Factor Xa Inhibitor

Aka: Factor Xa Inhibitor, FXa Inhibitor, Direct Factor Xa Inhibitors, Betrixiban

1. See Also
   1. Anticoagulants
   2. Clotting Pathway
2. Class
   1. Direct Factor Xa Inhibitor
   2. Factor Xa is the first step in the Common Clotting Cascade
3. 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
4. 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. May be associated with less GI Bleeding risk than Rivaroxaban or Dabigatran
      3. 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
            1. Bleeding complications: 10 per 1000 fewer than warfain each year
            2. Deaths: 4 per 1000 fewer than Warfarin each year
      4. References
         1. Mohammed (2012) J Cardiovasc Med 13(2):73-85 [PubMed]
   3. Fondaparinux (Arixtra)
   4. Betrixaban (Bevyxxa)
      1. Indicated in extended-duration VTE prophylaxis for up to 5-6 weeks following non-surgical hospitalizations
      2. May be used in patients with multiple VTE Risks (e.g. immobility, age)
      3. Expensive ($600) for an NNT 167 to prevent 1 VTE, and NNH 90 for 1 signficant bleeding episode
      4. Garland (2018) Ann Pharmacother +PMID: 29338293 [PubMed]
   5. Edoxaban (Savaysa)
   6. Otamixaban
5. Management: Reversal
   1. General measures
      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. No human data to suggest any non-specific reversal agent is significantly effective
   2. For serious, life threatening bleeding (e.g. CNS Hemorrhage following Head Trauma)
      1. See Emergent Reversal of Anticoagulation
      2. Andexxa or Andexanet Alfa (Inactivated Recombinant Factor Xa, to be released in 2018)
         1. Antidote for Eliquis (Apixaban) or Xarelto (Rivaroxaban), but not other Xa agents
         2. Binds Factor Xa Inhibitors
         3. Limits progression of bleeding within 12 hours of dose (onset as early as 1 hour)
         4. Expensive: $25,000 to 50,000 per patient
         5. Risk of Hypercoagulability complications (CVA, VTE)
         6. Ineffective in the 25% of patients who have low anti-Factor Xa Inhibitor
   3. References
      1. Deloughery and Orman in Majoewsky (2013) EM:Rap 13(9): 1
      2. Sun (2016) Crit Dec Emerg Med 30(8): 28
      3. Connolly (2019) N Engl J Med 380(14):1326-35 +PMID:30730782 [PubMed]
6. Management: Other bleeding complications
   1. Menorrhagia
      1. Expect Menses to be heavier than typical while on Factor Xa Inhibitors
      2. However, severe Menstrual Bleeding on Factor Xa Inhibitors is uncommon
      3. Patients should seek medical attention for 4 soaked pads in 4 hours or more than 10 pads in 24 hours
         1. Consider holding Factor Xa Inhibitor for one day and then restarting at same dose
      4. References
         1. Orman and Klein in Herbert (2017) EM:Rap 17(7): 9-11
7. References
   1. Wigle (2019) Am Fam Physician 100(7): 426-34 [PubMed]