Pharm

Direct Thrombin Inhibitor

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Direct Thrombin Inhibitor, Antithrombin, Hirudin, Lepirudin, Refludan

  • See Also
  1. Dabigatran (Pradaxa)
  2. Argatroban
  3. Bivalirudin
  4. Desirudin
  5. Anticoagulants
  6. Warfarin (Coumadin)
  • Indications
  1. Thrombus Prophylaxis (e.g. DVT Prophylaxis after hip surgery)
  2. Unstable Angina
  3. Percutaneous Coronary Intervention (PCI)
  4. Heparin-Induced Thrombocytopenia
  5. Atrial Fibrillation
  • Mechanism
  1. Selectively and reversibly inhibit free and clot-bound Thrombin
  2. Prevent conversion of Fibrinogen to Fibrin (which in turn prevents clot)
  • Dosing
  • Hirudins (bivalent peptide derivatives from Salivary Gland of medicinal leaches)
  1. Lepirudan (Refludan)
    1. See other references for dosing
  2. Bivalirudin (Angiomax)
    1. Used in Unstable Angina if Heparin contraindicated
    2. Coadminister with Aspirin
    3. Initial: 0.75 mg/kg IV bolus
    4. Later: 1.75 mg/kg/hour for 4 hours
    5. Maintenance: 0.2 mg/kg/hour for up to 20 hours
  3. Desirudin (Ipravask)
    1. DVT Prophylaxis: 15 mg SQ q12 hours after hip surgery
  • Dosing
  • Non-Hirudans (Univalent agents)
  1. Dabigatran (Pradaxa)
    1. See Dabigatran
  2. Ximelagatran (Exanta, Exarta)
    1. No longer available in United States due to hepatotoxicity
  3. Argatroban (Acova)
    1. Initial: 2 mcg/kg/minute
    2. Maintenance: Adjusted per PTT
  • Pharmacokinetics
  1. Clearance
    1. Renal Clearance for Hirudins
    2. Hepatic Clearance for L-Arginine derivatives
  • Precautions
  1. Allergic Reaction
    1. Serious Allergic Reactions including Anaphylaxis may occur with Hirudins
    2. Highest risk on Hirudin re-exposure or in GFR <30 ml/min
  2. Bleeding complications
    1. Epidural Hematoma
      1. High risk if Lumbar Puncture performed while on Direct Thrombin Inhibitors
  3. No antidote for bleeding except for Dabigatran (all recommendations per expert opinion)
    1. Dabigatran (Pradaxa) has a specific antidote (Praxbind)
    2. Stop offending agent (most have short Half-Life such as 12-14 hours for Dabigatran)
    3. Bleeding unlikely due to Direct Thrombin Inhibitor if aPTT <37 seconds and Thrombin Time <25 seconds
    4. Consider Activated Charcoal if presenting within 2 hours of suspected Overdose ingestion
    5. Hemodialysis is unlikely to be beneficial
      1. Logistics of placing large bore filtered catheters in actively bleeding, coagulopathic patients
    6. Life threatening bleeding - reversal agents
      1. See Emergent Reversal of Anticoagulation