Prothrombin complex concentrate use for urgent warfarin reversal compared to fresh frozen plasma and recombinant factor VIIa

Hua Xin Chen, James Coons

Abstract


Background:

Agents used to rapidly reverse warfarin include fresh frozen plasma (FFP), recombinant factor VIIa (rFVIIa), and prothrombin complex concentrates (PCCs). The recent approval of PCCs to the health system formulary allowed for a comparison of PCCs to the older agents FFP and rFVIIa. Additionally, limited data comparing rFVIIa and PCCs are available.

Objective:

To compare the effectiveness of PCCs and FFP/rFVIIa for the rapid reversal of warfarin.

Methods:

This retrospective study included hospitalized patients who received 4-factor PCC between July 1, 2013 and April 30, 2014 and those who received rFVIIa and/or FFP between October 19, 2010 and September 30, 2012. All reversals for patients receiving therapy with warfarin were included. The primary outcome was the proportion of reversals achieving INR £1.3 within 8 hours. Secondary outcomes included average INR reduction and the median time to INR £1.3.

Results:

The PCC cohort included 64 warfarin reversals. The historical cohorts included 394 reversals with FFP and 27 reversals with rFVIIa/FFP. The target INR was reached in 45.3% of PCC reversals, 10.2% of FFP-only reversals (p <0.001 vs. PCC), and 77.8% of rFVIIa/FFP reversals (p=0.004 vs. PCC). The median time to target INR for the PCC, FFP, and rFVIIa/FFP groups were 3.6h, 4.8h (p=0.17 vs. PCC), and 1.3h (p=0.002 vs. PCC), respectively.

Conclusions:

PCC use resulted in greater hemostasis compared to FFP alone. rFVIIa use resulted in the fastest and greatest proportion of INR reduction, though a larger sample size and adverse event data are needed to recommend its use.

Keywords


warfarin; reversal; hemostasis; recombinant factor VIIa; prothrombin complex concentrates

Full Text:

PDF

References


Nutescu EA, Dager WE, Kalus JS, Lewin JJ, and Cipolle MD. Management of bleeding and reversal strategies for oral anticoagulants: Clinical practice considerations. Am J Health-Syst Pharm 2013;70(21):1914-29. DOI: 10.2146/ajhp130243.

Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed. American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141 (2 Suppl):e152S-e184s. DOI: 10.1378/chest.11-2295.

Hedges A, Coons JC, Saul M, and Smith RE. Clinical effectiveness and safety outcomes associated with prothrombin complex concentrates. J Thromb Thrombolysis. 2016;42(1):6-10. DOI: 10.1007/s11239-015-1321-4.

Frontera JA, Gordon E, Zach V, et al. 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(3): 397-406. DOI: 10.1007/s12028-014-9972-0.

Demeyere R, Gillardin S, Arnout J, and Strengers PF. Comparison of fresh frozen plasma and prothrombin complex concentrate for the reversal of oral anticoagulants in patients undergoing cardiopulmonary bypass surgery: a randomized study. Vox Sang. 2010;99(3): 251-60. DOI: 10.1111/j.1423-0410.2010.01339.x.

Sarode R, Milling TJ Jr, Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013;128(11): 1234-43. DOI: 10.1161/CIRCULATIONAHA.113.002283.

Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015;385(9982): 2077-87. DOI: 10.1016/S0140-6736(14)61685-8.

Woo CH, Patel N, Conell C, et al. Rapid warfarin reversal in the setting of intracranial hemorrhage: a comparison of plasma, recombinant activated factor VII, and prothrombin complex concentrate. World Neurosurg. 2012;81(1): 110-5. DOI: 10.1016/j.wneu.2012.12.002.

Chapman SA, Irwin ED, Abou-Karam NM, et al. Comparison of 3-factor prothrombin complex concentrate and low-dose recombinant factor VIIa for warfarin reversal. World J Emerg Surg. April 2014;9:27. DOI: 10.1186/1749-7922-9-27.

Steiner T, Poli S, Griebe M, et al. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurol. 2016;15(6):566-573. DOI: 10.1016/S1474-4422(16)00110-1.

Barton CA, Johnson NB, Case J, et al. Risk of thromboembolic events after protocolized warfarin reversal with 3-factor PCC and factor VIIa. Am J Emerg Med. 33(11):1562-1566. DOI: 10.1016/j.ajem.2015.06.010.

DeLoughery EP, Lenfesty B, DeLoughery TG (2013) The use of recombinant factor VIIa in warfarin patients with traumatic brain injury: a retrospective case-control study. Blood Coagul Fibrinolysis. 2015;24(3):317-320. DOI: 10.1097/MBC.0b013e32835cc16b.

Chou HY, Cai X, Konigsberg RG, et al. Thromboembolic risks of recombinant factor VIIa use in warfarin-associated intracranial hemorrhage: a case-control study. BMC Neurol. Dec 2012;12:158-165. DOI: 10.1186/1471-2377-12-158.

Brown CVR, Sowery L, Curry E, et al. Recombinant factor VIIa to correct coagulopathy in patients with traumatic brain injury presenting to outlying facilities before transfer to the regional trauma center. Am Surg. 2012;78(1):57-60.

Sarode R, Matevosyan K, Bhagat R, Rutherford C, Madden C, and Beshay JE. Rapid warfarin reversal: a 3-factor prothrombin complex concentrate and recombinant factor VIIa cocktail for intracerebral hemorrhage. J Neurosurg. 2012;116(3):491-497. DOI: 10.3171/2011.11.JNS11836.




DOI: http://dx.doi.org/10.18103/imr.v4i2.661

Refbacks

  • There are currently no refbacks.
Copyright 2016. All rights reserved.