ORIGINAL ARTICLE
Hemostasis Control in Dental Extractions in Patients Receiving Oral Anticoagulant Therapy: An Approach With Calcium Sulfate Antonio Scarano, DDS, MD,* Bruna Sinjari, DDS,* Giovanna Murmura, MD, DDS,* Eitan Mijiritsky, DMD,† Flavia Iaculli, DDS,* Carmen Mortellaro, MD, DDS,‡ and Stefano Tetè, DDS, MD* Abstract: The aim of this study was to evaluate the use of calcium sulfate (CaS) as a hemostatic agent after tooth extraction in patients with anticoagulant drug therapy. A total of 30 patients undergoing anticoagulant therapy (22 women and 8 men) with a mean age of 54.6 years (SD = 9.2 years), needing dental extractions, were selected for this study. They were divided into 2 groups, control (group 1) and test (group 2), in a randomized way. In group 1 patients, the postextraction socket was managed with obliterative suture only. Group 2 patients were treated with CaS placed into the postextraction sockets. All the patients did not interrupt the anticoagulant therapy during the dental treatment. The healing pattern was found to be approximately similar in all treatment groups, showing significant improvement at each consecutive visit. However, a statistically significant difference in the adequate hemostasis was evident between groups 1 and 2 (P = 0.0056). The use of CaS helped to control the bleeding from inside the socket, producing instantly a very good hemostasis. Further studies are necessary to confirm the simplicity, possibilities, and limits of the proposed procedure. Key Words: Calcium sulfate hemihydrate, hemostasis, intraoral bleeding, oral anticoagulant therapy (J Craniofac Surg 2014;25: 843–846)
T
he dentist today is seeing increased numbers of patients with chronic medical illnesses. Among these patients are those who are being treated with anticoagulant drugs or antiplatelet agents to prevent venous or arterial thrombosis. Therefore, the likelihood of anticoagulant-treated patients requiring oral surgery is significant
From the *Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy; †Department of Oral Rehabilitation, School of Dental Medicine, Tel-Aviv University, Israel; and ‡Department of Medical Science, Faculty of Medicine, University of Eastern Piedmont, Novara, Italy. Received May 28, 2013. Accepted for publication January 25, 2014. Partially supported by the Ministry of Education, University and Research, Rome, Italy. Address correspondence and reprint requests to Antonio Scarano, DDS, MD, Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Frentani 98/B, 66100 Chieti, Italy; E-mail: [email protected] The authors report no conflicts of interest. Copyright © 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000000824
and is increasing every day. The coumarin compounds are used worldwide to provide anticoagulation. In Europe, warfarin (warfarin sodium and panwarfarin) is the most commonly used oral anticoagulant. Anticoagulants present management problems in oral surgery mainly due to prolonged intraoperative and postoperative bleeding. However, approximately 90% of postextraction hemorrhage is from other causes, including the following: • excessive operative trauma, particularly to oral soft tissues; • poor compliance with postoperative instructions; • interference with the extraction socket or operation site (eg, by sucking and tongue pushing; plasminogen activators are present in saliva and oral mucosa and can thus cause fibrinolysis); • inflammation at the extraction or operation site, with resultant fibrinolysis; • inappropriate use of analgesia with aspirin or other nonsteroidal anti-inflammatory drugs, which by interfering with platelet function, induce a bleeding tendency; and • uncontrolled hypertension.1 However, dental surgery in patients under anticoagulant therapy (ACT) may be difficult, as these patients present a significant risk for postoperative hemorrhagic complications. Various materials and methods are available to control excessive bleeding. Anesthetic solution with 1:50.000 epinephrine, ferric sulfate, oxidized cellulose, gelatin sponges, and antifibrinolytics are commonly used as hemostatic agents. Several protocols have also been proposed to control the hemorrhagic risk in patients under ACT. Gaspar et al2 have recommended a combination of local antifibrinolytic therapy and hemostatic agents for the prevention of postoperative bleeding due to oral surgery. Use of tranexamic acid for 2 days after the surgery may lead many patients to undergo oral surgical procedures without changes in their regular therapeutic anticoagulant regimen and without additional medical interventions.2,3 Carter et al have recommended the use of oxide cellulose and fibrin glue to protect the alveolar extraction sockets in association with tranexamic acid rinses after the surgery.4,5 Probably, the use of calcium sulfate (CaS) as an approach to hemostasis in alveolar extraction sockets surgery has not received enough attention. Other authors suggested that it was not necessary to stop ACT to perform extractions. Local hemostatic techniques such as obliterative sutures alone could be sufficient. However, it is important to know the prothrombin time of the patients at the time of surgery.6 Many authors have demonstrated that it is safe to perform most dental surgical procedures without risk of severe hemorrhages when the International Normalized Index (INR) is within the therapeutic levels.7 Although the hemostatic agents are widely used in dental field, different disadvantages have been reported. It has been reported that some of these agents, such as bone wax and ferric
The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
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The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
Scarano et al
sulfate, may produce an inflammatory response if left in situ.8–11 It has also been reported that the use of vasoconstrictors for hemorrhage control in endodontic surgery may produce a systemicvascular response.12–14 The aim of the current study was to describe a new approach for the control of hemostasis during dental extractions with the use of CaS.
MATERIALS AND METHODS Forty-two teeth (23 mandibular teeth, 19 maxillary teeth) in 30 patients (22 women and 8 men) with a mean age of 54.6 years (SD = 9.2 years) were included in the study. The number of teeth extracted in each patient ranged from 1 to 2. Most of the patients had a single extraction (73%) followed by 2 teeth (27%). The protocol of the study was approved by the ethics committee of the University of Chieti-Pescara. A total of 30 patients who were kept on warfarin as a maintenance dose for less than 1 year with INR of 2 to 3 and who required dental extractions were recruited for this study. Patients with history of chronic renal or liver disease or who were on drugs that could affect liver function or hemostasis, other than warfarin, were excluded. All patients were physically healthy, with no underlying systemic disease as determined by medical history screening and with at least 1 tooth to be extracted. Patients who met the study criteria were informed of the nature of the investigation and signed an informed consent form. All patients received basic periodontal therapy and exhibited good oral hygiene. All patients having 1 or more teeth scheduled for extraction were assigned to test and control groups in a randomized way. Study patients continued warfarin therapy during their extraction treatment. Sutures with Vicryl 4.0 (Ethicon FS-2; St. Stevens-Woluwe, Belgium) were used for wound closure for the patients in the control group (group 1). The test extraction socket (group 2) were filled with CaS in layers (P30, Ghimas, Bologna, Italy) (Fig. 1), and a solution of potassium chloride (4%) was used to buffer the surface of the mould, to get a strengthening and hardening of the CaS itself. Dental extraction was performed under local anesthesia using articaine with adrenaline 1:100.000. Local hygiene instructions and antibiotics (amoxicillin + clavulanic acid, 1 g twice per day; NeoDuplamox, Procter & Gamble, Rome, Italy) were added for 5 days, starting from 12 hours before surgery.15 The teeth were extracted with minimal trauma to the surrounding tissues, and the sockets were curetted gently. All patients were given detailed written postoperative instructions, the contents of which were verbally illustrated by the treating dentist. Patients were asked to wait for a minimum of 1 hour within the clinic area; they were closely monitored for bleeding status. All patients returned for postoperative follow-ups at days 1, 3, 5, and 7. An independent examiner, blinded to the treatment protocol for the 2 treatment groups, objectively monitored the status of bleeding and healing. Examiner evaluation was based on healing status and closure of the defect by scar-forming supporting tissue and on restoration of the form and functions of the damaged area. Incomplete wound closure or the absence of scar tissue formation was considered
poor healing. The presence of a solid clot covering the extraction socket was considered as no bleeding, whereas the presence of a fresh clot that shed easily or blood oozing was considered as positive bleeding. To examine the relationship between INR value and bleeding incidence, all patients within the 2 treatment groups were combined together and then categorized into 2 groups based on INR value (2–3 and >3). Data were analyzed using the McNemar test. For categorical correlations, Spearman test was used, whereas Chisquared test was applied for nonparametric comparisons. Ps < 0.05 were considered as significant.16
Statistical Analysis The statistical analysis was carried out using the Chi-squared test according to the Statistical Package for Social Science 8.0. P < 0.05 was considered as significant.12
RESULTS Healing pattern was found to be comparable in all treatment groups, showing significant improvement at each consecutive visit.
Group 1 At day 1, we observed a fresh clot that shed easily, or blood oozing. Bleeding at postoperative day 1 was significant, whereas it was significantly decreased by day 3 and almost eliminated by day 5. Cross-comparison among the 2 INR value groups did not show any significant difference in healing at the different postoperative visits.
Group 2 Bleeding was not present in any patient, and in the extraction sites, there was CaS and a solid clot covering the wound (day 1). A solid clot covering the extraction socket was observed, and bleeding was not significant at postoperative day 1. However, the presence of CaS seemed to be more favorable with regard to the absence of fresh clots that shed easily or blood oozing frequency in the extraction site. It should be mentioned here that bleeding incidences were of the mild transient type that may be provoked by local aggravating factors, that is, chewing on the extraction site. Value and bleeding incidence of all patients with CaS treatment was measured relative to the presence or absence of bleeding at the day 1 visit. Bleeding frequency at day 1 postoperatively was significantly less (lower) (Chi-squared = 22.65, P < 0.001) in patients treated with CaS as compared with patients without. However, bleeding was minimal and not present at the consecutive visits. Cross-comparison among the 2 INR value groups did not show any significant difference in healing at the different postoperative visits.
Statistical Analysis Cross-comparison among the 4 treatment groups did show a significant difference in healing at the different postoperative visits. A statistically significant difference in the adequate hemostasis was present between group 1 versus group 2 (P = 0.005) at days 1 and 3. No significant differences in healing at the different postoperative visits at days 5 and 7 were present.
DISCUSSION
FIGURE 1. Extraction socket filled with calcium sulfate produced a very good hemostasis.
844
Hemostatic failure is one of the most serious problems encountered by the dental professionals, because it may cause excessive postoperative bleeding delay in wound healing and increase risk of infection.17 Local hemostatic methods (nonresorbable sutures, fibrin glues), antifibrinolytic agents (tranexamic acid in mouthwash form), replacement therapy (recombinant or plasma-derived clotting factors, platelet-rich plasma) and desmopressin are the usual management.18,19 In our series, hemostasis was achieved in all of © 2014 Mutaz B. Habal, MD
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
the 30 patients. No patient had wound infection, and the healing process seemed to be normal. It is not necessary to reduce oral ACT in patients undergoing routine dental extractions with using local hemostasis.20 Reducing ACT and preventing undue hemorrhage against the associated increased risk from the diminution of the therapeutic benefit of ACT resulted in potentially life-threatening thromboembolism.21 For this reason, it is important to have a valid local hemostatic agent. A significant percentage of the population receives ACT in the prevention and treatment of thrombotic disease states, such as deep vein thrombosis, pulmonary embolism, cerebrovascular disease, numerous cardiac disorders, and the various prothrombotic states (ie, lupus and factor S and factor C deficiencies).22 Different methods and materials such as epinephrine, ferric sulfate, oxidized cellulose, gelatin sponges, and antifibrinolytics have been developed to prevent the hemorrhagic risk in these patients. In the current study, CaS was used as a hemostatic agent after the tooth extraction in patients with ACT. The present results showed a very good performance of the CaS on preventing the hemorrhage in these patients. No bleeding was present, and the wound healed in a normal way. The CaS on the wound did not cause any problem. On the other hand, in group 1, during the first day, bleeding was present, diminished gradually during the consecutive visits (days 3 and 5), and was not present by the last visit (day 7). The CaS was highly absorbent and was used for wound protection and for the control of oozing or bleeding in endodontic surgery procedure and surgical-orthodontic treatment of impacted teeth. As for application, this product should be held in place for approximately 1 to 3 minutes to achieve hemostasis and should be left in situ. The CaS material is completely resorbed within 1 to 4 mouths.23 In addition to serving as a mechanical obstruction to bleeding, these materials affect the coagulation process. It is reasonable to think that the CaS resorbs the blood proteins, therefore assuming a net negative charge. This resorption might start the intrinsic coagulation pathway.24 The resorption of factor XII might, in this case, assume an important role in the biomaterial-induced clotting.25 As has been recently shown in vitro, contact between a biomaterial and the blood determines the activation of factor XII as well as precallicrein. Other authors suggested the necessity of using an atraumatic surgical technique in these patients. They were also concerned with the application of local conventional measures to control hemostasis, in which the adequate suture is extremely important.26,27 Group 1 results of the current study agree with these studies. However, monitoring of the prothrombin time of these patients was recommended. Some authors suggest that an INR lower than 4.0 could be acceptable for simple dental extractions. Whereas in cases of impacted third molar surgeries or multiple extractions, the INR values have to be lower than 3.0.24 The INR values of our patients during the evaluation ranged from 2.2 to 3.4, with a mean value of 3.0. No consensus is present in the different studies reported in literature regarding the maximum values of INR considered safe for the patient to be submitted to dental extractions. In the current study, CaS has been used with the aim of controlling bleeding of the surgical site postoperatively. The CaS has also been used as a hemostatic agent in endodontic surgery28 and, in the disinclusion of impacted teeth, carries out a hemostatic effect through a compressive effect.29 These studies suggest that the biomaterial was totally resorbable and biocompatible, and no problems should arise if some CaS particles were left around the tooth at the end of the surgery.28,30 The CaS can give the dental profession more time and confidence during the surgical intervention. It is useful not only for the local hemostasis in endodontic surgery and dental extractions but also for wound healing and preventing infections. In addition, future studies are needed to clarify the role of this product in the area of dental surgery with hereditary bleeding disorders. The use of CaS
Hemostasis Control With Calcium Sulfate
seemed to be more favorable with regard to the absence of fresh clots that shed easily or the blood oozing frequency in the extraction site. It should be mentioned here that bleeding incidences were of the mild transient type that may be provoked by local aggravating factors, that is, chewing on the extraction site. It has the ability to act as a space maintainer and as an osteoconductive trellis for bone cells, promoting bone regeneration in the extraction sockets, and seems to accelerate the rate of vital bone formation.31–33 In conclusion, CaS was observed, in the current study, to successfully control bleeding related to dental extractions in patients receiving oral ACT.
REFERENCES 1. Scully C, Wolff A. Oral surgery in patients on anticoagulant therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:57–64 2. Gaspar R, Brenner B, Ardekian L, et al. Use of tranexamic acid mouthwash to prevent postoperative bleeding in oral surgery patients on oral anticoagulant medication. Quintessence Int 1997;28:375–379 3. 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 4. Campbell JH, Alvarado F, Murray RA. Anticoagulation and minor oral surgery: should the anticoagulation regimen be altered? J Oral Maxillofac Surg 2000;58:131–135 5. Beirne OR. Evidence to continue oral anticoagulant therapy for ambulatory oral surgery. J Oral Maxillofac Surg 2005; 63:540–545 6. Carter G, Goss A. Tranexamic acid mouthwash: a prospective randomized study of a 2-day regimen vs 5-day regimen to prevent postoperative bleeding in anticoagulated patients requiring dental extractions. Int J Oral Maxillofac Surg 2003;32:504–507 7. Carter G, Goss A, Lloyd J, et al. Tranexamic acid mouthwash versus autologous fibrin glue in patients taking warfarin undergoing dental extractions: a randomized prospective clinical study. J Oral Maxillofac Surg 2003;61:1432–1435 8. Pereira CM, Gasparetto PF, Carneiro DS et al. Tooth extraction 9 in patients on oral anticoagulants: prospective study conducted in 108 brazilian 10 patients. ISRN Dent 2011;2011:203619 9. Hirsh J, Guyatt G, Albers GW, et al. American College of Chest Physicians. Executive summary: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133(6 suppl):71S–109S 10. Ibarola JL, Bjorenson JE, Austin BP, et al. Osseous reactions to three hemostatic agents. J Endod 1985;11:75–83 11. Lemon RR, Steele PJ, Jeansonne BG. Ferric sulfate hemostasis: effect on osseous wound healing: left in situ for maximum exposure. J Endod 1993;19:170–173 12. Vy CH, Baumgartner JC, Marshall JG. Cardiovascular effects and efficacy of a hemostatic agent in periradicular surgery. J Endod 2004;30:379–383 13. Gogerty JH, Strand HA, Ogilvie AL, et al. Vasopressor effects of topical epinephrine in certain dental procedures. Oral Surg Oral Med Oral Pathol 1957;10:614–622 14. Witherspoon DE, Gutmann JL. Haemostasis in periradicular surgery. Int Endod J 1996;29:135–149 15. Lindeboom JA, Baas EM, Kroon FH. Prophylactic single-dose administration of 600 mg clindamycin versus 4-time administration of 600 mg clindamycin in orthognathic surgery: a prospective randomized study in bilateral mandibular sagittal ramus osteotomies. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:145–149 16. Colton T. Statistics in medicine. 1st ed. Boston, MA: Little, Brown and Company; 1974. 17. Israels S, Schwetz N, Boyar R, et al. Bleeding disorders: characterization, dental considerations and management. J Can Dent Assoc 72:827, 2006 18. Della VA, Sammartino G, Marenzi G, et al. Prevention of postoperative bleeding in anticoagulated patients undergoing oral surgery: use of platelet-rich plasma gel. J Oral Maxillofac Surg 2003;61:1275–1278
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19. Gomez-Moreno G, Cutando-Soriano A, Arana C, et al. Hereditary blood coagulation disorders: management and dental treatment. J Dent Res 2005;84:978–985 20. Sacco R, Sacco M, Carpenedo M, et al. Oral surgery in patients on oral anticoagulant therapy: a randomized comparison of different intensity targets. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:18–21 21. Sirois DA, Fatahzadeh M. Valvular heart disease. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:15–19 22. Walling J, Spain M, Edlund BJ. Anticoagulation therapy in older adults newly diagnosed with atrial fibrillation. J Gerontol Nurs 2011; 37:9–13 23. Strocchi R, Orsini G, Iezzi G, et al. Bone regeneration with calcium sulfate: evidence for increased angiogenesis in rabbits. J Oral Implantol 2002;28:273–278 24. Horbett TA. Principles underlying the role ofadsorbed plasma proteins in blood interactions with foreign materials. Cardiovasc Pathol 1993;2:137S–148S 25. Ziats N, Pankowsky DA, Tierney BP, et al. Adsorption of Hageman Factor (Factor XII) and other human plasma proteins to biomedical polymers. J Lab Clin Med 1990;116:687–696 26. Schardt-Sacco D. Update on coagulopathies. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:559–563
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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 2001;92:257–259 28. Scarano A, Artese L, Piattelli A, et al. Hemostasis control in endodontic surgery: a comparative study of calcium sulfate versus gauzes and versus ferric sulfate. J Endod 2012;38:20–23 29. Scarano A, Carinci F, Cimorelli E, et al. Application of calcium sulfate in surgical-orthodontic treatment of impacted teeth: a new procedure to control hemostasis. J Oral Maxillofac Surg 2010; 68:964–968 30. Scarano A, Degidi M, Iezzi G, et al. Maxillary sinus augmentation with different biomaterials: a comparative histologic and histomorphometric study in man. Implant Dent 2006;15:197–207 31. Scarano A, Orsini G, Pecora G, et al. Peri-implant bone regeneration with calcium sulfate: a light and transmission electron microscopy case report. Implant Dent 2007;16:195–203 32. Bagoff R, Mamidwar S, Chesnoiu-Matei I, et al. Socket preservation and sinus augmentation using a medical grade calcium sulfate hemihydrate and mineralized irradiated cancellous bone allograft composite. J Oral Implantol 2011;39:363–371 33. Douglass GL. Alveolar ridge preservation at tooth extraction. J Calif Dent Assoc 2005;33:223–231
© 2014 Mutaz B. Habal, MD
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
Hemostasis Control in Dental Extractions in Patients Receiving Oral Anticoagulant Therapy: An Approach With Calcium Sulfate Antonio Scarano, DDS, MD,* Bruna Sinjari, DDS,* Giovanna Murmura, MD, DDS,* Eitan Mijiritsky, DMD,† Flavia Iaculli, DDS,* Carmen Mortellaro, MD, DDS,‡ and Stefano Tetè, DDS, MD* Abstract: The aim of this study was to evaluate the use of calcium sulfate (CaS) as a hemostatic agent after tooth extraction in patients with anticoagulant drug therapy. A total of 30 patients undergoing anticoagulant therapy (22 women and 8 men) with a mean age of 54.6 years (SD = 9.2 years), needing dental extractions, were selected for this study. They were divided into 2 groups, control (group 1) and test (group 2), in a randomized way. In group 1 patients, the postextraction socket was managed with obliterative suture only. Group 2 patients were treated with CaS placed into the postextraction sockets. All the patients did not interrupt the anticoagulant therapy during the dental treatment. The healing pattern was found to be approximately similar in all treatment groups, showing significant improvement at each consecutive visit. However, a statistically significant difference in the adequate hemostasis was evident between groups 1 and 2 (P = 0.0056). The use of CaS helped to control the bleeding from inside the socket, producing instantly a very good hemostasis. Further studies are necessary to confirm the simplicity, possibilities, and limits of the proposed procedure. Key Words: Calcium sulfate hemihydrate, hemostasis, intraoral bleeding, oral anticoagulant therapy (J Craniofac Surg 2014;25: 843–846)
T
he dentist today is seeing increased numbers of patients with chronic medical illnesses. Among these patients are those who are being treated with anticoagulant drugs or antiplatelet agents to prevent venous or arterial thrombosis. Therefore, the likelihood of anticoagulant-treated patients requiring oral surgery is significant
From the *Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy; †Department of Oral Rehabilitation, School of Dental Medicine, Tel-Aviv University, Israel; and ‡Department of Medical Science, Faculty of Medicine, University of Eastern Piedmont, Novara, Italy. Received May 28, 2013. Accepted for publication January 25, 2014. Partially supported by the Ministry of Education, University and Research, Rome, Italy. Address correspondence and reprint requests to Antonio Scarano, DDS, MD, Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Frentani 98/B, 66100 Chieti, Italy; E-mail: [email protected] The authors report no conflicts of interest. Copyright © 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000000824
and is increasing every day. The coumarin compounds are used worldwide to provide anticoagulation. In Europe, warfarin (warfarin sodium and panwarfarin) is the most commonly used oral anticoagulant. Anticoagulants present management problems in oral surgery mainly due to prolonged intraoperative and postoperative bleeding. However, approximately 90% of postextraction hemorrhage is from other causes, including the following: • excessive operative trauma, particularly to oral soft tissues; • poor compliance with postoperative instructions; • interference with the extraction socket or operation site (eg, by sucking and tongue pushing; plasminogen activators are present in saliva and oral mucosa and can thus cause fibrinolysis); • inflammation at the extraction or operation site, with resultant fibrinolysis; • inappropriate use of analgesia with aspirin or other nonsteroidal anti-inflammatory drugs, which by interfering with platelet function, induce a bleeding tendency; and • uncontrolled hypertension.1 However, dental surgery in patients under anticoagulant therapy (ACT) may be difficult, as these patients present a significant risk for postoperative hemorrhagic complications. Various materials and methods are available to control excessive bleeding. Anesthetic solution with 1:50.000 epinephrine, ferric sulfate, oxidized cellulose, gelatin sponges, and antifibrinolytics are commonly used as hemostatic agents. Several protocols have also been proposed to control the hemorrhagic risk in patients under ACT. Gaspar et al2 have recommended a combination of local antifibrinolytic therapy and hemostatic agents for the prevention of postoperative bleeding due to oral surgery. Use of tranexamic acid for 2 days after the surgery may lead many patients to undergo oral surgical procedures without changes in their regular therapeutic anticoagulant regimen and without additional medical interventions.2,3 Carter et al have recommended the use of oxide cellulose and fibrin glue to protect the alveolar extraction sockets in association with tranexamic acid rinses after the surgery.4,5 Probably, the use of calcium sulfate (CaS) as an approach to hemostasis in alveolar extraction sockets surgery has not received enough attention. Other authors suggested that it was not necessary to stop ACT to perform extractions. Local hemostatic techniques such as obliterative sutures alone could be sufficient. However, it is important to know the prothrombin time of the patients at the time of surgery.6 Many authors have demonstrated that it is safe to perform most dental surgical procedures without risk of severe hemorrhages when the International Normalized Index (INR) is within the therapeutic levels.7 Although the hemostatic agents are widely used in dental field, different disadvantages have been reported. It has been reported that some of these agents, such as bone wax and ferric
The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
843
The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
Scarano et al
sulfate, may produce an inflammatory response if left in situ.8–11 It has also been reported that the use of vasoconstrictors for hemorrhage control in endodontic surgery may produce a systemicvascular response.12–14 The aim of the current study was to describe a new approach for the control of hemostasis during dental extractions with the use of CaS.
MATERIALS AND METHODS Forty-two teeth (23 mandibular teeth, 19 maxillary teeth) in 30 patients (22 women and 8 men) with a mean age of 54.6 years (SD = 9.2 years) were included in the study. The number of teeth extracted in each patient ranged from 1 to 2. Most of the patients had a single extraction (73%) followed by 2 teeth (27%). The protocol of the study was approved by the ethics committee of the University of Chieti-Pescara. A total of 30 patients who were kept on warfarin as a maintenance dose for less than 1 year with INR of 2 to 3 and who required dental extractions were recruited for this study. Patients with history of chronic renal or liver disease or who were on drugs that could affect liver function or hemostasis, other than warfarin, were excluded. All patients were physically healthy, with no underlying systemic disease as determined by medical history screening and with at least 1 tooth to be extracted. Patients who met the study criteria were informed of the nature of the investigation and signed an informed consent form. All patients received basic periodontal therapy and exhibited good oral hygiene. All patients having 1 or more teeth scheduled for extraction were assigned to test and control groups in a randomized way. Study patients continued warfarin therapy during their extraction treatment. Sutures with Vicryl 4.0 (Ethicon FS-2; St. Stevens-Woluwe, Belgium) were used for wound closure for the patients in the control group (group 1). The test extraction socket (group 2) were filled with CaS in layers (P30, Ghimas, Bologna, Italy) (Fig. 1), and a solution of potassium chloride (4%) was used to buffer the surface of the mould, to get a strengthening and hardening of the CaS itself. Dental extraction was performed under local anesthesia using articaine with adrenaline 1:100.000. Local hygiene instructions and antibiotics (amoxicillin + clavulanic acid, 1 g twice per day; NeoDuplamox, Procter & Gamble, Rome, Italy) were added for 5 days, starting from 12 hours before surgery.15 The teeth were extracted with minimal trauma to the surrounding tissues, and the sockets were curetted gently. All patients were given detailed written postoperative instructions, the contents of which were verbally illustrated by the treating dentist. Patients were asked to wait for a minimum of 1 hour within the clinic area; they were closely monitored for bleeding status. All patients returned for postoperative follow-ups at days 1, 3, 5, and 7. An independent examiner, blinded to the treatment protocol for the 2 treatment groups, objectively monitored the status of bleeding and healing. Examiner evaluation was based on healing status and closure of the defect by scar-forming supporting tissue and on restoration of the form and functions of the damaged area. Incomplete wound closure or the absence of scar tissue formation was considered
poor healing. The presence of a solid clot covering the extraction socket was considered as no bleeding, whereas the presence of a fresh clot that shed easily or blood oozing was considered as positive bleeding. To examine the relationship between INR value and bleeding incidence, all patients within the 2 treatment groups were combined together and then categorized into 2 groups based on INR value (2–3 and >3). Data were analyzed using the McNemar test. For categorical correlations, Spearman test was used, whereas Chisquared test was applied for nonparametric comparisons. Ps < 0.05 were considered as significant.16
Statistical Analysis The statistical analysis was carried out using the Chi-squared test according to the Statistical Package for Social Science 8.0. P < 0.05 was considered as significant.12
RESULTS Healing pattern was found to be comparable in all treatment groups, showing significant improvement at each consecutive visit.
Group 1 At day 1, we observed a fresh clot that shed easily, or blood oozing. Bleeding at postoperative day 1 was significant, whereas it was significantly decreased by day 3 and almost eliminated by day 5. Cross-comparison among the 2 INR value groups did not show any significant difference in healing at the different postoperative visits.
Group 2 Bleeding was not present in any patient, and in the extraction sites, there was CaS and a solid clot covering the wound (day 1). A solid clot covering the extraction socket was observed, and bleeding was not significant at postoperative day 1. However, the presence of CaS seemed to be more favorable with regard to the absence of fresh clots that shed easily or blood oozing frequency in the extraction site. It should be mentioned here that bleeding incidences were of the mild transient type that may be provoked by local aggravating factors, that is, chewing on the extraction site. Value and bleeding incidence of all patients with CaS treatment was measured relative to the presence or absence of bleeding at the day 1 visit. Bleeding frequency at day 1 postoperatively was significantly less (lower) (Chi-squared = 22.65, P < 0.001) in patients treated with CaS as compared with patients without. However, bleeding was minimal and not present at the consecutive visits. Cross-comparison among the 2 INR value groups did not show any significant difference in healing at the different postoperative visits.
Statistical Analysis Cross-comparison among the 4 treatment groups did show a significant difference in healing at the different postoperative visits. A statistically significant difference in the adequate hemostasis was present between group 1 versus group 2 (P = 0.005) at days 1 and 3. No significant differences in healing at the different postoperative visits at days 5 and 7 were present.
DISCUSSION
FIGURE 1. Extraction socket filled with calcium sulfate produced a very good hemostasis.
844
Hemostatic failure is one of the most serious problems encountered by the dental professionals, because it may cause excessive postoperative bleeding delay in wound healing and increase risk of infection.17 Local hemostatic methods (nonresorbable sutures, fibrin glues), antifibrinolytic agents (tranexamic acid in mouthwash form), replacement therapy (recombinant or plasma-derived clotting factors, platelet-rich plasma) and desmopressin are the usual management.18,19 In our series, hemostasis was achieved in all of © 2014 Mutaz B. Habal, MD
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
the 30 patients. No patient had wound infection, and the healing process seemed to be normal. It is not necessary to reduce oral ACT in patients undergoing routine dental extractions with using local hemostasis.20 Reducing ACT and preventing undue hemorrhage against the associated increased risk from the diminution of the therapeutic benefit of ACT resulted in potentially life-threatening thromboembolism.21 For this reason, it is important to have a valid local hemostatic agent. A significant percentage of the population receives ACT in the prevention and treatment of thrombotic disease states, such as deep vein thrombosis, pulmonary embolism, cerebrovascular disease, numerous cardiac disorders, and the various prothrombotic states (ie, lupus and factor S and factor C deficiencies).22 Different methods and materials such as epinephrine, ferric sulfate, oxidized cellulose, gelatin sponges, and antifibrinolytics have been developed to prevent the hemorrhagic risk in these patients. In the current study, CaS was used as a hemostatic agent after the tooth extraction in patients with ACT. The present results showed a very good performance of the CaS on preventing the hemorrhage in these patients. No bleeding was present, and the wound healed in a normal way. The CaS on the wound did not cause any problem. On the other hand, in group 1, during the first day, bleeding was present, diminished gradually during the consecutive visits (days 3 and 5), and was not present by the last visit (day 7). The CaS was highly absorbent and was used for wound protection and for the control of oozing or bleeding in endodontic surgery procedure and surgical-orthodontic treatment of impacted teeth. As for application, this product should be held in place for approximately 1 to 3 minutes to achieve hemostasis and should be left in situ. The CaS material is completely resorbed within 1 to 4 mouths.23 In addition to serving as a mechanical obstruction to bleeding, these materials affect the coagulation process. It is reasonable to think that the CaS resorbs the blood proteins, therefore assuming a net negative charge. This resorption might start the intrinsic coagulation pathway.24 The resorption of factor XII might, in this case, assume an important role in the biomaterial-induced clotting.25 As has been recently shown in vitro, contact between a biomaterial and the blood determines the activation of factor XII as well as precallicrein. Other authors suggested the necessity of using an atraumatic surgical technique in these patients. They were also concerned with the application of local conventional measures to control hemostasis, in which the adequate suture is extremely important.26,27 Group 1 results of the current study agree with these studies. However, monitoring of the prothrombin time of these patients was recommended. Some authors suggest that an INR lower than 4.0 could be acceptable for simple dental extractions. Whereas in cases of impacted third molar surgeries or multiple extractions, the INR values have to be lower than 3.0.24 The INR values of our patients during the evaluation ranged from 2.2 to 3.4, with a mean value of 3.0. No consensus is present in the different studies reported in literature regarding the maximum values of INR considered safe for the patient to be submitted to dental extractions. In the current study, CaS has been used with the aim of controlling bleeding of the surgical site postoperatively. The CaS has also been used as a hemostatic agent in endodontic surgery28 and, in the disinclusion of impacted teeth, carries out a hemostatic effect through a compressive effect.29 These studies suggest that the biomaterial was totally resorbable and biocompatible, and no problems should arise if some CaS particles were left around the tooth at the end of the surgery.28,30 The CaS can give the dental profession more time and confidence during the surgical intervention. It is useful not only for the local hemostasis in endodontic surgery and dental extractions but also for wound healing and preventing infections. In addition, future studies are needed to clarify the role of this product in the area of dental surgery with hereditary bleeding disorders. The use of CaS
Hemostasis Control With Calcium Sulfate
seemed to be more favorable with regard to the absence of fresh clots that shed easily or the blood oozing frequency in the extraction site. It should be mentioned here that bleeding incidences were of the mild transient type that may be provoked by local aggravating factors, that is, chewing on the extraction site. It has the ability to act as a space maintainer and as an osteoconductive trellis for bone cells, promoting bone regeneration in the extraction sockets, and seems to accelerate the rate of vital bone formation.31–33 In conclusion, CaS was observed, in the current study, to successfully control bleeding related to dental extractions in patients receiving oral ACT.
REFERENCES 1. Scully C, Wolff A. Oral surgery in patients on anticoagulant therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:57–64 2. Gaspar R, Brenner B, Ardekian L, et al. Use of tranexamic acid mouthwash to prevent postoperative bleeding in oral surgery patients on oral anticoagulant medication. Quintessence Int 1997;28:375–379 3. 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 4. Campbell JH, Alvarado F, Murray RA. Anticoagulation and minor oral surgery: should the anticoagulation regimen be altered? J Oral Maxillofac Surg 2000;58:131–135 5. Beirne OR. Evidence to continue oral anticoagulant therapy for ambulatory oral surgery. J Oral Maxillofac Surg 2005; 63:540–545 6. Carter G, Goss A. Tranexamic acid mouthwash: a prospective randomized study of a 2-day regimen vs 5-day regimen to prevent postoperative bleeding in anticoagulated patients requiring dental extractions. Int J Oral Maxillofac Surg 2003;32:504–507 7. Carter G, Goss A, Lloyd J, et al. Tranexamic acid mouthwash versus autologous fibrin glue in patients taking warfarin undergoing dental extractions: a randomized prospective clinical study. J Oral Maxillofac Surg 2003;61:1432–1435 8. Pereira CM, Gasparetto PF, Carneiro DS et al. Tooth extraction 9 in patients on oral anticoagulants: prospective study conducted in 108 brazilian 10 patients. ISRN Dent 2011;2011:203619 9. Hirsh J, Guyatt G, Albers GW, et al. American College of Chest Physicians. Executive summary: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133(6 suppl):71S–109S 10. Ibarola JL, Bjorenson JE, Austin BP, et al. Osseous reactions to three hemostatic agents. J Endod 1985;11:75–83 11. Lemon RR, Steele PJ, Jeansonne BG. Ferric sulfate hemostasis: effect on osseous wound healing: left in situ for maximum exposure. J Endod 1993;19:170–173 12. Vy CH, Baumgartner JC, Marshall JG. Cardiovascular effects and efficacy of a hemostatic agent in periradicular surgery. J Endod 2004;30:379–383 13. Gogerty JH, Strand HA, Ogilvie AL, et al. Vasopressor effects of topical epinephrine in certain dental procedures. Oral Surg Oral Med Oral Pathol 1957;10:614–622 14. Witherspoon DE, Gutmann JL. Haemostasis in periradicular surgery. Int Endod J 1996;29:135–149 15. Lindeboom JA, Baas EM, Kroon FH. Prophylactic single-dose administration of 600 mg clindamycin versus 4-time administration of 600 mg clindamycin in orthognathic surgery: a prospective randomized study in bilateral mandibular sagittal ramus osteotomies. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:145–149 16. Colton T. Statistics in medicine. 1st ed. Boston, MA: Little, Brown and Company; 1974. 17. Israels S, Schwetz N, Boyar R, et al. Bleeding disorders: characterization, dental considerations and management. J Can Dent Assoc 72:827, 2006 18. Della VA, Sammartino G, Marenzi G, et al. Prevention of postoperative bleeding in anticoagulated patients undergoing oral surgery: use of platelet-rich plasma gel. J Oral Maxillofac Surg 2003;61:1275–1278
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Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
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Scarano et al
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19. Gomez-Moreno G, Cutando-Soriano A, Arana C, et al. Hereditary blood coagulation disorders: management and dental treatment. J Dent Res 2005;84:978–985 20. Sacco R, Sacco M, Carpenedo M, et al. Oral surgery in patients on oral anticoagulant therapy: a randomized comparison of different intensity targets. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:18–21 21. Sirois DA, Fatahzadeh M. Valvular heart disease. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:15–19 22. Walling J, Spain M, Edlund BJ. Anticoagulation therapy in older adults newly diagnosed with atrial fibrillation. J Gerontol Nurs 2011; 37:9–13 23. Strocchi R, Orsini G, Iezzi G, et al. Bone regeneration with calcium sulfate: evidence for increased angiogenesis in rabbits. J Oral Implantol 2002;28:273–278 24. Horbett TA. Principles underlying the role ofadsorbed plasma proteins in blood interactions with foreign materials. Cardiovasc Pathol 1993;2:137S–148S 25. Ziats N, Pankowsky DA, Tierney BP, et al. Adsorption of Hageman Factor (Factor XII) and other human plasma proteins to biomedical polymers. J Lab Clin Med 1990;116:687–696 26. Schardt-Sacco D. Update on coagulopathies. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:559–563
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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 2001;92:257–259 28. Scarano A, Artese L, Piattelli A, et al. Hemostasis control in endodontic surgery: a comparative study of calcium sulfate versus gauzes and versus ferric sulfate. J Endod 2012;38:20–23 29. Scarano A, Carinci F, Cimorelli E, et al. Application of calcium sulfate in surgical-orthodontic treatment of impacted teeth: a new procedure to control hemostasis. J Oral Maxillofac Surg 2010; 68:964–968 30. Scarano A, Degidi M, Iezzi G, et al. Maxillary sinus augmentation with different biomaterials: a comparative histologic and histomorphometric study in man. Implant Dent 2006;15:197–207 31. Scarano A, Orsini G, Pecora G, et al. Peri-implant bone regeneration with calcium sulfate: a light and transmission electron microscopy case report. Implant Dent 2007;16:195–203 32. Bagoff R, Mamidwar S, Chesnoiu-Matei I, et al. Socket preservation and sinus augmentation using a medical grade calcium sulfate hemihydrate and mineralized irradiated cancellous bone allograft composite. J Oral Implantol 2011;39:363–371 33. Douglass GL. Alveolar ridge preservation at tooth extraction. J Calif Dent Assoc 2005;33:223–231
© 2014 Mutaz B. Habal, MD
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
