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Review Article Received Review completed Accepted : 02‑09‑14 : 22‑11‑14 : 30‑11‑14 BLEEDING DISORDER AND MINOR ORAL SURGERY: A REVIEW Hemant Gupta, * Subodh Shankar Natu, ** Sumit Gupta, *** Hemant Mehra, † Rashmi Agrawal, †† Sujeet Singh ††† * Professor and Head, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India ** Senior Lecturer, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India *** Reader, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India † Reader, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India †† Reader, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India ††† Post Graduate Student, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India _________________________________________________________________________ ABSTRACT Injury to the blood vessel wall, either by trauma or surgical intervention, stimulates a series of reaction that lead to the cessation of blood loss hence haemostasis is achieved. Primary haemostasis is achieved by the platelet plug formation followed by interaction between exposed subendothelial tissue factor and circulating blood thereby amplifying the steps of coagulation cascade resulting in clot formation and stabilization. Certain drugs and there preparation, any deficiency in the coagulation factors or platelet either qualitative or quantitative leads to deranged haemostasis. Prolonged postoperative bleeding in such patients could be life threatening hence surgeons must be aware of the complication and management strategies for such patients. This article reviews the pathophysiology of these disorders and management considerations. KEYWORDS: Blood coagulation disorder; complications; von willebrand’s disease; anticoagulant regimen (BL) INTRODUCTION Haemostasis, a finely balanced process, is physiology that stops bleeding following injury to a blood vessel, either surgical or otherwise by the stimulation of a pair of parallel yet associated amplification step which result in a clot.[1] Several drugs, including over the counter preparations, inherited and acquired abnormalities in these pathways can seriously compromise haemostasis. Also, in certain diseases or condition such as prosthetic heart valves, it is desirable to inhibit the haemostatic capacity and certain drugs to this effect are prescribed to such patients. These IJOCR Jan - Mar 2015; Volume 3 Issue 7 present significant concerns to surgeons conducting invasive procedures, who must be aware of the impact of bleeding tendencies. The surgical treatment of patients with bleeding tendencies has been widely discussed in the literatures with an aim of developing guidelines for the surgery in such patients. Hemostasis consists of 3 reactions to vessel wall injury: 1) Primary; 2) Secondary; 3) Tertiary: and is dependent on three general components: 1) Vascular wall; 2) Platelets; 3) The coagulation cascade Common bleeding disorders [2] A) Coagulation factor deficiencies 1) Congenital Hemophilia A and B von Willebrand’s disease Other factor deficiencies (rare) 2) Acquired Liver disease Vitamin K deficiency, warfarin use Disseminated intravascular coagulation B) Platelet disorders 1) Quantitative disorder (thrombocytopenia) Immune-mediated Idiopathic Drug-induced Collagen vascular disease Sarcoidosis Non-immune-mediated Disseminated intravascular coagulation Microangiopathic hemolytic anemia Leukemia Myelofibrosis 2) Qualitative disorder Congenital Glanzmann thrombasthenia von Willebrand’s disease 99 Bleeding disorder and minor oral surgery Platelet count (x 109/l) 100-150 50-100 30-50 <30 Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S Table I: Thrombocytopenia and management of surgery[18] Management in relation to type of oral surgery Severity of thrombocytopenia Dentoalveolar Maxillofacial Mild - No platelet transfusion - Local haemostatic measures* - Observe Moderate - Platelets may be needed - Local haemostatic measures* - Consider postoperative tranexamic acid mouthwash 25 mg/kg t.i.d for 3 days Severe - Platelets needed - Local haemostatic measures* Life-threatening - Platelets needed - Local haemostatic measures* - Avoid surgery where possible - Postoperative tranexamic acid mouthwash 25 mg/kg t.i.d for 3 days - Consider platelet transfusion - Local haemostatic measures* - Observe - Platelets needed - Local haemostatic measures* - Postoperative tranexamic acid mouthwash 25 mg/kg t.i.d for 3 days - Platelets needed - Local haemostatic measures* - Avoid surgery where possible - Postoperative tranexamic acid mouthwash 25 mg/kg t.i.d for 3 days - Platelets needed - Local haemostatic measures* - Avoid surgery where possible - Postoperative tranexamic acid mouthwash 25 mg/kg t.i.d for 3 days Table II : Management of patients with coagulation factor deficiencies, who require dental extraction or complex procedures[1] Bleeding disorder vWD, Type 1 vWD, Types 2A and 2B vWD, Types 2B and 3 Pretreatment for extraction or nerve block Desmopressin, 0.3 μg/kg (maximum dose 20 μg) IV over 20–30 minutes or subcutaneously Desmopressin, as above, if tested response or Humate-P, 50 IU of vWF:RCoF/kg Humate-P, 50 IU of vWF:RCoF/kg Hemophilia A (mild) Desmopressin, as above, if tested response is adequate Hemophilia A (moderate or severe) Recombinant Factor VIII concentrate, 20–25 IU/kg Re-evaluate postprocedure Hemophilia B (mild, moderate or severe) Recombinant Factor IX concentrate, 40–60 IU/kg Re-evaluate postprocedure Acquired Drug-induced Liver disease Alcoholism C) Vascular disorders Scurvy Purpura Hereditary hemorrhagic telangiectasia Cushing syndrome Ehlers-Danlos syndrome IJOCR Jan - Mar 2015; Volume 3 Issue 7 Postextraction treatment for all bleeding disorders Antifibrinolytic agents (e.g., tranexamic acid, 25 mg/kg t.i.d.) for 3–5 days Soft diet for 7 days Within 24 hours, assess need for repeat treatment D) Fibrinolytic defects Streptokinase therapy Disseminated intravascular coagulation GUIDELINES FOR PERFORMING SURGICAL TREATMENT OF PATIENTS WITH HAEMOSTATIC DEFECTS The management of bleeding for patients with haemostatic defects is a challenge to the physician and surgeons. In patients with coagulopathies, nerve-blocks are relatively contraindicated unless 100 Bleeding disorder and minor oral surgery Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S Table III : Flowchart for choice of treatment according to type of anesthesia and severity of the bleeding disorder [38] Severe Bleeding Tendencies General or Local Anesthesia Replacement Therapy - Severe or Moderate Hemophilia A - Severe or Moderate Hemophilia B - Type 3 Vwd Desmopressin or Replacement Therapy - Type 2 vWD Non-severe Bleeding Tendencies General Anesthesia or Nerve Trunk Local Anesthesia Infiltration Replacement Therapy - Mild No Treatment Hemophilia B - Mild - Non-responder Hemophilia B Hemophilia Amand type 1 vWD No Treatment or Desmopressin or Replacement Therapy Desmopressin - Mild - Mild Hemophilia A Hemophilia A - Type 1 vWD - Type 1 vWD - Platelet disorders - Platelet disorders Table IV : Pharmacological profile of Desmopressin [43] Chemical composition Route of administration and dose Mean factor increase over baseline Time to peak level Plasma half-life 1-deamino-8-arginine vasopressin Intravenous infusion: 0.3 mg/kg diluted in 50 ml saline solution over 30 min Subcutaneous injection: 0.3 mg/kg Intranasal spray: 300 mg/kg (concentrated solution) Factor VIII 3-5 times vWf 3-5 times 30-60 min after i.v. infusion 90-120 min after s.c. injection 6-8 hours for factor VIII 8-10 hours for vWf there is no better alternative.[3,4] Loose connective, non-fibrous, and highly vascularized tissue is predisposed to the development of a dissecting hematoma increasing the chance of morbidity compared to an area where the tissue is firm and confined. Hence the anatomy of the injection site plays an important role in development of hematoma after injection of local anesthesia. Extravasation of blood in the oropharyngeal area by an inferior alveolar block or in the pterygoid plexus can produce gross swelling, pain, dysphasia, respiratory obstruction and a resultant risk of death from asphyxia.[2,5-8] Even lingual infiltration is associated with risk of developing hematoma since the injection is into an area with a rich plexus of blood vessels and the invading needle is not adjacent to bone. Anesthetic infiltration and intraligamentary anesthesia are potential alternatives to nerve block in many cases.[2] Risk of hematoma in case of inferior alveolar nerve block is reduced by using the Gow Gate Technique.[1] For commonly used blocks the minimum concentration of clotting factors required is 20% - 30%.[2] A buccal infiltration, intraligamentary or interosseous IJOCR Jan - Mar 2015; Volume 3 Issue 7 technique can be used without any factor replacement.[9] Intrapulpal injections can usually be administered without much concern for bleeding and rarely require coverage with factor replacement. There are no restrictions regarding the type of local anesthetic agent used although those with vasoconstrictors may provide additional local hemostatis but following the risk v/s benefit ratio principle, should be avoided when contraindicated.[9] Alternative techniques, including sedation with diazepam or nitrous oxide-oxygen analgesia, can be employed to reduce or eliminate the need for anesthesia.[2] Surgeons must be cautious in prescribing analgesics at all times in patients with bleeding disorders as certain agents such as Aspirin, Phenylbutazone, Indomethacin etc potentiate the bleeding tendency by altering platelet function. Cyclooxygenase inhibitors like rofecoxib, celecoxib appear not to have a significant effect on platelets or INR.[10,11] Besides these Opiod analgesics like Codeine, Meperidine, Morphine, Hydromorphone does not affect platelet function hence can safely control pain for the bleeding disorder patients. Acetaminophen, Pentazocine, 101 Bleeding disorder and minor oral surgery Plain Propoxyphene are weak inhibitors of platelet function hence can be used safely.[12,13] PRE-OPERATIVE MEASURES Platelets have a vital role in hemostasis and are said to have 4 main functions: 1. Help in maintain the integrity of the capillaries; 2. From the initial plug in vessel injury; 3. Elaborate various metabolically active substances such as: Serotonin, adenosine diphosphate (ADP), and platelet-factor III; 4. Contain thrombasthenin – a contractile protein involved in clot retraction and consolidation of a fibrin plug. Where there is decreased platelet count or suppressed or altered platelet function platelet transfusion should be considered. Patients with severe thrombocytopenia, in which the platelet count is < 50,000/µl, are candidates for extensive and prolonged bleeding and definitely require platelet transfusion.[14] A platelet count of 100,000/µl is desirable for major surgery[15] while minor surgery resulting in only superficial wounds can be performed with undue risk with platelet counts of 30,000/ µl;[14] while Forbes CD recommend it to be 50,000/µl for minor surgeries.[16] Because of the relative inability to control hemorrhage in bony extraction sites by primarily closure, a platelet count of 100,000/µl is preferable. Regional local anaesthetic block injections can be given if the platelet levels are above 30x109/l.[14] The transfusion of viable, physiologically active platelets can be achieved with:[17] 1. Fresh whole blood; 2. Platelet-rich plasma (PRP): contains about 90% of the platelets from a unit of fresh blood in about half this volume 3. Platelet concentrates (PC): contains about 50% of the platelets from a unit of fresh whole blood in a volume of only 25 ml. 4. Platelet concentrates is the best source of platelets. Theoretically, the patient's body surface area or blood volume dictates the required number of platelet units to be transfused. However it should be determined in a case-specific manner. Certain systemic condition like splenomegaly lead to quick sequestration of platelets which further emphasizes the need for preoperative planning. A post transfusion platelet count should be obtained IJOCR Jan - Mar 2015; Volume 3 Issue 7 Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S before surgery. Additional platelets can be transfused intraoperatively, if necessary, depending on the expected level of hemorrhage (Table I).[14] The availability of concentrates of clotting factors has rendered surgery in haemophiliacs almost as safe as for normal subjects. Surgery should be avoided whenever possible, but when necessary, before surgery, it is essential to perform in vitro and in vivo tests to ensure that the patient has developed a specific level of coagulation factors. Replacement therapy allows rapid correction of the deficiency of one or more coagulation factors thereby making surgery in an individual with coagulation abnormalities possible, in most cases. Factors may be given in the form of Fresh whole blood, Fresh frozen plasma (FFP), Factor VIII concentrates like low or intermediate potency, cryoprecipitate or high potency human factor VIII, animal factor VIII, PPSB (factors II, VII, IX, X), Prothrombinex (factors II, IX, X), Fibrinogen.[17] Diagnosis of the bleeding tendency, severity and amount of tissue damage, coagulation defect, response to therapy determines the type and amount of blood product, duration of replacement therapy and rate of administration.[17] Irrespective of the type of coagulation abnormality, acute blood loss must always be replaced with adequate amounts of blood either as whole blood or appropriate fractions.[17] In major trauma, including surgery, greater correction of the coagulation abnormality is usually required, hence necessary to use concentrates of clotting factors to avoid fluid overload.[17] Treatment with concentrates should be controlled with factor assays, so as to adjust the amount required. Frequently, a single transfusion arrests bleeding due to minimal tissue damage in patients with very severe coagulation abnormalities but when tissue damage is extensive, it is usually advisable to repeat the transfusion at intervals of 24 hours or less for couple of days.[17] It is essential to continue correction of the coagulation abnormality before surgery and until healing occurs following surgery (Table II). The rate of administration should be rapid in order to obtain high peak blood concentrations of the deficient factor and thus optimum haemostatic effect.[17] Patients diagnosed with chronic renal failure should be managed the day after dialysis when heparin has been cleared from the system and the patient regains his/her 102 Bleeding disorder and minor oral surgery strength after the dialysis process.[19] Minor procedures, including tooth extraction, should also be carried out in hospital that provides special care for hemophiliacs. In case of patients lacking vitamin K, because of malabsorption syndrome, vitamin K supplement should be administered to restore liver function and the synthesis of coagulation factors before performing any surgical procedures. If the patient has liver failure, the dental management of the patient should also involve platelet transfusion in conjunction to transfusion of deficient factors in a hospital setting.[20] No elective surgery should be done until the patient has been treated with antibiotics and is free from acute infection[21] as in state of the infection patient tends to bleed more. Patient with deep-vein thrombosis, pulmonary embolism, atrial fibrillation, mechanical prosthetic heart valve, valvular heart disease, cerebrovascular accident, transient ischemic attacks, and myocardial infarction are on Anticoagulant regimen.[22-24] Anticoagulant medications reduce the risk of embolism but increase the probability of bleeding during and after the dental procedure. Although persons on chronic warfarin therapy are often managed by stopping the anticoagulant for a brief period before surgery, but this potentiates the risk for the condition for which they are being treated with anticoagulant. There are a number of case reports concerning serious thromboembolic events developing after the interruption of anticoagulation treatment;[25] owing to hypercoagulability that may ensue after cessation of anticoagulants, although some recent literature suggests this concern may not be of practical clinical significance. In some instances, the likelihood of a thromboembolic episode in patients who discontinued taking the anticoagulant medications is three times higher of a bleeding event in patients who remain on the anticoagulant regimen.[26] Hence detailed risk assessment should be performed on each patient, and the possibility of life-threatening situations should be taken into serious consideration before discontinuation of anticoagulation therapy. If warfarin is stopped, the coagulation status for almost all patients returns to near normal in approximately 4 days. The decision either continuation, reduction or withdrawal of anticoagulant should be based on the international IJOCR Jan - Mar 2015; Volume 3 Issue 7 Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S normalized ratio value, the invasiveness and extent of surgical procedure, current illnesses and medications.[27] The international normalized ratio is a key component in the treatment of these patients. International normalized ratio therapeutic levels for most medical conditions range between 2.5 and 3.5.[22] Medications enhancing the effect of coumarin, a diet rich in vitamin K and/ or compliance reasons may lead to increased INR values.[27] When the international normalized ratio is: <=3.5, minor surgical procedures can be carried out on these patients in a dental office;[20,27] Alteration of anticoagulation regimen may not be necessary for these patients.[28-30] 3.5, the anticoagulation regimen has to be adjusted. Detailed surgical procedure and risk for bleeding should be addressed to medical care provider by the surgeon so as to adjust the dose of anticoagulant.[26,31] International normalized ratio values can be normalized to 3.5 by making minor adjustments involving the reduction, but not the discontinuation, of coumarin. Entire withdrawal of coumarin is not recommended because of the rebound thrombotic effect noticed especially in patients with prosthetic cardiac valves.[25,27] A safe approach entails reduction of the coumarin dose 2-3 days before the procedure and repetition of international normalized ratio on the morning of the procedure to ensure that the value is <4.[20,23,27] Low-molecular-weight heparin an alternative substitute for coumarin may be fruitfull measure for patient on anticoagulant. Subcutaneous administration of low-molecularweight heparin provides the benefit of conveniently adjusting the anticoagulation regimen at the point of care.[23,32] Short half life of LMWH allow its discontination 4-6 hrs before surgery.[18] Withdrawal of heparin is adequate to reverse anticoagulation effect where this is deemed necessary, or in an emergency, this can be reversed with intravenous Protamine Sulphate given in a dose of 1 mg per 100 international units of heparin.[10] But it is less effective in reversing LMW Heparin. Interrupting Lowmolecular-weight heparin 4-6 hours before surgical procedure, substantially minimize the duration of suboptimal level of anticoagulation 103 Bleeding disorder and minor oral surgery and subsequently reducing the risk for a thromboembolic event, following surgical procedure anticoagulation treatment is resumed 12-18 hours post surgery.[33] If intravenous unfractionated heparin is used, then appropriate laboratory testing, a PTT should be done after discontinuation of the drug and before the procedure.[34] Patients taking aspirin should discontinue the medication at least 3 days, and up to 7 days, before the surgical procedure.[20,23,24,27,35] However, consultation with the physician is mandatory. In regard to other anti-platelet medications, such as ADP inhibitors and GP IIb-IIIa inhibitors, discontinuation of the medication 7 days before the procedure gives adequate time for the level of circulating functional platelets to be restored.[27,35] The American heart association and American college of cardiology scientific statement states that for patients undergoing dental procedures, tranexamic acid or EACA mouthwash can be applied without interrupting anticoagulant therapy.[36] The sixth American college of chest physicians (ACCP) consensus conference on antithrombotic therapy made several limited recommendations as follows:[37] For patients undergoing dental procedures who are not considered to be at high risk for bleeding, ACCP recommends that warfarin therapy not be discontinued. In patients at high risk of bleeding, ACCP recommends that warfarin therapy be discontinued. For patients undergoing dental procedure in which local bleeding must be controlled, tranexamic acid or EACA mouthwash can be administered without interrupting anticoagulant therapy. Flowchart for choice of treatment according to type of anesthesia and severity of the bleeding disorder (Table III).[38] INTRA -OPERATIVE MEASURES Intra-operative measures include a number of systemic and local measures to prevent unlikely bleeding diathesis. Inherited platelet disorders, leading to bleeding or increased risk for bleeding, are managed systemically with platelet transfusions.[14] Inherited coagulopathies are managed systemically with replacement of coagulation factors.[39] Intravenous infusion of deficient, or missing, coagulation factor starts 1 IJOCR Jan - Mar 2015; Volume 3 Issue 7 Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S hour before the procedure in order to achieve a level that is 30% above the normal plasma concentration of this particular factor.[40] The level has to be higher and to reach 50% of the normal amount when regional block anesthesia is administered.[40] Proper treatment planning should be done in accordance with addresses the half life of coagulation factors, and treatment sessions should be programmed accordingly. In mild and moderate inherited coagulopathies, desmopressin or 1-desamino-8-D arginine vasopressin can be useful.[41,42] Desmopressin was used for the first time in 1977 by Mannucci et al., to treat patients with mild hemophilia A and von Willebrand disease. Desmopressin, a synthetic analogue of the antidiuretic hormone vasopressin, raises the plasma levels of endogenous factor VIII and von Willebrand factor (vWf). The increase in vWf results in a shortening of the bleeding time and the increase in factor VIII results in a shortening of the activated partial thromboplastin time.[43] Desmopressin is an alternative to clotting factor concentrate transfusion[44] and is also efficient in platelet dysfunction (Table IV).[45] Management of patients with acquired bleeding disorders is focused mainly on local hemostatic measures that apply also to inherited bleeding disorders.[46] Local infiltration anesthesia with the use of vasoconstrictive agent is desirable. 1:100,000 epinephrine with Lidocaine 2% or Articaine 4% provides sufficient anesthesia for surgery in the mandible. Excessive bleeding can be prevented by meticulous handling of soft tissues, a conservative flap design and minimizing flap elevation. For surgical extractions, tooth sectioning helps preserving bone and minimizing the involvement of anatomic spaces around the surgical site. Mandibular molars should be approached with a buccal flap and no reflection of a lingual flap should be attempted. After surgery, primary closure of the flap accomplished with either nonresorbable or resorbable sutures followed by application of pressure for 10 minutes with moistened gauze on the flap has been suggested.[27] There are a number of commercially available local hemostatic agents that enhance clot stabilization. These include: Absorbable gelatin[42,47] Absorbable collagen[23] Microfibrillar collagen[23] 104 Bleeding disorder and minor oral surgery Collagen dressings[23] Oxidized regenerated cellulose[48] Tranexamic acid[49,50] Epsilon-amino caproic acid[51] Fibrin glue[35,48,49,52] Platelet-rich plasma[53] Gelfoam is an absorbable gelatin sponge material that provides a stable “scaffold” for clot formation.[54] Collagen, gelatin and cellulose products provide the scaffold for platelets to adhere to one another and form the platelet plug. Fibrin glue consists of: Thrombin which converts fibrinogen to fibrin and this contributes to the formation of the fibrin clot. Fibrinogen, Fibronectin - acts as a binding protein for the blood clot Aprotinin - delays the degradation of the hemostatic clot. Platelet-rich plasma contains growth factors released by the platelets that accelerate the healing process and thus enhance hemostasis.[46] Electrocautery another useful tool to slow intraoperative bleeding. However, it must be used cautiously to avoid excessive tissue necrosis. Not only will the necrosis delay healing but it may also become a source of postoperative bleeding when the necrotic tissue sloughs.[19] Activation of fibrinolysis is triggered by the presence of fibrin and tissue-type plasminogen activators at the site of fibrin formation, a process regulated by physiologic inhibitors such as α2-antiplasmin, histidine-rich glycoprotein and plasminogen activator inhibitor.[55] Plasminogen activator and plasminogen are present in oral environment in physiologic conditions whereas fibrinolysis is triggered after surgery.[56] As early as the 1960’s, Björlin started studying fibrinolysis in the oral cavity; Bajoslin G (1984). He considered the local fibrinolysis in the alveoli the probable cause of bleeding after dental extraction.[57] Tranexamic acid, along with epsilon aminocaproic acid, inhibits plasminogen action and reduces the fibrinolytic activity of the early formed hemostatic clot.[46] Epsilon-aminocaproic acid and tranexamic acid, two synthetic derivatives of the amino acid lysine, are antifibrinolytic agents hence help clot stabilization. They bind to plasminogen at the level of its lysine binding sites IJOCR Jan - Mar 2015; Volume 3 Issue 7 Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S and competitively antagonize the interaction of plasminogen with fibrin, thereby preventing plasmin generation in the fibrin clot.[57] Tranexamic acid is about 10-fold more potent than epsilon-aminocaproic acid and has a longer half-life. It is administered 15–20 mg per kg body weight is given two hours before surgery/extraction, and then repeated three times daily for 8-10 days. Mouth rinsing with 10 ml of a 5% solution of TA for two minutes four times daily for two days may be used. The beneficial effect of local application of EACA as mouthwash was first demonstrated by Berry et al.[58] Sindet-Pedersen advocated the use of TA mouthwashes because, after systemic administration, TA was not detectable in saliva in healthy volunteers who had received 1 g orally as a single dose. The maximum level in plasma was reached after approximately 120 minutes. On the other hand, after rinsing the mouth with 10 ml of a 5% aqueous solution for two minutes, a high concentration was achieved in the saliva, while TA was undetectable in plasma.[59] Antifibrinolytic amino acids are effective adjuvants for the control of mucosal bleeding, such as nose bleeding, oropharyngeal oozing and gastroenteric haemorrhages. Mouth washes with tranexamic acid are effective for bleeding prevention in patients undergoing dental extractions during oral anticoagulant therapy. Antifibrinolytic lysine analogues are useful to control bleeding in patients with liver cirrhosis, as hyperfibrinolysis mainly due to impaired hepatic clearance of tissue-type plasminogen activator and decreased α2 antiplasmin contributes to the haemostatic imbalance. Forbes et al., reported that in patients with hemophilia, treatment for five days with 1 g of TA three times daily starting two hours before surgery was associated with significantly less post-operative bleeding than in a placebo group.[60] Ramström and Blombäck reported that factor concentrate requirement and days spent in hospital could be decreased if TA and antibiotics were included in the regimen.[61] Vitamin K, a lipid soluble naphthoquinone derivative, required as coenzyme for the posttranslational γ-carboxylation of glutamic acid residues in the N-terminal regions of vitamin Kdependent clotting factors, namely prothrombin, factor VII, factor IX and factor X. The process of γ-carboxylation permits such coagulation proteins 105 Bleeding disorder and minor oral surgery to interact with phospholipid surfaces in the presence of calcium ions, which act as a bridge between γ-carbon dioxide of procoagulant factors and negative charged platelets and endothelial phospholipids.[43] Slow intravenous injection of Vitamin K, will reverse the effects of oral anticoagulants within 12 to 48 hours according to the dose administered. Vitamin K is generally ineffective in patients with parenchymal liver disease, and is of no value in the hereditary deficiencies of prothrombin, factor VII, factor IX and factor X. Dental extractions and associated bleeding are effectively managed with the insertion of a sponge into the site. The sponge can be presoaked with an antifibrinolytic agent, such as tranexamic acid or epsilon aminocaproic acid.[47] An absorbable gelatin sponge should only be used in conjunction with thrombin for this purpose.[23] Fabrication of a surgical splint for additional pressure, and protection of the site is recommended.[62,63] Cyanoacrylate has been used in the past to seal the extraction site.[64] POST-OPERATIVE MEASURES Postoperative management is crucial for preventing bleeding. General recommendations emphasize the importance of good care of the surgical area. Rinsing is prohibited on the day of surgery and the healing site must be left undisturbed. Specific attention should be given to tongue movements interfering with healing and food intake. Liquids and a high-protein diet are strongly recommended. Philip V & Kent P (2007): The use of antifibrinolytic mouthwash is highly recommended the surgery.[46] The regimen may comprise rinsing with 10 ml of 4.8-5% tranexamic acid solution, four times a day, for 2 minutes:[40,65] Aframian et al., (2007); Franchini M et al., (2005). The rinsing can be carried out over a period of 2-5 days and may be extended up to 8 days. The dental professional should exercise caution in prescribing antibiotics and pain medications. Antibiotics, such as penicillin, erythromycin, tetracycline, metronidazole, cephalosporin’s, ampicillin and amoxicillin + clavulanic acid, potentiate the coumarin action:[24,27,33] Herman WW et al., (1997), Lockhart PB et al., (2003), Scully C, Wolff A (2002). Scully C, Wolff A (2002): Clindamycin should be the antibiotic of choice in these patients, and a lower dose of acetaminophen for a short period of time is the regimen recommended IJOCR Jan - Mar 2015; Volume 3 Issue 7 Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S for postoperative pain control.[27] Lockhart PB et al., (2003): When other medications are administered that affect coumarin bioavailability or metabolism, supplemental international normalized ratio tests are performed to evaluate the anticoagulation effect.[20] Management of Postoperative Hemorrhage: [1] Techniques for managing postoperative bleeding episodes are: Reapplication of pressure packs. Often patients do not do this properly. The technique must be demonstrated to the patient to ensure that this simple technique is effective. Pressure packs must be kept in place at least 30 minutes without checking them before the need for other intervention is determined. Packing or repacking sockets with Gelfoam is usually the second step, with pressure packs replaced over the fresh Gelfoam; Seichshnaydre MA et al., (1994). Reinjection of local anesthetic with epinephrine can help slow hemorrhage and allow vessel constriction, platelet plug formation and stable clot formation. However, after epinephrine rebound, vasodilation can occur, which may lead to significant hemorrhage. Any large, exophytic clots should be removed down to the level of the socket as they may provide a pathway for continued bleeding and prevent application of adequate pressure to the site. The use of astringents may be considered, especially on incisions and raw areas. The “old tea-bag trick” refers to the practice of using a tea bag as a pressure pack. The tea contains the astringent tannic acid. Commercial preparations containing aluminum chloride produce a similar result. Zanon E et al., (2003). Patients should be instructed to limit physical exertion, to sit or sleep in a semi-sitting position and to avoid smoking and alcohol consumption. Ramstrom G, Blomback M (1974). CONFLICT OF INTEREST & SOURCE OF FUNDING The author declares that there is no source of funding and there is no conflict of interest among all authors. 106 Bleeding disorder and minor oral surgery BIBLIOGRAPHY 1. Israels S, Schwetz N, Boyar R, McNicol A. Bleeding disorders: characterization, dental considerations and management. J Can Dent Assoc 2006;72(9):827. 2. Gupta A, Epstein JB, Cabay RJ. Bleeding Disorders of Importance in Dental Care and Related Patient Management. www.cdaadc.ca/jcda, 2007;73(1). 3. Nazif M. Local anesthesia for patients with hemophilia. ASDC J Dent Child 1970;37(1):79-84. 4. Webster WP, Roberts HR, Penick GD. Dental care of patients with hereditary disorders of blood coagulation. In: Rantoff OD, editor. Treatment of hemorrhagic disorders. New York: Harper & Row; 1968. p. 93–110. 5. 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