Skip to main content
Erschienen in: Neurocritical Care 3/2016

06.11.2015 | Original Article

The Role of FEIBA in Reversing Novel Oral Anticoagulants in Intracerebral Hemorrhage

verfasst von: Jamil R. Dibu, Jonathan M. Weimer, Christine Ahrens, Edward Manno, Jennifer A. Frontera

Erschienen in: Neurocritical Care | Ausgabe 3/2016

Einloggen, um Zugang zu erhalten

Abstract

Background

Activated prothrombin complex concentrates factor eight inhibitor bypassing activity (FEIBA) has been recommended for reversing novel oral anticoagulants (NOAC) in the context of intracerebral hemorrhage (ICH), though few clinical studies report its use.

Methods

A prospective study of patients with spontaneous ICH was conducted from May 2013 to May 2015. Hospital complications including hemorrhage (gastrointestinal bleeding, anemia requiring transfusion, and surgical site bleeding) and thrombosis (pulmonary embolus, deep vein thrombosis, ischemic stroke, and myocardial infarction) were recorded. All ICH patients underwent baseline head CT and a follow-up stability scan in 6 h. NOAC taken within 48 h of presentation was reversed with FEIBA (50 u/kg) per protocol. Three-month outcomes were assessed using the modified rankin score (mRS).

Results

Of 127 ICH patients enrolled, 6 (5 %) had NOAC-related ICH including: oral factor XA inhibitor N = 5 (4 %; N = 4 rivaroxaban, N = 1 apixaban] and direct thrombin inhibitor N = 1 (0.8 %; dabigatran). The indication for NOAC was atrial fibrillation in all patients and the median CHADS2–VASC score was 4 (range 2–5). The median admission NIHSS was 2 (range 0–14) and the median ICH volume was 8 mL (range 1–20). Five patients (3 rivaroxaban, 1 apixaban, 1 dabigatran) presented within 48 h and received FEIBA within a median of 13 h (range 10–29 h) from their last NOAC dose and 8 h (range 4.5–20) from the time last known well. None of the patients had ICH expansion, hemorrhagic, or thrombotic complications. Three-month median mRS was 1 (range 0–6).

Conclusion

In this small case series, reversal of NOAC with FEIBA was not associated with ICH expansion or any thrombotic or hemorrhagic complications.
Literatur
1.
Zurück zum Zitat Magnani JW, Rienstra M, Lin H, Sinner MF, Lubitz SA, McManus DD, et al. Atrial fibrillation: current knowledge and future directions in epidemiology and genomics. Circulation. 2011;124:1982–93.CrossRefPubMedPubMedCentral Magnani JW, Rienstra M, Lin H, Sinner MF, Lubitz SA, McManus DD, et al. Atrial fibrillation: current knowledge and future directions in epidemiology and genomics. Circulation. 2011;124:1982–93.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs. aspirin in nonvalvular atrial fibrillation: an individual patient metaanalysis. JAMA. 2003;288:2441–8.CrossRef Van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs. aspirin in nonvalvular atrial fibrillation: an individual patient metaanalysis. JAMA. 2003;288:2441–8.CrossRef
3.
Zurück zum Zitat Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage facts and hypotheses. Stroke. 1995;26:1471–7.CrossRefPubMed Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage facts and hypotheses. Stroke. 1995;26:1471–7.CrossRefPubMed
4.
Zurück zum Zitat Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L, RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51. doi:10.1056/NEJMoa0905561 published correction appears in N Engl J Med. 2010;363:1877.CrossRefPubMed Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L, RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51. doi:10.​1056/​NEJMoa0905561 published correction appears in N Engl J Med. 2010;363:1877.CrossRefPubMed
5.
Zurück zum Zitat Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM, ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91. doi:10.1056/NEJMoa1009638.CrossRefPubMed Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM, ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91. doi:10.​1056/​NEJMoa1009638.CrossRefPubMed
6.
Zurück zum Zitat Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser SH, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan RS, Sim KH, Lewis BS, Van Mieghem W, Lip GY, Kim JH, Lanas-Zanetti F, GonzalezHermosillo A, Dans AL, Munawar M, O’Donnell M, Lawrence J, Lewis G, Afzal R, Yusuf S, AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806–17. doi:10.1056/NEJMoa1007432.CrossRefPubMed Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser SH, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan RS, Sim KH, Lewis BS, Van Mieghem W, Lip GY, Kim JH, Lanas-Zanetti F, GonzalezHermosillo A, Dans AL, Munawar M, O’Donnell M, Lawrence J, Lewis G, Afzal R, Yusuf S, AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806–17. doi:10.​1056/​NEJMoa1007432.CrossRefPubMed
7.
Zurück zum Zitat Chatterjee S, Sardar P, Biondi-Zoccai G, Kumbhani DJ. New oral anticoagulants and the risk of intracranial hemorrhage: traditional and Bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation. JAMA Neurol. 2013;70:1486–90. doi:10.1001/jamaneurol.2013.4021.PubMed Chatterjee S, Sardar P, Biondi-Zoccai G, Kumbhani DJ. New oral anticoagulants and the risk of intracranial hemorrhage: traditional and Bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation. JAMA Neurol. 2013;70:1486–90. doi:10.​1001/​jamaneurol.​2013.​4021.PubMed
8.
Zurück zum Zitat Hemphill JC III, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, Fung G, Goldstein J, Macdonald L, Mitchell P, Scott P. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46:2032.CrossRefPubMed Hemphill JC III, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, Fung G, Goldstein J, Macdonald L, Mitchell P, Scott P. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46:2032.CrossRefPubMed
9.
Zurück zum Zitat Turecek PL, Váradi K, Gritsch H, Schwarz HP. FEIBA: mode of action. Haemophilia. 2004;10(Suppl 2):3–9.CrossRefPubMed Turecek PL, Váradi K, Gritsch H, Schwarz HP. FEIBA: mode of action. Haemophilia. 2004;10(Suppl 2):3–9.CrossRefPubMed
10.
Zurück zum Zitat 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
11.
Zurück zum Zitat Perzborn E, Heitmeier S, Laux V, Buchmuller A. Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitro. Thromb Res. 2014;133(4):671–81.CrossRefPubMed Perzborn E, Heitmeier S, Laux V, Buchmuller A. Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitro. Thromb Res. 2014;133(4):671–81.CrossRefPubMed
12.
Zurück zum Zitat Schulman S, Ritchie B, Goy JK, Nahirniak S, Almutawa M, Ghanny S. Activated prothrombin complex concentrate for dabigatran-associated bleeding. Br J Haematol. 2013;164:296–310. Schulman S, Ritchie B, Goy JK, Nahirniak S, Almutawa M, Ghanny S. Activated prothrombin complex concentrate for dabigatran-associated bleeding. Br J Haematol. 2013;164:296–310.
13.
Zurück zum Zitat Wong H, Keeling D. Activated prothrombin complex concentrate for the prevention of dabigatran-associated bleeding. Br J Haematol. 2014;166:140–53.CrossRef Wong H, Keeling D. Activated prothrombin complex concentrate for the prevention of dabigatran-associated bleeding. Br J Haematol. 2014;166:140–53.CrossRef
15.
Zurück zum Zitat Dager W, Roberts A. Reversing dabigatran with FEIBA in a patient with a transseptal perforation during cardiac ablation. Crit Care Med. 2011;39(12):243. Dager W, Roberts A. Reversing dabigatran with FEIBA in a patient with a transseptal perforation during cardiac ablation. Crit Care Med. 2011;39(12):243.
16.
Zurück zum Zitat Heidbuchel H, Verhamme P, Alings M, et al. European heart rhythm association practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15:625–51.CrossRefPubMed Heidbuchel H, Verhamme P, Alings M, et al. European heart rhythm association practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15:625–51.CrossRefPubMed
17.
Zurück zum Zitat Meyer CS, Blebea J, Davis K Jr, Fowl RJ, Kempczinski RF. Surveillance venous scans for deep venous thrombosis in multiple trauma patients. Ann Vasc Surg. 1995;9(1):109–14.CrossRefPubMed Meyer CS, Blebea J, Davis K Jr, Fowl RJ, Kempczinski RF. Surveillance venous scans for deep venous thrombosis in multiple trauma patients. Ann Vasc Surg. 1995;9(1):109–14.CrossRefPubMed
18.
Zurück zum Zitat Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, Samama CM. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e227S–77S. doi:10.1378/chest.11-2297.CrossRefPubMedPubMedCentral Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, Samama CM. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e227S–77S. doi:10.​1378/​chest.​11-2297.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Kiraly A, Lyden A, Periyanayagam U, Chan J, Pang P. Management of hemorrhage complicated by novel oral anticoagulants in the emergency department: case report from the northwestern emergency medicine residency. Am J Ther. 2013;20:300–6.PubMed Kiraly A, Lyden A, Periyanayagam U, Chan J, Pang P. Management of hemorrhage complicated by novel oral anticoagulants in the emergency department: case report from the northwestern emergency medicine residency. Am J Ther. 2013;20:300–6.PubMed
20.
Zurück zum Zitat Maurice-Szamburski A, Graillon T, Bruder N. Favorable outcome after subdural hematoma treated with FEIBA in a 77-year-old patient treated by rivaroxaban. J Neurosurg Anesthesiol. 2014;26:2.CrossRef Maurice-Szamburski A, Graillon T, Bruder N. Favorable outcome after subdural hematoma treated with FEIBA in a 77-year-old patient treated by rivaroxaban. J Neurosurg Anesthesiol. 2014;26:2.CrossRef
21.
Zurück zum Zitat Lindahl TL, Wallstedt M, Gustafsson KM, Persson E, Hillarp A. More efficient reversal of dabigatran inhibition of coagulation by activated prothrombin complex concentrate or recombinant factor VIIa than by four-factor prothrombin complex concentrate. Thromb Res. 2015;135(3):544–7.CrossRefPubMed Lindahl TL, Wallstedt M, Gustafsson KM, Persson E, Hillarp A. More efficient reversal of dabigatran inhibition of coagulation by activated prothrombin complex concentrate or recombinant factor VIIa than by four-factor prothrombin complex concentrate. Thromb Res. 2015;135(3):544–7.CrossRefPubMed
22.
Zurück zum Zitat Khoo TL, Weatherburn C, Kershaw G, Reddel CJ, Curnow J, Dunkley S. The use of FEIBA(R) in the correction of coagulation abnormalities induced by dabigatran. Int J Lab Hematol. 2013;35(2):222–4.CrossRefPubMed Khoo TL, Weatherburn C, Kershaw G, Reddel CJ, Curnow J, Dunkley S. The use of FEIBA(R) in the correction of coagulation abnormalities induced by dabigatran. Int J Lab Hematol. 2013;35(2):222–4.CrossRefPubMed
23.
Zurück zum Zitat Aledort LM. Factor VIII inhibitor bypassing activity (FEIBA)-addressing safety issues. Haemophilia. 2008;14:39–43.CrossRefPubMed Aledort LM. Factor VIII inhibitor bypassing activity (FEIBA)-addressing safety issues. Haemophilia. 2008;14:39–43.CrossRefPubMed
24.
Zurück zum Zitat Dimichele D. Inhibitors: resolving diagnostic and therapeutic dilemmas. Haemophilia. 2002;8(3):280–7.CrossRefPubMed Dimichele D. Inhibitors: resolving diagnostic and therapeutic dilemmas. Haemophilia. 2002;8(3):280–7.CrossRefPubMed
25.
Zurück zum Zitat Glund S, Stangier J, Schmohl M, De Smet M, Gansser D, Lang B, Moschetti V, Ramael S, Reilly P. A specific antidote for dabigatran: immediate, complete and sustained reversal of dabigatran induced anticoagulation in healthy male volunteers. Circulation. 2013;128:A17765. Glund S, Stangier J, Schmohl M, De Smet M, Gansser D, Lang B, Moschetti V, Ramael S, Reilly P. A specific antidote for dabigatran: immediate, complete and sustained reversal of dabigatran induced anticoagulation in healthy male volunteers. Circulation. 2013;128:A17765.
26.
Zurück zum Zitat Glund S, Stangier J, Schmohl M, Moschetti V, Haazen W, Gansser M, Norris S, Lang B, Reilly P. Idarucizumab, a specific antidote for dabigatran: immediate, complete and sustained reversal of dabigatran induced anticoagulation in elderly and renally impaired subjects. Blood. 2014;124:A344.CrossRef Glund S, Stangier J, Schmohl M, Moschetti V, Haazen W, Gansser M, Norris S, Lang B, Reilly P. Idarucizumab, a specific antidote for dabigatran: immediate, complete and sustained reversal of dabigatran induced anticoagulation in elderly and renally impaired subjects. Blood. 2014;124:A344.CrossRef
28.
Zurück zum Zitat Lu G, DeGuzman FR, Hollenbach SJ, Karbarz MJ, Abe K, Lee G, Luan P, Hutchaleelaha A, Inagaki M, Conley PB, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013;19(4):446–51.CrossRefPubMed Lu G, DeGuzman FR, Hollenbach SJ, Karbarz MJ, Abe K, Lee G, Luan P, Hutchaleelaha A, Inagaki M, Conley PB, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013;19(4):446–51.CrossRefPubMed
29.
Zurück zum Zitat Crowther M, Vandana M, Michael K, et al. A Phase 2 randomized, double-blind, placebo-controlled trial demonstrating reversal of rivaroxaban-induced anticoagulation in healthy subjects by andexanet alfa (PRT064445), an antidote for Fxa inhibitors. 55th ASH annual meeting, New Orleans 2013. Crowther M, Vandana M, Michael K, et al. A Phase 2 randomized, double-blind, placebo-controlled trial demonstrating reversal of rivaroxaban-induced anticoagulation in healthy subjects by andexanet alfa (PRT064445), an antidote for Fxa inhibitors. 55th ASH annual meeting, New Orleans 2013.
30.
Zurück zum Zitat Crowther M, Levy G, Lu G, Leeds J, Barron L, Conley P, Castillo J, Curnutte J, Connolly S. ANNEXA-A: a phase 3 randomized, double-blind, placebo-controlled trial, demonstrating reversal of apixaban-induced anticoagulation in older subjects by andexanet alpha (PRT064445), a universal antidote for factor Xa (fXa) Inhibitors. Circulation. 2014;130:2105.CrossRef Crowther M, Levy G, Lu G, Leeds J, Barron L, Conley P, Castillo J, Curnutte J, Connolly S. ANNEXA-A: a phase 3 randomized, double-blind, placebo-controlled trial, demonstrating reversal of apixaban-induced anticoagulation in older subjects by andexanet alpha (PRT064445), a universal antidote for factor Xa (fXa) Inhibitors. Circulation. 2014;130:2105.CrossRef
31.
Zurück zum Zitat Laulicht B, Bakhru S, Jiang X, et al. Antidote for new oral anticoagulants: mechanism of action and binding specificity of PER977. Presented at the 24th Congress of the International Society on Thrombosis and Haematosis, Amsterdam, June 29–July 4, 2013. Laulicht B, Bakhru S, Jiang X, et al. Antidote for new oral anticoagulants: mechanism of action and binding specificity of PER977. Presented at the 24th Congress of the International Society on Thrombosis and Haematosis, Amsterdam, June 29–July 4, 2013.
32.
Zurück zum Zitat Bakhru S, Laulicht B, Jiang X, Chen L, Pan D, Grosso M, Morishima Y, Brown K, Masumoto H, Costin J, Steiner S. PER977: a synthetic small molecule which reverses over-dosage and bleeding by the new oral anticoagulants. Circulation. 2014;128:A18809. Bakhru S, Laulicht B, Jiang X, Chen L, Pan D, Grosso M, Morishima Y, Brown K, Masumoto H, Costin J, Steiner S. PER977: a synthetic small molecule which reverses over-dosage and bleeding by the new oral anticoagulants. Circulation. 2014;128:A18809.
33.
Zurück zum Zitat Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso M, Brown K, Dishy V, Noveck RJ, Costin JC. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014;371:2141–2. doi:10.1056/NEJMc1411800.CrossRefPubMed Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso M, Brown K, Dishy V, Noveck RJ, Costin JC. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014;371:2141–2. doi:10.​1056/​NEJMc1411800.CrossRefPubMed
Metadaten
Titel
The Role of FEIBA in Reversing Novel Oral Anticoagulants in Intracerebral Hemorrhage
verfasst von
Jamil R. Dibu
Jonathan M. Weimer
Christine Ahrens
Edward Manno
Jennifer A. Frontera
Publikationsdatum
06.11.2015
Verlag
Springer US
Erschienen in
Neurocritical Care / Ausgabe 3/2016
Print ISSN: 1541-6933
Elektronische ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-015-0213-y

Weitere Artikel der Ausgabe 3/2016

Neurocritical Care 3/2016 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Stuhltransfusion könnte Fortschreiten von Parkinson-Symptomen bremsen

03.05.2024 Parkinson-Krankheit Nachrichten

Kann eine frühzeitige Stuhltransplantation das Fortschreiten von Parkinson-Symptomen verlangsamen? Die Ergebnisse einer randomisierten Phase-2-Studie scheinen dafür zu sprechen.

Frühe Tranexamsäure-Therapie nützt wenig bei Hirnblutungen

02.05.2024 Hirnblutung Nachrichten

Erhalten Personen mit einer spontanen Hirnblutung innerhalb von zwei Stunden nach Symptombeginn eine Tranexamsäure-Therapie, kann dies weder die Hämatomexpansion eindämmen noch die Mortalität senken.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders scheint das auf weibliche Kranke zuzutreffen, wie eine Studie zeigt.

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Update Neurologie

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