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Management of anticoagulation in patients with prosthetic heart valves undergoing oral and maxillofacial operations
British Journal of Oral and Maxillofacial Surgery (2000) 38, 124–126 © 2000 The British Association of Oral and Maxillofacial Surgeons DOI: 10.1054/bjom.1999.0176
B BR RIIT TIIS SH H JJO OU UR RN NA AL L O OF F O OR RA AL L
& &M MA AX XIIL LL LO OFA FAC CIIA AL LS SU UR RG GE ERY RY
Management of anticoagulation in patients with prosthetic heart valves undergoing oral and maxillofacial operations K. Webster,* J. Wilde† *Senior Registrar, Department of Oral & Maxillofacial Surgery; †Consultant in Haemostasis and Thrombosis, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, UK SUMMARY. There is wide variation in the management of patients with mechanical prosthetic valves who are taking anticoagulants and who require non-cardiac surgery. In this paper, we outline a pragmatic, practical approach to the adjustment of anticoagulation in relation to both the degrees of surgical trauma during oral and maxillofacial surgery and the risk of thromboembolism associated with the prosthetic valve. For minor surgery, no adjustment of anticoagulation is undertaken if the International Normalized Ratio is less than 4.0, if local haemostatic methods and tranexamic acid mouthwashes are used. For major surgery, warfarin is stopped preoperatively and lowmolecular-weight heparin is used. For emergency surgery, partial reversal of anticoagulation with low-dose parenteral vitamin K is obtained. 4.0, warfarin should be discontinued and surgery retimed to be done when the INR is back within the therapeutic range. During operation, the use of a local anaesthetic combined with a vasoconstrictor, and local haemostatic methods, are recommended. At the end of the procedure, the operative field should be irrigated with 4.8% tranexamic acid solution (Cyklokapron®, Pharmacia). The sockets and mucoperiosteal flaps should then be sutured and oxidized cellulose gauze (such as Surgicel®, Johnson & Johnson) placed in the sockets. The patients should then rinse with 4.8% tranexamic acid solution 10 ml. On discharge, they are given instructions to rinse with 10 ml of the solution for 2 min four times a day for seven days.4
INTRODUCTION It is estimated that over 300 000 people in the UK are taking oral anticoagulants, and many of them are doing so to prevent thromboembolism from mechanical heart valves. The type and position of the prosthetic valve influence the risk of thromboembolism, and thromboembolic events occur more frequently with mitral than with aortic valves, and in people with co-existing atrial fibrillation (AF). The older types of ball valves are also more likely to be associated with fatal thromboembolic events than pivoting disc valves.1,2 The British Society for Haematology has balanced thromboembolic risks against the haemorrhagic risk of anticoagulation and recently revised the guidelines on anticoagulant control; it recommends a target International Normalized Ratio (INR) for prosthetic heart valves of 3.5, with an acceptable range of 3.0–4.0.3 Patients with prosthetic heart valves commonly require non-cardiac surgery, but there is little consensus on how to manage their anticoagulation perioperatively.4.5 Current practice, depending on the type of operation, ranges from no adjustment of anticoagulation, to reducing the dose of oral anticoagulant drugs, to substitution with heparin, to stopping oral anticoagulation completely.6–10 To rationalize the inconsistencies of current practice, and to attempt to strike a balance between thrombotic risk from stopping anticoagulation and haemorrhagic risk from continuing anticoagulation, we propose the following guidelines.
Major surgery (such as parotidectomy or neck dissection) Warfarin should not be taken on the three evenings before admission. The patient should be admitted on the day before operation and given a subcutaneous injection of a low-molecular-weight heparin in a prophylactic dose if the INR has fallen below 2.0. On the day of operation, the INR should be checked to ensure that the prothrombin time is within normal limits (INR <1.3), and a prophylactic dose of lowmolecular-weight heparin given subcutaneously 2 h preoperatively. If the INR has not returned to the normal range and it is not possible to retime the operation, vitamin K 1 mg should be given intravenously. This should result in return of the INR to the normal range within 2–3 h, and is not a large enough dose to make the patient refractory to the subsequent re-introduction of oral anticoagulants. Warfarin can be started on the night of operation, at a dose twice that of the patient’s normal maintenance dose. The INR should be checked daily, and
PROPOSED GUIDELINES Minor surgery (such as skin biopsy, extractions, and surgical removal of teeth) The anticoagulation regimen does not require alteration if the INR is less than 4.0. If the INR is above 124
Management of anticoagulation in patients with prosthetic heart valves
the warfarin dose adjusted accordingly. Subcutaneous heparin should be continued daily in a prophylactic dose until the INR has been back within the therapeutic range for 48 h.
Emergency surgery If emergency surgery can be deferred for a few hours, oral anticoagulation can be partially reversed by giving a low dose of vitamin K (1 mg) intravenously. Vitamin K should be given to sustain the reversal of anticoagulation during the operative period. If immediate surgery is required, fresh frozen plasma or prothrombin complex concentrate (if available) should be given to enable immediate correction of coagulation. We recommended that, in an emergency, the advice of a haematologist be sought.
DISCUSSION There are no large randomized studies that compare different perioperative anticoagulant regimens for patients with mechanical heart valves having operations. For patients on oral anticoagulants who require minor oral surgical procedures, a number of authors have recommended that up to an INR of 4.0, the dose of anticoagulant does not need to be modified, provided that local haemostatic measures such as the use of tranexamic acid mouth washes are followed.4,8,11–14 In a recent prospective randomized study by Souto et al. of such patients undergoing oral surgery, those who were included in schedules in which the dose of warfarin was not modified and who used local tranexamic did not experience excessive bleeding.4 This study endorsed the efficacy of local fibrinolytic therapy as previously reported by Sindet-Pedersen et al. in patients with mechanical heart valves who were having operations and for whom anticoagulation dose was not reduced.12 Blinder et al. reported that fibrin sealants are also useful as local haemostatic agents either as an adjunct or alternative to tranexamic acid.15 Based on the above results, we recommend that there is no need to modify oral anticoagulant treatment in patients with mechanical heart valve prostheses who require minor oral surgical procedures, provided that effective local measures are used. Because of the high risk of haemorrhage if anticoagulation is continued in patients having more major oral and maxillofacial operations, it is accepted that the INR should be within the normal range before the procedure. In patients with heart valves, both the European Society of Cardiology and the Fourth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy have recommended perioperative heparinization to minimize the risk of thrombosis and embolization resulting from the return to the normal range of the INR.1,6,17 However, over a five-day perioperative period of undercoagulation, the risk of thromboembolism has been estimated to be as low as 0.06%.18 It is not clear whether stopping oral anticoagulation abruptly is
125
associated with a higher risk of thrombosis as a result of rebound hypercoagulability. Even if this were the case, the actual risk is unlikely to be much higher than that cited.18 In the study by Katholi et al., 116 patients with prosthetic valves were followed up for four years after their valve replacement. During this time, 44 required non-cardiac operations. In the subgroup of aortic valve recipients there were no perioperative thromboembolic events after the 25 operations for which anticoagulation was discontinued, compared with three episodes of major haemorrhage in three of the six patients in whom anticoagulation was continued. In patients with mixed valvar prostheses, there were two fatal thromboembolic strokes in 10 patients in whom anticoagulation was discontinued three to five days preoperatively, compared with no events in the patients maintained on anticoagulation.19 In another retrospective study of 159 patients with predominantly metallic ball-and-cage valves who had 180 non-cardiac operations, Tinker and Tarhan reported no thromboembolic events within two years of operation in any of the patients who had oral anticoagulation discontinued perioperatively.5 Based on a review of published reports, Kearon and Hirsch have recently recommended that as the risk of thromboembolism from prosthetic valves associated with a few days of perioperative subtherapeutic anticoagulation is low, and the haemorrhagic risk associated with perioperative heparin is relatively high, the INR can be returned to the normal range preoperatively without the need for heparin substitution.10 A major advantage of merely discontinuing oral anticoagulation preoperatively is that it can be done without admitting the patient to hospital and avoids the prolonged preoperative stay that would be required for intravenous heparin substitution. A study from the USA has estimated that this would result in appreciable savings.20 Owing to the higher risk of thromboembolism in certain patients such as those with mechanical mitral valves and ball valves, particularly if they also have atrial fibrillation or left ventricular dysfunction, there is a reluctance to discontinue anticoagulation completely. In these patients, the use of heparin both before and after operation has been recommended.21,22 Taking these views into account, we recommend that oral anticoagulation is discontinued three days before operation in people who are to have major procedures, and that as a compromise between no anticoagulation and intravenous heparin, subcutaneous conventional heparin or low-molecular-weight heparin in prophylactic doses is substituted preoperatively. A dose of heparin should be given immediately preoperatively in patients at high risk of thromboembolic events and the heparin continued the day after operation until the INR has been back within the therapeutic range for at least 48 h, to enable a reduction in all the vitamin-K-dependent clotting factors. It is impossible for clinical practice guidelines to cover all the aspects of a particular treatment strategy. However, it is important to have a set of recommendations that are simple and will encompass most circumstances. We accept that there is limited medical-based evidence for the guidelines that we present, but feel
126
British Journal of Oral and Maxillofacial Surgery
that they represent a sensible approach to a common clinical problem. Further studies are required to investigate optimal management strategies, but these may never be undertaken. References 1. Cannegeiter SC, Rosendaal FR, Wintzen AR, van de Meer FJM, Vandenbroucke JP, Briet E. Optimal anticoagulation therapy in patients with mechanical heart valves. N Engl J Med 1995; 333: 11–17. 2. Coulshed DS, Fitzpatrick MA, Lee CH. Drug treatment associated with heart valve replacement. Drugs 1995; 49: 897–911. 3. Haemostasis and Thrombosis Task Force for the British Committee for Standards in Haematology. Guidelines on oral anticoagulation, 3rd edn. Br J Haematol 1998; 101: 374–387. 4. Souto JC, Oliver A, Zuazu-Jausoro I et al. Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: a prospective randomized study. J Oral Maxillofac Surg 1996; 54: 27–32. 5. Tinker JH, Tarhan S. Discontinuing anticoagulant therapy in surgical patients with cardiac valve prostheses. J Am Med Assve 1978; 239: 738–739. 6. Weibert RT. Oral anticoagulant therapy in patients undergoing dental surgery. Clin Pharmacol 1992; 11: 857–864. 7. Madura JA, Rookstool M, Wease G. The management of patients on chronic coumarin therapy undergoing subsequent surgical procedures. Am Surg 1994; 60: 542–546. 8. Devani P, Lavery KM, Howell CJT. Dental extractions in patients on warfarin: is alteration of anticoagulant regime necessary? Br J Oral Maxillofac Surg 1998; 36: 107–111. 9. Bryan AJ, Butchart EG. Prosthetic heart valves and anticoagulant management during non-cardiac surgery. Br J Surg 1995; 82: 577–578. 10. Kearon C, Hirsch J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997; 336: 1506–1511. 11. Beirne OR, Koehler JR. Surgical management of patients on warfarin sodium. J Oral Maxillofac Surg 1996; 54: 1115–1118. 12. Sindet-Pedersen S, Ramstrom G, Bernvil S, Blomback M. Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med 1989; 320: 840–843. 13. Borea G, Montebugnoli L, Capuzzi P, Magelli C. Tranexamic acid as a mouthwash in anticoagulant-treated patients undergoing oral surgery. An alternative method to discontinuing anticoagulant therapy. Oral Surg Oral Med Oral Pathol 1993; 75: 29–31.
14. Lippert S, Gutschick E. Views of cardiac-valve prosthesis patients and their dentists on anticoagulation therapy. Scand J Dent Res 1994; 102: 168–174 15. Blinder D, Martinowitz U, Ardekian L, Peleg M, Taicher S. Oral surgical procedures during anticoagulant therapy. Harefuah 1996; 130: 727+681–727+683 16. Stein PD, Alpert JS, Copeland J, Dalen JE, Goldman S, Turpie AG. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 1995; 108: 371S–379S. 17. Ad Hoc committee of the Working Group on Valvular Heart Disease. European Society of Cardiology. Guidelines for the prevention of thromboembolic events in valvular heart disease. J Heart Valve Dis 1993; 2: 398–410. 18. Butler AC, Tait RC. Management of oral anticoagulantinduced intracranial haemorrhage. Blood Rev 1998; 12: 35–44. 19. Kahtoli RE, Nolan SP, McGuire LB. Living with prosthetic heart valves: subsequent non-cardiac operations and the risk of thromboembolism or hemorrhage. Am Heart J 1976; 92: 162–167. 20. Eckman MH, Beshansky JR, Durand-Zaleski I, Levine HJ, Pauker SG. Anticoagulation for noncardiac procedures in patients with prosthetic heart valves: does low risk mean high cost? J Am Med Assoe 1990; 263: 1513–1521. 21. Vongpatanasin W, Hillis LD, Lange RA. Prosthetic heart valves. N Engl J Med 1996; 335: 407–416. 22. Spandorfer J, Merli G, Lowson SM et al. Anticoagulation and elective surgery [2]. N Engl J Med 1997; 337: 938–940.
The Authors Keith Webster FDSRCS, FRCS (MaxFac) Senior Registrar Department of Oral & Maxillofacial Surgery Jonathan Wilde MA, MD, FRCP, FRCPath Consultant in Haemostasis and Thrombosis University Hospital Birmingham NHS Trust Edgbaston Birmingham, UK Correspondence and requests for offprints to: Keith Webster, Department of Oral and Maxillofacial Surgery, University Hospital Birmingham NHS Trust, Selly Oak Hospital, Raddlebarn Road, Birmingham B29 6JD, UK Paper received 15 September 1998 Accepted 11 June 1999
B BR RIIT TIIS SH H JJO OU UR RN NA AL L O OF F O OR RA AL L
& &M MA AX XIIL LL LO OFA FAC CIIA AL LS SU UR RG GE ERY RY
Management of anticoagulation in patients with prosthetic heart valves undergoing oral and maxillofacial operations K. Webster,* J. Wilde† *Senior Registrar, Department of Oral & Maxillofacial Surgery; †Consultant in Haemostasis and Thrombosis, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, UK SUMMARY. There is wide variation in the management of patients with mechanical prosthetic valves who are taking anticoagulants and who require non-cardiac surgery. In this paper, we outline a pragmatic, practical approach to the adjustment of anticoagulation in relation to both the degrees of surgical trauma during oral and maxillofacial surgery and the risk of thromboembolism associated with the prosthetic valve. For minor surgery, no adjustment of anticoagulation is undertaken if the International Normalized Ratio is less than 4.0, if local haemostatic methods and tranexamic acid mouthwashes are used. For major surgery, warfarin is stopped preoperatively and lowmolecular-weight heparin is used. For emergency surgery, partial reversal of anticoagulation with low-dose parenteral vitamin K is obtained. 4.0, warfarin should be discontinued and surgery retimed to be done when the INR is back within the therapeutic range. During operation, the use of a local anaesthetic combined with a vasoconstrictor, and local haemostatic methods, are recommended. At the end of the procedure, the operative field should be irrigated with 4.8% tranexamic acid solution (Cyklokapron®, Pharmacia). The sockets and mucoperiosteal flaps should then be sutured and oxidized cellulose gauze (such as Surgicel®, Johnson & Johnson) placed in the sockets. The patients should then rinse with 4.8% tranexamic acid solution 10 ml. On discharge, they are given instructions to rinse with 10 ml of the solution for 2 min four times a day for seven days.4
INTRODUCTION It is estimated that over 300 000 people in the UK are taking oral anticoagulants, and many of them are doing so to prevent thromboembolism from mechanical heart valves. The type and position of the prosthetic valve influence the risk of thromboembolism, and thromboembolic events occur more frequently with mitral than with aortic valves, and in people with co-existing atrial fibrillation (AF). The older types of ball valves are also more likely to be associated with fatal thromboembolic events than pivoting disc valves.1,2 The British Society for Haematology has balanced thromboembolic risks against the haemorrhagic risk of anticoagulation and recently revised the guidelines on anticoagulant control; it recommends a target International Normalized Ratio (INR) for prosthetic heart valves of 3.5, with an acceptable range of 3.0–4.0.3 Patients with prosthetic heart valves commonly require non-cardiac surgery, but there is little consensus on how to manage their anticoagulation perioperatively.4.5 Current practice, depending on the type of operation, ranges from no adjustment of anticoagulation, to reducing the dose of oral anticoagulant drugs, to substitution with heparin, to stopping oral anticoagulation completely.6–10 To rationalize the inconsistencies of current practice, and to attempt to strike a balance between thrombotic risk from stopping anticoagulation and haemorrhagic risk from continuing anticoagulation, we propose the following guidelines.
Major surgery (such as parotidectomy or neck dissection) Warfarin should not be taken on the three evenings before admission. The patient should be admitted on the day before operation and given a subcutaneous injection of a low-molecular-weight heparin in a prophylactic dose if the INR has fallen below 2.0. On the day of operation, the INR should be checked to ensure that the prothrombin time is within normal limits (INR <1.3), and a prophylactic dose of lowmolecular-weight heparin given subcutaneously 2 h preoperatively. If the INR has not returned to the normal range and it is not possible to retime the operation, vitamin K 1 mg should be given intravenously. This should result in return of the INR to the normal range within 2–3 h, and is not a large enough dose to make the patient refractory to the subsequent re-introduction of oral anticoagulants. Warfarin can be started on the night of operation, at a dose twice that of the patient’s normal maintenance dose. The INR should be checked daily, and
PROPOSED GUIDELINES Minor surgery (such as skin biopsy, extractions, and surgical removal of teeth) The anticoagulation regimen does not require alteration if the INR is less than 4.0. If the INR is above 124
Management of anticoagulation in patients with prosthetic heart valves
the warfarin dose adjusted accordingly. Subcutaneous heparin should be continued daily in a prophylactic dose until the INR has been back within the therapeutic range for 48 h.
Emergency surgery If emergency surgery can be deferred for a few hours, oral anticoagulation can be partially reversed by giving a low dose of vitamin K (1 mg) intravenously. Vitamin K should be given to sustain the reversal of anticoagulation during the operative period. If immediate surgery is required, fresh frozen plasma or prothrombin complex concentrate (if available) should be given to enable immediate correction of coagulation. We recommended that, in an emergency, the advice of a haematologist be sought.
DISCUSSION There are no large randomized studies that compare different perioperative anticoagulant regimens for patients with mechanical heart valves having operations. For patients on oral anticoagulants who require minor oral surgical procedures, a number of authors have recommended that up to an INR of 4.0, the dose of anticoagulant does not need to be modified, provided that local haemostatic measures such as the use of tranexamic acid mouth washes are followed.4,8,11–14 In a recent prospective randomized study by Souto et al. of such patients undergoing oral surgery, those who were included in schedules in which the dose of warfarin was not modified and who used local tranexamic did not experience excessive bleeding.4 This study endorsed the efficacy of local fibrinolytic therapy as previously reported by Sindet-Pedersen et al. in patients with mechanical heart valves who were having operations and for whom anticoagulation dose was not reduced.12 Blinder et al. reported that fibrin sealants are also useful as local haemostatic agents either as an adjunct or alternative to tranexamic acid.15 Based on the above results, we recommend that there is no need to modify oral anticoagulant treatment in patients with mechanical heart valve prostheses who require minor oral surgical procedures, provided that effective local measures are used. Because of the high risk of haemorrhage if anticoagulation is continued in patients having more major oral and maxillofacial operations, it is accepted that the INR should be within the normal range before the procedure. In patients with heart valves, both the European Society of Cardiology and the Fourth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy have recommended perioperative heparinization to minimize the risk of thrombosis and embolization resulting from the return to the normal range of the INR.1,6,17 However, over a five-day perioperative period of undercoagulation, the risk of thromboembolism has been estimated to be as low as 0.06%.18 It is not clear whether stopping oral anticoagulation abruptly is
125
associated with a higher risk of thrombosis as a result of rebound hypercoagulability. Even if this were the case, the actual risk is unlikely to be much higher than that cited.18 In the study by Katholi et al., 116 patients with prosthetic valves were followed up for four years after their valve replacement. During this time, 44 required non-cardiac operations. In the subgroup of aortic valve recipients there were no perioperative thromboembolic events after the 25 operations for which anticoagulation was discontinued, compared with three episodes of major haemorrhage in three of the six patients in whom anticoagulation was continued. In patients with mixed valvar prostheses, there were two fatal thromboembolic strokes in 10 patients in whom anticoagulation was discontinued three to five days preoperatively, compared with no events in the patients maintained on anticoagulation.19 In another retrospective study of 159 patients with predominantly metallic ball-and-cage valves who had 180 non-cardiac operations, Tinker and Tarhan reported no thromboembolic events within two years of operation in any of the patients who had oral anticoagulation discontinued perioperatively.5 Based on a review of published reports, Kearon and Hirsch have recently recommended that as the risk of thromboembolism from prosthetic valves associated with a few days of perioperative subtherapeutic anticoagulation is low, and the haemorrhagic risk associated with perioperative heparin is relatively high, the INR can be returned to the normal range preoperatively without the need for heparin substitution.10 A major advantage of merely discontinuing oral anticoagulation preoperatively is that it can be done without admitting the patient to hospital and avoids the prolonged preoperative stay that would be required for intravenous heparin substitution. A study from the USA has estimated that this would result in appreciable savings.20 Owing to the higher risk of thromboembolism in certain patients such as those with mechanical mitral valves and ball valves, particularly if they also have atrial fibrillation or left ventricular dysfunction, there is a reluctance to discontinue anticoagulation completely. In these patients, the use of heparin both before and after operation has been recommended.21,22 Taking these views into account, we recommend that oral anticoagulation is discontinued three days before operation in people who are to have major procedures, and that as a compromise between no anticoagulation and intravenous heparin, subcutaneous conventional heparin or low-molecular-weight heparin in prophylactic doses is substituted preoperatively. A dose of heparin should be given immediately preoperatively in patients at high risk of thromboembolic events and the heparin continued the day after operation until the INR has been back within the therapeutic range for at least 48 h, to enable a reduction in all the vitamin-K-dependent clotting factors. It is impossible for clinical practice guidelines to cover all the aspects of a particular treatment strategy. However, it is important to have a set of recommendations that are simple and will encompass most circumstances. We accept that there is limited medical-based evidence for the guidelines that we present, but feel
126
British Journal of Oral and Maxillofacial Surgery
that they represent a sensible approach to a common clinical problem. Further studies are required to investigate optimal management strategies, but these may never be undertaken. References 1. Cannegeiter SC, Rosendaal FR, Wintzen AR, van de Meer FJM, Vandenbroucke JP, Briet E. Optimal anticoagulation therapy in patients with mechanical heart valves. N Engl J Med 1995; 333: 11–17. 2. Coulshed DS, Fitzpatrick MA, Lee CH. Drug treatment associated with heart valve replacement. Drugs 1995; 49: 897–911. 3. Haemostasis and Thrombosis Task Force for the British Committee for Standards in Haematology. Guidelines on oral anticoagulation, 3rd edn. Br J Haematol 1998; 101: 374–387. 4. Souto JC, Oliver A, Zuazu-Jausoro I et al. Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: a prospective randomized study. J Oral Maxillofac Surg 1996; 54: 27–32. 5. Tinker JH, Tarhan S. Discontinuing anticoagulant therapy in surgical patients with cardiac valve prostheses. J Am Med Assve 1978; 239: 738–739. 6. Weibert RT. Oral anticoagulant therapy in patients undergoing dental surgery. Clin Pharmacol 1992; 11: 857–864. 7. Madura JA, Rookstool M, Wease G. The management of patients on chronic coumarin therapy undergoing subsequent surgical procedures. Am Surg 1994; 60: 542–546. 8. Devani P, Lavery KM, Howell CJT. Dental extractions in patients on warfarin: is alteration of anticoagulant regime necessary? Br J Oral Maxillofac Surg 1998; 36: 107–111. 9. Bryan AJ, Butchart EG. Prosthetic heart valves and anticoagulant management during non-cardiac surgery. Br J Surg 1995; 82: 577–578. 10. Kearon C, Hirsch J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997; 336: 1506–1511. 11. Beirne OR, Koehler JR. Surgical management of patients on warfarin sodium. J Oral Maxillofac Surg 1996; 54: 1115–1118. 12. Sindet-Pedersen S, Ramstrom G, Bernvil S, Blomback M. Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med 1989; 320: 840–843. 13. Borea G, Montebugnoli L, Capuzzi P, Magelli C. Tranexamic acid as a mouthwash in anticoagulant-treated patients undergoing oral surgery. An alternative method to discontinuing anticoagulant therapy. Oral Surg Oral Med Oral Pathol 1993; 75: 29–31.
14. Lippert S, Gutschick E. Views of cardiac-valve prosthesis patients and their dentists on anticoagulation therapy. Scand J Dent Res 1994; 102: 168–174 15. Blinder D, Martinowitz U, Ardekian L, Peleg M, Taicher S. Oral surgical procedures during anticoagulant therapy. Harefuah 1996; 130: 727+681–727+683 16. Stein PD, Alpert JS, Copeland J, Dalen JE, Goldman S, Turpie AG. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 1995; 108: 371S–379S. 17. Ad Hoc committee of the Working Group on Valvular Heart Disease. European Society of Cardiology. Guidelines for the prevention of thromboembolic events in valvular heart disease. J Heart Valve Dis 1993; 2: 398–410. 18. Butler AC, Tait RC. Management of oral anticoagulantinduced intracranial haemorrhage. Blood Rev 1998; 12: 35–44. 19. Kahtoli RE, Nolan SP, McGuire LB. Living with prosthetic heart valves: subsequent non-cardiac operations and the risk of thromboembolism or hemorrhage. Am Heart J 1976; 92: 162–167. 20. Eckman MH, Beshansky JR, Durand-Zaleski I, Levine HJ, Pauker SG. Anticoagulation for noncardiac procedures in patients with prosthetic heart valves: does low risk mean high cost? J Am Med Assoe 1990; 263: 1513–1521. 21. Vongpatanasin W, Hillis LD, Lange RA. Prosthetic heart valves. N Engl J Med 1996; 335: 407–416. 22. Spandorfer J, Merli G, Lowson SM et al. Anticoagulation and elective surgery [2]. N Engl J Med 1997; 337: 938–940.
The Authors Keith Webster FDSRCS, FRCS (MaxFac) Senior Registrar Department of Oral & Maxillofacial Surgery Jonathan Wilde MA, MD, FRCP, FRCPath Consultant in Haemostasis and Thrombosis University Hospital Birmingham NHS Trust Edgbaston Birmingham, UK Correspondence and requests for offprints to: Keith Webster, Department of Oral and Maxillofacial Surgery, University Hospital Birmingham NHS Trust, Selly Oak Hospital, Raddlebarn Road, Birmingham B29 6JD, UK Paper received 15 September 1998 Accepted 11 June 1999