J Oral Maxillofac Surg 70:521-526, 2012

Risk Factors Affecting Hemorrhage After Tooth Extraction in Patients Undergoing Continuous Infusion With Unfractionated Heparin
Yoshinari Morimoto, DDS, PhD,* Hitoshi Niwa, DDS, PhD, and Kazuo Minematsu, MD, PhD
Purpose: To identify the risk factors affecting the incidence of postoperative hemorrhage (POH)

associated with tooth extraction in patients undergoing continuous infusion with unfractionated heparin.
Patients and Methods: In the present retrospective study, the medical records of patients who had

undergone tooth extraction during continuous infusion of unfractionated heparin were reviewed. The primary predictor variables were demographics (age, gender), heparin dose and degree of anticoagulant effect (activated partial thromboplastin time [APTT]), total number of extracted teeth and number of extracted teeth per occasion, and type of tooth extraction (simple extraction or surgical extraction). The primary outcome variable was the incidence of POH. The incidence of POH in each APTT category was also evaluated. The Mann-Whitney U test, 2 test, or Fisher exact test were used for comparison between the non-POH and POH groups and the incidence of POH stratied by the categorized APTT values. Logistic regression analysis was then used to detect the factors affecting POH. The level of statistical signicance was P .05. Results: Tooth extraction was performed on 35 occasions in 31 patients. POH occurred 10 times (28.6%). The comparison of the POH group (10 occasions) and non-POH group (25 occasions) showed that the median APTT value in the POH group (62 seconds) was signicantly prolonged compared with that in the non-POH group (42 seconds). The incidence of POH was signicantly greater in the group with an APTT of 57 seconds or greater. Logistic regression analysis revealed that the APTT was the only factor related to the occurrence of POH. Conclusions: The results of the present study suggest that POH in tooth extraction occurs often in patients with an APTT of 57 seconds or greater when the continuous heparin infusion cannot be stopped. 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:521-526, 2012 During tooth extraction in patients receiving oral antithrombotic therapy, continuous administration of maintenance doses of warfarin and/or antiplatelet drugs is recommended.1-16 For these patients, bridging therapy, by discontinuing warfarin and switching to either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH), is recommended during surgery.17-20
*Associate Professor, Department of Dental Anesthesiology, Osaka University Graduate School of Dentistry, Osaka, Japan. Professor, Department of Dental Anesthesiology, Osaka University Graduate School of Dentistry, Osaka, Japan. Director, Cerebrovascular Division, Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan. Address correspondence and reprint requests to Dr Morimoto: Department of Dental Anesthesiology, Osaka University Graduate

With UFH, warfarin should be stopped 5 days before surgery to maintain the prothrombin time international normalized ratio (PT-INR) at less than 1.5. Then, the UFH is adjusted to increase the activated partial thromboplastin time (APTT) to 1.5 to 2.0 times the upper normal limit. UFH is stopped 4 hours before surgery, surgery is performed, and within 24 hours after surgery has been completed, after hemoSchool of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 Japan; e-mail: ysn-mori@dent.osaka-u.ac.jp
2012 American Association of Oral and Maxillofacial Surgeons

0278-2391/12/7003-0$36.00/0 doi:10.1016/j.joms.2011.08.016

521

522 stasis has been conrmed, the therapy is resumed. With LMWH, treatment doses are given twice daily, subcutaneously, until 24 hours before surgery (last dose is one half of the dosage). With heparin bridging therapy, no differences in the incidence of thromboembolism or hemorrhage have been reported between the use of UFH and LMWH.17-20 Overall, with heparin bridging, the incidence of thromboembolism is only about 1%20; however, many hemorrhagic events have been reported, including severe bleeding in about 3%,20 and minor bleeding in about 7% to 9%21-23 of cases. Thus, the risk of thromboembolism and hemorrhage must be considered when determining the indications for bridging treatment. In contrast, during continuous infusion of UFH for acute cardiovascular disease treatment (eg, cerebral infarction or acute coronary syndrome), oral surgery procedures, including tooth extraction, are sometimes necessary. In these cases, control of bleeding during treatment when UFH is continued can also be a problem. However, we have no suggestions regarding the hemostatic management for tooth extraction during continuous UFH infusion. The purpose of the present study was to identify the risk factors affecting the incidence of postoperative hemorrhage (POH) in tooth extraction in patients receiving continuous heparin therapy and to suggest criteria for safer management of this condition. The present study was performed to retrospectively evaluate the incidence and management of POH in patients undergoing tooth extraction with continuous infusion of UFH for the treatment of cardiovascular disease.

POSTOPERATIVE HEMORRHAGE IN HEPARIN THERAPY

predictor variables. The incidence of POH was the primary outcome variable. Systemic disease as the reason for heparin therapy, dental disease (marginal periodontitis, periapical periodontitis, and third molar pericoronitis), and antithrombotic regimen (heparin alone, heparin plus warfarin, heparin plus warfarin plus antiplatelet drug, or heparin plus antiplatelet drug) were also investigated. The incidence of POH in each APTT category stratied by the median and interquartile range was also evaluated. In patients receiving concomitant therapy with warfarin, the PT-INR was measured on the day of tooth extraction. Also, the POH and non-POH groups were compared to examine the factors affecting the occurrence of POH. In addition, in patients with POH, the time of onset of POH and the local hemostatic treatments given were reviewed. In our institution, the APTT standard range is 25 to 38 seconds. All patients had platelet counts of 10 104/ mm3 or greater. Acute inammation was dened as 1 or more of the following ndings: redness, swelling, or pus discharge of the soft tissues surrounding the tooth to be extracted or severe percussion pain of the tooth. In these cases, tooth extraction was performed after 1 week of treatment with an antibiotic administered orally. In patients with a risk of infective endocarditis, antibiotics were prescribed according to the guidelines for infective endocarditis prophylaxis from the Japanese Circulation Society.24 For analgesia, loxoprofen sodium or acetaminophen was administered as needed.
TOOTH EXTRACTION AND LOCAL HEMOSTATIC CONTROL

Patients and Methods

STUDY DESIGN AND PATIENTS

The institutional research board and ethics committee of the National Cerebral and Cardiovascular Center approved the present retrospective study. To identify the risk factors affecting the incidence of POH after tooth extraction with continuous infusion of UFH, we designed and implemented a retrospective observational study. The study population included all patients who had undergone tooth extraction with continuous infusion of UFH during hospitalization at the National Cerebral and Cardiovascular Center from April 2002 to March 2009. In the present study, the medical records of the patients were reviewed to evaluate the patient demographics (age, gender), heparin dose and degree of anticoagulant effect (APTT on the day of tooth extraction), total number of extracted teeth and number of extracted teeth per occasion, type of tooth extraction (simple extraction or surgical extraction), and acute inammation of the extracted tooth as the primary

Tooth extraction was performed with the maintenance doses of heparin and concomitant warfarin or antiplatelet drugs continued. The procedures were performed by a single oral surgeon. For local anesthesia, 3% prilocaine (containing 0.054 IU felypressin, Dentsply-Sankin, Tokyo, Japan) was used. Tooth extraction was performed with a minimally invasive procedure using an elevator and forceps. Inammatory granulation tissue was thoroughly curetted. As local hemostatic treatment after extraction of an erupted tooth, oxidized cellulose (Surgicel, Ethicon, Somerville, NJ) was inserted in to the extraction socket, and horizontal mattress sutures were placed using 4-0 silk to retain it. For extraction of an impacted tooth, oxidized cellulose was inserted in the extraction wound, and the wound was closed with 4-0 silk suture. If hemostasis was not achieved with these procedures, electrocautery was used to cauterize, in the smallest area possible, the bleeding points in the soft tissue. Next, for compression, the patients were asked to bite down on gauze for 30 minutes, and hemostasis was conrmed. No splints were used at

MORIMOTO ET AL

523 thrombus in 4, disseminated intravascular coagulation (thoracic arterial aneurysm), perioperative period of valve replacement and replacement of warfarin by heparin because of pregnancy in 2 patients each, and pulmonary embolism, deep venous thrombosis, and warfarin resistance in 1 patient each. In all cases, tooth extraction was performed after the initial treatment for systemic disease had been completed, during a period in which the systemic disease was relatively stable. Extraction was performed on 35 occasions, with a total of 63 teeth (median 1 tooth/occasion). Antithrombotic therapy was with heparin alone in 14 patients (16 extractions), heparin plus warfarin in 11 patients (12 extractions), heparin plus warfarin plus antiplatelet drug in 2 patients (3 extractions), and heparin plus antiplatelet drug in 4 patients (4 extractions). The type of tooth extraction was simple extraction for 29 occasions (54 teeth) and surgical extraction for 6 (9 teeth). Marginal periodontitis was seen in 40 teeth, periapical periodontitis in 18, and third molar pericoronitis in 5 teeth. Acute inammation was present in 4 extractions and absent in 31. POH occurred on 10 occasions (28.6%).
ANALYSIS OF FACTORS AFFECTING POH

the extraction. However, when POH was observed, the wounds were protected by a surgical acrylic splint with a periodontal pack, as needed. The sutures were removed after 1 week. Tranexamic acid mouthwash is not approved in Japan and was not used.
ASSESSMENT OF POH

POH was dened as oozing requiring the patient to bite down on gauze as compression for hemostasis or oozing or severe bleeding for which, despite gauze compression by the patient, hemostasis could not be achieved and requiring hemostatic management by an oral maxillofacial surgeon (eg, compression, hematoma removal, insertion of oxidized cellulose, and resuturing, electrocautery, and splinting). A telephone call was made, in the evening of the day of extraction and the following morning, to the nurse in charge at the patients hospital ward to inquire about postoperative hemostasis. In addition to a dental examination 3 days and 1 week after extraction to conrm the wound status, the medical records were reviewed, and the patient was asked personally about hemostasis. Hemostasis was assessed from 30 minutes to 1 week after extraction.
STATISTICAL ANALYSIS

Statistical analysis was performed using the Statistical Package for Social Sciences, version 16.0, software (SPSS Japan, Tokyo, Japan). The data, including age, number of extracted teeth per occasion, heparin dose, PT-INR, and APTT, are presented as the median (interquartile range), because they did not exhibit a normal distribution. Statistical analysis of patient age, number of extracted teeth per occasion, PT-INR, heparin dose, and APTT was performed using the Mann-Whitney U test. Gender, dental disease, antithrombotic therapy, surgical extraction, acute inammation, and the incidence of POH stratied by the categorized APTT values were examined using the 2 test or Fisher exact test. For correlation between age and APTT and between the number of extracted teeth per occasion and APTT, Pearson correlation coefcient was used. Logistic regression analysis was used to detect the factors affecting the incidence of POH. For all analyses, the level of statistical signicance was P .05.

Results
PATIENT CHARACTERISTICS

A total of 31 patients, including 19 males and 12 females, aged 16 to 89 years (median 72, interquartile range 64 to 85.25), were included in the study. UFH treatment was prescribed for cerebral infarction in 12 patients, acute coronary syndrome in 6, intracardiac

Of the 35 tooth extraction procedures performed, POH occurred 10 times and did not occur 25 times (Table 1). Gender, type of dental disease, antithrombotic regimen, heparin dose, PT-INR in patients taking warfarin, number of surgically extracted teeth, and acute inammation did not signicantly differ between the 2 groups. The median APTT value was 44 seconds (interquartile range 38.75 to 56.75) in all patients. However, the APTT in the POH group (median 62 seconds, interquartile range 49.75 to 75.75) was signicantly prolonged compared with that in the non-POH group (median 42 seconds, interquartile range 35.5 to 45.0). Stratifying the incidence of POH by the categorized APTT values using the median and interquartile range, the POH rate was signicantly greater in the group with an APTT of 57 seconds or more (Table 2). In addition, age and number of extracted teeth per occasion were lower in the POH group (Table 1). Age and APTT showed a correlation (correlation coefcient 0.419, P .015); however, the number of extracted teeth per occasion and APTT showed no correlation (correlation coefcient 0.269, P .124). Logistic regression analysis found that APTT was the only factor related to POH (odds ratio 1.18, 95% condence interval 1.01 to 1.37, P .035). Age and number of extracted teeth per occasion were not related (Table 3).

524

POSTOPERATIVE HEMORRHAGE IN HEPARIN THERAPY

Table 1. COMPARISON OF FACTORS FOR POSTOPERATIVE HEMORRHAGE

Postoperative Hemorrhage Variable Age (yr) Median Interquartile range Gender Male Female Dental disease Marginal periodontitis Periapical periodontitis Pericoronitis Antithrombotic therapy Heparin Heparin warfarin Heparin warfarin antiplatelet drug Heparin antiplatelet drug Extracted teeth (n/occasion) Median Interquartile range Type of tooth extraction (n) Surgical Simple Heparin (U/d) Median Interquartile range PT-INR Median Interquartile range APTT (s) Median Interquartile range Acute inammatory ndings Yes No
Positive (n 10 patients) Negative (n 25 patients)

Statistical Analysis P .001 (2 10.10)

63.0 32.0-69.75 4 6 5 3 2 4 3 3 0 1.0 1-1.25 3 7 10,000 10,000-13,500 1.40 1.27-1.85 62.0 49.75-75.75 2 8

77.5 68.25-87.5 16 9 15 9 1 12 9 0 4 2.0 1-3 3 22 10,000

P .118 (2 2.45) P .107 (2 2.60)

P .936 (2 0.006)

P .033 (2 4.53) P .208 (2 1.58) P .154 (2 2.04) P .093 (2 2.83)

1.18 1.10-1.58 42.0 35.5-45.0 2 23

P .001 (2 12.42) P .368 (2 0.811)

Abbreviations: PT-INR prothrombin time-international normalized ratio; APTT activated partial thromboplastin time.
Morimoto et al. Postoperative Hemorrhage in Heparin Therapy. J Oral Maxillofac Surg 2012.

ANALYSIS OF CASES OF POH

In the 10 patients with POH, the time of onset ranged from 1 to 5 days (median 4, interquartile range 2.5 to 4.5) after extraction. The frequency of hemorrhage by the time of onset was 3 patients each on postoperative

days 4 and 5, 2 patients on postoperative day 1, and 1 patient each on postoperative days 2 and 3. Local hemostatic measures taken at POH included hematoma removal plus insertion of oxidized celluTable 3. CORRELATION FACTORS FOR POSTOPERATIVE HEMORRHAGE

Table 2. HEMORRHAGIC EVENTS IN EACH APTT GROUP

Variable
57-110

P Value .059 .495 .035

Odds Ratio (95% CI) 0.93 (0.87-1.01) 0.60 (0.14-2.60) 1.18 (1.01-1.37)

APTT (s) Variable Patients (n) Hemorrhage (n) P .001, 2 12.42.

Morimoto et al. Postoperative Hemorrhage in Heparin Therapy. J Oral Maxillofac Surg 2012.
22-38 39-44 45-56

9 0

9 2

9 1

8 7

Age Number of extracted teeth/ occasion APTT (s)

Abbreviations: CI, condence interval; APTT, activated partial thromboplastin time.

Morimoto et al. Postoperative Hemorrhage in Heparin Therapy. J Oral Maxillofac Surg 2012.

MORIMOTO ET AL

525 formed. POH tended to occur in patients with an APTT exceeding 57 seconds. In the patient with the greatest APTT of 110 seconds, although hemostasis was achieved during the procedure, bleeding occurred later. Spyropoulos et al18,19 reported that heparin use postoperatively was an independent predictive factor for major bleeding. In our study, infusion of UFH was also continued postoperatively; thus, POH was more common. When the APTT is prolonged with UFH administration, even if hemostasis is initially achieved during tooth extraction, irritation by movement of the tongue during eating or speaking could provoke bleeding again. Thus, wound protection with a splint might be advisable. In the present study, POH occurred often in patients with an APTT of 57 seconds or greater. With heparin (UFH) bridging, UFH is discontinued 4 hours before surgery.17 As a result, when surgery starts, the APTT is sufciently decreased because the half-life of UFH has been reached. The APTT at that time should be adjusted to less than 57 seconds. In addition, when resuming UFH after surgery, caution should be exercised when the APTT increases to 57 seconds or greater. The time of onset of POH ranged from 1 to 5 days (median 4). Bailey et al25 and Morimoto et al12 reported that when tooth extraction was performed when the warfarin or antiplatelet drugs were continued, POH often occurred up to 5 days after the procedure, a nding in agreement with our results. For local hemostatic treatment, hematoma removal, insertion of oxidized cellulose, and resuturing were necessary because of a risk of hematoma formation in patients taking warfarin. In addition, electrocautery or splinting was required in one half of the cases. In 1 patient, because it was difcult to achieve hemostasis, brin glue was also used. For local hemostasis after tooth extractions in patients taking warfarin, brin glue, oxidized cellulose, and gelatin sponges have been reported to be equally effective26,27; however, in patients receiving continuous heparin infusion, local hemostasis might be more difcult to achieve than with warfarin. In our study, the lower the age and number of extracted teeth per occasion, the greater the incidence of POH. An examination of the correlation between age and APTT showed that the younger the age, the greater the APTT. Thus, the younger the patient, the more potent the effects of anticoagulant therapy with UFH. This is consistent with our results that POH was more dependent on the APTT than on patient age. Logistic regression analysis also showed that patient age was not a related factor. In contrast, no correlation was found between the number of extracted teeth per occasion and APTT; thus, the relation between the number of extracted teeth and POH is unclear. However, the median number of extracted teeth per occasion was 1 tooth in the POH

lose plus compression in 3 patients and, in addition, resuturing in 2 patients. Also, electrocautery was used in 3 patients and a splint in 2 patients. Also, because of difcult hemostasis, brin glue was used in 1 patient. None of the patients with POH had serious bleeding requiring blood transfusion.

Discussion
The purpose of the present study was to identify the risk factors affecting POH in tooth extraction during continuous infusion of UFH. Our study found that the POH rate was about 28.6%; the APTT in the POH group was signicantly prolonged compared to the non-POH group; and APTT was a risk factor for POH in tooth extraction of patients receiving continuous UFH infusion. In particular, the incidence of POH increased when the APTT was 57 seconds or greater. POH occurred by 5 days (median 4) after extraction. Local hemostatic treatment, in addition to hematoma removal, insertion of oxidized cellulose, compression, and resuturing, required the use of electrocautery or a splint in one half of the cases; in 1 patient, brin glue was also used. Complications with heparin bridging therapy during minor surgery in patients taking warfarin have been reported in several studies. After minor surgery (eg, tooth extraction, endoscopic procedure) in patients taking warfarin, Garcia et al21 reported that when warfarin was interrupted and LMWH administered, although thromboembolism did not occur, the incidence of serious bleeding (eg, subdural hemorrhage, gastrointestinal bleeding) was 3.7%, and the incidence of minor bleeding (eg, wound bleeding) was 9.3%. Bajkin et al,22 after stopping warfarin 3 to 4 days before tooth extraction, administered LMWH (nadroparin 2,850 to 5,700 IU) twice daily subcutaneously, maintained the INR at less than 1.5, and then performed tooth extraction. They reported a POH rate of 7.3%.22 Hong et al23 reported a POH rate of 7.1% when they administered LMWH (enoxaparin 30 to 40 mg) 1 to 2 times daily subcutaneously to perform tooth extraction. Previous reports on tooth extraction in patients taking warfarin have reported POH rates of 2% to 26%.2,4-8,11-13 When heparin is used, although the thromboembolism rate is low, the incidence of serious systemic bleeding is 3.7%, and the incidence of minor bleeding such as wound bleeding is high, at 7% to 10%. Thus, the indications for heparin bridging therapy must take into account the risks and benets.17 In our study, the POH rate was about 28%, higher than previously reported. This is probably because UFH was continued, without interruption, in the perioperative period when tooth extraction was per-

526 group and 2 teeth in the non-POH group. This is not a marked clinical difference. In patients taking warfarin or antiplatelet drugs, Scully and Wolff28 reported that acute inammation such as gingivitis was a risk factor for POH; however, in our study, because of the small number of cases, no clear trend was observed. Also, the effect of antibiotics and nonsteroidal anti-inammatory drugs is not clear. One limitation of the present study was that it was a retrospective observational study; hence, the patient background data, type of treatment, and administration of antibiotics and nonsteroidal anti-inammatory drugs for each patient were not controlled. In the future, randomized controlled trials with a larger number of patients should be performed. The results of the present study suggest that POH in tooth extraction occurs often in patients with an APTT of 57 seconds or greater when continuous heparin infusion cannot be stopped. Therefore, in patients who require heparin infusion continuously, adjusting the APTT to less than 57 seconds during tooth extraction might reduce the incidence of POH. However, these criteria might not be accepted owing to the increased thromboembolic risk associated with heparin therapy. Thus, a consensus between the dentist and physician should be established.

POSTOPERATIVE HEMORRHAGE IN HEPARIN THERAPY

10. Aframian DJ, Lalla RV, Peterson DE: Management of dental patients taking common hemostasis-altering medications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103(Suppl. 1): S45.e1, 2007 11. Ferrieri GB, Castiglioni S, Carmagnola D, et al: Oral surgery in patients on anticoagulant treatment without therapy interruption. J Oral Maxillofac Surg 65:1149, 2007 12. Morimoto Y, Niwa H, Minematsu K: Hemostatic management of tooth extractions in patients on oral antithrombotic therapy. J Oral Maxillofac Surg 66:51, 2008 13. Nematullah A, Alabousi A, Blanas N, et al: Dental surgery for patients on anticoagulant therapy with warfarinA systemic review and meta-analysis. J Can Dent Assoc 75:41, 2009 14. Wahl MJ: Dental surgery in anticoagulated patients. Arch Intern Med 158:1610, 1998 15. Blacker DJ, Wijdicks FM, McClelland RL: Stroke risk in anticoagulated patients with atrial brillation undergoing endoscopy. Neurology 61:964, 2003 16. Maulaz AB, Bezerra DC, Michael P, et al: Effect of discontinuing aspirin therapy on the risk of brain ischemic stroke. Arch Intern Med 62:1217, 2005 17. Douketis JD, Berger PB, Dunn AS, et al: The perioperative management of antithrombotic therapy: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest 133(Suppl.):299, 2008 18. Spyropoulos AC, Turpie AGG, Spandorfer J, et al: Clinical outcomes with unfractionated heparin or low-molecularweight heparin as bridging therapy in patients on long-term oral anticoagulants: The REGIMEN registry. J Thromb Haemost 4:1246, 2006 19. Spyropoulos AC, Turpie AGG, Dunn AS, et al: Perioperative bridging therapy with unfractionated heparin or low-molecular-weight heparin in patients with mechanical prosthetic heart valves on long-term oral anticoagulants (from the REGIMEN registry). Am J Cardiol 102:883, 2008 20. Spyropoulos AC: To bridge or not to bridge: That is the question. The argument for bridging therapy in patients on oral anticoagulants requiring temporary interruption for elective procedures. J Thromb Thrombolysis 29:192, 2010 21. Garcia DA, Regan S, Henault LE, et al: Risk of thromboembolism with short-term interruption of warfarin therapy. Arch Intern Med 168:63, 2008 22. Bajkin BV, Popovic SL, Selakovic SDJ: Randomized, prospective trial comparing bridging therapy using low-molecular-weight heparin with maintenance of oral anticoagulation during extraction of tooth. J Oral Maxillofac Surg 67:990, 2009 23. Hong CHL, Napeas JJ, Brennan MT, et al: Frequency of bleeding following invasive dental procedures in patients on lowmolecular-weight heparin therapy. J Oral Maxillofac Surg 68: 975, 2010 24. Miyatake K, Akaishi M, Kawazoe K, et al: Guidelines for the prevention and treatment of infective endocarditis (JCS2003). Circ J 67(Suppl.):1039, 2003 25. Bailey BMW, Fordyce AM: Complications of dental extractions in patients receiving warfarin anticoagulant therapyA controlled clinical trial. Br Dent J 155:308, 1983 26. Blinder D, Manor Y, Martinowitz U, et al: Dental extractions in patients maintained on continued oral anticoagulantComparison of local hemostatic modalities. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88:137, 1999 27. Halfpenny W, Fraser JS, Adlam DM: Comparison of 2 hemostatic agents for the prevention of postextraction hemorrhage in patients on anticoagulants. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 92:257, 2001 28. Scully C, Wolff A: Oral surgery in patients on anticoagulant therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 94:57, 2002

References
1. Souto JC, Oliver A, Jausoro IZ, et al: Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: A prospective randomized study. J Oral Maxillofac Surg 54:27, 1996 2. Devani P, Lavery KM, Howell CJT: Dental extractions in patients on warfarin: Is alteration of anticoagulant regime necessary? Br J Oral Maxillofac Surg 36:107, 1998 3. Campbell JH, Alvarado F, Murray RA: Anticoagulation and minor oral surgery: Should the anticoagulation regimen be altered? J Oral Maxillofac Surg 58:131, 2000 4. Blinder D, Manor Y, Martinowitz U, et al: Dental extractions in patients maintained on oral anticoagulant therapy: Comparison of INR value with occurrence of postoperative bleeding. Int J Oral Maxillofac Surg 30:518, 2001 5. Evans IL, Sayers MS, Gibbons AJ, et al: Can warfarin be continued during dental extraction? Results of a randomized controlled trial. Br J Oral Maxillofac Surg 40:248, 2002 6. Sacco R, Sacco M, Carpenedo M, et al: Oral surgery in patients on oral anticoagulant therapyA randomized comparison of different intensity targets. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:e18, 2007 7. Al-Mubarak S, Ali NA, Rass MA, et al: Evaluation of dental extractions, suturing and INR on postoperative bleeding of patients maintained on oral anticoagulant therapy. Br Dent J 203:E15, 2007 8. Salam S, Yusuf H, Milosevic A: Bleeding after dental extractions in patients taking warfarin. Br J Oral Maxillofac Surg 45:463, 2007 9. Perry DJ, Noakes TJC, Helliwell PS, et al: Guidelines for the management of patients on oral anticoagulants requiring dental surgery. Br Dent J 203:389, 2007