{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:05:57Z","timestamp":1783472757878,"version":"3.55.0"},"reference-count":68,"publisher":"Georg Thieme Verlag KG","issue":"01","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n            Introduction\u2003Four-factor prothrombin complex concentrate (4F-PCC) is recommended for vitamin K antagonist reversal in patients with major bleeding or in need of surgery. The most important risk associated with the use of 4F-PCC is the occurrence of thromboembolic events (TEEs). In this review, we aim to evaluate the safety profile of a 4F-PCC (Kcentra\u00ae\/Beriplex\u00ae P\/N; CSL Behring, Marburg, Germany) by reviewing pharmacovigilance data.<\/jats:p><jats:p>\n            Methods\u2003A retrospective analysis of postmarketing pharmacovigilance data of Kcentra\u00ae\/Beriplex\u00ae P\/N from February 1996 to April 2022 was performed and complemented by a review of clinical studies published between January 2012 and April 2022.<\/jats:p><jats:p>\n            Results\u2003A total of 2,321,443 standard infusions of Kcentra\u00ae\/Beriplex\u00ae P\/N were administered during the evaluation period. Adverse drug reactions (ADRs) were reported in 614 cases (\u223c1 per 3,781 standard infusions) and 233 of these cases (37.9%) experienced suspected TEEs related to 4F-PCC (\u223c1 per 9,963 standard infusions); most of these cases had pre-existing or concomitant conditions likely to be significant risk factors for thrombosis. TEE rates were similar when 4F-PCC was used on-label or off-label for direct oral anticoagulant-associated bleeding. Thirty-six cases (5.9%) reported hypersensitivity type reactions (\u223c1 per 64,485 standard infusions). No confirmed case of viral transmission related to 4F-PCC use was reported. The published literature also revealed a favorable safety profile of 4F-PCC.<\/jats:p><jats:p>\n            Conclusion\u2003Analysis of postmarketing pharmacovigilance safety reports demonstrated that treatment with 4F-PCC was associated with few ADRs and a low rate of TEEs across multiple indications and settings, thus confirming a positive safety profile of 4F-PCC.<\/jats:p>","DOI":"10.1055\/s-0044-1788305","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T23:51:38Z","timestamp":1722297098000},"page":"046-057","source":"Crossref","is-referenced-by-count":10,"title":["Long-Term Safety of a Four-Factor Prothrombin Complex Concentrate (Kcentra\u00ae\/Beriplex\u00ae P\/N): An Updated Pharmacovigilance Review"],"prefix":"10.1055","volume":"125","author":[{"given":"Truman J.","family":"Milling","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Tilman J. Fertitta Family College of Medicine, University of Houston, Houston, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Voronov","sequence":"additional","affiliation":[{"name":"CSL Behring Australia Pty Ltd, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk S.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"CSL Behring GmbH, Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edelgard","family":"Lindhoff-Last","sequence":"additional","affiliation":[{"name":"Cardiology Angiology Center Bethanien, CCB Coagulation Research Center, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s12028-015-0222-x","article-title":"Guideline for reversal of 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