II. Class
- Direct Factor Xa Inhibitor
- Factor Xa is the first step in the Common Clotting Cascade
III. Mechanism: Based on naturally occurring substances
- Antistasin
- Isolated in 1980s from Mexican leach extract
- Tick Anticoagulant peptide (TAP)
- Isolated from the tick Ornithodoros moubata
IV. Preparations
-
Rivaroxaban (Xarelto)
- Anticoagulation in Venous Thromboembolism (especially in Deep Vein Thromboembolism)
- Anticoagulation in Atrial Fibrillation
- Oral Anticoagulant for Atrial Fibrillation as a second line alternative to Warfarin or Dabigatran (Pradaxa)
- Bridging to Transesophageal Echocardiogram and early cardioversion in Atrial Fibrillation (ideal indication)
-
Apixaban (Eliquis)
- Oral anticoagluant for Atrial Fibrillation (released in United States in 2013)
- May be associated with less GI Bleeding risk than Rivaroxaban or Dabigatran
- Appears more effective than Warfarin with less risk of bleeding
- References
- Fondaparinux (Arixtra)
- Betrixaban (Bevyxxa)
- Indicated in extended-duration VTE prophylaxis for up to 5-6 weeks following non-surgical hospitalizations
- May be used in patients with multiple VTE Risks (e.g. immobility, age)
- Expensive ($600) for an NNT 167 to prevent 1 VTE, and NNH 90 for 1 signficant bleeding episode
- Garland (2018) Ann Pharmacother +PMID: 29338293 [PubMed]
- Edoxaban (Savaysa)
- Otamixaban
V. Management: Reversal
-
General measures
- Stop offending Xa agent
- Consider Activated Charcoal if presenting within 2 hours of suspected Overdose ingestion
- Bleeding unlikely due to Xa agent if Anti-Xa level <0.1 IU/ml
- Dialysis is not effective (Protein bound)
- No human data to suggest any non-specific reversal agent is significantly effective
- For serious, life threatening bleeding (e.g. CNS Hemorrhage following Head Trauma)
- See Emergent Reversal of Anticoagulation
- Andexxa or Andexanet Alfa (Inactivated Recombinant Factor Xa, to be released in 2018)
- Antidote for Eliquis (Apixaban) or Xarelto (Rivaroxaban), but not other Xa agents
- Binds Factor Xa Inhibitors
- Limits progression of bleeding within 12 hours of dose (onset as early as 1 hour)
- Expensive: $25,000 to 50,000 per patient
- Risk of Hypercoagulability complications (CVA, VTE)
- Ineffective in the 25% of patients who have low anti-Factor Xa Inhibitor
- References
- Deloughery and Orman in Majoewsky (2013) EM:Rap 13(9): 1
- Sun (2016) Crit Dec Emerg Med 30(8): 28
- Connolly (2019) N Engl J Med 380(14):1326-35 +PMID:30730782 [PubMed]
VI. Management: Other bleeding complications
-
Menorrhagia
- Expect Menses to be heavier than typical while on Factor Xa Inhibitors
- However, severe Menstrual Bleeding on Factor Xa Inhibitors is uncommon
- Patients should seek medical attention for 4 soaked pads in 4 hours or more than 10 pads in 24 hours
- Consider holding Factor Xa Inhibitor for one day and then restarting at same dose
- References
- Orman and Klein in Herbert (2017) EM:Rap 17(7): 9-11
VII. References
Images: Related links to external sites (from Bing)
Related Studies
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 |