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The outcomes of three-factor prothrombin complex concentrate (3F-PCC) in warfarin anticoagulation reversal: a prospective, single-arm, open-label, multicentre study

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Abstract

There is a wide variation on the efficacy of three-factor Prothrombin Complex Concentrate (3F-PCC) in warfarin reversal. We aimed to determine the efficacy and safety of 3F-PCC in warfarin reversal. This multicentre prospective study analysed data from adult patients on warfarin who received 3F-PCC (Prothrombinex-VF®) for anticoagulation reversal between June 2019 to October 2020. Purposive sampling was used in this study. Study endpoints included target INR achievement, adverse drug reactions (ADRs), and in-hospital all-cause mortality. Logistic regression analyses were used to assess independent predictors of study endpoints. One-hundred thirty-seven patients with a median age of 68 (59–76) years were recruited, who were predominantly male (59.9%, n = 82). A total of 102 patients required 3F-PCC for life-threatening (40.9%, n = 56) and clinically significant bleeding (33.6%, n = 46). Initial INRs ranged from 1.55 to undetectable high (> 26). All patients had INR reduction, of which 62% (n = 85) achieved target INR, whereas 12.4% (n = 17) achieved INR below the target range. Median INR was reduced from 4.76 (3.14–8.32) to 1.54 (1.27–1.88) post-3F-PCC (p < 0.001). The use of adjunctive reversal agents and initial INR < 3.6 were the significant predictors for target INR achievement. Six (4.4%) ADRs were observed. Two (1.5%) cases with the suspected acute coronary syndrome were associated with mortality. Ischemic stroke occurred in one (0.7%) patient. The incidence of in-hospital all-cause mortality was 21.2% (n = 29). The rate of INR achievement was 62% in our study without apparent increased risk of thromboembolic events and in-hospital all-cause mortality.

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Acknowledgements

We would like to thank the Director-General of Health Malaysia for his permission to publish this article. The authors thank pharmacists from the 19 hospitals and the National Blood Bank of Malaysia involved in data collection; Swee Chong Lii, Farah Fauziah Abd. Rahim, Siti Nasihah Harif, Low Yuet Man, Chow Li Wei, Koo Shuk Kuan, Wan Najwa Wan Suraya Wan Ahmad Kamil, Amy Lau Siew Ching, Jude Siong Yip Kiong, Ting Sie Ming, Sunny Ooi Hooi Sun, Lim Chi Hao, Kevin Liew Yen Wei, Muhammad Zulhafiz Zulkupli, Yong Hui Xian Catherine, Farrah Idayu Zakaria, Aina Fairuz Abd. Latif, Lim Tiong Hoe, Siti Rosnah Suradi, Lim Chong Teck, Low Shin Yee, Rafidah Abd Razak, Noor Nazmelia Mustapa, Lee Lay Chin, Soliha Zainal Abidin, Zetty Ellyssa Sallehuddin, Nik Azlean Nik Ismail, Tay Szu Lynn, Tang Jiaa Yinn, and Jivanraj R Nagarajah.

Funding

This study was self-funded work.

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Authors and Affiliations

  1. Pharmacy Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia

    Hock Peng Koh, Nirmala Jagan & Hong Thai Lim

  2. Pharmacy Department, Hospital Raja Permaisuri Bainun, Ipoh, Malaysia

    Doris George

  3. Pharmacy Department, Hospital Melaka, Malacca, Malaysia

    Wardati Mazlan-Kepli

  4. Pharmacy Department, Hospital Tengku Ampuan Afzan, Kuantan, Malaysia

    Sahimi Mohamed

  5. Medical Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia

    Noel Thomas Ross

  6. National Blood Center, Ministry of Health, Kuala Lumpur, Malaysia

    Ailin Mazuita Mazlan

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  1. Hock Peng Koh
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Contributions

HPK and NJ contributed to the idea and study design. All authors contributed to the data collection, data entry, interpretation of results, and critically reviewed the final manuscript. HPK wrote the first manuscript and performed all statistical analyses. All authors contributed to the reviewed and approved the manuscript before submission.

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Correspondence to Hock Peng Koh.

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Ethics approval was granted by the Malaysian Medical Research and Ethics Committee.

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Koh, H.P., Jagan, N., George, D. et al. The outcomes of three-factor prothrombin complex concentrate (3F-PCC) in warfarin anticoagulation reversal: a prospective, single-arm, open-label, multicentre study. J Thromb Thrombolysis 52, 836–847 (2021). https://doi.org/10.1007/s11239-021-02426-2

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