Anticoagulants, Antifibrinolytic, and Antiplatelet Drugs

• Haemostasis steps:

  1. Constriction of damaged vessels
  2. Mechanical blockage of the hole by a platelet plug
  3. Coagulation cascade
  4. Thrombolysis
• Platelet activation:

  • Thromboxane A2 synthesis
  • Platelet activation initiates the arachidonic acid pathway to produce TXA2 -> platelet activation and aggregation
• Platelet aggregation is stimulated by ADP, thromboxane. Fibrinogen - links adjacent platelets.
• Dynamic platelet/coagulation cascade interplay = thrombin also activates platelets
• Thrombolysis occurs when fibrin mesh is prevented from increasing and slowly dissolved by the enzyme plasmin.
• Prevention/treatment of atherosclerosis, arterial and venous thrombosis:

  • Antiplatelet therapy
  • Anticoagulant therapy
  • Thrombolytic therapy
• Antiplatelet drugs:

  • Cyclooxygenase inhibitors
  • ADP (adenosine diphosphate) receptor antagonists
  • Adenosine re-uptake inhibitors
• Indications for antiplatelet therapy:

  • Previous myocardial infarction
  • Acute myocardial infarction
  • Previous stroke or TIA
  • Acute stroke (some)
  • Stable angina
  • Intermittent claudication
  • Atrial fibrillation
• Aspirin (or another antiplatelet drug) prevents serious vascular events in a wide range of high-risk patients
• Antiplatelet drugs in acute cardiac events:

  • Reduce the risk of complications - aspirin in unstable angina halves the risk of mortality
  • Improve prognosis eg aspirin in acute myocardial infarction: 25% reduction in mortality
• Aspirin-Cyclooxygenase Inhibitor (aspirin):

  • Irreversible inhibitor of platelet thromboxane
  • Effects for 7-10 days
  • Used therapeutically to reduce risk of thromboembolic disorders (low dose - 75mg/day - prophylactic use)
  • Risk of post-operative haemorrhage
  • Local measures
  • Platelet transfusion
• 300mg dose of aspirin given to pt in chewable tablet form if you think they might be having an acute myocardial infarction.
• Contraindications to aspirin:

  • Allergy
  • Age <12 years (risk of Reye's syndrome - swelling of the liver and brain)
  • Active peptic ulceration
  • Recent gastrointestinal bleeding
  • Recent intracranial bleeding
  • Bleeding disorders
  • Severe liver disease
• CLOPIDOGREL - ADP Receptor Antagonist:

  • Inhibitors of the Platelet ADP receptor
  • Safer regarding GI bleeding than aspirin
  • Safer (less haematological toxicity)
  • Clopidogrel can now be prescribed (in combination with aspirin) for pts suffering from acute coronary syndrome
  • Used if complications occur whilst on aspirin
  • If taking clopidogrel alone then no need to stop it before a procedure that would induce bleeding (eg extraction)
• Adenosine re-uptake inhibitor: Dipyridamole - used:

  • As an adjunct to oral anticoagulation for prophylaxis of thromboembolism associated with prosthetic heart valves
  • As an alternative (or in addition) to aspirin
  • Contraindicated in uncontrolled angina, which it may exacerbate
• Anticoagulant - Heparin - Vitamin K Antagonist:

  • Enhances activity of antithrombin III
  • Inactivates prothrombin
  • Impairs platelet function
• Heparin:

  • Can be given parenterally - poorly absorbed from GIT
  • Low doses -> subcutaneously
  • High doses -> IV
  • Metabolised in the liver
  • Immediate onset of action half-life of 1-5 hours
  • Low molecular weight heparins (LMWHs) are also available
  • Monitoring: APTT (activated partial thromboplastin time) - equivalent of the INR (international normalised ratio)
  • Effects of heparin - reversed by protamine sulphate
• Low molecular weight heparin (LMWH):

  • Short chains of polysaccharide
  • Once daily dosing
  • No need to monitor APTT (activated partial thromboplastin time)
  • Smaller bleeding risk
  • Reduced risk of thrombocytopaenia (platelet count is too low)
  • HOWEVER less reversible than polymeric heparin
• Advantages of low molecular weight heparin (LMWH):

  • Can be given subcutaneously - therefore can be used for outpatients
  • DVT (deep vein thrombosis) & PE (pulmonary embolism), which previously required hospitalisation, can now be managed on an outpatient bases
• Unwanted effects of heparin:

  • Haemorrhage - GIT
  • Transient thrombocytopaenia
  • Allergy, long-term -> osteoporosis & impaired liver function
• Coumarin anticoagulants - Vitamin K Antagonist:

  • Warfarin
  • Active orally, extensively protein-bound (98%)
  • Half-life 35-37 hours
  • Actions
  • Inhibits vitamin-K dependent clotting factors (II, VII, IX, X)
  • Antagonis drug - vitamin K
• Warfarin interacts with lots of things, therefore if you need to prescribe something that interacts with it, you may just need to prescribe it at a reduced dose - but check the BNF! Main ones are:

  • Aspirin + warfarin
  • Fluconazole, miconazole + warfarin
  • Erythromycin + warfarin
  • Metronidazole + warfarin
• Warfarin uses:

  • To prevent DVT (deep vein thrombosis)
  • Treatment of PE (pulmonary embolism)
  • Atrial fibrillation - to prevent risk of embolisation
  • Prosthetic heart valves to prevent emboli developing on valves
• INR is a ratio, therefore anything greater than 1 means that the patient is anti-coagulated. Usually the therapeutic range for warfarin is around 2-3, so likely not to need to reduce the dose ahead of bleeding procedures.
• Oral anticoagulant therapy - problems:

  • Is there an increased risk of bleeding from dental surgical procedures if patients continue their anticoagulant therapy? (Not if INR<4)
  • Is the risk of stopping anticoagulant therapy greater than the risk of prolonged bleeding? Yes!
• Thrombolytics: Plasminogen Activators:

  • Streptokinase
  • Alteplase
• Indications for accelerated thrombolysis:

  • Venous thromboembolic disease
  • Arterial thrombosis:
  • Peripheral
  • Coronary
• INR is required for procedures where there is a risk of significant bleeding, such as:

  • Extractions
  • Surgery that involves lifting a flap or making an incision
  • Very extensive root surface debridement but not always routine scaling (a clinical judgement should be made)
  • Administration of inferior alveolar block local analgesia
  • Most restorative procedures can be conducated without an INR - most teeth in the mandible can be anaesthetised without the need for block analgesia
• Dabigatran - direct oral anticoagulant (DOAC):

  • Direct thrombin inhibitor
  • Not reflected in INR
  • Linear dose-response
• DOACs - low risk of bleeding (SDCEP):

  • Simple extractions (1-3 teeth)
  • Incision and drainage
  • Detailed perio examination
  • RSI (root surface instrumentation)
  • Restorations with subgingival margins
• DOACs - higher risk of bleeding:

  • Complex/adjacent extractions
  • Flap raising procedures
  • Gingival re-contouring
  • Biopsises
• If higher risk:

  • Dabigatran - if twice a day miss morning dose and give evening dose - providing is >4 hours after haemostasis
  • Rivaroxaban once a day - morning
  • Delay morning dose - give dose 4 hours post haemostasis
  • Rivaroxaban once a day - evening
  • Give dose at usual time in the evening - so long as >4 hours post-haemostasis