Haemostatic agents in oral survey: A brief review

Headnote

Abstract

During oral surgical procedures, persistent minor oozing of blood is common, although occasionally a bleeding episode prevents the continuation of the procedure and requires immediate attention. Having a broad knowledge of the management approaches will allow the clinician to know when to apply a particular approach. Unfortunately, some of the most useful preventive measures and management techniques are not utilized because of a lack of understanding ofthe coagulation process and/or the approaches and materials that are available. One ofthe more common methods of intraoperative hemorrhage control involves the use of a topical hemostatic agent. Although a comprehensive explanation of all the methods of haemorrhage control is beyond the scope of this article, we attempt to review some ofthe more common hemostatic agents used in dental surgery.

Key words: Bleeding, hemostasis, dental surgery.

Introduction

Dentists perform a variety of surgical procedures frequently requiring the need for a hemostatic agent. Exodontia. tissue biopsies, placement of endosseous implants and periodontal surgery are some of the examples where hemostatic agents may be beneficial. Not only are these agents useful for specific procedures, but they also are valuable for certain patient groups, specifically those with coagulation defects.1 Though rare, life threatening hemorrhage has been reported with common surgical dental procedures ranging from endosseous implant placement to third molar removal, the risk of encountering hemorrhagic complications is still remote, but a serious possibility.26 Knowledge of predisposing factors, physiologic responses to hemorrhage and clinical management of excessive hemorrhage may prove useful for health care providers in such situations.7

Prevention of peri-operative hemorrhage

The best management of perioperative hemorrhage is prevention. This includes a thorough preoperative patient history, necessary medical consultations, familiarity with managing patients with possible bleeding diathesis, meticulous intra-operative technique and appropriate postoperative instructions, care and follow-up. Although these areeasilyhsted, applications practice can be challenging. Multiple obstacles may prevent the implementation ofthe management steps listed. Some of these hurdles include treating patients with an undisclosed or undiagnosed medical condition, improper information retrieval or difficult surgical conditions. Poor patient compliance with medication or postoperative instructions are also the factors to be considered.1

Management of intraoperative bleeding

With systemically healthy patients, the possibility of uncontrolled hemorrhage resulting from a dental procedure seems remote. In fact, the risk of moderate to severe bleedinginducedbydentaltreatmentislessthanl%forthe average patient.8'9 Improved understanding of cardiovascular physiology and advances in the management and treatment of cardiovascular disease have rendered oral anticoagulation therapy amainstay of modern medicine. In addition to pre-operative consideration of a patient's medication profile, anticipated blood loss from the planned proceduremmtbe considered. Expectantbloodlossfroma restorative procedure such as a dental amalgam will be considerably different from that of a surgical procedure such as dental implant placement, periodontal flap procedure or impacted third molar extraction.10

Studies evaluating blood loss from restorative procedures have reported minimal hemorrhagic complications, while those evaluating surgical operations such as flap-osseous procedures have found up to 592ml of blood loss from a single surgical site.1011 Blood loss from surgical procedures is also influenced by the experience level ofthe provider. Surgeries performed by less experienced providers have been shown to take up to three times longer and may result in nearly twice as much blood loss as those performed by more experienced practitioners.10 In general, however. most studies have found that blood loss from dental procedures is under 200ml and may be even less if the duration of the procedure does not exceed 2 hours.1214 Considering that a pint of blood, the amount generally taken during blood donation, is 473ml, the amount of blood lost during most dental procedures is well within the limits of safety9 Stated in other words, the chances of any patient suffering from any serious complication due to blood loss while undergoing any dental procedure is less, because much more amount of blood is withdrawn during blood donation procedure safely.

If an intraoperative bleeding episode is encountered, the clinician should consider several steps. A quick mental review ofthe patient's medical history is first. If the hemorrhagic episode is difficult to manage, injection of 1/50,000 solution of epinephrine into the area may be needed. It is useful to control bleeding from incision site, even in extra-oral incisions, it may be of use in a dental setting. This will likely provide temporary reduction of bleeding as a result of local vasoconstriction. The site may need to be packed and the clinician will need to consider the seriousness of the event. If very serious, a call to an emergency medical service may be necessary. Further, if the deist is properly trained, starting an intravenous line to initiate fluid resuscitation may be advisable. The process of immediate delivery of the patient to a medical facility for possible transfusions, anticoagulant reversal and general life support measures can be initiated. However, a careful clinician will rarely encounter such an event in an outpatient office setting. More commonly, dentists confront patients with inconvenient, non-emergent bleeding events that require a response.1'5 In dental settings, it is unlikely that life threatening hemorrhages may occur, they are more of a inconvenience,ratherthanan emergency.

The usual sources for intraoperative bleeding episodes are incision into an area of granulomatous tissue, vessels in the periosteum or mucosa or encountering nutrient arteries in the alveolar bone. Identification of the source of the bleeding requires good illumination, adequate retraction, and thorough suctioning. Once identified, the bleeding site should be packed, clamped, cauterized, burnished, debri-ded and/or sutured for control. Topical hemostatic agents should be available and if necessary, applied. The dentist should be familiar with the range of methods, techniques, materials and their application during different types of bleeding episodes.1

Local hemostatic agents used in dental surgery (Table 1)

With proper management, nearly all scenarios of excessive bleeding can be adequately managed with relatively simple localmeasures,suchasoutlinedbeloww

1. Positive Pressure

2. Electrocautery

3. Vasoconstrictor

4. Gelfoam (Pharmacia)

5. Surgicel (Johnson and Johnson)

6. Hemostatic Collagen e.g. CollaTape, CollaPlug (Sulzer Dental)

7. 4.8% Tranexamic Acid

8. Topical Thrombin

9. Avitene (Davol)

10. Tisseel (Baxter)

11. HemCon (HemCon Medical Technologies)

12.BoneWax(Ethicon)

Positive Pressure

Positive pressure aids hemostasis by promoting occlusion of the site of injury and providing mechanical aid to clot formation.16 Positive pressure to intraoral wounds is typically accomplished by compressing moistened gauze on the site of hemorrhage. Suturing wound margins or severed vessels is another method in which compressive force may be applied to bleeding areas." In many cases, minor hemorrhaging is often controlled with positive pressure alone.9

Electrocautery

Electrocautery involves the application of ahigh frequency electric current to cauterize tissue and induce blood coagulation. In dentistry, this process is typically accomplished with monophasic electrosurgical units. In comparison to other local means of hemostasis management, electrocautery may induce collateral thermal damage to adjacent tissues.1819 As such, this treatment option is typically reserved for severe hemorrhaging scenarios.9

Vasoconstrictors

Dental anesthetics contain a vasoconstrictor primarily to increase their duration of action and minimize the risk of local anesthetic toxicity20 Epinephrine, the most commonly utilized vasoconstrictor in dental local anesthetics, is a catecholamine that facilitates vasoconstriction via the activation of alpha adrenergic receptors. Alpha adrenergic activation by sympathomimietic drugs such as epinephrine induces smooth muscle contraction within blood vessels and ultimately leads to short term vasoconstriction.9

Gelfoam (Pharmacia)

Gelfoam (Pharmacia) is one of the more commonly employed agents for the control of minor bleeding. It is a porous, pliable sponge made from dried and sterilized porcine skin gelatin. Gelfoam's mode of action is not completely understood, but unlike collagen, it is believed toberelatedtoformationofamechanicalmatrix that facilitates clotting rather than affecting the blood-clotting mechanism.2124 This agent can retain in its interstices 45 times its weight in blood. Gelfoam liquefies in one week and is completely resorbed in 4 to 6 weeks. Its use is not associated with excessive scar formation.2528 Reported adverse reactions are giant cell granuloma and hematoma formation, foreign body reactions, excessive fibrosis, toxic shock syndrome, fever, and failure of absorption.1

Surgicel (Johnson and Johnson)

Surgicel (Johnson and Johnson) is a resorbable oxidized cellulose material and is an expensive but useful option in oral surgery. It is prepared as a sterile fabric meshwork. Its mechanism of action is not completely understood, but appears to be physical rather than involve an alteration of the clotting mechanism. After it is fully absorbed with blood, it swells into a brownish/black gelatinous mass that aids in clotting. A thrombus forms when nonclotted blood contacts the oxidized cellulose. The thrombus formation is thought to be a result of the physical properties of the knitted fabric rather than an alteration of the normal clotting mechanism. Upon saturation with blood, the fabric swells into a gelatinous mass, which is eventually absorbed. Unlike traditional surgical sponges, oxidized cellulose has bactericidal effects in vitro against a wide variety of aerobic and anaerobic bacteria, and in a number of animal experiments,itdecreasedthenumberoforganisms relative to controls. Excessive amounts of the material should be removed if possible to prevent delayed healing. Specific dental indications include, use as an adjunct to control bleeding in exodontia and other oral surgical procedures.1 This material may be more useful in soft tissue procedures due to its shape, consistency, and interference with osteogenesis.42 Its use should be avoided in contaminated wounds where persistent drainage is desired. Encapsulation of fluid and foreign body reactions have been reported 2931 and a burning sensation has been noted when the product is placedinunanesthetizednasalpassages.1

Absorbable Collagen Products

Absorbable collagen products such as collagen tape. collagen plugs and collagen foam are derived from bovine deep flexor tendons and typically resorb completely within 14 days. Additional bovine derived products such as Avitene8, UltraFoam(TM) and UltraWrap(TM) (Traatek, Inc. Fort Lauderdale, FL.) have similar properties. In addition to providing a simple occlusive matrix, these products promote hemostasis by virtue of their collagen content which activates the intrinsic coagulation cascade.9

TranexamicAcid

Tranexamic acid is an anticoagulant oral rinse that binds to lysine receptor sites on plasmin and plasminogen,32 ultimately inhibiting fibrin binding and fibrinolysis.32 This rinse is supplied in a 4.8% solution and patients may be instructed to rinse with 10ml four times daily for 7 days following surgery.33 Rinsing with tranexamic acid solution results in therapeutic levels (>100mg/ml) within the saliva for 2-3 hours. Wounds healing in the presence of tranexamic acid have demonstrated increased tensile strength, thus making theclotmoreresistanttomechanicaldisruption.9-34

Topical Thrombin

Topical thrombin facilitates clot stabilization by enhancing the conversion of fibrinogen to fibrin and forming a reinforcing meshwork for initial platelet plugs. Medical grade topical thrombin is often bovine derived and is typically supplied as a freeze dried sterile powder that must be reconstituted with sterile saline. For general use in dental applications, a topical thrombin solution of 100 International Units/ml is recommended. Topical thrombin is often delivered via pump/syringe spray or combined with a carrier such as ahemostatic gelatin sponge.9

Chitosan derived products

Chitosan derived products such as HemCon® (HemCon Medical Technologies Inc. Portland, OR.) are extremely effective at promoting hemostasis. Chitosan is a naturally occurring polysaccharide that is commercially produced via the deacetylation of crustacean chitin. Positively charged chitosan molecules readily attract negatively charged red blood cells and the two forms an extremely strong seal that acts as a primary occlusive barrier for hemorrhagic sites. With hemorrhaging limited and/or stopped by this initial seal, the natural coagulation cascade ensues. Like oxidized regenerated cellulose, chitosan derived products have locally active antibacterial properties.35 Unlike oxidized regenerated cellulose which relies on low pH for its antibacterial activity, however, chitosan derived products achieve antibacterial properties via active cell wall disruption.936

Bone Wax (Ethicon)

Bone Wax (Ethicon) is a sterile mixture of beeswax. paraffin and isopropyl palmitate (a softening agent) that is packaged in individual foil envelopes. It is useful when bleeding is from a visualized local vascular channel within bone, commonly referred to as a "bone bleeder" at the surgical site. This occurs commonly during the extraction of mandibular third molars and if not adequately addressed during surgery can be a reason for postoperative bleeding. The wax is pliable enough to be placed within a vascular channel, immediately tamponading the vascular source. Bone Wax isnon-resorbableand dm: to its possible adverse effect on osteogenesis, caution should be used where regeneration of bone is expected (e.g. a future implant site). Mild inflammatory reactions have been reported in tissues adj acent to the site of bone wax implantation and this agent may preventthe clearing of bacteria from infected sites.1

Complications due to excessive hemorrhage

The most immediate danger for a healthy patient with severe post-oral surgery hemorrhage is airway compromise. Active bleeding that is not controlled by local measures in the dental office should be referred to the nearest hospital emergency department so that the airway can be secured and the hemorrhage managed appropriately15 Life threatening situations resulting from excessive blood loss are often due to hypovolemia induced hemorrhagic shock.37 Blood loss exceeding 1000ml, or 1/5 of an adult's average blood volume, may precipitate hypovolemic shock and lead to inadequate tissue perfusion/oxygenation.938 Compensatory signs of hypovolemia include tachycardia, hypotension, tachypnea, pallor, diaphoresis, anxiety, nausea. thirst, and light headedness. If left untreated, hemorrhagic shock may progress to loss of consciousness, coma, or even death.

When the source of bleeding is known, primary goals in the treatment of hemorrhagic shock are to stop the source of hemorrhaging and restore circulating blood volume. The "three-to-one" rule for the treatment of hemorrhagic shock dictates the administration of 3ml of crystalloid (Lactated Ringers solution or normal saline) for every 1ml of blood loss replaced.39 Although hemorrhagic shock does not typically occur until blood loss exceeds 1000ml, dental literature recommends fluid replacement when blood loss exceeds 500ml to account for postoperative hemorrhagic oozing.4042 A pragmatic approach to fluid resuscitation in outpatient dental settings is limited to cases with less than 1000ml of blood loss and the ability to control hemorrhage. Cases exceeding these parameters should be referred to a higher echelon of care.'lt is always advisable to seek medical assistance in cases of excessive hemorrhage as soon as possible.

Conclusion

Dental literature clearly demonstrates that under most circumstances and with proper management, the risk of uncontrolled hemorrhage attributed to dental procedures is minimal. Proper management in these scenarios involves adequate pre-operative patient assessment, proficiency with local hemostatic control measures and familiarity with hypovolemic treatment protocols. As more general dentists now routinely perform surgical procedures that induce blood loss, such a knowledge base is essential and mayonedayprove life saving.9

References

References

1. McBee WL, Koemer KR. Review of Hemostatic Agents Used in Dentistry. Dent Today 2005;24(3):62-65.

2. Mason M, Triple* R, Alfonso W. Ufe-threatemng hemorrhage from placement of a dental implant. J Oral Maxillofac Surgl990;48(2):201-04.

3. Kalpidis C, Konstantinidis A. Critical hemorrhage in the floor of the mouth during implant placement in the first mandibular premolar position: A case report. Implant Dent 2005;14(2):117-24.

4. Misch C. Implants and the general practitioner. Dent Today 2007;26(8): 48-52.

5. Cottrell D, Reebye U, Blyer S, Hunter M, Mehta N. Referral patterns of general dental practitioners for oral surgical procedures. J Oral Maxillofac Surg 2007;65(4):686-90.

6. Lanning S, Best A, Hunt R. Periodontal services rendered by general practitioners. J Periodontal 2007;78(5):823-32.

7. Starr C, Maksoud M. Implant treatment in an urban general dentistry residency program: A 7 year retrospective study. J Oral Implantol2006;32(3): 142-47.

8. Curtis J, McLain J, Hutchinson R. The incidence and severity of complications and pain following periodontal surgery. J Periodontal 1985 ;56(10): 597-01.

9. Holtzclaw D, Toscano N. Management of the Actively Bleeding and Hypovolemic Dental Patient. J Implant Adv ClinDent2009;l(8):19-26.

10. BaabD,AmmonsW,SelrpskyH.Bloodlossdurrngperiodontal flap surgery. I Periodontal 1997;48(11):693-98.

11. Rooney T. General dentistry during continuous anticoagulation therapy. Oral Surg Oral Med Oral Pathol 1983;56 (3):252-55.

12. Berdon I. Blood loss during gingival surgery. I Periodontal 1965;36(2):102-07.

13. Mclvor J, Wengraf A. Blood-loss in periodontal surgery. Dent Pract Dent Rec 1966;16(12):448-51.

14. Hecht A, App A. Blood volume lost during gingivectomy using two different anesthetic techniques. I Periodontal 1974;45(1):9-12.

15. Moghadam H, Caminiti M. Life-threatening hemorrhage after extraction of third molars: case report and management protocol. ICanDent Assoc 2002;68(ll):670-74.

16. Meehan S, Schmidt M, Mitchell P. The international normalized ratio as a measure of anticoagulation: Significance for the management of the dental outpatient. Spec Care Dentist 1997; 17(3):94-96.

17. Purcell C. Dental management of the anticoagulated patient. NewZealandDentJ1997;93(413):87-92.

18. Noble W, McClatchey K, Douglass G. A histologic comparison of effects of electrosurgical resection using different electrodes. JProsthet Dent 1976;35(5):575-79.

19. Arashiro D, Rapley J, Cobb C, Killoy W. Histologic evaluation of porcine skin incisions produced by C02 laser, electrosurgery, and scalpel. Int J Periodontics Restorative Dent 1996;16(5): 479-91.

20. Malamed S. Handbook of Local Anesthesia. 5th Edition St. LouisMosby,2004:416.

21. Correll JT Prentice HR, Wise EC. Biologic investigations of a now absorbable sponge. Surg Gynecol Obstet 1945; 181: 585-89.

22. Jenkins HP, Janda R. Studies on the use of gelatin sponge or foam as a hemostatic agent in experimental liver resections andinjuries to large veins. AnnSurg 1946;124:952-61.

23. Jenkins HP, Janda R, Clarke J. Clinical and experimental observations on the use of gelatin sponge or foam. Surgery 1946;20:124-32.

24. Guralnick W, Berg L. Gelfoam in oral surgery. Oral Surg 1948;1:629-32.

25. Jenkins HP, Senz EH, Owen HW, Jampolis RW. Present status of gelatin sponge for control of hemorrhage. J Am MedAssoc 1946;132(11):614-19.

26. Treves N. Prophylaxis of post mammectomy lymphedema bythe use of gelfoam laminated rolls. Cancer 1952;5:73-83.

27. Barnes AC. The use of gelatin foam sponges in obstetrics and gynecology. Am J Obstet Gynecol 1963 ;86:105-07.

28. Rarig HR. Successful use of gelatin foam sponge in surgical restoration of fertility. Am J Obstet Gynecol 1963;86:136.

29. Kothbauer KF, Jallo GI, Siffert J, Jiminez E, Allen JC Epstein FJ. Foreign body reaction to hemostatic materials mimicking recurrent brain tumor-report of three cases. J Neurosurg2001;95(3):503-06.

30. Ibrahim MF, Ape C. Young CP A foreign body reaction to Surgical mimicking an abscess following cardiac surgery (letter). Eur J Cardiothorac Surg 2002;22:489-90.

31. Krishnan LK, Mohanty M, Umashankar PR, Lai AV. Comparative evaluation of absorbable hemostats: advantages of fibrin based sheets. Biomaterials 2004;25(24): 5557-63.

32. Caspar R, Brenner B, Ardekian L, Peled M, Laufer D. Use of tranexamic acid mouthwash to prevent postoperative bleeding in oral surgery patients on oral anticoagulant medication. Quintessence Int 1997;28(6):375-79.

33. Bandrowsky T, Vorono A, Borris T, Marcantoni H. Amoxicillin-related postextraction bleeding in an anticoagulated patient with tranexamic acid rinses. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82(6):610-12.

34. Bjorlin G, Nilsson I. The effect of antifibrinolytic agents on wound healing. Int J Oral Maxillofac Surg 1988;17(4):275-76.

35. Muzzarelli R, Tarsi R, Filippini O, Giovanetti E, Biagini G. Varaldo P. Antimicrobial properties of N-carboxybutyl chitosan. Antimicrob Agents Chemother 1990;34(10): 2019-23.

36. Andres Y, Giraud L, Gerente C, Le Cloirec P. Antibacterial effects of chitosan powder: mechanisms of action. Environ Technol2007; 28(12): 1357-63.

37. Perry M, O'Hare J, Porter G Advanced trauma life support (ATLS) and facial trauma: Can one size fit all? Part 3: Hypo volaemia and facial injuries in the multiply injured patient. Int J Oral Maxillofac Surg 2008;37(5):405-14.

38. Gutierrez G, Reines H, Wulf-Gutierrez M. Clinical review: hemorrhagic shock. Crit Care 2004;8(5):373-81.

39. Healey M, Davis R, Liu F, Loomis W, Hoyt D. Lactated Ringers is superior to normal saline in a model of massive hemorrhage andresuscitation. JTraumal998;45(5):894-99.

40. Gores R, Royer R, Mann F. Blood loss during operation for multiple extractions with alveoloplasty and other oral surgical procedures. J Oral Surg 1955;13(4):299-06.

41. Johnson R. Blood loss in oral surgery. J Dent Res 1956;35 (2):175-84.

42. Rosenquist J, FinneK. An experimental study on the effect of local hemostatics on bone healing in rabbits. Int J Oral Surgeryl974;3(4):166-70.