Skip to main content
Top
Published in: American Journal of Cardiovascular Drugs 3/2020

01-06-2020 | Atrial Fibrillation | Original Research Article

Reversal of Apixaban and Rivaroxaban Using Activated Prothrombin Complex Concentrates in Patients with Major Bleeding

Authors: Marwan Sheikh-Taha, R. Monroe Crawley

Published in: American Journal of Cardiovascular Drugs | Issue 3/2020

Login to get access

Abstract

Background

Clinical experience with using activated prothrombin complex concentrates (aPCCs) to reverse the effects of factor Xa inhibitors is limited.

Objectives

Our objective was to assess the achievement of effective clinical hemostasis using aPCC in patients on chronic apixaban or rivaroxaban therapy presenting with major bleeding in whom a reversal agent is warranted. We also assessed the safety of the drug.

Methods

A retrospective medical records review was conducted at a tertiary referral medical center in the USA. Patients presenting with major bleeding while receiving apixaban or rivaroxaban and treated with aPCC were included. Clinical hemostasis was assessed using International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria.

Results

A total of 35 patients were included in the study. The most common site of bleeding was intracerebral hemorrhage (ICH) (n = 18 [51.4%]), followed by gastrointestinal bleed (n = 10 [28.6%]). Clinical hemostasis was achieved in 24 (68.6%) patients; 11 patients (31.4%) did not achieve clinical hemostasis; nine of these patients had ICH. Seven of the patients who did not achieve hemostasis died during hospitalization. Three (8.6%) patients experienced thromboembolic events during hospitalization. In total, 21 (60%) patients were receiving concomitant medications that interact with anti-factor Xa inhibitors and can increase the risk of bleeding.

Conclusions

Our study suggests that aPCC could be an option in patients with major bleeding associated with apixaban or rivaroxaban. It may be an alternative for patients who need anticoagulation reversal if the specific antidote, andexanet alfa, is unavailable.
Literature
1.
go back to reference Barnes GD, Lucas E, Alexander GC, Goldberger ZD. National trends in ambulatory oral anticoagulant use. Am J Med. 2015;128(12):1300–5.CrossRef Barnes GD, Lucas E, Alexander GC, Goldberger ZD. National trends in ambulatory oral anticoagulant use. Am J Med. 2015;128(12):1300–5.CrossRef
3.
go back to reference Dickneite G, Hoffman M. Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence? Thromb Haemost. 2014;112(02):189–98. Dickneite G, Hoffman M. Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence? Thromb Haemost. 2014;112(02):189–98.
4.
go back to reference Majeed A, Ågren A, Holmström M, Bruzelius M, Chaireti R, Odeberg J, Hempel EL, Magnusson M, Frisk T, Schulman S. Management of rivaroxaban-or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood. 2017;130(15):1706–12.CrossRef Majeed A, Ågren A, Holmström M, Bruzelius M, Chaireti R, Odeberg J, Hempel EL, Magnusson M, Frisk T, Schulman S. Management of rivaroxaban-or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood. 2017;130(15):1706–12.CrossRef
5.
go back to reference Sheikh-Taha M. Treatment of apixaban-and rivaroxaban-associated major bleeding using 4-factor prothrombin complex concentrate. Intern Emerg Med. 2019;14(2):265–9.CrossRef Sheikh-Taha M. Treatment of apixaban-and rivaroxaban-associated major bleeding using 4-factor prothrombin complex concentrate. Intern Emerg Med. 2019;14(2):265–9.CrossRef
6.
go back to reference Schulman S, Gross PL, Ritchie B, Nahirniak S, Lin Y, Lieberman L, Carrier M, Crowther MA, Ghosh I, Lazo-Langner A, Zondag M. Prothrombin complex concentrate for major bleeding on factor Xa inhibitors: a prospective cohort study. Thromb Haemost. 2018;118(05):842–51.CrossRef Schulman S, Gross PL, Ritchie B, Nahirniak S, Lin Y, Lieberman L, Carrier M, Crowther MA, Ghosh I, Lazo-Langner A, Zondag M. Prothrombin complex concentrate for major bleeding on factor Xa inhibitors: a prospective cohort study. Thromb Haemost. 2018;118(05):842–51.CrossRef
7.
go back to reference Tornkvist M, Smith JG, Labaf A. Current evidence of oral anticoagulant reversal: a systematic review. Thromb Res. 2018;1(162):22–31.CrossRef Tornkvist M, Smith JG, Labaf A. Current evidence of oral anticoagulant reversal: a systematic review. Thromb Res. 2018;1(162):22–31.CrossRef
8.
go back to reference Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692–4.CrossRef Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692–4.CrossRef
9.
go back to reference Khorsand N, Majeed A, Sarode R, Beyer-Westendorf J, Schulman S, Meijer K, Subcommittee on Control of Anticoagulation. Assessment of effectiveness of major bleeding management: proposed definitions for effective hemostasis: communication from the SSC of the ISTH. J Thromb Haemost. 2016;14(1):211–4.CrossRef Khorsand N, Majeed A, Sarode R, Beyer-Westendorf J, Schulman S, Meijer K, Subcommittee on Control of Anticoagulation. Assessment of effectiveness of major bleeding management: proposed definitions for effective hemostasis: communication from the SSC of the ISTH. J Thromb Haemost. 2016;14(1):211–4.CrossRef
10.
go back to reference Tomaselli GF, Mahaffey KW, Cuker A, Dobesh PP, Doherty JU, Eikelboom JW, Florido R, Hucker W, Mehran R, Messé SR, Pollack CV. 2017 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70(24):3042–67.CrossRef Tomaselli GF, Mahaffey KW, Cuker A, Dobesh PP, Doherty JU, Eikelboom JW, Florido R, Hucker W, Mehran R, Messé SR, Pollack CV. 2017 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70(24):3042–67.CrossRef
11.
go back to reference Smith MN, Deloney L, Carter C, Weant KA, Eriksson EA. Safety, efficacy, and cost of four-factor prothrombin complex concentrate (4F-PCC) in patients with factor Xa inhibitor-related bleeding: a retrospective study. J Thromb Thrombolysis. 2019;2:1–6. Smith MN, Deloney L, Carter C, Weant KA, Eriksson EA. Safety, efficacy, and cost of four-factor prothrombin complex concentrate (4F-PCC) in patients with factor Xa inhibitor-related bleeding: a retrospective study. J Thromb Thrombolysis. 2019;2:1–6.
12.
go back to reference Cucchiara B, Messe S, Sansing L, Kasner S, Lyden P. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke. 2008;39(11):2993–6.CrossRef Cucchiara B, Messe S, Sansing L, Kasner S, Lyden P. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke. 2008;39(11):2993–6.CrossRef
13.
go back to reference Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage: facts and hypotheses. Stroke. 1995;26(8):1471–7.CrossRef Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage: facts and hypotheses. Stroke. 1995;26(8):1471–7.CrossRef
14.
go back to reference Kaatz S, Kouides PA, Garcia DA, Spyropolous AC, Crowther M, Douketis JD, Chan AK, James A, Moll S, Ortel TL, Van Cott EM. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87(S1):S141–5.CrossRef Kaatz S, Kouides PA, Garcia DA, Spyropolous AC, Crowther M, Douketis JD, Chan AK, James A, Moll S, Ortel TL, Van Cott EM. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87(S1):S141–5.CrossRef
15.
go back to reference Piran S, Khatib R, Schulman S, Majeed A, Holbrook A, Witt DM, Wiercioch W, Schünemann HJ, Nieuwlaat R. Management of direct factor Xa inhibitor-related major bleeding with prothrombin complex concentrate: a meta-analysis. Blood Adv. 2019;3(2):158–67.CrossRef Piran S, Khatib R, Schulman S, Majeed A, Holbrook A, Witt DM, Wiercioch W, Schünemann HJ, Nieuwlaat R. Management of direct factor Xa inhibitor-related major bleeding with prothrombin complex concentrate: a meta-analysis. Blood Adv. 2019;3(2):158–67.CrossRef
16.
go back to reference Lexi-Comp Inc. Lexi-Drugs®. Hudson: Lexi-Comp Inc; 2018. Lexi-Comp Inc. Lexi-Drugs®. Hudson: Lexi-Comp Inc; 2018.
Metadata
Title
Reversal of Apixaban and Rivaroxaban Using Activated Prothrombin Complex Concentrates in Patients with Major Bleeding
Authors
Marwan Sheikh-Taha
R. Monroe Crawley
Publication date
01-06-2020
Publisher
Springer International Publishing
Published in
American Journal of Cardiovascular Drugs / Issue 3/2020
Print ISSN: 1175-3277
Electronic ISSN: 1179-187X
DOI
https://doi.org/10.1007/s40256-019-00383-z

Other articles of this Issue 3/2020

American Journal of Cardiovascular Drugs 3/2020 Go to the issue