The Role of FEIBA in Reversing Novel Oral Anticoagulants in Intracerebral Hemorrhage
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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.
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).
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).
In this small case series, reversal of NOAC with FEIBA was not associated with ICH expansion or any thrombotic or hemorrhagic complications.
KeywordsIntracerebral hemorrhage Novel oral anticoagulants Activated prothrombin complex concentrate Anticoagulant-related intracerebral hemorrhage reversal
Complaince with Ethical Standards
Conflict of Interest
The authors have nothing to disclose.
- 4.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.CrossRefPubMedGoogle Scholar
- 5.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.CrossRefPubMedGoogle Scholar
- 6.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.CrossRefPubMedGoogle Scholar
- 7.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.PubMedGoogle Scholar
- 8.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.CrossRefPubMedGoogle Scholar
- 12.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.Google Scholar
- 15.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.Google Scholar
- 18.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.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.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.CrossRefPubMedGoogle Scholar
- 25.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.Google Scholar
- 26.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.CrossRefGoogle Scholar
- 29.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.Google Scholar
- 30.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.CrossRefGoogle Scholar
- 31.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.Google Scholar
- 32.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.Google Scholar