{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:07:38Z","timestamp":1789542458814,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":257,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatrics International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Severe congenital protein C deficiency (\n SCPCD<\/jats:styled-content>\n ) is a rare disorder associated with life\u2010threatening thrombotic complications. Protein C concentrate is recommended for both acute and long\u2010term management of\n SCPCD<\/jats:styled-content>\n . However, no efficacy and safety data in Japanese patients have been reported.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this extension phase of an open\u2010label, phase 1\/2 clinical trial (\n ClinicalTrials.gov<\/jats:ext-link>\n :\n NCT04984889<\/jats:styled-content>\n ), Japanese patients with\n SCPCD<\/jats:styled-content>\n could receive intravenous protein C concentrate for on\u2010demand treatment, short\u2010term prophylaxis, or long\u2010term prophylaxis. Efficacy of on\u2010demand treatment was assessed using a predefined efficacy evaluation scale. For prophylaxis, efficacy was assessed based on the occurrence of purpura fulminans and thromboembolic complications during prophylaxis treatment. Safety was evaluated by recording adverse events (\n AEs<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n All five patients who completed the pharmacokinetics phase of the study participated in this extension phase (mean [\n SD<\/jats:styled-content>\n ] age: 15.2 [8.9] years). At data cutoff, four patients had received eight on\u2010demand treatments of protein C concentrate for purpura fulminans; all were rated as effective. Protein C concentrate was administered for short\u2010term prophylaxis in one patient undergoing tooth extraction, with no thromboembolic complications observed. Six\n AEs<\/jats:styled-content>\n were reported in three patients who received on\u2010demand treatment; none were treatment\u2010related. No\n AEs<\/jats:styled-content>\n were observed during short\u2010term prophylaxis. There were no deaths or\n AEs<\/jats:styled-content>\n leading to treatment discontinuation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Protein C concentrate was effective for on\u2010demand treatment and short\u2010term prophylaxis, and had an acceptable safety profile in this study population. These results support the use of protein C concentrate in the clinical management of patients with\n SCPCD<\/jats:styled-content>\n in Japan.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov<\/jats:ext-link>\n registration number: NCT04984889.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ped.70506","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:57:26Z","timestamp":1789541846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Human Protein C Concentrate in Japanese Patients With Severe Congenital Protein C Deficiency"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0476-4978","authenticated-orcid":false,"given":"Katsuyoshi","family":"Koh","sequence":"first","affiliation":[{"name":"Department of Hematology\/Oncology Saitama Children's Medical Center Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2415-2194","authenticated-orcid":false,"given":"Keiji","family":"Nogami","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nara Medical University Kashihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3264-894X","authenticated-orcid":false,"given":"Harumi","family":"Kakuda","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Chiba Children's Hospital Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Okimoto","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Chiba Children's Hospital Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7056-1020","authenticated-orcid":false,"given":"Moeko","family":"Hino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2692-7210","authenticated-orcid":false,"given":"Chihiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Plasma\u2010Derived Therapies Strategy Unit, PDT R&D Takeda Pharmaceutical Company Limited Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souhei","family":"Terashio","sequence":"additional","affiliation":[{"name":"Plasma\u2010Derived Therapies Strategy Unit, PDT R&D Takeda Pharmaceutical Company Limited Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Ueda","sequence":"additional","affiliation":[{"name":"Japan Medical Office Takeda Pharmaceutical Company Limited Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2426-7792","authenticated-orcid":false,"given":"Shouichi","family":"Ohga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1111\/j.1365-2516.2008.01838.x","article-title":"Protein C Deficiency","volume":"14","author":"Goldenberg N. A.","year":"2008","journal-title":"Haemophilia"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1136\/adc.2010.199919","article-title":"Purpura Fulminans: Recognition, Diagnosis and Management","volume":"96","author":"Chalmers E.","year":"2011","journal-title":"Archives of Disease in Childhood"},{"key":"e_1_2_11_4_1","first-page":"51","article-title":"Use of Human Protein C Concentrates in the Treatment of Patients With Severe Congenital Protein C Deficiency","volume":"4","author":"Kroiss S.","year":"2010","journal-title":"Biologics"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1111\/jth.15732","article-title":"Diagnosis and Management of Severe Congenital Protein C Deficiency (SCPCD): Communication From the SSC of the ISTH","volume":"20","author":"Minford A.","year":"2022","journal-title":"Journal of Thrombosis and Haemostasis"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1160\/TH15-10-0786","article-title":"Efficacy and Safety of Protein C Concentrate to Treat Purpura Fulminans and Thromboembolic Events in Severe Congenital Protein C Deficiency","volume":"116","author":"Manco\u2010Johnson M. J.","year":"2016","journal-title":"Thrombosis and Haemostasis"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.jpeds.2021.07.001","article-title":"Clinical Impact of Heritable Thrombophilia on Neonatal\u2010Onset Thromboembolism: A Nationwide Study in Japan","volume":"238","author":"Egami N.","year":"2021","journal-title":"Journal of Pediatrics"},{"key":"e_1_2_11_8_1","unstructured":"US Food & Drug Administration \u201cCEPROTIN Prescribing Information \u201d(2007)."},{"key":"e_1_2_11_9_1","unstructured":"European Medicines Agency \u201cCEPROTIN Summary of Product Characteristics \u201d(2007)."},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.tru.2024.100159","article-title":"Real\u2010World Treatment of Patients With Severe Congenital Protein C Deficiency With Protein\u00a0C Concentrate: A Physician Survey","volume":"14","author":"Wang M.","year":"2024","journal-title":"Thrombosis Update"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"e165","DOI":"10.1111\/1346-8138.14194","article-title":"Purpura Fulminans in Congenital Protein C Deficiency Successfully Treated With Fresh Frozen Plasma and Thrombomodulin","volume":"45","author":"Hayami T.","year":"2018","journal-title":"Journal of Dermatology"},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.27686","article-title":"Management of Severe Congenital Protein C Deficiency With a Direct Oral Anticoagulant, Edoxaban: A Case Report","volume":"66","author":"Watanabe K.","year":"2019","journal-title":"Pediatric Blood & Cancer"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/hae.12097","article-title":"Paediatric Presentation and Outcome of Congenital Protein C Deficiency in Japan","volume":"19","author":"Ohga S.","year":"2013","journal-title":"Haemophilia"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1056\/NEJM199111283252207","article-title":"Treatment of Homozygous Protein C Deficiency and Neonatal Purpura Fulminans With a Purified Protein C Concentrate","volume":"325","author":"Dreyfus M.","year":"1991","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/ajh.2830410106","article-title":"Protein C Survival During Replacement Therapy in Homozygous Protein C Deficiency","volume":"41","author":"Marlar R. A.","year":"1992","journal-title":"American Journal of Hematology"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1007\/s12185-019-02645-7","article-title":"Hemostatic Assessment of Combined Anticoagulant Therapy Using Warfarin and Prothrombin Complex Concentrates in a Case of Severe Protein C Deficiency","volume":"109","author":"Ogiwara K.","year":"2019","journal-title":"International Journal of Hematology"},{"key":"e_1_2_11_17_1","first-page":"405","article-title":"Pharmacokinetics of Protein C Concentrate in Ethnically Diverse Protein C\u2010Deficient Patients","volume":"9","author":"Li Z.","year":"2025","journal-title":"Research and Practice in Thrombosis and Haemostasis"},{"key":"e_1_2_11_18_1","article-title":"A Phase 1\/2, Open\u2010Label, Single\u2010Dose, Multicenter Study to Evaluate the Pharmacokinetics and Safety of Human Plasma\u2010Derived Protein C Concentrate in Japanese Patients with Severe Congenital Protein C Deficiency (SCPCD)","volume":"17","author":"Koh K.","year":"2026","journal-title":"Journal of Blood Medicine"}],"container-title":["Pediatrics International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ped.70506","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ped.70506","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ped.70506","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:57:32Z","timestamp":1789541852000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ped.70506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/ped.70506"],"URL":"https:\/\/doi.org\/10.1111\/ped.70506","archive":["Portico"],"relation":{},"ISSN":["1328-8067","1442-200X"],"issn-type":[{"value":"1328-8067","type":"print"},{"value":"1442-200X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-06-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70506"}}