Anticoagulant

• Thrombus


  Formation of clot in an arterial or venous vessel

  
• Virchow's triad

  • Three factors necessary for the formation of thrombosis: Endothelial Injury, Hypercoagubility, Circulatory Stasis
• Arteries


  Blood vessels through which the blood flows from the heart to periphery: brain, internal organs, legs & arms

  
• Veins


  Blood vessels that carry blood back to the heart
• Thrombus in the vein are mostly composed of Fibrin
• Anticoagulation


  Process of slowing down the normal blood clotting to prevent the formation of blood clots

  
• Heparin


  Inhibits with the coagulation process by interfering with the clotting cascade and thrombin formation

  
• Regular/Unfractionated Heparin


  • Cannot be absorbed well in the GI tract, administered parenterally via continuous IV infusion
  • Given subcutaneously or IV infusion, cannot be administered via IM
  • Regular monitoring of aPTT is needed

  
• LMWH (low molecular weight heparins)


  • Derived by decomposing regular(unfractionated) heparin into simpler compounds
  • Advantage: prolonged circulating half-life, can be administered subcutaneously 1x or 2x daily
  • Preferred to use because it can be given subcutaneously
  • Provides effective and stable anticoagulation, potentially reducing the risk of rebound ischemic events
  • Eliminates the need to monitor aPTT results regularly

  
• Mechanism of Action of Anticoagulants

  1. Combines with ANTITHROMBIN III, a substance that inactivates THROMBIN

  2. By inhibiting the action of thrombin, conversion of fibrinogen to fibrin does not occur and the formation of a fibrin clot is prevented

  
• Protamine sulfate


  Heparin antagonist (suspends the effect of Heparin), 10mg for 1000 unit of heparin

  
• Partial thromboplastin time (PTT) & activated partial thromboplastin time (aPTT)


  • Laboratory tests used to detect deficiencies of certain clotting factors & these tests are used to monitor heparin therapy
  • aPTT is a more sensitive version of the PTT and is used to monitor the patient's response to heparin therapy

  
• Reference Range: aPTT = 30 - 40 secs, PTT = 60 - 70 seconds. In patients receiving anticoagulant therapy, the reference range is 1.5-2.5 times the control value in secs
• Warfarin


  Most commonly used oral anticoagulant, synthesized from dicumarol, absorbed rapidly and almost completely when taken orally
• Oral Anticoagulants


  • Inhibits the liver synthesis of the Vitamin K clotting factors – II, VII, IX & X
  • Prolong clotting time & monitored by the prothrombin time (PT)
  • International normalized ratio (INR) is the laboratory test most frequently used to report PT results

  
• Three commonly used oral anticoagulant given to patients after heparin therapy: Warfarin (Coumadin), Dicumarol, Anisindone

  
• Direct thrombin inhibitors mechanism of action


  1. Directly inhibit thrombin from converting fibrinogen to fibrin

  2. Interfere with the blood clotting mechanism by blocking the direct activity of soluble and clot-bound thrombin

  3. Inhibit platelet activation, granule release, and aggregation

  4. Inhibit fibrinogen cleavage and fibrin formation and further activation of the clotting cascade