II. Class

  1. Direct Factor Xa Inhibitor
  2. Factor Xa is the first step in the Common Clotting Cascade

III. Mechanism: Based on naturally occurring substances

  1. Antistasin
    1. Isolated in 1980s from Mexican leach extract
  2. Tick Anticoagulant peptide (TAP)
    1. Isolated from the tick Ornithodoros moubata

IV. Preparations

  1. Rivaroxaban (Xarelto)
    1. Anticoagulation in Venous Thromboembolism (especially in Deep Vein Thromboembolism)
    2. Anticoagulation in Atrial Fibrillation
      1. Oral Anticoagulant for Atrial Fibrillation as a second line alternative to Warfarin or Dabigatran (Pradaxa)
      2. Bridging to Transesophageal Echocardiogram and early cardioversion in Atrial Fibrillation (ideal indication)
  2. Apixaban (Eliquis)
    1. Oral anticoagluant for Atrial Fibrillation (released in United States in 2013)
    2. Appears more effective than Warfarin with less risk of bleeding
      1. Prevents 3 more strokes per 1000 patients per year than Warfarin
      2. Complications are less than Warfarin including 10 fewer bleeding complications and 4 fewer deaths per 1000 patients per year
    3. References
      1. Mohammed (2012) J Cardiovasc Med 13(2):73-85 [PubMed]
  3. Fondaparinux (Arixtra)
  4. Betrixaban
  5. Edoxaban (Savaysa)
  6. Otamixaban

V. Management: Reversal

  1. Stop offending Xa agent
  2. Consider Activated Charcoal if presenting within 2 hours of suspected Overdose ingestion
  3. Bleeding unlikely due to Xa agent if Anti-Xa level <0.1 IU/ml
  4. Dialysis is not effective (protein bound)
  5. For serious bleeding (e.g. CNS Hemorrhage following Head Trauma)
    1. Specific antidote pending approval in U.S. (all other recommendations per expert opinion)
      1. No human data to suggest any non-specific reversal agent is significantly effective
    2. Step 1
      1. Prothrombin Complex Concentrate 4 (PCC4, Kcentra or outside U.S. Octaplex, Beriplex) OR
      2. Andexanet (Factor Xa decoy protein) 400 mg IV bolus
        1. Not available yet as of 2016 (pending FDA approval in U.S.)
    3. Step 2 (if no response)
      1. Consult Hematology
      2. Factor VII Inhibitor Bypass Activity (FEIBA) 50-75 units/kg IV once (up to maximum 7500 units)
      3. Consider Recombinant activated Clotting Factor VII (rFVIIa or NovoSeven) 90 mcg/kg IV once (up to maximum 10 mg)
        1. Improves lab data, but not effective in animal models
      4. Consider Prothrombin Complex Concentrate 4 (PCC4, Kcentra or outside U.S. Octaplex, Beriplex)
        1. Consider combined protocol (rFVIIa and PCC4)
  6. References
    1. Deloughery and Orman in Majoewsky (2013) EM:Rap 13(9): 1
    2. Sun (2016) Crit Dec Emerg Med 30(8): 28

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Ontology: Direct Factor Xa Inhibitors (C3653500)

Concepts Pharmacologic Substance (T121)
MSH D065427
LNC LP175669-3
English Direct factor Xa inhibitors, Direct Factor Xa inhibitors, Direct Factor Xa Inhibitors

Ontology: Factor Xa inhibitors (C3669283)

Definition (MSH) Endogenous factors and drugs that inhibit or block the activity of FACTOR XA.
Concepts Pharmacologic Substance (T121)
MSH D065427
LNC LP175668-5
English Factor Xa inhibitors, Inhibitors, Factor Xa, Factor Xa Inhibitors