ABSTRACT

Aim: The aim of the study was to evaluate the influence of aspirin on post extraction bleeding in a clinical setup.

Materials and Method: 200 Patients aged between 50 to 65 years, who were indicated for dental extraction was selected from outpatient department of Oral and Maxillofacial Surgery. All the patients were randomly divided in aspirin continuing group (Group A) and aspirin discontinuing group (Group B). After checking all the vital signs extractions were carried out. Bleeding time and clotting time was recorded for evaluation by Chi Square Test.

Results: Chi Square test asserted that the bleeding time increased (3.8±0.75) in Group B patients who continued with the antiplatelet therapy while it decreased in Group A patients who discontinued aspirin. Similarly clotting time increased in group B patient and decreased in Group A patient. But in both the groups, bleeding and clotting time remained within normal limits.

Conclusion: Assessing most of the dental and medical literature it can be concluded that there is absolutely no need to discontinue anti platelet therapy for any ambulatory dental procedure and even if practitioner wishes to discontinue, it should not be more than 3 days. This is also stated in the guidelines of American Heart Association.

Keywords:

Anti platelet drugs, Aspirin, Bleeding time, Tooth extraction.

INTRODUCTION

Medical practitioners commonly advice their patients who are on antiplatelet therapy to either stop or alter their medications prior to surgical procedures due to fear of excessive and uncontrolled bleeding. This is a proven fact that aspirin causes increased risk of intraoperative as well as postoperative bleeding and also increased risk of thromboembolic events such as myocardial infraction and cerebrovascular accidents if the drug is continued

¹

. Thrombotic and thromboembolic occlusions of blood vessels are the main cause of ischaemic events in heart, lungs and brain

²

. In case of blood vessel injury hemostatic mechanism is responsible for stopping the extravasation. Mainly hemostatic mechanism in characterized by two consecutive phases primary and secondary. Primary mechanism arrests early bleeding as a result of platelet plug formation

³

. Secondary hemostasis phase is mediated by complex cascade of clotting factors which helps in formation of fibrin clot

⁴

. In recent years lot of research and progress have been made in the field of antiplatelet agents and anticoagulants. These drugs have been utilized for the management of arterial thrombosis also

²

. Even though a number of antiplatelet and anticoagulant agents have been developed, aspirin and warfarin remains the standard drug of choice

⁵

.

Development of aspirin dates back to 1897 and is considered as one of the safest and cheapest drug worldwide. A general practitioner Lawrence Craven prescribed low dose aspirin (Baby Aspirin) to his 400 patients and none of them developed myocardial infraction

⁶

. This was probably the first time in medical history where aspirin was used to prevent myocardial infarction. Since then it has become the drug of choice for cardiologists.

The antithrombotic effect of aspirin is mediated by irreversible inhibition of cyclooxygenase activity in platelets. Phospholipase-A2 acts on the cell membrane to release arachidonic acid on activation. Cyclooxygenase acts on arachidonic acid to produce thromboxane A2. Thromboxane A2 is a potent platelet stimulant leading to degranulation of platelet and platelet aggregation. Aspirin inhibits cyclooxygenase enzyme and decreases the level of platelet stimulant thromboxane A2,

⁵

thus increasing the bleeding time. This is the important reason for a medical practitioner to stop aspirin 3 to 7 days prior to any invasive surgery.

The purpose of this study was to investigate the influence of aspirin on post extraction bleeding.

MATERIALS AND METHOD

This study was conducted at the outpatient Department of Oral and Maxillofacial Surgery. Patients who were on aspirin therapy, aged between 50 to 65 years and who had to undergo tooth extraction were selected for the study. Patients on warfarin, non-steroidal anti-inflammatory drugs, heparin, steroids or suffering from blood disorders and diabetes were excluded from the study. Informed consent was obtained from the patients with the ethical committee clearance.

Two hundred patients including both males and females whose teeth were indicated for extraction were included in the study. Patients were randomly divided into Group A and Group B of 100 patients each. Group A patients continued to receive aspirin preoperatively while Group B patients were asked to stop aspirin 7 days prior to extraction.

Pre operatively all the vital signs (Blood Pressure and Pulse) were measured. Bleeding time (White and Lee technique) and clotting time (Ivy’s technique) was calculated. Extractions were carried out only if the above parameters were within normal range. After tooth was extracted presence or absence of bleeding and bleeding time was recorded. Analgesics and antibiotics were prescribed as needed for pain and infection control.

Chi square test was used to evaluate the relative frequencies of patients in both groups. Differences of parametric variables were tested with analysis of variance.

RESULTS

After applying Chi square test, mean bleeding time was calculated as 2.1±0.52 minutes in the patients who discontinued baby aspirin (Group B) 7 days prior to extraction. Bleeding time of Group A patients who continued aspirin through the entire study was found to be 3.8±0.75 minutes. This difference was statistically significant (p=0.002) [Table 1]. Although there is significant increase in the bleeding time of Group A patients it should be noted that bleeding time of both the groups was within the normal limits. Clotting time of Group B patients was 3.8±0.75 and Group A was 4.7±0.74 which was also within the normal limits (Normal range according to Ivy’s Method: 3 to 5 minutes).

DISCUSSION

Historically aspirin was used as an anti-inflammatory, analgesic and antipyretic drug for a short period of disease activity. Lawrence Craven in 1950 reported for the first time its long term use to prevent myocardial infarction

⁶

. He advocated a lower dose for antiplatelet action. Antiplatelet activity of aspirin occurs at doses ranging as low as 40 mg/day

⁷

to 320

⁸

mg daily. Doses above 320 mg/day decrease the effectiveness of aspirin as antiplatelet agent due to inhibition of prostacyclin production

⁹

. However recent clinical trial indicates that 160 mg/day is optimal for antiplatelet action

¹⁰

. In emergencies where urgent antithrombotic action is required a loading dose of 300 mg is advocated

⁹

. Usually in United States daily dose of 81 mg, 160 mg or 325 mg are prescribed while in Europe and other countries daily dose of 75 mg, 150mg or 300 mg are prescribed

¹⁰

.

Risk of continuing aspirin therapy prior to surgery is that, with the alteration of platelet function longer time period is required to stop the bleeding from a surgical site. This is attributed to the alteration in primary hemostatic mechanism. Burger et al stated that, in patients on aspirin, the average risk of bleeding increases 1.5 folds. At the same time there is a risk in stopping the aspirin prior to surgery leading to a potential risk of rebound of thromboembolic vascular events. On stopping aspirin thromboxane A

₂

activity increases to a greater extent with decrease in fibrinolytic activity

¹¹

. Ferrari et al showed the existence of biological platelet rebound phenomenon on interruption of aspirin therapy. This could create a prothrombotic state which may lead to fatal thromboembolic events. Approximately 20% of these episodes are fatal and another 40% can lead to permanent disability

¹²

.

Practitioners who advocate the stoppage of aspirin have been debating among themselves regarding the time limit to stop aspirin. Literature wise the effect of aspirin on platelets is irreversible. The effect lasts for 7 to 10 days which is the life span of platelets

^{13, 14}

. Therefore since early days it was recommended to stop aspirin 7 days prior to surgical procedure

^15-19

. Sonksen et al in their study comprising of 52 healthy individuals showed that withdrawal of aspirin for more than 5 days was not recommended

²⁰

. Wahl et al advocated that aspirin should be discontinued for 3 days only as after 3 days of interruption of aspirin, sufficient number of newer platelets would be present in circulation for hemostasis

^{21, 22}

.

Now again the debate arises whether to stop aspirin therapy or not? Fear for uncontrolled bleeding encourages the practitioners to discontinue the aspirin therapy. Few studies have shown that there is always an increased risk of bleeding in patients continuing aspirin

^{23, 24}

. Hence few studies recommended stopping of aspirin therapy prior to surgical procedure

^{17, 19, 25}

. However if the aspirin therapy is discontinued, there is increased risk of thromboembolic events which can be fatal but none of these have been reported in dental literature. Fijnheer et al in his article mentioned that there is scarcity of literature regarding dental surgeries involving patients on aspirin medication

²⁶

. Little et al recommended that unless bleeding time is increased above 20 minutes aspirin affected platelets would not cause significant bleeding complication

²²

. Similar claims were made by Sonksen et al and Gaspar et al

^{20, 27}

.

Canigral et al conducted a research involving surgical extraction in patients on antithrombotic therapy. In 92% cases bleeding stopped within 10 minutes with pressure alone. This result was in accordance with the present study

⁴

. Gaspar et al advocated that ambulatory oral surgical procedures can be performed in patients without discontinuing the use of aspirin

²⁷

. A recent recommendation from American Heart Association and American College of Cardiology is that, either continuing aspirin or clopidogrel therapy for minor oral surgical procedures in patients with coronary artery stents or delaying treatment until prescribed regimen will be complicated.

The present study demonstrated that there was significant increase in the bleeding time in both the groups but in no case it was difficult to stop the bleeding. Although bleeding time increased in the Group A patients but it still remained within the normal range, regardless of whether patients continued or discontinued their aspirin therapy

^{28, 29, 30}

. This result was similar to the study done by Canigral et al

⁴

. Valerin et al conducted a study with 17 patients randomized to aspirin and 19 to placebo and found no differences in bleeding outcomes for patients on aspirin. This finding suggested that there was no need to discontinue aspirin prior to any ambulatory oral surgical procedures

³¹

.

Adchariyapetch compared the postoperative bleeding on subjects who stopped or continued taking the aspirin for seven days prior to extraction. The mean bleeding time in both the groups was in normal range. After the procedure there was no difficulty in achieving hemostasis. Therefore they concluded that surgical extraction did not require discontinuation of antiplatelet therapy

³²

. Matocha in his study concluded that risk of bleeding after dental extraction is very minimal in the patients with aspirin therapy and did not exceed 0.2 to 2.3%

³³

.

Murphy et al concluded with a survey that 86% of the dental practitioners who advised the patient to stop antiplatelet drugs prior to dental extraction did so with the consultation of the patient’s physician and found that the protocol followed by the physicians and dentists was not based on the current recommendations and guidelines

³⁴

.

Napenas et al concluded that the risk of stopping antiplatelet therapy and predisposing the patient to thromboembolic events overweighed the minimal risk of bleeding from dental procedures. Similar results were found in the study done by Nielsen et al

³⁵

. Wahl in a research study reported that in 950 patients receiving anticoagulation therapy, only 12 required (<1.3%) more than local measures to stop the bleeding. He concluded that while discontinuation of anticoagulation therapy has been a common practice, bleeding after dental surgery rarely was life threatening.

CONCLUSION

Thus according to dental and medical literature it can be concluded that if a practitioner wishes to discontinue the aspirin therapy, it should not exceed for more than three days. Risk of stopping antiplatelet therapy and predisposing the patient to thromboembolic events overweighed the minimal risk of bleeding from dental procedures. Although in the present study there was increase in bleeding time but it was not beyond the normal range. Hence it can be concluded that low dose of aspirin should not be discontinued prior to dental extractions and predispose the patient to unwanted thromboembolic events.

REFERENCES

1. S. M. Jafri, B. Zarowitz, S. Goldstein, M. Lesch. The role of antiplatelet therapy in acute coronary syndromes and for secondary prevention following a myocardial infarction. Progress in Cardiovascular Diseases 1993;36(1):75–83.
2. C. D. Owens, M. Belkin. Thrombosis and coagulation: operative management of the anticoagulated patient. Surgical Clinics of North America 2005;85(6)1179–89.
3. M. Shah, D. Dave, R. Dave, A. Bharwani, A Shah. Management of medically compromised patient in periodontal practice. Advances in Human Biology 2013;3(1):1-6.
4. Canigral, F.J. Silvestre, G. Canigral, M. Alos, A. Garcia-Herraiz, Anda. Plaza. Evaluation of bleeding risk and measurement methods in dental patients. Medicina Oral, Patologia Oraly Cirugia Bucal 2010;15(6):e863–e868.
5. J.M. Dogne, X. de Leval, P. Benoit, J. Delarge, B. Masereel, J.L. David. Recent advances in antiplatelet agents. Current Medicinal Chemistry 2002;9(5):577–89.
6. L. L. Craven. Acetylsalicylic acid, possible preventive of coronary thrombosis. Annals of Western Medicine and Surgery 1950;4(2):95.
7. M. T. Brennan, R. L. Wynn, C. S. Miller. Aspirin and bleeding in dentistry: an update and recommendations. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology 2007;104(3):316–23.
8. C. Patrono, G. Ciabarroni, P. Patrignani et al. Clinical pharmacology of platelet cyclooxygenase inhibition. Circulation 1985;72(6):1177–84.
9. Antithrombotic Trialists Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. British Medical Journal 2002;324:71–86.
10. J. E. Dalen. Aspirin to prevent heart attack and stroke: what’s the right dose? American Journal of Medicine 2006;119(3):198–202.
11. J.P. Collet, G. Montalescot. Premature withdrawal and alternative therapies to dual oral antiplatelet therapy. European Heart Journal Supplements 2006;8:G46–G52.
12. C. S. Anderson, K. D. Jamrozik, R. J. Broadhurst, E. G. Stewart-Wynne. Predicting survival for 1 year among different subtypes of stroke: results from The Perth Community Stroke Study. Stroke1994;25(10):1935–44.
13. J. C. Merritt, D. L. Bhatt. The efficacy and safety of perioperative antiplatelet therapy. Journal of Thrombosis and Thrombolysis 2002;13(2):97–103.
14. I. Schafer. Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. Journal of Clinical Pharmacology 1995;35(3):209–19.
15. J. E. Watson, A. M. Deane, P. T. Doyle, K. N. Bullock. Identifiable factors in post-prostatectomy haemorrhage: the role of aspirin. British Journal of Urology 1990;66(1):85–7.
16. L. Kitchen, R. B. Erichson, H. Sideropoulos. Effect of drug induced platelet dysfunction on surgical bleeding. American Journal of Surgery 1982;143(2):215–7.
17. C. R. Conti. Aspirin and elective surgical procedures. Clinical Cardiology 1992;15(10):709–10.
18. K. S. Scher. Unplanned reoperation for bleeding. American Surgeon 1996;62(1):52–5.
19. J. A. Speechley, F. P. Rugman. Some problems with anticoagulants in dental surgery. Dental Update 1992;19(5):204–6.
20. J. R. Sonksen, K. L. Kong, R. Holder. Magnitude and time course of impaired primary haemostasis after stopping chronic low and medium dose aspirin in healthy volunteers. British Journal of Anaesthesia 1999;82(3):360–5.
21. M. J. Wahl. Myths of dental surgery in patients receiving anticoagulant therapy. The Journal of the American Dental Association 2000;131(1):77–81.
22. J. W. Little, C. S. Miller, R. G. Henry, B. A. McIntosh. Antithrombotic agents: implications in dentistry. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 2002;93(5):544–51.
23. V.A. Ferraris, S. P. Ferraris, F. C. Lough, W. R. Berry. Preoperative aspirin ingestion increases operative blood loss after coronary artery bypass grafting. Annals of Thoracic Surgery 1988;45(1):71–4.
24. D. P. Taggart, A. Siddiqui, D. J. Wheatley. Low-dose preoperative aspirin therapy, postoperative blood loss, and transfusion requirements. Annals of Thoracic Surgery 1990;50(3):425–8.
25. V. A. Ferraris, E. Swanson. Aspirin usage and perioperative blood loss in patients undergoing unexpected operations. Surgery Gynecology and Obstetrics 1983;156(4):439–42.
26. C. Lawrence, A. Sakuntabhai, S. Tiling-Grosse. Effect of aspirin and nonsteroidal antiinflammatory drug therapy on bleeding complications in dermatologic surgical patients. Journal of the American Academy of Dermatology 1994;31(6):988–92.
27. R. Gaspar, L. Ardekian, B. Brenner, M. Peled, D. Laufer. Ambulatory oral procedures on low-dose aspirin. Harefuah 1999;136(2):108–10.
28. W. Burger, J.M. Chemnitius, G. D. Kneissl, G. Rucker. Low-close aspirin for secondary cardiovascular prevention—cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation—review and meta-analysis: Journal of Internal Medicine 2005;257(5):399–414.
29. Harker LA, Slichter SJ. The bleeding time as a screening test for evaluation of platelet function. N Engl J Med 1972; 287(4):155-9.
30. K.A. Shah, M.A. Patel, R. Tatu, V. Patel. Relationship between use of Aspirin and post extraction bleeding time: A randomized control and single blind study in fifty patients. Journal of Research and Advancement in Dentistry 2013;2(3s):167-72.
31. Valerin MA, Brennan MT, Noll JL, Napeñas JJ, Kent ML, Fox PC, et al. Relationship between aspirin use and postoperative bleeding from dental extractions in a healthy population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 102:326.
32. Adchariyapetch R. Dental extraction in patients on aspirin. Vajira Med J 2009;53(3):283-89.
33. D. L. Matocha. Postsurgical complications. Emergency Medicine Clinics of North America 2000;18(3):549–64.
34. J. Murphy, E. Twohig, S. R. McWilliams. Dentists’ approach to patients on anti-platelet agents and warfarin: a survey of practice. Journal of the Irish Dental Association 2010;56(1):28–31.
35. J.D. Nielsen, C.A. Laetgaard, S. Schou, S. S. Jensen. Minor dentoalveolar surgery in patients undergoing antithrombotic therapy. Ugeskrift for Laeger 2009;171(17):1407–9.