Anticoagulants

• Define Haemostasis

  Mechanism to prevent blood loss after injury to the blood vessel
• What are the 4 stages of Haemostasis?

  • Blood vessel contraction
  • Platelet plug formation
  • Clot formation
  • Fibrinolysis
• What do anticoagulant do?

  Reduces intravasular clotting
• Thrombi - venous thrombosis
• emboli - stroke, MI, Pulmonary embolism
• Conditions when patients be taking anticoagulants?

  Patient’s with a history of:

  • Myocardial infarction
  • Cerebrovascular thrombosis
  • Venous thrombosis
  • Pulmonary Embolism
  • Prosthetic heart valves
  • Post-operative prophylaxis
  • Disemminated intravascular coagulation
• Heparin

  • Sulphated acidic mucopolysaccharide
  • Widely distributed in the body
  • Two types: Unfractional heparin and Low Molecular Weight Heparin (LMWH)
  • LMWH has superseded unfractional heparin
  • MI, Thrombophlebitis, renal dialysis, DVT, pulmonary embolism, post-op prophylaxis. Short 1/2 life so need to be given frequently by infusion.
• Unfractional Heparin:

  Poorly absorbed by the gut, pt in hospital, overdose antidote = protamine sulphate, activates antithrombin III, inactivates thrombin and other proteases, especially factor Xa
• LMWH:

  inhibits factor Xa, required 1x daily, pt can administer it themselves, eliminated by renal excretion, protamine sulphate only partially effective.
• Warfarin:

  Oral administrations, Vit K antimetabolite, interferes with synthesis of factors VII, XI, X and prothrombin, takes 48-72 for effect to develop fully, long term treatment.
• Warfarin Adverse Effects:

  • Narrow therapeutic index
  • Haemorrhage - look for petechial hard palate, mild trauma
  • teratogenesis
  • Rashes
  • Osteoporosis
  • Purple toe syndrome
  • Warfarin Induces Skin Necrosis (acquired protein c deficiency)
• How does aspirin interact with warfarin?

  Serious drug interactions, bleeding and fatal haemorrhage, aspirin alters platelet adhesiveness and decreases their clotting ability, aspirin competes for the same binding site, knocking off warfarin, increasing free warfarin increasing its anticoagulant effect.
• How does paracetamol interact with paracetamol?

  Prolonged use enhances anticoagulant properties, but is pain relief of choice short term
• Ibuprofen and naproxen

  • have minor interaction with warfarin
  • still increased risk of bleeding, especially gastricbleeds.
• What are NSAIDS?

  Nonsteroidal anti-inflammatory drugs.
• What are the interactions of warfarin and antibiotics?

  • Increases effect of warfarin
  • reduces flora that synthesis Vit K, reducing absorption.
  • Amoxicillin and clindamycin have no effect.
  • Little effect – doxycycline and tetracycline.
  • Erythromycin and metronidazole has the biggest effect. Metronidazole also interferes with metabolism.
• What can be caused from interactions between warfarin and metronidazole?

  Subconjunctival haemorrhage
• What is the effect of Barbiturates with warfarin?

  stimulates warfarin metabolism
• What is the effect of alcohol on warfarin?

  Chronic use - stimulates metabolism

  Acute use - inhibits metabolism
• How would we manage patient on warfarin?

  • INR within 24 hours, Record.
  • If needs to be lowered, consult physician.
  • Recommence warfarin immediately after surgery.
  • Low risk procedures INR ≤ 4.
  • Moderate risk at ≤ 3.5.
  • Avoid IDB.
  • Local haemostatic measures, e.g. pressure, suturing and oxidised cellulose gauze.
  • Post-op instructions: advise seek advise should bleeding recommence, Do not allow patient to leave until HA.
• What do you do if a warfarin pt does not stop bleeding?

  Tranexamic Acid Mouthwash 5%. Rinse 10mls for 2 minutes Use 4 times a day for 5-7 days Avoid eating or drinking 1 hour after rinse
• What does INR stand for?

  International Normalised Ratio
• What does INR measure?

  the extrinsic pathway of coagulation, to be used to determine clotting tendency of blood
• Describe a low risk procedure:

  Simple single XLA, LAI, IDB, restorations including Endo, scaling and RSD
• Describe moderate risk procedures:

  Multiple XLA, biopsy, soft tissue surgery, low risk procedures involving grossly inflamed tissues.
• Describe high risk procedures:

  complex or major surgery
• What are DOAC?

  • Direct oral anticoagulants
  • group of anticoagulants commonly used over warfarin.
  • NHS use 2008.
  • prevention of stroke in none valvular AF and management of venous thromboembolism
  • dibigatran, rivaoxaban, apixaban, edoxaban
• What are the general characteristics of DOAC's?

  Short half life, excreted from kidney, quick effective mode of action, wider safety margin than warfarin, not affected by food and not sensitive to other drugs
• What are the pros of DOAC'S compared to warfarin?

  Lower rate of intracranial bleeds and haemorrhagic strokes, no need for routine lab monitoring, fewer drug and food interactions.
• What are the cons of DOAC's compared to warfarin?

  Higher drug cost, lack of reversal agent available, increased risk of gastrointestinal bleeding, higher rebound rate of VTA events in pt with poor adherence.
• How does aspirin work?

  Main antiplatelet drug, inhibits production of thromboxane A2, works irreversibly, low dose, side effects include gastric intolerances, upper gastro-intestinal bleeds
• Clopidogrel:

  • when aspirin not tolerated or when combined antiplatelet therapy
  • effect of drug prolonged + lasts platelet lifetime
  • binds irreversibly and inhibits platelet ADP receptors
  • SE = Haemorrhage, nausea, vomiting, constipation or diarrhoea, vertigo, rashes. Sometimes used in combination with Aspirin
• List some other anticoagulants:

  Fondaparinus, hirdudin, streptokinase, alterplase