Skip to main content
Top
Published in: Journal of Medical Case Reports 1/2018

Open Access 01-12-2018 | Case report

Activated prothrombin complex concentrate to reverse the factor Xa inhibitor (apixaban) effect before emergency surgery: a case series

Authors: Nina Haagenrud Schultz, Runar Lundblad, Pål Andre Holme

Published in: Journal of Medical Case Reports | Issue 1/2018

Login to get access

Abstract

Background

The lack of an antidote against factor Xa inhibitors in case of major bleeding or need for urgent surgery is a concern to clinicians. Guidelines on managing major bleeding in patients under anticoagulation with a factor Xa inhibitor suggest several hemostatic agents to reverse the effect, but there is no consensus regarding the choice of drug or appropriate dose. The ability of prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa to reverse the effect of factor Xa inhibitors has been evaluated in animal studies, in vitro studies, and healthy volunteers, but not yet in randomized clinical studies.

Case presentation

We report a consecutive case series of patients under factor Xa inhibitor (apixaban) treatment who received activated prothrombin complex concentrate to reverse the anticoagulation effect before emergency cardiovascular surgery. Patient 1, a 63-year-old white man, was operated with replacement of the aortic valve; patient 2, a 65-year-old white man, underwent heart transplantation; patient 3, a 68-year-old white man, was operated for acute type A aortic dissection. They all received activated prothrombin complex concentrate 25 IU/kg immediately before surgery. In two of the cases, the global coagulation assay thromboelastometry (ROTEM™) was performed before and after administering activated prothrombin complex concentrate. The ROTEM™ clotting time was reduced from 1900 seconds to 740 seconds and from 1482 to 807 seconds, respectively, after administering a dose of 25 IU/kg activated prothrombin complex concentrate. The apixaban concentration before reversal was within the range considered to be the therapeutic level in all cases. No bleeding complications occurred during surgery, but one case was complicated with bleeding postoperatively. No thromboembolic complications were observed during or after surgery.

Conclusions

Activated prothrombin complex concentrate 25 IU/kg reversed the anticoagulation effect of apixaban effectively and safely before emergency cardiovascular surgery.
Literature
1.
go back to reference van Es N, Coppens M, Schulman S, Middeldorp S, Buller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood. 2014;124(12):1968–75.CrossRefPubMed van Es N, Coppens M, Schulman S, Middeldorp S, Buller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood. 2014;124(12):1968–75.CrossRefPubMed
2.
go back to reference Eikelboom JW, Quinlan DJ, Hirsh J, Connolly SJ, Weitz JI. Laboratory monitoring of non-vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation: a review. JAMA Cardiol. 2017;2:566–74. Eikelboom JW, Quinlan DJ, Hirsh J, Connolly SJ, Weitz JI. Laboratory monitoring of non-vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation: a review. JAMA Cardiol. 2017;2:566–74.
3.
go back to reference Loo SY, Dell'Aniello S, Huiart L, Renoux C. Trends in the prescription of novel oral anticoagulants in UK primary care. Br J Clin Pharmacol. 2017;83(9):2096–106.CrossRefPubMed Loo SY, Dell'Aniello S, Huiart L, Renoux C. Trends in the prescription of novel oral anticoagulants in UK primary care. Br J Clin Pharmacol. 2017;83(9):2096–106.CrossRefPubMed
4.
go back to reference Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 2015;373(25):2413–24.CrossRefPubMed Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 2015;373(25):2413–24.CrossRefPubMed
5.
go back to reference Faraoni D, Levy JH, Albaladejo P, Samama CM. Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants. Crit Care. 2015;19(1):203.CrossRefPubMedPubMedCentral Faraoni D, Levy JH, Albaladejo P, Samama CM. Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants. Crit Care. 2015;19(1):203.CrossRefPubMedPubMedCentral
6.
go back to reference Majeed A, Ågren A, Holmström M, Bruzelius M, Chaireti R, Odeberg J, et al. Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood. 2017;130(15):1706–12.CrossRefPubMed Majeed A, Ågren A, Holmström M, Bruzelius M, Chaireti R, Odeberg J, et al. Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood. 2017;130(15):1706–12.CrossRefPubMed
7.
go back to reference Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012;108(2):217–24.CrossRefPubMed Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012;108(2):217–24.CrossRefPubMed
8.
go back to reference Escolar G, Fernandez-Gallego V, Arellano-Rodrigo E, Roquer JC, Reverter JC, Sanz VV, Molina P, Lopez-Vilchez I, Diaz-Ricart M, Galan AM. Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood. PLoS One. 2013;8:e78696.CrossRefPubMedPubMedCentral Escolar G, Fernandez-Gallego V, Arellano-Rodrigo E, Roquer JC, Reverter JC, Sanz VV, Molina P, Lopez-Vilchez I, Diaz-Ricart M, Galan AM. Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood. PLoS One. 2013;8:e78696.CrossRefPubMedPubMedCentral
9.
go back to reference Schultz NH, Tran HT, Bjornsen S, Henriksson CE, Sandset PM, Holme PA. The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII against anticoagulation of Xa inhibitor. Thromb J. 2017;15:6.CrossRefPubMedPubMedCentral Schultz NH, Tran HT, Bjornsen S, Henriksson CE, Sandset PM, Holme PA. The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII against anticoagulation of Xa inhibitor. Thromb J. 2017;15:6.CrossRefPubMedPubMedCentral
10.
go back to reference Schultz NH, Tran HTT, Bjørnsen S, Henriksson CE, Sandset PM, Holme PA. The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII in apixaban-treated patients in vitro. Research and Practice in. Thromb Haemost. 2017;1:49–56. Schultz NH, Tran HTT, Bjørnsen S, Henriksson CE, Sandset PM, Holme PA. The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII in apixaban-treated patients in vitro. Research and Practice in. Thromb Haemost. 2017;1:49–56.
11.
go back to reference Martin AC, Gouin-Thibault I, Siquret V, Mordohay A, Samama CM, Gaussem P, Le Bonniec B, Godier A. Multimodal assessment of non-specific hemostatic agents for apixaban reversal. J Thromb Haemost. 2015;13:426–36.CrossRefPubMed Martin AC, Gouin-Thibault I, Siquret V, Mordohay A, Samama CM, Gaussem P, Le Bonniec B, Godier A. Multimodal assessment of non-specific hemostatic agents for apixaban reversal. J Thromb Haemost. 2015;13:426–36.CrossRefPubMed
12.
go back to reference Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124:1573–9.CrossRefPubMed Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124:1573–9.CrossRefPubMed
13.
go back to reference Sorensen B, Johansen P, Christiansen K, Woelke M, Ingerslev J. Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation. J Thromb Haemost. 2003;1(3):551–8.CrossRefPubMed Sorensen B, Johansen P, Christiansen K, Woelke M, Ingerslev J. Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation. J Thromb Haemost. 2003;1(3):551–8.CrossRefPubMed
14.
go back to reference Adelmann D, Wiegele M, Wohlgemuth RK, Koch S, Frantal S, Quehenberger P, et al. Measuring the activity of apixaban and rivaroxaban with rotational thrombelastometry. Thromb Res. 2014;134(4):918–23.CrossRefPubMed Adelmann D, Wiegele M, Wohlgemuth RK, Koch S, Frantal S, Quehenberger P, et al. Measuring the activity of apixaban and rivaroxaban with rotational thrombelastometry. Thromb Res. 2014;134(4):918–23.CrossRefPubMed
15.
go back to reference Rinehart DR, Lockhart NR, Hamilton LA, Langdon JR, Rowe AS. Management of apixaban-associated subdural hematoma: a case report on the use of factor eight inhibitor bypassing activity. Crit Care Med. 2015;43(6):e203–7.CrossRefPubMed Rinehart DR, Lockhart NR, Hamilton LA, Langdon JR, Rowe AS. Management of apixaban-associated subdural hematoma: a case report on the use of factor eight inhibitor bypassing activity. Crit Care Med. 2015;43(6):e203–7.CrossRefPubMed
16.
go back to reference Douxfils J, Chatelain C, Chatelain B, Dogne JM, Mullier F. Impact of apixaban on routine and specific coagulation assays: a practical laboratory guide. Thromb Haemost. 2013;110(2):283–94.PubMed Douxfils J, Chatelain C, Chatelain B, Dogne JM, Mullier F. Impact of apixaban on routine and specific coagulation assays: a practical laboratory guide. Thromb Haemost. 2013;110(2):283–94.PubMed
Metadata
Title
Activated prothrombin complex concentrate to reverse the factor Xa inhibitor (apixaban) effect before emergency surgery: a case series
Authors
Nina Haagenrud Schultz
Runar Lundblad
Pål Andre Holme
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Medical Case Reports / Issue 1/2018
Electronic ISSN: 1752-1947
DOI
https://doi.org/10.1186/s13256-018-1660-9

Other articles of this Issue 1/2018

Journal of Medical Case Reports 1/2018 Go to the issue