Management of Patients on Anticoagulants. Haemostasis. Coagulation cascade. Cell-based model 19/11/2013

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1 Management of Patients on Anticoagulants National Coal Mining Museum 11 Nov 2013 Navneet Lad StR Special Care Dentistry Aims: Discuss the different anti-platelet drugs available. Discuss the new generation of oral anticoagulant drugs available. Educational Objectives: Highlight some of the treatment planning issues for patients taking anti-coagulants. The need to liaise with medical colleagues when dealing with some anti-coagulated Haemostasis Primary Haemostasis Vascular spasm and platelet activity aspirin Secondary Haemostasis Coagulation cascade to form fibrin warfarin, heparin, rivaroxaban and dabigatran Tertiary Haemostasis (fibrinolysis) Inhibition of fibrinolysis Tranexamic acid Previously had the Classical model: Intrinsic pathway Extrinsic pathway Resulting in final common pathway Coagulation cascade Cell-based model Evolved to better understand clotting in vivo Three overlapping stages: Initiation occurs on a TF bearing cell Amplification platelets etc. activated for large scale thrombin generation Propagation occurs on surface platelets, propagates thrombin production 1

2 Common Antiplatelet Drugs Aspirin (acetyl salicylic acid) First anti-platelet agent, irreversibly inhibits cyclooxygenase 1 enzyme preventing the conversion of arachidonic acid to thromboxane A2 Long term reduction in subsequent MI, stroke, or vascular death by 20-25% Low potency produces partial inhibition of platelet aggregation Some patients resistant to aspirin In patients with high risk of GI bleeding add PPI Common anti-platelet agents cont. Thienopyridine antiplatelet drugs: Ticlopidine, clopidogrel (Plavix) and prasugrel. Prodrugs that are activated by either one or two stages (hepatic activation ). Specifically and irreversibly inhibits P2Y12 subtype of ADP receptor important. Used alone or in combination with aspirin. Clopidogrel variable platelet inhibition based on genetic polymorphism, prasugrel is more consistent and 10-fold higher potency Prasugrel particularly useful in diabetics Increased bleeding risk if take NSAIDs. Uncommon antiplatelet drugs cont. Non-thienopyridine derivatives: Ticagrelor, cangrelor and elinogrel. Produce a direct and reversible P2Y12 receptor inhibition. Do not require metabolic activation, but ticagrelor produces 1 active metabolite- more rapid onset and pronounced platelet inhibition Offset of action 1-2 days (~5 days). Requires twice daily dosing. Side effects: ed bleeding, dyspnoea, ventricular pauses Uncommon antiplatelet drugs cont. Dipyridamole a phosphodiesterase inhibitor. Modified-release dipyridamole with aspirin in secondary prevention of stroke, TIA or thromboembolic events in pts. with mechanical heart valves in combination with warfarin. Inhibits platelet adenosine uptake, reducing platelet aggregation. Uncommon antiplatelet drugs Glycoprotein IIb/IIIa inhibitors 3 different compounds available: abciximab, eptifibatide and tirofiban Very potent inhibitors of platelet activation and aggregation used in acute coronary syndrome and percutaneous coronary intervention. Bind to both non-stimulated and stimulated platelets Block bonding of fibrinogen to activated GP 2b/3a Only given via intravenous administration and for specialist use only Safety concerns: bleeding risk and thrombocytopenia Common Oral Anticoagulant Drugs Coumarins Warfarin Inhibit synthesis of Vit K-dependant coagulation factors ( II, VII, IX and X) Delayed onset of action (days) Narrow therapeutic window INR DVT INR 3.5 prosthetic heart valve Dose-response variability Interactions with dietary vit K and other medications including: Amoxicillin, erythromycin, metronidazole, fluconazole, miconazole, aspirin, NSAIDs and?paracetamol High incidence of intracranial bleeding, esp. among Asian Reversible with Vit K and prothrombin complex 2

3 Uncommon oral anticoagulants continued Dabigatran etexilate (Pradaxa) A direct thrombin inhibitor more specific Absorbed via GI tract and hydrolysed by non-specific esterases in gut, plasma and liver to dabigatran. Half life hours, rapid onset Nice approval in 2008 for VTE prevention following hip/knee surgery in adults In 2012 received NICE approval for stroke and systemic embolism prevention in AF Fixed once/twice daily dose Minimal drug or food interactions avoid NSAID s, erythromycin and clarithromycin No therapeutic monitoring required TT and APTT to assess anticoagulant effect No reversible agent Direct FXa inhibitor Rivaroxaban (Xarelto), apixaban. Half-life of 5-9 hours approved for VTE prevention in adults following hip/knee surgery approved for DVT and prevention of stroke and systemic embolism prevention in AF. Fixed once/twice daily dose. Minimal drug or food interactions avoid NSAID s and miconazole if impaired renal function No therapeutic monitoring required prothrombin time and anti-xa assay. No reversible agent. Parenteral Anticoagulants Heparin Unfractionated rapid initiation but short acting Daily aptt monitoring LMWH e.g. enoxaparin sodium (clexane) longer duration of action Less likely to cause heparin-induced thrombocytopenia Routine monitoring not required Heparin reversed by protamine sulphate Treatment Planning History Medical beware of co-morbidities, in particular ask about bleeding tendencies. Dental Social Examination Special Tests Close communication and liaison with haematology/gmp Patient Identification History DVT PE Ischaemic heart disease Secondary stroke prevention Renal dialysis Hospitalised patient Chemotherapy patient Co-morbidities Liver disease and/or alcoholism Bone marrow disease Haemophilia or other disorder of haemostasis Mal-absorption Renal disease Cancers such as leukaemia Acute/chronic infection Commitant use of medications such as: Antibiotics antifungal Other anti-coagulants NSAID s or pain relief 3

4 Special Tests INR ratio of patients PT/control PT APTT heparin Clotting screen also includes TT Planning Treatment Where to treat the pt.? When to do the Rx? Method of LA Alternatives Prevention of post-operative bleeding Where to treat the patient? Non-invasive procedure Potentially suitable for primary care: Endodontics Extractions 1-3 simple forceps extractions in one quadrant Sub-gingival scaling Minor oral surgery May want to refer into 2 or 3 care: Biopsies If have co-morbidities More involved surgical procedure e.g. implants Articaine Use of infiltrations and intra-ligamentary injections Beware of IDB and lingual infiltrations Alternatives: Air abrasion cariosolv Local Anaesthetic When to do the treatment? Early in week, early in the day. Aspirin/clopidogrel/dipyridamole/prasugrel Do not change pt.'s regime and take extra precautions with haemostasis Warfarin Check INR 72 hours prior if stable only Otherwise check INR morning of appt Safe to do treatment if stable INR in therapeutic range 2-4 (i.e. <4) cont. Heparin Sparse literature about treating this group of Due to short acting stop the morning of treatment and start again evening of treatment. Dabigatran and Rivaroxaban/Apixaban Level of anti-coagulation comparable to INR < 4 Do not discontinue No routine blood tests required Additional local haemostatic measures 4

5 Prevention of post-operative Bleeding But always liaise with the patients GMP/haematology team. Adequate use of pressure/swabs Additional measures such as: Oxidised cellulose surgicel Gelatin sponges Sutures Tranexamic acid mouthwash Absele Give post-operative instructions? Post-op antibiotics to prevent 2º infection but may interact with anticoagulant Tranexamic Acid Mouthwash If prescribed systemically does not reach therapeutic levels in saliva 5% w/v solution 10 mls Held in mouth for 2 minutes Do not swallow Qds 7 days References Kuzniatsova, N. and Gregory, YHL. Antithrombotic therapy: what the dental surgeon has to know. Faculty Dent J 2010; 1 (3): Guidelines for the management of patients on oral anticoagulants requiring dental surgery. BDJ 2007; 203: Renton, T., Woolcombe, S., Taylor, T. and Hill, C.M. Oral Surgery: part 1. Introduction and the management of the medically compromised patient. BDJ 2013; 215 (5) : Sime, G. Dental Management of patients taking oral anticoagulant drugs. April available at : ts.doc BNF Thank you for listening. Prettysinister.blogspot.com 5

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