{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T03:35:10Z","timestamp":1784000110919,"version":"3.55.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Thromb Thrombolysis"],"published-print":{"date-parts":[[2019,8]]},"DOI":"10.1007\/s11239-019-01846-5","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T17:03:46Z","timestamp":1554224626000},"page":"250-255","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Safety, efficacy, and cost of four-factor prothrombin complex concentrate (4F-PCC) in patients with factor Xa inhibitor-related bleeding: a retrospective study"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5058-2801","authenticated-orcid":false,"given":"Melanie N.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Deloney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle A.","family":"Weant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evert A.","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,2]]},"reference":[{"issue":"20","key":"1846_CR1","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1001\/jama.2016.16201","volume":"316","author":"N Shehab","year":"2016","unstructured":"Shehab N, Lovegrove MC, Geller AI, Rose KO, Weidle NJ, Budnitz DS (2016) US emergency department visits for outpatient adverse drug events, 2013\u20132014. JAMA 316(20):2115\u20132125. \n                    https:\/\/doi.org\/10.1001\/jama.2016.16201","journal-title":"JAMA"},{"issue":"12","key":"1846_CR2","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1056\/NEJMoa1607887","volume":"375","author":"SJ Connolly","year":"2016","unstructured":"Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, Crowther M, ANNEXA-4 Investigators (2016) Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 375(12):1131\u20131141. \n                    https:\/\/doi.org\/10.1056\/NEJMoa1607887","journal-title":"N Engl J Med"},{"key":"1846_CR3","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1814051","author":"SJ Connolly","year":"2019","unstructured":"Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, Yue P, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Demchuk AM, Pallin DJ, Concha M, Goodman S, Leeds J, Souza S, Siegal DM, Zotova E, Meeks B, Ahmad S, Nakamya J, Milling TJ Jr, ANNEXA-4 Investigators (2019) Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. \n                    https:\/\/doi.org\/10.1056\/nejmoa1814051","journal-title":"N Engl J Med"},{"key":"1846_CR4","unstructured":"ANDEXXA [package insert] (2018) Portola Pharmaceuticals, Inc, South San Francisco"},{"issue":"6","key":"1846_CR5","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1016\/j.wneu.2015.08.042","volume":"84","author":"R Grandhi","year":"2015","unstructured":"Grandhi R, Newman WC, Zhang X, Harrison G, Moran C, Okonkwo DO, Ducruet AF (2015) Administration of four-factor prothrombin complex concentrate as an antidote for intracranial bleeding in patients taking direct factor Xa inhibitors. World Neurosurg 84(6):1956\u20131961. \n                    https:\/\/doi.org\/10.1016\/j.wneu.2015.08.042","journal-title":"World Neurosurg"},{"issue":"5","key":"1846_CR6","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1055\/s-0038-1636541","volume":"118","author":"S Schulman","year":"2018","unstructured":"Schulman S, Gross PL, Ritchie B, Nahirniak S, Lin Y, Lieberman L, Carrier M, Crowther MA, Ghosh I, Lazo-Langner A, Zondag M, Study Investigators (2018) Prothrombin complex concentrate for major bleeding on factor Xa inhibitors: a prospective cohort study. Thromb Haemost 118(5):842\u2013851. \n                    https:\/\/doi.org\/10.1055\/s-0038-1636541","journal-title":"Thromb Haemost"},{"issue":"15","key":"1846_CR7","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1182\/blood-2017-05-782060","volume":"130","author":"A Majeed","year":"2017","unstructured":"Majeed A, Agren A, Holmstrom M, Bruzelius M, Chaireti R, Odeberg J, Hempel EL, Magnusson M, Frisk T, Schulman S (2017) Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood 130(15):1706\u20131712. \n                    https:\/\/doi.org\/10.1182\/blood-2017-05-782060","journal-title":"Blood"},{"issue":"22","key":"1846_CR8","doi-asserted-by":"publisher","first-page":"3257","DOI":"10.1182\/bloodadvances.2018024893","volume":"2","author":"DM Witt","year":"2018","unstructured":"Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J, Shehab N, Mock J, Myers T, Dentali F, Crowther MA, Agarwal A, Bhatt M, Khatib R, Riva JJ, Zhang Y, Guyatt G (2018) American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv 2(22):3257\u20133291. \n                    https:\/\/doi.org\/10.1182\/bloodadvances.2018024893","journal-title":"Blood Adv"},{"issue":"24","key":"1846_CR9","doi-asserted-by":"publisher","first-page":"3042","DOI":"10.1016\/j.jacc.2017.09.1085","volume":"70","author":"GF Tomaselli","year":"2017","unstructured":"Tomaselli GF, Mahaffey KW, Cuker A, Dobesh PP, Doherty JU, Eikelboom JW, Florido R, Hucker W, Mehran R, Messe SR, Pollack CV Jr, Rodriguez F, Sarode R, Siegal D, Wiggins BS (2017) 2017 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College Of Cardiology task force on expert consensus decision pathways. J Am Coll Cardiol 70(24):3042\u20133067. \n                    https:\/\/doi.org\/10.1016\/j.jacc.2017.09.1085","journal-title":"J Am Coll Cardiol"},{"key":"1846_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-016-1265-x","author":"R Rossaint","year":"2016","unstructured":"Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, Neugebauer EA, Ozier Y, Riddez L, Schultz A, Vincent JL, Spahn DR (2016) The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care. \n                    https:\/\/doi.org\/10.1186\/s13054-016-1265-x","journal-title":"Crit Care"},{"issue":"5","key":"1846_CR11","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.chest.2018.07.040","volume":"154","author":"GYH Lip","year":"2018","unstructured":"Lip GYH, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, Lane DA, Ruff CT, Turakhia M, Werring D, Patel S, Moores L (2018) Antithrombotic therapy for atrial fibrillation: chest guideline and expert panel report. Chest 154(5):1121\u20131201. \n                    https:\/\/doi.org\/10.1016\/j.chest.2018.07.040","journal-title":"Chest"},{"issue":"11","key":"1846_CR12","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1161\/CIRCULATIONAHA.113.002283","volume":"128","author":"R Sarode","year":"2013","unstructured":"Sarode R, Milling TJ Jr, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN (2013) 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 128(11):1234\u20131243. \n                    https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.113.002283","journal-title":"Circulation"},{"key":"1846_CR13","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s40560-018-0303-y","volume":"6","author":"J Tao","year":"2018","unstructured":"Tao J, Bukanova EN, Akhtar S (2018) Safety of 4-factor prothrombin complex concentrate (4F-PCC) for emergent reversal of factor Xa inhibitors. J Intensive Care 6:34. \n                    https:\/\/doi.org\/10.1186\/s40560-018-0303-y","journal-title":"J Intensive Care"},{"issue":"2","key":"1846_CR14","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1182\/bloodadvances.2018024133","volume":"3","author":"S Piran","year":"2019","unstructured":"Piran S, Khatib R, Schulman S, Majeed A, Holbrook A, Witt DM, Wiercioch W, Schunemann HJ, Nieuwlaat R (2019) Management of direct factor Xa inhibitor-related major bleeding with prothrombin complex concentrate: a meta-analysis. Blood Adv 3(2):158\u2013167. \n                    https:\/\/doi.org\/10.1182\/bloodadvances.2018024133","journal-title":"Blood Adv"},{"issue":"1","key":"1846_CR15","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1111\/jth.13148","volume":"14","author":"N Khorsand","year":"2016","unstructured":"Khorsand N, Majeed A, Sarode R, Beyer-Westendorf J, Schulman S, Meijer K, Subcommittee on Control of Anticoagulation (2016) Assessment of effectiveness of major bleeding management: proposed definitions for effective hemostasis: communication from the SSC of the ISTH. J Thromb Haemost 14(1):211\u2013214. \n                    https:\/\/doi.org\/10.1111\/jth.13148","journal-title":"J Thromb Haemost"},{"key":"1846_CR16","doi-asserted-by":"publisher","DOI":"10.1177\/0885066618800657","author":"TA Allison","year":"2018","unstructured":"Allison TA, Lin PJ, Gass JA, Chong K, Prater SJ, Escobar MA, Hartman HD (2018) Evaluation of the use of low-dose 4-factor prothrombin complex concentrate in the reversal of direct oral anticoagulants in bleeding patients. J Intensive Care Med. \n                    https:\/\/doi.org\/10.1177\/0885066618800657","journal-title":"J Intensive Care Med"},{"key":"1846_CR17","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.jcrc.2018.08.031","volume":"48","author":"M Santibanez","year":"2018","unstructured":"Santibanez M, Lesch CA, Lin L, Berger K (2018) Tolerability and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) for warfarin and non-warfarin reversals. J Crit Care 48:183\u2013190. \n                    https:\/\/doi.org\/10.1016\/j.jcrc.2018.08.031","journal-title":"J Crit Care"},{"key":"1846_CR18","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-018-1977-9","author":"M Sheikh-Taha","year":"2018","unstructured":"Sheikh-Taha M (2018) Treatment of apixaban- and rivaroxaban-associated major bleeding using 4-factor prothrombin complex concentrate. Intern Emerg Med. \n                    https:\/\/doi.org\/10.1007\/s11739-018-1977-9","journal-title":"Intern Emerg Med"},{"issue":"4","key":"1846_CR19","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/j.1538-7836.2005.01204.x","volume":"3","author":"S Schulman","year":"2005","unstructured":"Schulman S, Kearon C, The Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3(4):692\u2013694. \n                    https:\/\/doi.org\/10.1111\/j.1538-7836.2005.01204.x","journal-title":"J Thromb Haemost"}],"container-title":["Journal of Thrombosis and Thrombolysis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11239-019-01846-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11239-019-01846-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11239-019-01846-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T23:41:19Z","timestamp":1585698079000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11239-019-01846-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,2]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["1846"],"URL":"https:\/\/doi.org\/10.1007\/s11239-019-01846-5","relation":{},"ISSN":["0929-5305","1573-742X"],"issn-type":[{"value":"0929-5305","type":"print"},{"value":"1573-742X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,2]]},"assertion":[{"value":"2 April 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"This manuscript has been read and approved for submission by all authors. There was no financial support provided for this manuscript. The authors declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This study was approved by the institutional review board. All procedures performed involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"A waiver of informed consent was approved by the institutional review board due to the retrospective nature of the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}