Reversal of novel anticoagulants in emergent surgery and trauma

A comprehensive review and proposed management algorithm

Leonidas Palaiodimos, Jeremy Miles, Damianos G. Kokkinidis, Christos Barkolias, Anil K. Jonnalagadda, Dimitrios Papaconstantinou, Maximos Frountzas, Evangelos P. Misiakos, Dimitrios Schizas

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Non-vitamin K oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, are increasingly used for thromboembolism prevention. Contrary to older anticoagulants, such as coumadin, when antidotes existed and were broadly used in cases of emergent surgery and bleeding, antidotes for NOACs have not been developed until recently. Moreover, the monitoring of NOAC’s anticoagulant effect varies across different hospital settings and the absence of a single test that can accurately predict the degree of anticoagulation achieved increases the uncertainty. These uncertainties often result in management dilemmas for clinicians when patients who are on NOACs need a reversal of anticoagulation. Until recently, available antidotes for NOACs included only prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII and the less optimal fresh frozen plasma (FFP). Recently though, novel antidotes for NOACs have been developed, including idarucizumab, which is a monoclonal antibody fragment that binds dabigatran, and andexanet alfa, a modified decoy form of the activated factor X (FXa) that binds FXa inhibitors and AT III. Another option, ciraparantag, which is a small molecule that binds to heparin, thrombin inhibitors and FXa inhibitors, is still in phase I development. In this review, we summarize the current evidence and present the available bypassing and novel reversal agents. Finally, we propose an algorithm for the management of patients who take NOACs and present to the emergency department with either trauma and active bleeding or need for emergent surgery.

Original languageEnglish (US)
Pages (from-to)4540-4553
Number of pages14
JournalCurrent Pharmaceutical Design
Volume24
Issue number38
DOIs
StatePublished - Jan 1 2018

Fingerprint

Anticoagulants
Antidotes
Wounds and Injuries
Uncertainty
Hemorrhage
Factor VIIa
Immunoglobulin Fragments
Factor Xa
Thromboembolism
Warfarin
Thrombin
Heparin
Hospital Emergency Service
Monoclonal Antibodies

Keywords

  • Anticoagulation
  • Bleeding
  • Emergency
  • Novel anticoagulants
  • Reversal
  • Surgery
  • Trauma

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Reversal of novel anticoagulants in emergent surgery and trauma : A comprehensive review and proposed management algorithm. / Palaiodimos, Leonidas; Miles, Jeremy; Kokkinidis, Damianos G.; Barkolias, Christos; Jonnalagadda, Anil K.; Papaconstantinou, Dimitrios; Frountzas, Maximos; Misiakos, Evangelos P.; Schizas, Dimitrios.

In: Current Pharmaceutical Design, Vol. 24, No. 38, 01.01.2018, p. 4540-4553.

Research output: Contribution to journalArticle

Palaiodimos, L, Miles, J, Kokkinidis, DG, Barkolias, C, Jonnalagadda, AK, Papaconstantinou, D, Frountzas, M, Misiakos, EP & Schizas, D 2018, 'Reversal of novel anticoagulants in emergent surgery and trauma: A comprehensive review and proposed management algorithm', Current Pharmaceutical Design, vol. 24, no. 38, pp. 4540-4553. https://doi.org/10.2174/1381612825666181226150629
Palaiodimos, Leonidas ; Miles, Jeremy ; Kokkinidis, Damianos G. ; Barkolias, Christos ; Jonnalagadda, Anil K. ; Papaconstantinou, Dimitrios ; Frountzas, Maximos ; Misiakos, Evangelos P. ; Schizas, Dimitrios. / Reversal of novel anticoagulants in emergent surgery and trauma : A comprehensive review and proposed management algorithm. In: Current Pharmaceutical Design. 2018 ; Vol. 24, No. 38. pp. 4540-4553.
@article{60d2a7c5a5e841558db292b666a53e96,
title = "Reversal of novel anticoagulants in emergent surgery and trauma: A comprehensive review and proposed management algorithm",
abstract = "Non-vitamin K oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, are increasingly used for thromboembolism prevention. Contrary to older anticoagulants, such as coumadin, when antidotes existed and were broadly used in cases of emergent surgery and bleeding, antidotes for NOACs have not been developed until recently. Moreover, the monitoring of NOAC’s anticoagulant effect varies across different hospital settings and the absence of a single test that can accurately predict the degree of anticoagulation achieved increases the uncertainty. These uncertainties often result in management dilemmas for clinicians when patients who are on NOACs need a reversal of anticoagulation. Until recently, available antidotes for NOACs included only prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII and the less optimal fresh frozen plasma (FFP). Recently though, novel antidotes for NOACs have been developed, including idarucizumab, which is a monoclonal antibody fragment that binds dabigatran, and andexanet alfa, a modified decoy form of the activated factor X (FXa) that binds FXa inhibitors and AT III. Another option, ciraparantag, which is a small molecule that binds to heparin, thrombin inhibitors and FXa inhibitors, is still in phase I development. In this review, we summarize the current evidence and present the available bypassing and novel reversal agents. Finally, we propose an algorithm for the management of patients who take NOACs and present to the emergency department with either trauma and active bleeding or need for emergent surgery.",
keywords = "Anticoagulation, Bleeding, Emergency, Novel anticoagulants, Reversal, Surgery, Trauma",
author = "Leonidas Palaiodimos and Jeremy Miles and Kokkinidis, {Damianos G.} and Christos Barkolias and Jonnalagadda, {Anil K.} and Dimitrios Papaconstantinou and Maximos Frountzas and Misiakos, {Evangelos P.} and Dimitrios Schizas",
year = "2018",
month = "1",
day = "1",
doi = "10.2174/1381612825666181226150629",
language = "English (US)",
volume = "24",
pages = "4540--4553",
journal = "Current Pharmaceutical Design",
issn = "1381-6128",
publisher = "Bentham Science Publishers B.V.",
number = "38",

}

TY - JOUR

T1 - Reversal of novel anticoagulants in emergent surgery and trauma

T2 - A comprehensive review and proposed management algorithm

AU - Palaiodimos, Leonidas

AU - Miles, Jeremy

AU - Kokkinidis, Damianos G.

AU - Barkolias, Christos

AU - Jonnalagadda, Anil K.

AU - Papaconstantinou, Dimitrios

AU - Frountzas, Maximos

AU - Misiakos, Evangelos P.

AU - Schizas, Dimitrios

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Non-vitamin K oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, are increasingly used for thromboembolism prevention. Contrary to older anticoagulants, such as coumadin, when antidotes existed and were broadly used in cases of emergent surgery and bleeding, antidotes for NOACs have not been developed until recently. Moreover, the monitoring of NOAC’s anticoagulant effect varies across different hospital settings and the absence of a single test that can accurately predict the degree of anticoagulation achieved increases the uncertainty. These uncertainties often result in management dilemmas for clinicians when patients who are on NOACs need a reversal of anticoagulation. Until recently, available antidotes for NOACs included only prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII and the less optimal fresh frozen plasma (FFP). Recently though, novel antidotes for NOACs have been developed, including idarucizumab, which is a monoclonal antibody fragment that binds dabigatran, and andexanet alfa, a modified decoy form of the activated factor X (FXa) that binds FXa inhibitors and AT III. Another option, ciraparantag, which is a small molecule that binds to heparin, thrombin inhibitors and FXa inhibitors, is still in phase I development. In this review, we summarize the current evidence and present the available bypassing and novel reversal agents. Finally, we propose an algorithm for the management of patients who take NOACs and present to the emergency department with either trauma and active bleeding or need for emergent surgery.

AB - Non-vitamin K oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, are increasingly used for thromboembolism prevention. Contrary to older anticoagulants, such as coumadin, when antidotes existed and were broadly used in cases of emergent surgery and bleeding, antidotes for NOACs have not been developed until recently. Moreover, the monitoring of NOAC’s anticoagulant effect varies across different hospital settings and the absence of a single test that can accurately predict the degree of anticoagulation achieved increases the uncertainty. These uncertainties often result in management dilemmas for clinicians when patients who are on NOACs need a reversal of anticoagulation. Until recently, available antidotes for NOACs included only prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII and the less optimal fresh frozen plasma (FFP). Recently though, novel antidotes for NOACs have been developed, including idarucizumab, which is a monoclonal antibody fragment that binds dabigatran, and andexanet alfa, a modified decoy form of the activated factor X (FXa) that binds FXa inhibitors and AT III. Another option, ciraparantag, which is a small molecule that binds to heparin, thrombin inhibitors and FXa inhibitors, is still in phase I development. In this review, we summarize the current evidence and present the available bypassing and novel reversal agents. Finally, we propose an algorithm for the management of patients who take NOACs and present to the emergency department with either trauma and active bleeding or need for emergent surgery.

KW - Anticoagulation

KW - Bleeding

KW - Emergency

KW - Novel anticoagulants

KW - Reversal

KW - Surgery

KW - Trauma

UR - http://www.scopus.com/inward/record.url?scp=85063277972&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063277972&partnerID=8YFLogxK

U2 - 10.2174/1381612825666181226150629

DO - 10.2174/1381612825666181226150629

M3 - Article

VL - 24

SP - 4540

EP - 4553

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

IS - 38

ER -