Skip to main content
Erschienen in: Journal of Thrombosis and Thrombolysis 4/2018

21.03.2018

Prothrombin complex concentrate for reversal of direct factor Xa inhibitors prior to emergency surgery or invasive procedure: a retrospective study

verfasst von: Siavash Piran, Caroline Gabriel, Sam Schulman

Erschienen in: Journal of Thrombosis and Thrombolysis | Ausgabe 4/2018

Einloggen, um Zugang zu erhalten

Abstract

Direct oral factor Xa (FXa) inhibitors are widely used for anticoagulation but a targeted antidote is not available. Four-factor prothrombin complex concentrate (4FPCC) has been shown in observational studies to support hemostasis in most patients with major bleeding related to FXa inhibitors with an acceptable rate of thromboembolic events. However, the effectiveness of 4FPCC for reversal of FXa inhibitors prior to emergency surgery or invasive procedures is unclear. A retrospective chart review was performed in patients that received 4FPCC at Hamilton General Hospital from 2015 to 2017. The primary effectiveness outcome was based on the comment of the surgeon on the adequacy of the hemostasis. If no such comment was documented, the case was discussed with a surgeon specialized in the type of surgery/procedure performed to obtain their best opinion. The principal safety outcome was thromboembolic events including venous thromboembolism, ischemic stroke, systemic embolism or myocardial infarction during 7 days after surgery. A total of 247 patients that had received 4FPCC were initially screened and 21 were on a FXa inhibitor and had emergency surgery/procedure. The mean age was 74 ± 11 years, and 14 (66.7%) were males. Hemostasis was rated as good in most patients (18 of 21, 85.7%). There were no thromboembolic events. The all-cause mortality rate was 28.6%; 2/3 of these patients had an intracranial hemorrhage. Hemostasis was rated as good in most patients with no thromboembolic events observed. Prospective studies assessing the safety and effectiveness of 4FPCC for this indication are needed.
Literatur
1.
Zurück zum Zitat Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomized trials. Lancet 383:955–962 Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomized trials. Lancet 383:955–962
2.
Zurück zum Zitat Kakkos SK, Kirkilesis GI, Tsolakis IA (2014) Editor’s Choice - efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials. Eur J Vasc Endovasc Surg 48(5):565–575CrossRefPubMed Kakkos SK, Kirkilesis GI, Tsolakis IA (2014) Editor’s Choice - efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials. Eur J Vasc Endovasc Surg 48(5):565–575CrossRefPubMed
3.
Zurück zum Zitat Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Royle G, Sellke FW, Stangier J, Steiner T, Verhamme P, Wang B, Young L, Weitz JI (2017) Idarucizumab for dabigatran reversal – full cohort analysis. N Engl J Med 377(5):431–441CrossRefPubMed Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Royle G, Sellke FW, Stangier J, Steiner T, Verhamme P, Wang B, Young L, Weitz JI (2017) Idarucizumab for dabigatran reversal – full cohort analysis. N Engl J Med 377(5):431–441CrossRefPubMed
4.
Zurück zum Zitat Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, Crowther M (2016) ANNEXA-4 investigators. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 375(12):1131–1141CrossRefPubMedPubMedCentral Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, Crowther M (2016) ANNEXA-4 investigators. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 375(12):1131–1141CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Marlu R, Hodaj E, Paris A, Albaladejo P, Crackowski JL, Pernod G (2012) Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost 108(2):217CrossRefPubMed Marlu R, Hodaj E, Paris A, Albaladejo P, Crackowski JL, Pernod G (2012) Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost 108(2):217CrossRefPubMed
6.
Zurück zum Zitat Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M (2011) Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 124(14):1573–1579CrossRefPubMed Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M (2011) Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 124(14):1573–1579CrossRefPubMed
7.
Zurück zum Zitat Levi M, Moore KT, Castillejos CF, Kubitza D, Berkowitz SD, Goldhaber SZ, Raghoebar M, Patel MR, Weitz JI, Levy JH (2014) Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers. J Thromb Haemost 12(9):1428–1436CrossRefPubMed Levi M, Moore KT, Castillejos CF, Kubitza D, Berkowitz SD, Goldhaber SZ, Raghoebar M, Patel MR, Weitz JI, Levy JH (2014) Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers. J Thromb Haemost 12(9):1428–1436CrossRefPubMed
8.
Zurück zum Zitat Zahir H, Brown KS, Vandell AG, Desai M, Maa JF, Dishy V, Lomeli B, Feussner A, Feng W, He L, Grosso MA, Lanz HJ, Antman EM (2015) Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation 131(1):82–90CrossRefPubMed Zahir H, Brown KS, Vandell AG, Desai M, Maa JF, Dishy V, Lomeli B, Feussner A, Feng W, He L, Grosso MA, Lanz HJ, Antman EM (2015) Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation 131(1):82–90CrossRefPubMed
9.
Zurück zum Zitat Grandhi R, Newman WC, Zhang X, Harrison G, Moran C, Okonkwo DO, Ducruet AF (2015) Administration of 4-factor prothrombin complex concentrate as an antidote for intracranial bleeding in patients taking direct factor Xa inhibitors. World Neurosurg 84(6):1956–1961CrossRefPubMed Grandhi R, Newman WC, Zhang X, Harrison G, Moran C, Okonkwo DO, Ducruet AF (2015) Administration of 4-factor prothrombin complex concentrate as an antidote for intracranial bleeding in patients taking direct factor Xa inhibitors. World Neurosurg 84(6):1956–1961CrossRefPubMed
10.
Zurück zum Zitat Majeed A, Ågren A, Holmström M, Bruzelius M, Chaireti R, Odeberg J, Hempel EL, Magnusson M, Frisk T, Schulman S (2017) Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood 130(15):1706–1712CrossRefPubMed Majeed A, Ågren A, Holmström M, Bruzelius M, Chaireti R, Odeberg J, Hempel EL, Magnusson M, Frisk T, Schulman S (2017) Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood 130(15):1706–1712CrossRefPubMed
11.
Zurück zum Zitat Schulman S, Gross PL, Ritchie B, Nahirniak S, Lin Y, Lieberman L, Carrier M, Crowther MA, Ghosh I, Lazo-Langner A, Zondag M (2018) Prothrombin complex concentrate for major bleeding on factor Xa inhibitors: a prospective cohort study. Accepted in Thromb Haemost Schulman S, Gross PL, Ritchie B, Nahirniak S, Lin Y, Lieberman L, Carrier M, Crowther MA, Ghosh I, Lazo-Langner A, Zondag M (2018) Prothrombin complex concentrate for major bleeding on factor Xa inhibitors: a prospective cohort study. Accepted in Thromb Haemost
12.
Zurück zum Zitat Frontera JA, Lewin JJ 3rd, Rabinstein AA, Aisiku IP, Alexandrov AW, Cook AM, del Zoppo GJ, Kumar MA, Peerschke EI, Stiefel MF, Teitelbaum JS, Wartenberg KE, Zerfoss CL (2016) Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care 24(1):6–46CrossRefPubMed Frontera JA, Lewin JJ 3rd, Rabinstein AA, Aisiku IP, Alexandrov AW, Cook AM, del Zoppo GJ, Kumar MA, Peerschke EI, Stiefel MF, Teitelbaum JS, Wartenberg KE, Zerfoss CL (2016) Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care 24(1):6–46CrossRefPubMed
13.
Zurück zum Zitat Tomaselli GF, Mahaffey KW, Cuker A, Dobesh PP, Doherty JU, Eikelboom JW, Florido R, Hucker W, Mehran R, Messé SR, Pollack CV Jr, Rodriguez F, Sarode R, Siegal D, Wiggins BS (2017) 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 70(24):3042–3067CrossRefPubMed Tomaselli GF, Mahaffey KW, Cuker A, Dobesh PP, Doherty JU, Eikelboom JW, Florido R, Hucker W, Mehran R, Messé SR, Pollack CV Jr, Rodriguez F, Sarode R, Siegal D, Wiggins BS (2017) 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 70(24):3042–3067CrossRefPubMed
14.
Zurück zum Zitat Pabinger I, Brenner B, Kalina U, Knaub S, Nagy A, Ostermann H (2008) Beriplex P/N Anticoagulation Reversal Study Group. Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost 6(4):622–631CrossRefPubMed Pabinger I, Brenner B, Kalina U, Knaub S, Nagy A, Ostermann H (2008) Beriplex P/N Anticoagulation Reversal Study Group. Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost 6(4):622–631CrossRefPubMed
15.
Zurück zum Zitat Altorjay Á, Szabó É, Boda Z, Kramer L, Ngo LY, Engl W, Firth CL, Ahlstrom ER, Gelmont DM, Pabinger I (2015) An international, multicenter, prospective study of a prothrombin complex, Prothromplex Total complex®, in anticoagulant reversal. Thromb Res 135(3):485–491CrossRefPubMed Altorjay Á, Szabó É, Boda Z, Kramer L, Ngo LY, Engl W, Firth CL, Ahlstrom ER, Gelmont DM, Pabinger I (2015) An international, multicenter, prospective study of a prothrombin complex, Prothromplex Total complex®, in anticoagulant reversal. Thromb Res 135(3):485–491CrossRefPubMed
16.
Zurück zum Zitat Majeed A, Kim YK, Roberts RS, Holmström M, Schulman S (2010) Optimal timing of resumption of warfarin after intracranial hemorrhage. Stroke 41(12):2860–2866CrossRefPubMed Majeed A, Kim YK, Roberts RS, Holmström M, Schulman S (2010) Optimal timing of resumption of warfarin after intracranial hemorrhage. Stroke 41(12):2860–2866CrossRefPubMed
17.
Zurück zum Zitat Frost C, Wang J, Nepal S, Schuster A, Barrett YC, Mosqueda-Garcia R, Reeves RA, LaCreta F (2013) Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br J Clin Pharmacol 75(2):476–487CrossRefPubMed Frost C, Wang J, Nepal S, Schuster A, Barrett YC, Mosqueda-Garcia R, Reeves RA, LaCreta F (2013) Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br J Clin Pharmacol 75(2):476–487CrossRefPubMed
18.
Zurück zum Zitat Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M (2005) Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939—an oral, direct Factor Xa inhibitor—after multiple dosing in healthy male subjects. Eur J Clin Pharmacol 61(12):873–880CrossRefPubMed Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M (2005) Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939—an oral, direct Factor Xa inhibitor—after multiple dosing in healthy male subjects. Eur J Clin Pharmacol 61(12):873–880CrossRefPubMed
19.
Zurück zum Zitat Kubitza D, Becka M, Roth A, Mueck W (2008) Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin 24(10):2757–2765CrossRefPubMed Kubitza D, Becka M, Roth A, Mueck W (2008) Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin 24(10):2757–2765CrossRefPubMed
20.
Zurück zum Zitat Cuker A, Siegal D (2015) Monitoring and reversal of direct oral anticoagulants. Hematol Am Soc Hematol Educ Program 2015:117–124 Cuker A, Siegal D (2015) Monitoring and reversal of direct oral anticoagulants. Hematol Am Soc Hematol Educ Program 2015:117–124
Metadaten
Titel
Prothrombin complex concentrate for reversal of direct factor Xa inhibitors prior to emergency surgery or invasive procedure: a retrospective study
verfasst von
Siavash Piran
Caroline Gabriel
Sam Schulman
Publikationsdatum
21.03.2018
Verlag
Springer US
Erschienen in
Journal of Thrombosis and Thrombolysis / Ausgabe 4/2018
Print ISSN: 0929-5305
Elektronische ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-018-1645-y

Weitere Artikel der Ausgabe 4/2018

Journal of Thrombosis and Thrombolysis 4/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.