{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T08:48:02Z","timestamp":1781945282608,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,3,21]],"date-time":"2016-03-21T00:00:00Z","timestamp":1458518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Academic Emergency Medicine"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Clinicians often need to rapidly reverse vitamin K antagonists (<jats:styled-content style=\"fixed-case\">VKA<\/jats:styled-content>s) in the setting of major hemorrhage or urgent need for surgery. Little is known about the safety profile of the traditional reversal agent, plasma, or the newly approved agent, four\u2010factor prothrombin complex concentrate (4F\u2010<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content>), in a randomized setting. This is an integrated analysis of safety data from two clinical trials that evaluated 4F\u2010<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content> versus plasma for the treatment of patients requiring rapid <jats:styled-content style=\"fixed-case\">VKA<\/jats:styled-content> reversal for acute major bleeding or prior to an urgent surgical\/invasive procedure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This descriptive analysis comprised adverse event (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>) data from two phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>b, randomized, controlled trials. The bleeding and surgical studies were performed across 36 and 33 sites, respectively, in nine countries, with the integrated analysis comprising 388 patients (4F\u2010<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content>,<jats:italic> n<\/jats:italic> = 191; plasma, <jats:italic>n<\/jats:italic> = 197) aged \u2265 18 years, who required <jats:styled-content style=\"fixed-case\">VKA<\/jats:styled-content> reversal due to major bleeding or prior to an urgent surgical\/invasive procedure. Patients received either 4F\u2010<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content>, containing nonactivated factors <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> VII<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> IX<\/jats:styled-content>, and X and proteins C and S (Beriplex\/Kcentra, <jats:styled-content style=\"fixed-case\">CSL<\/jats:styled-content> Behring) or plasma, both dosed according to baseline international normalized ratio and body weight. Patients were also to receive vitamin K1. <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s and serious <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s (<jats:styled-content style=\"fixed-case\">SAE<\/jats:styled-content>s) were assessed up to days 10 and 45, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The proportion of patients with <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s (4F\u2010<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content>, 115\/191 [60.2%]; plasma, 124\/197 [62.9%]) and <jats:styled-content style=\"fixed-case\">SAE<\/jats:styled-content>s (4F\u2010<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content>, 54\/191 [28.3%]; plasma, 49\/197 [24.9%]) was similar between groups. The proportion of patients with thromboembolic events was also similar between groups (4F\u2010<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content>, 14\/191 [7.3%]; plasma, 14\/197 [7.1%]). There were 13 (6.8%) deaths in the 4F\u2010<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content> group and 13 (6.6%) in the plasma group. Fluid overload events occurred in more patients in the plasma group than the 4F\u2013<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content> group (25 [12.7%] and 9 [4.7%], respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These safety data represent the largest controlled assessment of a 4F\u2010<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content> to date. For patients requiring urgent <jats:styled-content style=\"fixed-case\">VKA<\/jats:styled-content> reversal, 4F\u2010<jats:styled-content style=\"fixed-case\">PCC<\/jats:styled-content> had a safety profile similar to that of plasma (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s, <jats:styled-content style=\"fixed-case\">SAE<\/jats:styled-content>s, thromboembolic events, and deaths), but was associated with fewer fluid overload events.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acem.12911","type":"journal-article","created":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T10:38:11Z","timestamp":1454063891000},"page":"466-475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Safety of a Four\u2010factor Prothrombin Complex Concentrate Versus Plasma for Vitamin K Antagonist Reversal: An Integrated Analysis of Two Phase <scp>III<\/scp>b Clinical Trials"],"prefix":"10.1111","volume":"23","author":[{"suffix":"Jr","given":"Truman J.","family":"Milling","sequence":"first","affiliation":[{"name":"Seton Clinical Research Institute Dell University of Texas Medical School Dell Children's Medical Center University Medical Center at Brackenridge Austin TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majed A.","family":"Refaai","sequence":"additional","affiliation":[{"name":"University of Rochester Medicine Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Sarode","sequence":"additional","affiliation":[{"name":"UT Southwestern Medical Center Dallas TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Lewis","sequence":"additional","affiliation":[{"name":"St. Joseph Regional Health Center Bryan Texas A&amp;M Health Science Center College Station TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette","family":"Mangione","sequence":"additional","affiliation":[{"name":"CSL Behring King of Prussia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billie L.","family":"Durn","sequence":"additional","affiliation":[{"name":"CSL Behring King of Prussia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Harman","sequence":"additional","affiliation":[{"name":"CSL Behring King of Prussia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin L.","family":"Lee","sequence":"additional","affiliation":[{"name":"UCLA School of Public Health Los Angeles CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua N.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,21]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"IMS data US National Prescription Audit","year":"2013"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa1103053"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.167.13.1414"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-2292"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181895bd8"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-2295"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08753.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc12685"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/EJA.0b013e32835f4d5b"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002283"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61685-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-0670"},{"key":"e_1_2_7_14_1","unstructured":"Kcentra Highlights of Prescribing Information. 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