A review of reversal of oral anticoagulants, old and new, in major bleeding and the need for urgent surgery

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2 Citations (Scopus)

Abstract

Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial fibrillation. However, blocking elements of the clotting cascade carries an inherent risk of bleeding. Also, anticoagulated patients sometimes require urgent surgery or invasive procedures. This has led to the emergence of a body of scientific literature on the reversal of anticoagulation in these two settings. Traditionally, vitamin K antagonists (VKAs), which indirectly inactivate clotting factors II, VII, IX and X (and natural anticoagulant proteins C and S), had been the mainstay of oral anticoagulation for half a century. Only a few years ago, the US Food and Drug Administration (FDA) approved a specific VKA reversal agent, 4-Factor Prothrombin Complex Concentrate (4F-PCC). The last decade has seen the rise of non-Vitamin K oral anticoagulants (NOACs), which target specific factors, i.e. Factors IIa and Xa. Investigators have rapidly developed reversal agents for these agents as well, idarucizumab for the Factor IIa inhibitor dabigatran (Pradaxa) and andexanet alfa for the entire class of Factor Xa inhibitors (FXaIs), currently four drugs: rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa) and betrixaban (Bevyxxa). Clinicians still use off-label PCC for reversing FXaIs in some settings, and a universal reversal agent, ciraparantag, remains in development. This review summarizes the safety and efficacy of these reversal agents in the setting of anticoagulant-associated major bleeding and the need for urgent surgery.

Original languageEnglish (US)
JournalTrends in Cardiovascular Medicine
DOIs
StatePublished - Jan 1 2019

Fingerprint

Anticoagulants
Hemorrhage
Vitamin K
Off-Label Use
Literature
Factor X
Factor VII
Blood Coagulation Factors
Protein S
Venous Thromboembolism
Prothrombin
United States Food and Drug Administration
Risk Reduction Behavior
Protein C
Atrial Fibrillation
Stroke
Research Personnel
Safety
Therapeutics
Pharmaceutical Preparations

Keywords

  • Andexanet alfa
  • Anticoagulant
  • Apixaban
  • Coumadin
  • Dabigatran
  • Direct oral anticoagulants
  • Idarucizumab
  • Kcentra, 4-factor prothrombin complex concentrate
  • Major bleeding
  • Non-Vitamin K oral anticoagulants
  • Reversal
  • Rivaroxaban
  • Vitamin K antagonists
  • Warfarin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{62b11aba71c04fd1a081355f97d96cf7,
title = "A review of reversal of oral anticoagulants, old and new, in major bleeding and the need for urgent surgery",
abstract = "Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial fibrillation. However, blocking elements of the clotting cascade carries an inherent risk of bleeding. Also, anticoagulated patients sometimes require urgent surgery or invasive procedures. This has led to the emergence of a body of scientific literature on the reversal of anticoagulation in these two settings. Traditionally, vitamin K antagonists (VKAs), which indirectly inactivate clotting factors II, VII, IX and X (and natural anticoagulant proteins C and S), had been the mainstay of oral anticoagulation for half a century. Only a few years ago, the US Food and Drug Administration (FDA) approved a specific VKA reversal agent, 4-Factor Prothrombin Complex Concentrate (4F-PCC). The last decade has seen the rise of non-Vitamin K oral anticoagulants (NOACs), which target specific factors, i.e. Factors IIa and Xa. Investigators have rapidly developed reversal agents for these agents as well, idarucizumab for the Factor IIa inhibitor dabigatran (Pradaxa) and andexanet alfa for the entire class of Factor Xa inhibitors (FXaIs), currently four drugs: rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa) and betrixaban (Bevyxxa). Clinicians still use off-label PCC for reversing FXaIs in some settings, and a universal reversal agent, ciraparantag, remains in development. This review summarizes the safety and efficacy of these reversal agents in the setting of anticoagulant-associated major bleeding and the need for urgent surgery.",
keywords = "Andexanet alfa, Anticoagulant, Apixaban, Coumadin, Dabigatran, Direct oral anticoagulants, Idarucizumab, Kcentra, 4-factor prothrombin complex concentrate, Major bleeding, Non-Vitamin K oral anticoagulants, Reversal, Rivaroxaban, Vitamin K antagonists, Warfarin",
author = "Truman Milling and Christopher Ziebell",
year = "2019",
month = "1",
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doi = "10.1016/j.tcm.2019.03.004",
language = "English (US)",
journal = "Trends in Cardiovascular Medicine",
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AU - Milling, Truman

AU - Ziebell, Christopher

PY - 2019/1/1

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N2 - Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial fibrillation. However, blocking elements of the clotting cascade carries an inherent risk of bleeding. Also, anticoagulated patients sometimes require urgent surgery or invasive procedures. This has led to the emergence of a body of scientific literature on the reversal of anticoagulation in these two settings. Traditionally, vitamin K antagonists (VKAs), which indirectly inactivate clotting factors II, VII, IX and X (and natural anticoagulant proteins C and S), had been the mainstay of oral anticoagulation for half a century. Only a few years ago, the US Food and Drug Administration (FDA) approved a specific VKA reversal agent, 4-Factor Prothrombin Complex Concentrate (4F-PCC). The last decade has seen the rise of non-Vitamin K oral anticoagulants (NOACs), which target specific factors, i.e. Factors IIa and Xa. Investigators have rapidly developed reversal agents for these agents as well, idarucizumab for the Factor IIa inhibitor dabigatran (Pradaxa) and andexanet alfa for the entire class of Factor Xa inhibitors (FXaIs), currently four drugs: rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa) and betrixaban (Bevyxxa). Clinicians still use off-label PCC for reversing FXaIs in some settings, and a universal reversal agent, ciraparantag, remains in development. This review summarizes the safety and efficacy of these reversal agents in the setting of anticoagulant-associated major bleeding and the need for urgent surgery.

AB - Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial fibrillation. However, blocking elements of the clotting cascade carries an inherent risk of bleeding. Also, anticoagulated patients sometimes require urgent surgery or invasive procedures. This has led to the emergence of a body of scientific literature on the reversal of anticoagulation in these two settings. Traditionally, vitamin K antagonists (VKAs), which indirectly inactivate clotting factors II, VII, IX and X (and natural anticoagulant proteins C and S), had been the mainstay of oral anticoagulation for half a century. Only a few years ago, the US Food and Drug Administration (FDA) approved a specific VKA reversal agent, 4-Factor Prothrombin Complex Concentrate (4F-PCC). The last decade has seen the rise of non-Vitamin K oral anticoagulants (NOACs), which target specific factors, i.e. Factors IIa and Xa. Investigators have rapidly developed reversal agents for these agents as well, idarucizumab for the Factor IIa inhibitor dabigatran (Pradaxa) and andexanet alfa for the entire class of Factor Xa inhibitors (FXaIs), currently four drugs: rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa) and betrixaban (Bevyxxa). Clinicians still use off-label PCC for reversing FXaIs in some settings, and a universal reversal agent, ciraparantag, remains in development. This review summarizes the safety and efficacy of these reversal agents in the setting of anticoagulant-associated major bleeding and the need for urgent surgery.

KW - Andexanet alfa

KW - Anticoagulant

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KW - Coumadin

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KW - Direct oral anticoagulants

KW - Idarucizumab

KW - Kcentra, 4-factor prothrombin complex concentrate

KW - Major bleeding

KW - Non-Vitamin K oral anticoagulants

KW - Reversal

KW - Rivaroxaban

KW - Vitamin K antagonists

KW - Warfarin

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DO - 10.1016/j.tcm.2019.03.004

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