Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2022 Oct;54(3):470-479.
doi: 10.1007/s11239-022-02695-5. Epub 2022 Aug 19.

Thromboembolism after treatment with 4-factor prothrombin complex concentrate or plasma for warfarin-related bleeding

Alan S Go  1   2   3   4 , Thomas K Leong  5 , Sue Hee Sung  5 , Rong Wei  6 , Teresa N Harrison  6 , Nigel Gupta  7 , Nicole Baker  8 , Brahm Goldstein  8 , Quazi Ataher  8 , Matthew D Solomon  5   9 , Kristi Reynolds  10   6 ; REVERSAL Study
Affiliations
Observational Study

Thromboembolism after treatment with 4-factor prothrombin complex concentrate or plasma for warfarin-related bleeding

Alan S Go et al. J Thromb Thrombolysis. 2022 Oct.

Abstract

Limited data exist in large, representative populations about whether the risk of thromboembolic events varies after receiving four-factor human prothrombin complex concentrate (4F-PCC) versus treatment with human plasma for urgent reversal of oral vitamin K antagonist therapy. We conducted a multicenter observational study to compare the 45-day risk of thromboembolic events in adults with warfarin-associated major bleeding after treatment with 4F-PCC (Kcentra®) or plasma. Hospitalized patients in two large integrated healthcare delivery systems who received 4F-PCC or plasma for reversal of warfarin due to major bleeding from January 1, 2008 to March 31, 2020 were identified and were matched 1:1 on potential confounders and a high-dimensional propensity score. Arterial and venous thromboembolic events were identified up to 45 days after receiving 4F-PCC or plasma from electronic health records and adjudicated by physician review. Among 1119 patients receiving 4F-PCC and a matched historical cohort of 1119 patients receiving plasma without a recent history of thromboembolism, mean (SD) age was 76.7 (10.5) years, 45.6% were women, and 9.4% Black, 14.6% Asian/Pacific Islander, and 15.7% Hispanic. The 45-day risk of thromboembolic events was 3.4% in those receiving 4F-PCC and 4.1% in those receiving plasma (P = 0.26; adjusted hazard ratio 0.76; 95% confidence interval 0.49-1.16). The adjusted risk of all-cause death at 45 days post-treatment was lower in those receiving 4F-PCC compared with plasma. Among a large, ethnically diverse cohort of adults treated for reversal of warfarin-associated bleeding, receipt of 4F-PCC was not associated with an excess risk of thromboembolic events at 45 days compared with plasma therapy.

Keywords: Bleeding; Death; Plasma; Prothrombin complex concentrate; Thromboembolism.

PubMed Disclaimer

Conflict of interest statement

N.B., B.G. and Q.A. are employees of CSL Behring. The other authors have no conflict of interest to disclose.

Figures

Fig. 1
Fig. 1
Identification of eligible adults treated with 4F-PCC or plasma for acute VKA reversal due to major bleeding
Fig. 2
Fig. 2
Multivariable association of 4F-PCC vs. plasma therapy with risk of thromboembolism at 7, 14 and 45 days post-treatment
Fig. 3
Fig. 3
Multivariable association of 4F-PCC vs. plasma therapy with risk of death from any cause at 7, 14 and 45 days post-treatment
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Sarode R, Milling TJ, Jr., Refaai MA, Mangione A, Schneider A, Durn BL, 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. - DOI - PMC - PubMed
    1. Goldstein JN, Refaai MA, Milling TJ, Jr., Lewis B, Goldberg-Alberts R, Hug BA, 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. - DOI - PMC - PubMed
    1. Endres K, St Bernard R, Chin-Yee I, Hsia C, Lazo-Langner A. Efficacy and safety of four-factor prothrombin complex concentrate fixed, weight-based dosing for reversal of warfarin anticoagulation. Hematology. 2020;25(1):489–493. doi: 10.1080/16078454.2020.1855745. - DOI - PubMed
    1. Jones GM, Erdman MJ, Smetana KS, Mohrien KM, Vandigo JE, Elijovich L. 3-Factor versus 4-factor prothrombin complex concentrate for warfarin reversal in severe bleeding: a multicenter, retrospective, propensity-matched pilot study. J Thromb Thrombolysis. 2016;42(1):19–26. doi: 10.1007/s11239-015-1330-3. - DOI - PubMed
    1. Kuroski JE, Young S. Comparison of the safety and efficacy between 3-factor and 4-factor prothrombin complex concentrates for the reversal of warfarin. Am J Emerg Med. 2017;35(6):871–4. doi: 10.1016/j.ajem.2017.01.049. - DOI - PubMed

Publication types