The Management of Anti-Coagulant Therapies within a Dental Clinic
With around 3,400 hospital-acquired episodes of venous thromboembolism occurring each year and being responsible for 7% of all deaths within Australian hospitals, it is clear venous thromboembolism is one of the main causes of morbidity and mortality in Australia, alongside dementia and lung cancer.1,2,3 The accessibility and development of current anti-coagulant and antiplatelet drugs on the market have allowed individuals to effectively manage this preventable condition and hence, have a better quality of life. It is quintessential for dentists to tell their patients with a high risk of thromboembolic events whether to stop or continue to take these prophylactic medications prior to treatment. This is due to an increased risk of bleeding from a cut if not stopped before treatment and a greater risk of a thromboembolic event such as stroke to occur if stopped before treatment.4 Thus, this paper will discuss the causes of venous thromboembolism and the importance of developing an effective treatment plan to minimise the risk of bleeding prior to and after the dental procedure.
Mechanism of Haemostasis
Haemostasis is the body’s natural ability of maintaining a balance between blood clot formation to minimise haemorrhage at the injured site and the preventing thrombosis from forming beyond the site of tissue injury.5 There are two stages that are associated with haemostasis. Primary haemostasis occurs when there is an initial damage to the endothelial cells within the blood vessels.6 With platelets and fibrinogen reacting together, a platelet plug can be formed to seal the injured tissue.6 Despite the presence of the platelet plug, excessive bleeding forces secondary haemostasis to occur and this involves a number of complex chemical reactions that converts soluble fibrinogen into insoluble fibrin proteins.6 As a result, this establishes a framework of fibrin which aids in supporting and strengthening the blood clot.6
During the secondary phase of haemostasis, the interaction between the anti-coagulant and pro-coagulant system is essential for the formation of the clotting factor, thrombin .7 An imbalance between the plasma concentrations of these two systems due to an impaired regulatory mechanism for thrombin formation can give rise to venous thrombosis.7 Furthermore, the role of anti-coagulants is to block the coagulation cascade, causing an increase in platelet reactivity and ultimately, enhances the risk for thrombotic events to occur.8 Therefore, it is imperative for dentists to understand the mechanism of haemostasis and how it can be affected when using anti-coagulants.
Management of Patient and Risk of Bleeding in Dental Treatment
It is important for dental practitioners to have a complete medicolegal record of the patient. This includes obtaining the name of their general physician as they may need to be contacted to assess and discuss the patient’s overall health status and prescribed anti-coagulant medication.9 Additionally, it allows dentists to create a treatment plan to effectively minimise the risk of unplanned bleeding. For future treatment, it is quintessential for the dentists to update information regarding medication changes as well as the patient’s health status.9
Prior to conducting an invasive dental procedure, it is essential for dental practitioners to recognise what type of anti-coagulant agent is used by the patient, especially for those that take new anti-coagulants as they are prescribed at certain doses.10 Furthermore, an interaction between anti-coagulants and other medication such as anti-biotics can increase the effect of these prophylactic agents.10 As a result, for patients that are subjected to a decreased renal function and liver disease, they become more susceptible to bleeding.10
Additionally, dentists should be aware of the increased risk of bleeding when conducting invasive procedures such as surgical tooth extractions.11 As a result, the risks and benefits of the treatment plan should be assessed, elucidated and discussed with the patient for effective care in the clinic.
Over the last 70 years, heparin and vitamin K antagonists have been prominently used to medically treat and prevent thromboembolic events.11 Various issues that stemmed from using these traditional anti-coagulants has led to further research discovering a new class of oral anti-coagulants.12 The mechanism of these new drugs involves targeting factor X and thrombin. As a result, it is important to be kept up to date of how different types of anti-coagulants affect the human body as they become more developed and commercially available in the future.12
Heparin is an injectable anti-coagulant that prevents the formation of blood clots during and upon completing dental extractions.13 The biological activity of this drug involves activating anti-thrombin III, a substance found in plasma that binds and inhibits thrombin and factor Xa activity.13 This inhibits the last stage of the coagulation cascade from occurring.14 Therefore, it is favourable for patients with previous history to thromboembolic events, including venous thrombosis, myocardial infarction etc. to use heparin.14
Additionally, this drug can be characterised as being high or low in molecular weight.14 To determine the anti-coagulant effect of high molecular weight heparins which is linked to the risk of developing thrombocytopenia, the activated partial thromboplastin time needs to be monitored. Low molecular weight heparins (LMWH) such as Enoxaparin provides a better anti-coagulant response than high molecular weight heparins and as a result, LMWH do not require monitoring.14 When using this drug, it is important for dental practitioners to be aware of its anti-clotting properties as this can give rise to excessive bleeding.13
Vitamin K Antagonists
Warfarin is a commonly used oral vitamin K antagonist for the prevention of thromboembolic episodes.15 Warfarin produces its anti-coagulant effect by restricting the activity of vitamin K epoxide reluctase, an enzyme that is responsible for recovering oxidised vitamin K.14 Due to a lack of activated vitamin K–dependent factors, the post-translational modification of anti-coagulation proteins C and S and subsequently, the coagulating factors II, VII, IX and X are inhibited.12 Studies by Franchini, Liumbruno, Bonfanti, and Lippi have shown the use of warfarin reduced the likelihood for venous thromboembolism to occur again by more than 90%.12 Despite this, Khalil and Abdullah’s research mentioned that the percentage for warfarin induced life threatening bleeding ranged from 0.4-7.2%.16 Hence, it is important for dental practitioners to realise the likelihood for death to occur by excessive bleeding due to warfarin’s anti-coagulating activity .16
Moreover, the effects of warfarin including its interaction with other drugs and food and narrow therapeutic index makes it clear for dental practitioners to realise the importance of regulating warfarin’s activity.17 This is done by frequently monitoring the International Normalised Ratio (INR), a standardised measure which is used to determine the time taken for blood to clot.17 Additionally, blood tests that are used to obtain INR should not be conducted more than 72 hours before the dental treatment.17 Patients that do not take warfarin have an INR value of 1.17 An INR value that is greater than 1 indicates a longer time for blood to clot and hence, there is an increased risk of haemorrhage.17 It is essential for the INR value to lie within the range of 2.5 to 4 for at least two days straight as there is the possibility for INR to vary due to changes in the patient’s food intake, utilising other medication without notifying the dentist etc.18
Within a clinical environment, if the INR value is greater or equal to 4, the dentist must stop treatment and contact their patient’s general practioner.17 With excessive bleeding, the patient must be referred to the hospital.17 For the dentist to continue with their procedure, the patient’s INR level must be lower than 4.17 Additionally, an INR value that is less than 4 allows the dentist to treat the patient normally whilst advising them to continue taking warfarin.17
Non-Vitamin K Antagonists Oral Anti-Coagulants (NOACs)
With a greater pharmacokinetic stability, Non-Vitamin K Antagonist Oral Coagulants have recently replaced warfarin to minimise the risk of stroke and embolic episodes.19 In Australia, the three NOACs that are available are apixaban, dabigatran, and rivaroxaban.19
There are two types of NOACs: direct factor Xa inhibitors and direct thrombin inhibitors.19 Apixaban and rivaroxaban are direct factor Xa inhibitors that inhibit the activity of factor Xa in the coagulation cascade, preventing the formation of thrombin.14 Additionally, these agents are used for venous thromboembolic prophylaxis after the completion of a hip or knee replacement surgery.19 The daily dose requirement for apixaban and rivaroxaban are 2.5mg and 10mg respectively.19 It is important for dentists to never inject azole antifungals or HIV protease inhibitors alongside rivaroxaban or apixaban.19 Furthermore, dabigatran is a direct thrombin inhibitor that prevents blood from clotting by inhibiting thrombin from converting fibrinogen into fibrin.14 150mg of dabigatran is needed to be taken twice a day for venous thromboembolic prophylaxis follow a hip or knee surgery as well as thromboprophylaxis for non-valvular atrial fibrillation.14,19
Recently, there have been debates regarding the use of NOACs as a more effective and safer anti-coagulant than warfarin. The advantages of using NOACs include being prescribed at specific dosages, no need to constantly monitor INR, a low chance for the drug to interact with other foods and medication and has a rapid onset of two to three hours.20 For patients with impaired renal function, they should not use NOACs as these agents are mostly removed via the renal system.19 Additionally, there are no reversal agents that are currently available to stop further bleeding from occurring when using rivaroxaban.14
Overall, it is more favourable for NOACs to be used as future anti-coagulants instead of warfarin as they do not require frequent INR monitoring and have greater selective actions. However, dentists must be mindful of the increased risk for excessive bleeding to occur when using these new anti-coagulants.
Post-operative Bleeding Management
It is common for bleeding to occur after the extraction of a tooth as the vasoconstricting effect of the local anaesthetics wears away.21 Local measures to stop this includes the dentist telling the patient to bite down on a folded piece of gauze at the site of injury.21 If further bleeding occurs, the use of haemostatic materials such as gelatin sponge (gel foam) or topical thrombin can inhibit this problem.22 Both these agents are applied onto the bleeding surface and promotes the formation a matrix that enhances blood clot development.22
After the completion of oral surgery, most patients taking anti-coagulants tend to bleed for another two to three days.23 This is caused by the accumulation of plasminogen and plasminogen activators within the oral cavity and results in fibrinolysis.23 Therefore, it is essential for the patient to be carefully monitored until the bleeding is adequately stopped.23 Moreover, it is recommended to use 4.8% tranexamic acid mouth rinse twice a day for a period of two to five days to inhibit fibrinolysis.23 For patients that are prescribed with anti-coagulants, the dentist should not use COX-2 inhibitors or NSAIDs for analgesia as complex chemical reactions and possible interactions with other medication can occur.24
Evidently, different types of anti-coagulant and anti-platelet drugs can be used to minimise venous thromboembolic induced deaths within Australia. It is essential for dentists to understand the complications associated with using these prophylactic agents to effectively create a treatment plan for their patient. Thus, the risk of bleeding can be minimised preoperatively and postoperatively.
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Australian Commission on Safety and Quality in Health Care. Venous Thromboembolism Prevention Clinical Care Standard. https://www.safetyandquality.gov.au/our-work/clinical-care-standards/venous-thromboembolism-prevention-clinical-care-standard/. Updated 2018. Accessed September 25,2018.
Australian Bureau of Statistics. Australia’s leading causes of death, 2016. http://www.abs.gov.au/ausstats/[email protected]/Lookup/by%20Subject/3303.0~2016~Main%20Features~Australia’s%20leading%20causes%20of%20death,%202016~3. Updated September 25,2018. Accessed September 25,2018.
myDR. Anticoagulants. http://www.mydr.com.au/heart-stroke/anticoagulants. Accessed September 26,2018.
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Bertina RM. The role of procoagulants and anticoagulants in the development of venous thromboembolism. Thromb Res. 2009;123 Suppl 4:S41-5. https://www.ncbi.nlm.nih.gov/pubmed/19303503. Accessed September 27,2018.
Angiolillo DJ, Tello-Montoliu A. Anticoagulant Therapy. https://www.thecardiologyadvisor.com/cardiology/anticoagulant-therapy/article/584436/. Updated 2018. Accessed September 28,2018.
Moses G, Daly C. Treating dental patients on new anticoagulant drugs. Aust Prescr. 2017; 40:48. https://www.nps.org.au/australian-prescriber/articles/treating-dental-patients-on-new-anticoagulant-drugs. Accessed September 28,2018.
Moses G, Daly C. Treating dental patients on new anticoagulant drugs. Aust Prescr. 2017; 40:48. https://www.nps.org.au/australian-prescriber/articles/treating-patients-on-new-anticoagulant-drugs. Accessed September 28,2018.
Shi Q, Xu J, Zhang T, Zhang B, Liu H. Post-operative Bleeding Risk in Dental Surgery for Patients on Oral Anticoagulant Therapy: A Meta-analysis of Observational Studies. Front Pharmacol. 2017; 8: 58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296357/. Accessed September 29,2018.
Franchini M, Liumbruno CM, Bonfanti C, Lippi G. The evolution of anticoagulant therapy. Blood Transfus. 2016 Mar; 14(2): 175–184. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781787/. Accessed September 29,2018.
Encylocopaedia Britannica. Heparin Anticoagulant Drug. https://www.britannica.com/science/heparin. Updated 2018. Accessed September 29,2018.
Centegra. Anticoagulants. http://centegra.org/wp-content/uploads/2013/06/Anticoagulants-08-13.pdf. Published August 2013. Accessed September 30,2018.
Abdullah WA, Khalil H. Dental extraction in patients on warfarin treatment. Clin Cosmet Investig Dent. 2014 Aug 19; 6:65-9. https://www.ncbi.nlm.nih.gov/pubmed/25170281. Accessed September 30,2018.
Abdullah WA, Khalil H. Dental extraction in patients on warfarin treatment. Clin Cosmet Investig Dent. 2014 Aug 19; 6:65-9. https://www.dovepress.com/dental-extraction-in-patients-on-warfarin-treatment-a-series-of-35-pat-peer-reviewed-fulltext-article-CCIDE. Accessed September 31,2018.
Scottish Dental Clinical Effectivness Programme. Management of Dental Patients Taking Anticoagulants or Antiplatelet Drugs Dental Clinic Guidance. http://www.sdcep.org.uk/wp-content/uploads/2015/09/SDCEP-Anticoagulants-Guidance.pdf. Accessed September 31,2018.
Kuruvilla M, PharmaD, Gurk-Turner C, RPH. A review of warfarin dosing and monitoring. Proc (Bayl Univ Med Cent). 2001 Jul; 14(3): 305–306.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1305837/. Accessed September 31,2018.
Brieger D, Curnow J. Anticoagulation: a GP primer on the new oral anticoagulants. Cardiology. 2014 May; 43(5): 254-259. https://www.racgp.org.au/afp/2014/may/anticoagulation/. Accessed September 31,2018.
Emergency Care Institute New South Wales. Novel Oral Anticoagulants (NOACs). https://www.aci.health.nsw.gov.au/networks/eci/clinical/clinical-resources/clinical-tools/anticoagulation/noacs. Published September 19,2017. Accessed October 1,2018.
Reichman EF. Post-Extraction Bleeding Management. https://accessemergencymedicine.mhmedical.com/content.aspx?bookid=683;sectionid=45343828;jumpsectionID=45357501. Published May 22,2013. Accessed October 1,2018.
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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. http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.610.9180;rep=rep1;type=pdf. Accessed October 1,2018.
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