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Coagulopathy Reversal (Nonwarfarin Agents)

Coagulopathy Reversal (Nonwarfarin Agents) is a topic covered in the 5-Minute Emergency Consult.

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Basics

Description

  • Patient on anticoagulant medications with minor, major, or clinically significant bleeding needing close monitoring +/− anticoagulant reversal
  • Anticoagulant medication
    • Indirect inhibitors of thrombin
      • Unfractionated heparin (UFH)
      • Low–molecular-weight heparin (LMWH)
        • Enoxaparin
        • Dalteparin
        • Tinzaparin
    • Anti-platelet agents
      • Aspirin
      • Clopidogrel hydrogen sulfate (Plavix)
    • Factor Xa inhibitors (FXa inhibitors)
      • Fondaparinux (Arixtra)
      • Rivaroxaban (Xarelto)
    • Direct thrombin inhibitors (DTIs)
      • Argatroban
      • Bivalirudin (Angiomax)
      • Dabigatran (Pradaxa)
      • Hirudin derivatives
        • Desirudin
        • Lepiruden (Refludan)

Pediatric Considerations
  • Heparin and LMWH are the most commonly utilized anticoagulants beyond warfarin
  • Routine use of DTIs is being studied


Geriatric Considerations
Excretion primarily renal with FXa inhibitors, Dabigatran, and Hirudin derivatives necessitating caution with impaired renal function

Epidemiology

Incidence and Prevalence Estimates
  • Indirect inhibitors of thrombin
    • Up to 1/3 patients develop bleeding complication
    • 2–6% of bleeding is major
  • Anti-platelet agents
    • >300 over-the-counter medications contain aspirin
    • Conflicting studies regarding increased hematoma expansion and mortality
  • FXa Inhibitors
    • Unknown
  • DTIs
    • Unknown

Etiology

  • Indirect inhibitors of thrombin
    • Combines with antithrombin III to inactivate activated FXa and also inhibits thrombin
    • LMWH has a reduced ability to inactivate thrombin
    • Half-life is dose dependent (30–150 min), can be up to 8 hr with LMWH
  • Anti-platelet agents
    • Inactivates cyclooxygenase-1 (COX-1) preventing formation of thromboxane A2, which inactivates platelets
    • Single dose suppresses for 1 wk
    • New platelet production recovers 10%/day
    • Patients may manifest normal hemostasis with as few as 20% platelets with normal COX1 activity
    • Aspirin half-life 15–30 min
    • Clopidogrel half-life 8 hr
  • FXa inhibitors
    • Binds to antithrombin III, catalyzing FXa inhibition
    • No direct inhibitory effect on thrombin
    • Half-life 12–21 hr in normal renal function
  • DTIs
    • Competitively targets active site of thrombin +/− exosite (substrate binding site)
    • Half-life long with dabigatran (14–17 hr) and short with others (20–45 min)

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Citation

Rosen, Peter, et al., editors. "Coagulopathy Reversal (Nonwarfarin Agents)." 5-Minute Emergency Consult, 5th ed., Lippincott Williams & Wilkins, 2016. Emergency Central, emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307697/all/Coagulopathy_Reversal__Nonwarfarin_Agents_.
Coagulopathy Reversal (Nonwarfarin Agents). In: Rosen P, Shayne P, Barkin AZ, et al, eds. 5-Minute Emergency Consult. 5th ed. Lippincott Williams & Wilkins; 2016. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307697/all/Coagulopathy_Reversal__Nonwarfarin_Agents_. Accessed April 25, 2019.
Coagulopathy Reversal (Nonwarfarin Agents). (2016). In Rosen, P., Shayne, P., Barkin, A. Z., Wolfe, R. E., Hayden, S. R., Barkin, R. M., & Schaider, J. J. (Eds.), 5-Minute Emergency Consult. Available from https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307697/all/Coagulopathy_Reversal__Nonwarfarin_Agents_
Coagulopathy Reversal (Nonwarfarin Agents) [Internet]. In: Rosen P, Shayne P, Barkin AZ, Wolfe RE, Hayden SR, Barkin RM, Schaider JJ, editors. 5-Minute Emergency Consult. Lippincott Williams & Wilkins; 2016. [cited 2019 April 25]. Available from: https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307697/all/Coagulopathy_Reversal__Nonwarfarin_Agents_.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Coagulopathy Reversal (Nonwarfarin Agents) ID - 307697 ED - Rosen,Peter, ED - Shayne,Philip, ED - Barkin,Adam Z, ED - Wolfe,Richard E, ED - Hayden,Stephen R, ED - Barkin,Roger M, ED - Schaider,Jeffrey J, BT - 5-Minute Emergency Consult UR - https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307697/all/Coagulopathy_Reversal__Nonwarfarin_Agents_ PB - Lippincott Williams & Wilkins ET - 5 DB - Emergency Central DP - Unbound Medicine ER -