{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:38:42Z","timestamp":1792654722856,"version":"4.5.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Type 1 plasminogen deficiency (PLGD\u20101), or hypoplasminogenaemia, is an ultra\u2010rare autosomal\u2010recessive disorder characterised by fibrin\u2010rich lesions on mucous membranes, often leading to serious complications if left untreated. Prior treatments have shown limited and inconsistent success, but IV PLG concentrate (Ryplazim) offers a targeted therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study investigated the long\u2010term safety and efficacy of IV PLG concentrate treatment for PLGD\u20101 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A long\u2010term study (NCT03642691) followed 12 participants who had previously been included in pivotal or expanded access trials of IV PLG concentrate. Participants received 6.6\u00a0mg\/kg IV PLG concentrate infusions, with dosing frequency adjusted based on clinical response and plasminogen levels. Safety assessments and plasminogen level measurements were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The median treatment duration during this long\u2010term follow\u2010up study was 41 months (range: 25\u201342 months). The median total exposure for participants in this study throughout the clinical development was 68 months (range: 28\u201371 months). No new or recurring ligneous lesions occurred when participants adhered to the prescribed regimen. Temporary disruptions in the drug supply led to some lesion recurrences, which resolved upon resuming the prescribed dosing frequency. A total of 2165 infusions were administered in this study, and most adverse events were mild. No anti\u2010plasminogen antibodies or treatment\u2010related fatalities occurred.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Long\u2010term treatment with IV PLG concentrate is safe and effective for PLGD\u20101, demonstrating the potential for tailored dosing regimens. This study highlights the importance of individualised treatment and provides valuable insights into managing this ultra\u2010rare disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.70019","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T05:37:18Z","timestamp":1742276238000},"page":"477-484","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Safety and Efficacy of Long\u2010Term Treatment of Type 1 Plasminogen Deficient Patients With Intravenous Plasminogen Replacement Therapy"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2821-7159","authenticated-orcid":false,"given":"Amy D.","family":"Shapiro","sequence":"first","affiliation":[{"name":"Indiana Hemophilia and Thrombosis Center  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"McDaniel","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Decker","sequence":"additional","affiliation":[{"name":"Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6301-0812","authenticated-orcid":false,"given":"Charles","family":"Nakar","sequence":"additional","affiliation":[{"name":"Indiana Hemophilia and Thrombosis Center  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4341-2721","authenticated-orcid":false,"given":"Jeremy","family":"Lorber","sequence":"additional","affiliation":[{"name":"Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Thukral","sequence":"additional","affiliation":[{"name":"Indiana Hemophilia and Thrombosis Center  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Parker","sequence":"additional","affiliation":[{"name":"Consultant to Kedrion Biopharma  Fort Lee New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6109-2953","authenticated-orcid":false,"given":"Karen","family":"Thibaudeau","sequence":"additional","affiliation":[{"name":"Global Medical Affairs, Kedrion S.p.A  Laval Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(03)00056-0"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02776.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008951"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20191865"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01825.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1953.00920020166004"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(14)72619-4"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-137690"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.10.3457.410k03_3457_3466"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199812033392305"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1999.tb01527.x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-996099"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-022-02329-7"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH10-04-0216"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(87)33341-X"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5876(02)00365-8"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-137538"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-837657"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-017350"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-137177"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13418"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26779"},{"key":"e_1_2_11_24_1","unstructured":"U.S. Food & Drug Administration.RYPLAZIM.2022 https:\/\/www.fda.gov\/vaccines\u2010blood\u2010biologics\/ryplazim."},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14849"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-806729"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.241158"},{"key":"e_1_2_11_28_1","volume-title":"Safety and Efficacy of Long\u2010Term Treatment of Type 1 Plasminogen Deficiency Patients With Intravenous Plasminogen Replacement Therapy","author":"Shapiro A. D.","year":"2024"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70019","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.70019","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:52:48Z","timestamp":1792651968000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.70019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/hae.70019"],"URL":"https:\/\/doi.org\/10.1111\/hae.70019","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]},"assertion":[{"value":"2024-11-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}