Top

Published in:

01-08-2017 | Original Article

Safety and Effectiveness of Factor VIII Inhibitor Bypassing Activity (FEIBA) and Fresh Frozen Plasma in Oral Anticoagulant-Associated Intracranial Hemorrhage: A Retrospective Analysis

Authors: Ellen B. Yin, Benedict Tan, Thuy Nguyen, Miguel Salazar, Kimberly Putney, Pramod Gupta, Jose I. Suarez, Eric M. Bershad

Published in: Neurocritical Care | Issue 1/2017

Abstract

Background

Oral anticoagulant (OAT)-associated intracranial hemorrhage (ICH) is a life-threatening emergency for which prothrombin complex concentrates (PCC) are considered first-line reversal agents. The only approved PCC in the USA for warfarin-associated ICH is non-activated PCC. Little data are available regarding the safety and effectiveness of factor VIII inhibitor bypassing activity (FEIBA) which is an activated prothrombin complex concentrate (aPCC). The aim of this analysis was to assess the safety and effectiveness of FEIBA compared to fresh frozen plasma (FFP) for reversal of OAT-associated ICH.

Methods

Data were retrospectively collected to compare coagulation markers and in-hospital clinical outcomes in patients who received aPCC with or without FFP versus FFP alone for the reversal of OAT-associated ICH.

Results

Eighty-four patients met inclusion criteria; 50 patients received FFP alone, and 34 patients received FEIBA (mean dose 20 U/kg) with or without FFP for OAT-associated ICH. The proportion of diagnosed thrombotic events during hospitalization was similar in both groups (8% in the FFP group vs. 12% in the FEIBA group; P = 0.56). Median time to INR < 1.5 was achieved faster in the FEIBA group versus the FFP group (0.5 h [IQR 0.5–1.] vs. 10 h [IQR 5–16.3], respectively; P < 0.001) reflecting a trend toward shorter median time to neurosurgical intervention. Hematoma expansion, length of stay, and all-cause mortality were similar between both groups.

Conclusions

Administration of FEIBA does not appear to increase the risk of thrombotic events compared with FFP. FEIBA administration resulted in faster INR reversal with a trend toward shorter time to neurosurgical intervention. However, there was no difference in hematoma expansion, mortality or length of stay.

Steiner T, Rosand J, Diringer M. Intracerebral hemorrhage associated with oral anticoagulant therapy: current practices and unresolved questions. Stroke. 2006;27:256–62.CrossRef

Bershad E, Suarez J. Prothrombin complex concentrates for oral anticoagulant therapy-related intracranial hemorrhage: a review of the literature. Neurocrit Care. 2010;12:403–13.CrossRefPubMed

Dowlatshahi D, Butcher KS, Asdaghi N, Nahirniak S, Bernbaum ML, Guilivi A, et al. Poor prognosis in warfarin-associated intracranial hemorrhage despite anticoagulation reversal. Stroke. 2012;43:1812–7.CrossRefPubMed

Wojcik C, Schymik M, Cure E. Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy. Int J Emerg Med. 2009;2:217–25.CrossRefPubMedPubMedCentral

Desmurs-Clavel H, Huchon C, Chatard B, Negrier C, Dargaud Y. Reversal of the inhibitory effect of fondaparinux on thrombin generation by rFVIIa, aPCC, and PCC. Thromb Res. 2009;123:796–8.CrossRefPubMed

Turecek PL, Varadi K, Gritsch H, Schwarz HP. FEIBA: mode of action. Haemophilia. 2004;10(Suppl 2):3–9.CrossRefPubMed

Awad N, Cocchio C. Activated prothrombin complex concentrates for the reversal of anticoagulant-associated coagulopathy. Pharm Ther. 2013;38(11):696–701.

Babilonia K, Trujillo T. The role of prothrombin complex concentrates in reversal of target specific anticoagulants. Thromb J. 2014;12:8–16.CrossRefPubMedPubMedCentral

Lankiewicz MW, Hays J, Friedman KD, Tinkoff G, Blatt PM. Urgent reversal of warfarin with prothrombin complex concentrate. J Thromb Haemost. 2006;4:967–70.CrossRefPubMed

10.

Pabinger I, Tiede A, Kalina U, Knaub S, Germann R, Ostermann H. Beriplex P/N anticoagulation reversal study group. Impact of infusion speed on the safety and effectiveness of prothrombin complex concentrate: a prospective clinical trial of emergency anticoagulation reversal. Ann Hematol. 2010;89:967–70.CrossRef

11.

Bagot CN, Cregg R, Patel RK, Shariff A, Arya R. Perioperative myocardial infarction in a patient receiving low-dose prothrombin complex concentrates. Thromb Haemost. 2007;98:1141–2.PubMed

12.

Imberti D, Barillari G, Biasioli C, Bianchi M, Contino L, Duce R, et al. Prothrombin complex concentrates for urgent anticoagulation reversal in patients with intracranial hemorrhage. Pathophysiol Haemost Thromb. 2007;36:256–65.

13.

Teasdale G, Jennett B. Assessment of coma and impaired consciousness. Lancet. 1974;304(7872):81–4.CrossRef

14.

Brott T, Adams HP, Olinger C, Marler JR, Barsan WG, Biller J, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20(7):864–70.CrossRefPubMed

15.

Van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJA, Van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19:604–7.CrossRefPubMed

16.

Charlson ME, Pompei P, Ales K, Ronald MC. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.CrossRefPubMed

17.

Hemphill JC, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001;32(4):891–7.CrossRefPubMed

18.

Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke. 1996;27:1304–5.CrossRefPubMed

19.

Stewart WS, Pettit H. Experiences with an activated 4-factor prothrombin complex concentrate (FEIBA) for reversal of warfarin-related bleeding. Am J Emerg Med. 2013;31(8):1251–4.CrossRefPubMed

20.

Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin complex concentrate in the emergency department. Circulation. 2013;128:360–4.CrossRefPubMed

21.

Evans G, Luddington R, Baglin T. Beriplex P/N reverses severe warfarin-induced overanticoagulation immediately and completely in patients presenting with major bleeding. Br J Haematol. 2001;115:998–1001.CrossRefPubMed

22.

Chapman SA, Irwin ED, Beal AL, Kulinski NM, Hutson KE, Thorson MA. Prothrombin complex concentrate versus standard therapies for INR reversal in trauma patients receiving warfarin. Ann Pharmacother. 2011;45(7–8):869–75.CrossRefPubMed

23.

Cabral KP, Fraser GL, Duprey J, Gibbons BA, Hayes T, Florman JE, Seder DB. Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding. Clin Neurol Neurosurg. 2013;115(6):770–4.CrossRefPubMed

24.

Huttner HB, Schellinger PD, Hartmann M, Kohrmann M, Juettler E, Wikner J, et al. Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke. 2006;37(6):1465–70.CrossRefPubMed

25.

Frontera JA, Gordon E, Zach V, Jovine M, Uchino K, Hussain M, Aledort L. Reversal of coagulopathy using prothrombin complex concentrates is associated with improved outcome compared to fresh frozen plasma in warfarin-associated intracranial hemorrhage. Neurocrit Care. 2014;21:397–406.CrossRefPubMed

26.

Edavettal M, Rogers A, Rogers F, Horst M, Leng W. Prothrombin complex concentrate accelerates international normalized ratio reversal and diminishes the extension of intracranial hemorrhage in geriatric trauma patients. Am Surg. 2014;80(4):372–6.PubMed

27.

Kuwashiro T, Yasaka M, Itabashi R, Nakagaki H, Miyashita F, Naritomi H, Minematsu K. Effect of prothrombin complex concentrate on hematoma enlargement and clinical outcome in patients with anticoagulant-associated intracerebral hemorrhage. Cerebrovasc Dis. 2001;31(2):170–6.CrossRef

28.

Kuramatsu J, Gerner S, Schellinger P, Glahn J, Endres M, Sobseky J, Flechsenhar J, et al. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA. 2015;313(8):824–36.CrossRefPubMed

29.

Hemphill JC, Greenberg S, Anderson C, Becker K, Bendok BR, Cushman M, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46:1–30.CrossRef

Title: Safety and Effectiveness of Factor VIII Inhibitor Bypassing Activity (FEIBA) and Fresh Frozen Plasma in Oral Anticoagulant-Associated Intracranial Hemorrhage: A Retrospective Analysis
Authors: Ellen B. Yin
Benedict Tan
Thuy Nguyen
Miguel Salazar
Kimberly Putney
Pramod Gupta
Jose I. Suarez
Eric M. Bershad
Publication date: 01-08-2017
Publisher: Springer US
Published in: Neurocritical Care / Issue 1/2017
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI: https://doi.org/10.1007/s12028-017-0383-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Safety and Effectiveness of Factor VIII Inhibitor Bypassing Activity (FEIBA) and Fresh Frozen Plasma in Oral Anticoagulant-Associated Intracranial Hemorrhage: A Retrospective Analysis

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2017

Changes in Cerebral Perfusion with Induced Hypertension in Aneurysmal Subarachnoid Hemorrhage: A Pilot and Feasibility Study

Noninvasive Neuromonitoring: Current Utility in Subarachnoid Hemorrhage, Traumatic Brain Injury, and Stroke

Physiological Effects of Early Incremental Mobilization of a Patient with Acute Intracerebral and Intraventricular Hemorrhage Requiring Dual External Ventricular Drainage

An Association Between ICP-Derived Data and Outcome in TBI Patients: The Role of Sample Size

Elevated Serum Glial Fibrillary Acidic Protein (GFAP) is Associated with Poor Functional Outcome After Cardiopulmonary Resuscitation

Monitoring of Electrical Activity of the Diaphragm Shows Failure of T-Piece Trial Earlier than Protocol-Based Parameters in Prolonged Weaning in Non-communicative Neurological Patients