Direct Thrombin Inhibitor


Direct Thrombin Inhibitor, Antithrombin, Hirudin, Lepirudin, Refludan, Bivalirudin, Angiomax, Desirudin, Ipravask, Argatroban, Acova

  • Indications
  1. Thrombus prophylaxis, treatment or Unstable Angina and
  2. Heparin-Induced Thrombocytopenia
  • 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. Serious Allergic Reactions may occur to Hirudins
  2. 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. Dialysis 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