dosage ranged from 4 months to 348 months in group 1 (⫾ SD of 83 months), and between 1 and 348 months in group 2 (⫾ SD of 50 months). In the first 2 groups, 15 patients gave a history of having undergone extractions after the initiation of antiplatelet therapy. Of these, 8 had stopped their medication before the extractions on the advice of their physician. This duration of interruption before the extractions ranged from 2 to 7 days. The remaining 7 did not alter their medications, because they had not consulted their physician before the dental extractions. However, none of these 15 patients reported any event of uncontrolled or prolonged bleeding after their dental extractions. In group 1, interruption of antiplatelet therapy ranged from 1 to 10 days, with a mean of 4.7 days. The BT estimate among patients in group 1 ranged from 1 minute and 45 seconds to 12 minutes and 50 seconds, with a mean of 3 minutes (⫾ SD of 2 minutes and 45 seconds), whereas in group 2, this range was from 1 minute and 45 seconds to 5 minutes and 45 seconds, with a mean of 2 minutes and 45 seconds (⫾ SD of 1 minute and 38 seconds). Group 3 BT values ranged from 1 minute and 5 seconds to 3 minutes and 25 seconds, with a mean of 1 minute and 49 seconds (⫾ SD of 0 minutes and 39 seconds). The CT values 2065 KRISHNAN, SHENOY, AND ALEXANDER Table 2. COMPLEXITY OF EXODONTIA PROCEDURE Group Extracted Group 1 Group 2 Group 3 Type of Teeth Extracted Number of Teeth Anterior Premolars Molars Anterior Premolars Molars Anterior Premolars Molars 5 6 17 11 10 19 6 11 13 Krishnan, Shenoy, and Alexander. Exodontia and Antiplatelet Therapy. J Oral Maxillofac Surg 2008. ranged from 3 minutes and 15 seconds to 10 minutes and 15 seconds, with a mean of 5 minutes and 4 seconds (⫾ SD of 1 minute and 38 seconds) in group 1, whereas in group 2, CT values ranged from 3 minutes and 35 seconds to 7 minutes and 10 seconds, with a mean of 4 minutes and 52 seconds (⫾ SD of 1 minute and 4 seconds). Group 3 CT values ranged from 3 minutes and 10 seconds to 10 minutes and 40 seconds, with a mean of 3 minutes and 42 seconds (⫾ SD of 1 minute and 53 seconds). All these values were within acceptable limits, and no significant statistical difference was observed among the 3 groups. Twenty patients in group 1 underwent extraction of a single tooth, and 5 had multiple teeth extracted. In group 2, 10 patients underwent removal of multiple teeth, whereas the control group contained only 4 patients with extraction of multiple teeth. The 3 groups did not differ in the complexity of their operative procedures (Table 2). No patient in any group had any episode of prolonged or significant bleeding from the extraction sites. Local hemostasis had been satisfactorily obtained in all cases with the use of a pressure pack for 30 minutes. Discussion Until the early 1980s, aspirin was used as an antiinflammatory, analgesic, and antipyretic drug. Side effects of aspirin, such as gastrointestinal irritation and ulcers, and asthma-like attacks in asthmatic patients, limited the administration of aspirin to short periods. However, the antiplatelet effect of aspirin is elicited at low doses of 0.5 to 1.5 mg/kg/day, whereas analgesic and anti-inflammatory effects are achieved at doses of 5 to 10 mg/kg/day and more than 30 mg/kg/day, respectively.3 Platelets play a key role in thrombosis, atherosclerosis, and acute coronary syndromes such as myocardial infarction and angina. Consequently, the concept of inhibition of platelet activity as an appropriate antithrombotic therapy gained considerable support, and has been achieved with low doses of aspirin. The Anti-Platelet Trialists Collaboration,4 in a meta-analysis of 287 studies involving 135,000 patients, confirmed the prophylactic effects of aspirin and other oral antiplatelet drugs after a previous myocardial infarction, in angina, after stroke, and after bypass surgery, and established the efficacy of these drugs in both genders. Vascular events are reduced by 20% to 25% in the first few years after the index event, and all-case mortality is reduced by 12%. The last few decades have seen an increased use of low-dose aspirin, either alone or in combination with other drugs, as a secondary preventive drug. Platelets provide a lipoprotein surface that catalyzes reactions such as formation of thrombin. In addition, a contractile protein, thrombosthenin, present in platelets, plays an important role in clot retraction.5 It was reported that estimation of BT might reflect the extent to which platelet function might be affected by medications such as aspirin.6 The CT test was also suggested to measure platelet function in patients on aspirin therapy.7 However, a correlation between BT test results and rate of surgical bleeding complications has not been established.8 Bleeding time does not specifically or accurately reflect in vivo platelet function, and abnormal BTs were reported in various disorders not associated primarily with hematologic disturbances.9 Little et al10 suggested that aspirin-affected platelets did not lead to a significant bleeding problem unless the BT was greater than 20 minutes. Gaspar et al11 and Sonksen et al12 claimed that prolongation of BT, within acceptable limits, did not exert any significant effect on intraoperative or postoperative bleeding after dental extractions. However, the scientific rationale for considering this time period of 20 minutes as safe is not clear. More expensive options such as platelet function analyzers, the ristocetin test, and flow cytometry have been used to analyze platelet function, but none can accurately assess the increased risk of bleeding in patients taking antiplatelet drugs. The easy availability of both BT and CT tests was the sole reason for their use in this study. Considerable controversy has been generated regarding patients on aspirin therapy requiring surgical procedures. Recommendations to stop the drug 7 to 10 days before the procedure appear to be based on the irreversible effect exerted by aspirin on platelets.13,14 Sonksen et al,12 in a study of 52 healthy volunteers on a 7-day course of aspirin, showed that the BT was below 10 minutes within 48 hours of stopping aspirin therapy. Hence, withdrawal of the drug for 5 or more days, as recommended, appears to be erroneous. However, this test was performed on healthy volunteers, and a simple extrapolation to patient subgroups may be unjustified. Also, 2066 considerable interindividual variability in the magnitude of aspirin’s effect on primary hemostasis is present and may have influenced the results. Fijhneer et al,15 in conducting a review, pointed out the scarcity of literature regarding dermatologic, cataract, ear, nose, and throat, and dental surgeries involving patients on aspirin therapy. Although some studies in patients undergoing cardiovascular surgery concluded that aspirin involved a risk for increased bleeding,16,17 similar studies in the dermatologic,18 ophthalmic,19 and orthopedic20 literature support the view that it is not necessary to stop aspirin before undergoing minor surgical procedures. Shalom and Wong21 compared patients using aspirin to those without while undergoing excision of cutaneous and subcutaneous lesions, and found no differences in the bleeding patterns of the 2 groups. Studies by Gaspar et al11 and others22-24 concluded that hemostasis posed no problems during ambulatory oral surgical procedures among patients on aspirin therapy, and recommended continuation of antiplatelet therapy without any interruption. These findings are in concurrence with our observations. Whereas various haemostatic measures such as gelatin sponge, tranexamic acid mouth rinse, and fibrin glue have been used to control bleeding, a routine pressure-pack application was sufficient to control bleeding in all patients in our study, and required no additional measures. The drawbacks of our study may include a failure to homogenize the duration of interruption of antiplatelet therapy in group 1, which ranged from 1 to 10 days. This was because some patients had stopped aspirin as per the advice of their physicians and wanted the extractions done the same day of their visit to the department. However, this did not significantly alter the results. Patients with no previous history of extractions were advised by their dental school physician to interrupt aspirin therapy for 5 days before their extractions. There is a possibility that by choosing their own treatment, patients might have introduced bias into the study, based on their own past surgical/bruising/ bleeding tendencies, regardless of their recorded bleeding times. However, this possibility seems minimal, because none of the 15 patients who had a previous history of extraction had reported any incident of uncontrolled postextraction bleeding. An initial attempt at randomization had to be abandoned because several patients refused to provide consent. It was evident that patients were more comfortable following their physician’s advice or choosing treatment on their own, rather than being placed in either group randomly. This study concludes that routine dental extractions can be safely performed in patients on longterm, low-dose aspirin, with no interruption of the EXODONTIA AND ANTIPLATELET THERAPY medication, and such patients do not have an increased risk of prolonged or excessive postoperative bleeding. References 1. Jafri SM, Zarowitz B, Goldstein S, et al: The role of antiplatelet therapy in acute coronary syndromes and for secondary prevention following a myocardial infarction. Prog Cardiovasc Dis 36:75, 1993 2. UK Medicines Information, North West Information Centre, Liverpool: Surgical management of the primary dental patient on antiplatelet medication. Available at: www.ukmi.nhs.uk/ specialistservices/drugsindentistry. Accessed March 2007 3. Patrono C, Garcia Rodriguez LA, et al: Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 353:2373, 2005 4. Anti-Platelet Trialists Collaboration: Collaborative overview of randomized trials of antiplatelet therapy: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Br Med J [Clin Res] 308:81, 1994 5. Little JW, Falace DA, Miller S, et al: Dental Management of Medically Compromised Patient (ed 6). St Louis, Mosby, 1993, p 340 6. Terezhalmy GT, Lichtin AE: Antithrombotic, anticoagulant and thrombolytic agents. Dent Clin North Am 40:649, 1996 7. Laskin DM: Oral and Maxillofacial Surgery, Volume 1. St. Louis, C.V. Mosby, 1996, p 329 8. De Caterina R, Lanza M, Manca G, et al: Bleeding time and bleeding: An analysis of the relationship of the bleeding time test with parameters of surgical bleeding. Blood 84:3363, 1994 9. Leibman H, Chinowsky M, Valdin J, et al: Increased fibrinolysis and amyloidosis. Arch Intern Med 143:678, 1983 10. Little JW, Miller CS, Henry RG, et al: Antithrombotic agents: Implications in dentistry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93:544, 2002 11. Gaspar R, Ardekian L, Brenner B, et al: Ambulatory procedures in patients on low dose aspirin. Harefuah 136:108, 1999 12. Sonksen JR, Kong KL, Holder R: Magnitude and time course of impaired primary hemostasis after stopping chronic low and medium dose aspirin in healthy volunteers. Br J Anaesth 82: 360, 1999 13. Watson CJ, Deane AM, Doyle PT, et al: Identifiable factors in post-prostatectomy hemorrhage: The role of aspirin. Br J Urol 66:85, 1990 14. Kitchen L, Erichson RB, Sideropoulos H: Effect of drug-induced platelet dysfunction on surgical bleeding. Am J Surg 143:215, 1982 15. Fijhneer R, Urbanus RT, Nieuwenhuis HK: Withdrawing use of acetylsalicylic acid prior to an operation usually not necessary. Ned Tijdschr Geneeskd 147:21, 2003 16. Ferraris VA, Ferraris SP, Lough FC, et al: Preoperative aspirin ingestion increases operative blood loss after coronary artery bypass grafting. Ann Thorac Surg 45:71, 1998 17. Taggart DP, Siddiqui A, Wheatley DJ: Low dose preoperative aspirin therapy, postoperative blood loss, and transfusion requirements. Ann Thorac Surg 50:424, 1990 18. Barlett GR: Does aspirin affect the outcome of minor cutaneous surgery? Br J Plast Surg 52:214, 1999 19. Assia EI, Raskin T, Kaiserman I, et al: Effect of aspirin intake on bleeding during cataract surgery. J Cataract Refract Surg 24: 1243, 1998 20. Anekstein Y, Tamir R, Halperi N, et al: Aspirin therapy during proximal femoral fracture surgery. Clin Orthop 418:205, 2004 21. Shalom A, Wong L: Outcome of aspirin use during excision of cutaneous lesions. Ann Plast Surg 50:296, 2000 22. Ardekian L, Gaspar R, Peled M: Does low-dose aspirin complicate oral surgical procedures? J Am Dent Assoc 131:331, 2000 23. Madan G, Madan S, Madan G, et al: Minor oral surgery without stopping daily low dose aspirin therapy. A study of 51 patients. J Oral Maxillofac Surg 63:1262, 2005 24. Daniel NG: Antiplatelet drugs: Is there a surgical risk? J Can Dent Assoc 68:683, 2002