|Year : 2012 | Volume
| Issue : 1 | Page : 15-19
Continuing antiplatelet therapy throughout dental procedures: A clinical dilemma
Sheeraz Badal1, Syed Ahmed1, Rohit Shrikanthan2, Afreen Badal1
1 Department of Oral & Maxillofacial Surgery, MIDSR Dental College and Hospital, Latur, India
2 Department of Oral & Maxillofacial Surgery, Raja Rajeshwari Dental College, Bangalore, India
|Date of Web Publication||22-Mar-2012|
Department of Oral & Maxillofacial Surgery, MIDSR Dental College and Hospital, Latur
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Antiplatelet therapy is commonly recommended for the prevention of the thromboembolic events, including the myocardial infarction and stroke. It has reduced the mortality and morbidity of cardiovascular diseases remarkably. A considerable number of patients presenting before a dentist give a history of antiplatelet therapy. A clinical dilemma exists whether to discontinue the antiplatelet therapy or to continue during the routine and invasive dental procedures. Continuing antiplatelet therapy during surgery minimizes the risk of thromboembolic complications but theoretically increases the risk of hemorrhage. Discontinuing antiplatelet therapy may expose patients to life-threatening thromboembolic events, while presumably reducing the risk of hemorrhagic complications. Diverse opinions exist regarding the management of such patients. Some advice continuation of the antiplatelet therapy rather than inviting possible thromboembolic event, while others encourages its discontinuation.
Keywords: Antiplatelet therapy, cardiovascular diseases, hemorrhagic complications, thromboembolic events
|How to cite this article:|
Badal S, Ahmed S, Shrikanthan R, Badal A. Continuing antiplatelet therapy throughout dental procedures: A clinical dilemma. J Interdiscip Dentistry 2012;2:15-9
|How to cite this URL:|
Badal S, Ahmed S, Shrikanthan R, Badal A. Continuing antiplatelet therapy throughout dental procedures: A clinical dilemma. J Interdiscip Dentistry [serial online] 2012 [cited 2019 Jul 16];2:15-9. Available from: http://www.jidonline.com/text.asp?2012/2/1/15/94186
| Introduction|| |
Antiplatelet drugs are used in clinical practice to prevent the adverse sequelae of thrombosis in atherosclerotic arteries of the heart, brain, and limbs. Cardiovascular diseases account for the highest mortality and morbidity worldwide.  With increasing awareness and health consciousness, there is a striking decrease of cardiovascular mortality with the Introduction of preventive and maintenance antiplatelet therapy.  Antiplatelets are commonly recommended for the prevention of thromboembolic events including myocardial infarction and stroke,  and are recommended for individuals with diabetes, who are at risk of cardiovascular disease.  But it is often discontinued prior to routine and invasive dental procedures because of concern for bleeding complications. Discontinuing therapy may expose patients to life-threatening thromboembolic events. The aim of this manuscript is to evaluate the need of stopping antiplatelet drugs before extended oral or dental surgeries.
| Discussion|| |
Platelets are small disk-shaped cells without a nucleus, derived from bone marrow, and when released into the blood have a life span of 10 days. They provide the initial haemostatic plug at the site of a vascular injury. They are also involved in pathological processes and are an important contributor to arterial thrombosis leading to myocardial infarction and ischemic stroke in patients with cardiovascular diseases. Patients with such diseases are treated with antiplatelet therapy to reduce the risk of thromboembolic events. Antiplatelet therapy has been reported to have reduced the overall mortality of vascular disease by 15% and non-fatal vascular complications by 30%. 
A considerable number of patients presenting before a dentist give a history of antiplatelet therapy. A clinical dilemma whether to discontinue the antiplatelet therapy or continue the same always confronts the practitioner. Diverse opinions exist regarding the management of such patients. While one group of researchers advice continuation of antiplatelet therapy rather than invite remote, but possible, thromboembolic events, another group encourages discontinuation for variable periods.
With millions of health conscious people using antiplatelet therapy, dental practitioners are frequently confronted with clinical situations where a decision has to be made about patient management, in view of the medical history. Till the very recent past, the recommendation was to stop antiplatelet therapy, to avoid excessive postoperative bleeding. Available antiplatelet medications include low-dose aspirin, clopidogrel and dipyridamole.
Studies conducted on aspirin since the early 1980s have shown that the antiplatelet effect is elicited at low doses of about 0.5-1.0 mg per kilogram per day, while the analgesic and antipyretic effects occur only at a daily dosage of 5-10 mg/kg, and the anti-inflammatory effect is achieved at a dosage of more than 30 mg/kg/day.  Thus, low doses of aspirin are sufficient for achieving anticoagulation with reduced side effects. Therefore, within the last decade we have seen a rapid increase in the use of low-dose aspirin as a secondary preventive drug by patients who have cardiovascular and peripheral vascular diseases. But at daily doses of aspirin, lower or up to 300 mg is associated with a twofold increased risk of upper gastrointestinal complications due to inhibition of cyclo-oxygenase1 pathway, for which periodic screening with physician is necessary.  The increasing popularity of aspirin, either alone or in combination with other drugs, has presented physicians and dentists with the dilemma of whether to advise patients to discontinue aspirin therapy before surgical procedures are performed.
Discontinuing aspirin therapy is usually recommended for 3-7 days before the planned event by most of the dentists because of the risk of bleeding.
To understand the rationale of the whole phenomenon, a brief recapitulation of the basic issues need to be reviewed. Patients taking low doses of aspirin have bleeding times that remain within normal limits and normal hemostasis may be retained when approximately 20% of platelets have normal COX-1 activity after aspirin is stopped.  Aspirin inhibits platelet aggregation irreversibly within one hour of ingestion; this inhibition lasts for the life of the platelets (7-10 days). Only the production of new platelets will overcome this inhibiting effect. Therefore discontinuing aspirin therapy for only a few days does not reverse the inhibition. 
Discontinuation of aspirin is often suggested prior to invasive dental procedures, but no clear guidelines exist for dose alteration.  Case reports of bleeding following dental procedures have appeared in the literature. , Clinical trials of aspirin have been contradictory, with some studies showing increased bleeding and others showing no evidence of excessive post-operative bleeding following dental procedures. 
At least 160 mg soluble aspirin is required to maximally inhibit platelet function within 30 minutes and the daily doses accumulate and it has been seen that doses as low as 40 mg/day are effective.  A loading dose as high as 300 mg is sometimes recommended when an immediate antithrombotic effect is required. The present consensus states that a daily aspirin dosage of 75-150 mg is recommended for the long-term prevention of serious vascular events in high-risk patients.  Increasing to higher doses does not necessarily improve platelet inhibition and in fact, may be counterproductive.
Earlier case reports suggest episodes of oral bleeding in patients taking aspirin, but it is unclear whether it is directly related to aspirin or to other factors. , More recently, prospective clinical trials have examined the impact of aspirin on post-extraction bleeding. In a randomized study  of 39 persons on 100 mg aspirin/day, group 1 continued aspirin through dental extractions, while group 2 stopped aspirin 7 days prior to extractions and resumed the day after surgery. The cutaneous bleeding time was higher in group 1, but within the normal range for both groups. No episodes of excessive intra-or post-operative bleeding were found in either group.  The study  of 51 patients (32 males, 19 females), ranging in age from 45 to 70 years was carried out at Madan Dental Hospital, Ahmedabad, India from May 2002 to May 2003, on patients with long-term low-dose aspirin therapy regimens (acetylsalicylic acid 75-100 mg/day) who underwent minor dental surgical procedures under local anasthesia continuing aspirin therapy. None of the patients experienced intraoperative or postoperative bleeding, except one who had insignificant intraoperative bleeding.  In a retrospective analysis of 475 patients admitted to hospital with a myocardial infarction, 11 (2.3%) had discontinued aspirin therapy within 15 days prior to admission for general surgical procedure. Nine patients discontinued aspirin 3 days prior to a planned surgical procedure, one of which was a dental procedure. The dental patient had been stable and symptom free on aspirin for 10 years but suffered a myocardial infarction 10 days after stopping aspirin therapy. 
Despite the absence of a clear link between aspirin use and significant bleeding following invasive dental procedures, there are still recommendations to delay invasive procedures for a minimum of 3 days following cessation of aspirin, until a time when the numbers of new, functional platelets have returned to a sufficient level.  The problems associated with this practice include a delay in treatment for emergent odontogenic problems, the loss of the antithrombotic benefit of aspirin when it is prescribed for cardiovascular disease, and unnecessary time and expense for unwarranted bleeding time testing.
Given the goal for aspirin in these clinical conditions, discontinuation of aspirin must be weighed against the potential for significant bleeding during or following an invasive dental procedure if aspirin is continued.
Although aspirin can increase the cutaneous bleeding time test result, and one study showed an increase in blood loss in persons taking aspirin, the literature suggests that increased cutaneous bleeding time does not predict increased blood loss from surgery. Platelet aggregation tests are also affected by aspirin, but once again the predictive power of this test for intraoperative or postoperative bleeding has not been well documented. 
Current recommendations and consensus favor no discontinuation of antiplatelet therapy. This recommendation, however, comes with a rider to use caution and consider other mitigating factors as well.
Clopidogrel is a prodrug, the action of which may be related to an adenosine diphosphate (ADP) receptor on platelet cell membranes. The drug specifically and irreversibly inhibits the P2Y 12 subtype of ADP receptor, which is important in aggregation of platelets and cross-linking by the protein fibrin.  Clopidrogel is most commonly available under the trade names Plavix, as 75-mg oral tablets. Clopidogrel is a newer thienopyridine that has fewer harmful side effects. It is also superior to aspirin at preventing ischemic events.  Clopidogrel is extensively metabolized and has a half-life of 7.2 to 7.6 hours.  Clopidogrel has been shown to lengthen the bleeding time and increase the risk of postoperative bleeding after coronary artery bypass surgery.  No prospective study has been conducted on the risk of bleeding among patients undergoing dental procedures who are taking thienopyridines. Current recommendations on the use of thienopyridines are based solely on expert opinion. Most reports of increased bleeding due to thienopyridine refer to major surgery, such as cardiac surgery. ,
Dipyridamole is a phosphodiesterase inhibitor that blocks the reuptake of adenosine after vessel injury; the drug activates adenosine on the platelets. Dipyridamole is used to prevent stroke; however, thrombocytopenia has been reported after treatment with this drug. Dipyridamole affects the bleeding time less than thienopyridines, and its effects are reversible 24 hours after discontinuation of the drug.  Dipyridamole alone has little antiplatelet effect, it is currently used in combination with aspirin or warfarin in the prophylaxis of thromboembolic disorders. It is also used in stress testing for myocardial perfusion imaging. Its use should not be stopped before simple dental procedures.
Glycoprotein IIb-IIIa receptor blockers compete with platelet ligands (e.g., fibrinogen). Three compounds in clinical use are abciximab (an antibody fragment), tirofiban, and eptifibatide (both of which are low-molecular-weight compounds).  The glycoprotein IIb/IIIa inhibitors are used parenterally in patients with acute coronary syndromes by specialists. Dental procedures should be avoided while the patient receives intravenous glycoprotein IIb-IIIa receptor blockers.
Combinations of antiplatelet agents
A combination of aspirin and clopidogrel can improve the outcome of coronary intervention, and has been recommended for use in the month after surgery.  Concomitant use of low-dose clopidogrel (2×75 mg) and aspirin (150 mg) has been shown to significantly increase the bleeding time from 7.6 (standard deviation, 3.4) minutes to 17.5 (8.6) minutes, probably through a synergistic antiplatelet action.  An aspirin and dipyridamole combination has been used to prevent stoke, and produces better results than with just each drug alone. In patients undergoing minor dental procedures, minor dermatological procedures, or cataract surgery, aspirin can be continued.  Clopidogrel can be discontinued at least 5 days (preferably 10 days) prior to the procedure in patients not at high cardiac risk. Patients who have had a bare metal coronary stent placed within the previous six weeks, and those who have had a drug-eluting stent placed within the past 12 months should continue clopidogrel. 
Several reports in the literature have discussed the advantages and disadvantages of different ways of managing antiplatelet therapy before invasive dental procedures. Some articles recommend withholding medication, without consideration for the possible negative outcomes and some advice to continue. There are well-documented examples of inappropriate discontinuation of antiplatelet therapy prior to dental procedures which have led to a devastating outcome (e.g., thromboembolism, cerebrovascular accident or myocardial infarction).  Since antiplatelet activity increase the bleeding time which may result in prolonging bleeding time, but literature suggests that this resultant bleeding is not that significant to cause any damage to the patient and can be managed with local hemostatic methods. In many cases, suturing is the only hemostatic technique necessary. 
Assessing the risk of thromboembolism versus potential bleeding
When contemplating dental procedures for a patient taking antiplatelet drugs, several important factors must be considered: Is the surgery urgent or elective? Is the patient at high or low risk of thromboembolism if the drug is discontinued? Can the procedure be done safely without discontinuing the drug? Does the patient understand the nature of the dental procedure and the risks associated with continuing or discontinuing the drug? What degree of risk are the patient and the provider willing to accept? Finally, is the patient on a single antiplatelet drug or on combination therapy with another drug. 
Although the Ivy bleeding time has been used to assess platelet function, it is not suitable for estimating the hemorrhagic risk of a patient taking antiplatelet medication. Patients taking aspirin or other platelet-inhibiting drugs may have prolonged bleeding times, although these may not be clinically relevant for procedures such as the removal of one or two teeth, the placement of implants, or other minor procedures, as postoperative bleeding can be controlled using local measures. Significant bleeding usually does not result unless the bleeding time is greater than 20 minutes.
However, its ability to determine the likelihood that a patient will bleed excessively during surgery has yet to be established detecting platelet dysfunction due to aspirin ingestion.  Patients who have had previous thrombotic events are considered to be at risk for other thrombotic events. 
Patients who are at high risk of perioperative thromboembolic events include those with mechanical heart valves who have atrial fibrillation, older aortic valve prostheses, recent deep venous thromboses (DVT), hypercoagulable states, or a history of recent life-threatening thromboembolic events.
Patients at moderate risk include those with mechanical valves and a normal sinus rhythm, DVT more than three months prior to planned dental treatment, and atrial fibrillation with coexisting coronary artery disease, diabetes or hypertension.
Patients at low risk include those with atrial fibrillation without a history of stroke, a hypercoagulable state without recent or life-threatening thrombosis, or a history of DVT treated remotely.
A patient who has had a previous thrombotic event should be considered to be at risk for thromboembolism, if the ongoing antiplatelet therapy is discontinued. A provider who is uncomfortable making the decision concerning treatment while the patient is taking antiplatelet drugs may consult with the patient's primary care physician or specialist. 
Local measures to use in the event of a bleeding episode
Bleeding that lasts for more than 12 hours after surgery, causes the patient to return to an emergency room.it can result in a large hematoma or ecchymosis of the oral soft tissues, or merits a blood transfusion may be defined as a significant bleeding event in the postoperative period.  Less than 20 mL of blood loss is considered mild; between 20 mL and 50 mL is considered moderate; and more than 50 mL is considered severe. 
Postoperative bleeding after minor dental procedures usually can be controlled using local measures.  For patients taking low-dose aspirin, most cases of postoperative bleeding require only suturing for hemostasis.  An absorbable hemostatic dressing (such as oxidized cellulose, collagen sponge, microfibrillar collagen flour, or resorbable gelatin sponge) can be packed gently in sockets and sutured, followed with gauze pressure for at least 30 minutes.  Resorbable sutures are thought to attract less plaque than other materials. Non-resorbable sutures should be removed after 4-7 days.  Extensive dental surgeries (such as a total odontectomy, periodontal surgery, or extensive deep scaling) may require sutures, superficial laser, oxidized cellulose, microfibrillar collagen, or absorbable gelatin sponge to control hemostasis. Blood clots in extraction sites and postoperative oozing also can be stabilized by 10% tranexamic acid, which neutralizes oral fibrinolytic activators and can be added to local packing, applied topically, or used as a rinse for two minutes, four times a day.  Tranexamic acid both inhibits bleeding and rebleeding.  Epsilon aminocaproic acid (250 mg/mL) is another hemostatic agent that can be added to local packing or applied topically to inhibit or block fibrinolysis of the clot.  Patients who are taking combinations of antiplatelet drugs or higher doses of aspirin especially those with bleeding times of more than 20 minutes should consult with their treating physician.
Emergency surgery for patients taking high doses of aspirin with prolonged bleeding times may be treated with desmopressin acetate.  It can be given parenterally (0.3 μg/kg of body weight) or by nasal spray (300 mg/kg). Consultation with the patient's physician or hematologist is recommended prior to this therapy, especially among older patients.
| Conclusions|| |
Current research suggests no indication for discontinuing aspirin therapy for individuals requiring routine and invasive dental procedures as any resultant bleeding can be easily managed by local hemostatic methods. In many cases, suturing is the only hemostatic technique necessary. Thus, when balancing benefits and risks of continuing versus discontinuing medications perioperatively, existing data support continuing medically necessary antiplatelet therapy throughout the routine and invasive dental procedures. To stop otherwise may expose patients unnecessarily to increased risks of potentially life-threatening complications.
It therefore draws a conclusion that patients on antiplatelet therapy undergoing invasive dental procedures should continue taking the medication to avoid the risk of thromboembolism, cerebrovascular accident or myocardial Infarction.
If clopidogrel is used in combination with antiplatelet therapy, then clopidogrel can be discontinued at least 5 days (preferably 10 days) prior to the procedure in patients not at high cardiac risk. In case of high cardiac risk, it is better to continue clopidogrel. Hence we all should be familiar with the compelling data that suggest that antiplatelet therapy should be continued during routine and invasive dental procedures.
| References|| |
|1.||Collet JP, Montalescot G. Premature withdrawal and alternative therapies to dual oral antiplatelet THERAPY. Eur Heart J 2006;8:46-52. |
|2.||Stafford RS, Monti V, Ma J. Underutilization of aspirin persists in US ambulatory care for the secondary and primary prevention of cardiovascular disease. PLoS Med 2005;2:353. |
|3.||Colwell JA. American Diabetes Association. Aspirin therapy in diabetes. Diabetes Care 2004;27:72-3. |
|4.||Ardekian L, Gaspar R, Peled M, Brener B, Laufer D. Does low-dose aspirin therapy complicate oral surgical procedures? J Am Dent Assoc 2000;131:331-5. |
|5.||Hankey GJ, Eikelboom JW. Antiplatelet drugs. Med J Aust 2003;178:568-74. |
|6.||Scully C, Wolff A. Oral surgery in patients on anticoagulant therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:57-64. |
|7.||Little JW, Miller CS, Henry RG, McIntosh BA. Antithrombotic agents: implications in dentistry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:544-51. |
|8.||Thomason JM, Seymour RA, Murphy P, Brigham KM, Jones P. Aspirin-induced post-gingivectomy haemorrhage: A timely reminder. J Clin Periodontol 1997;24:136-8. |
|9.||Brennan MT, Wynn RL, Miller CS, Charlotte NC, Lexington KY. Aspirin and bleeding in dentistry: An update and recommendations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:316-23. |
|10.||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 Maxfac Surg 2005;63:1262-5. |
|11.||Collet JP, Himbert D, Steg PG. Myocardial infarction after aspirin cessation in stable coronary artery disease patients. Int J Cardiol 2000;76:257-8. |
|12.||Ryan WL, Hakenkamp K, Sullivan E. A new platelet function test. Thromb Res 1990;58:163-73. |
|13.||Savi P, Zachayus JL, Delesque-Touchard N, Labouret C, Hervé C, Uzabiaga MF, et al. The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts. Proceedings of the National Academy of Sciences of the USA 2006;103:11069-74. |
|14.||Alvarez JM, Harper RW, Peverill RE. Emergency coronary artery bypass grafting (CABG) after failed coronary artery intervention- caution regarding the combined use of aspirin, ticlopidine and abciximab. Aust N Z J Med 1998;28:463-4. |
|15.||Yende S, Wunderink RG. Effect of clopidogrel on bleeding after coronary artery bypass surgery. Crit Care Med 2001;29:2271-5. |
|16.||Lin SY. Edward Man-Fuk Leung. Antiplatelet drugs and dental practice. Hong Kong Dent J 2004;1:85-7. |
|17.||Lenz TL, Hilleman DE. Aggrenox: A fixed-dose combination of aspirin and dipyridamole. Ann Pharmacother 2000;34:1283-90. |
|18.||Randall C, editor. Surgical management of the primary care dental patient on antiplatelet medication. Available from: http://www.nelm.nhs.uk/Documents/QA33.2_Surgical_management_of_the_primary_%20care_dental_patient_on_antiplatelet_medication.pdf. [Last Accessed on 2008 January]. |
|19.||Payne DA, Hayes PD, Jones CI, Belham P, Naylor AR, Goodall AH. Combined therapy with clopidogrel and aspirin significantly increases the bleeding time through a synergistic antiplatelet action. J Vasc Surg 2002;35:1204-9. |
|20.||Forbes CD. Secondary stroke prevention with low-dose aspirin, sustained release dipyridamole alone and in combination. ESPS Investigators. European Stroke Prevention Study. Thromb Res 1998;92 (Suppl 1):1-6. |
|21.||Douketis JD, Berger PB, Dunn AS, Jaffer AK, Spyropoulos AC, Becker RC, et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133:299-309. |
|22.||Evans IL, Sayers MS, Gibbons AJ, Price G, Snooks H, Sugar AW. Can warfarin be continued during dental extraction? Results of a randomized controlled trial. Br J Oral Maxillofac Surg 2002;40:248-52. |
|23.||Aubertin MA. The patient taking antiplatelet drugs: A review with dental management considerations. Gen Dent 2008;5:363-9. |
|24.||Kumar AJ, Kumari MM, Arora N, Haritha A. Is anti-platelet therapy interruption a real clinical issue? Its implications in dentistry and particularly in periodontics. J Indian Soc Periodontol 2009;13:121-5. |
|25.||Muskett A, Barber WH 5th, Lineaweaver WC. The plastic surgeon′s guide to drugs affecting hemostasis. Ann Plast Surg 2005;54:570-6. |
|26.||Schardt-Sacco D. Update on coagulopathies. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:559-63. |
|27.||Kovesi T, Royston D. Is there a bleeding problem with platelet-active drugs? Brit J Anes 2002;88:159-63. |
|28.||Patatanian E, Fugate SE. Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Ann Pharmacother 2006;40:2205-10. |