{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T21:12:56Z","timestamp":1769202776152,"version":"3.49.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T00:00:00Z","timestamp":1533168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008087","name":"Suomen Anestesiologiyhdistys","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008087","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007788","name":"Blood Disease Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007788","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Lysinuric protein intolerance (LPI), a rare autosomal recessive transport disorder of cationic amino acids lysine, arginine and ornithine, affects intestines, lungs, liver and kidneys. LPI patients may display potentially life\u2010threatening bleeding events, which are poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To characterize alterations in haemostatic and fibrinolytic variables associated with LPI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled 15 adult patients (8 female) and assessed the clinical ISTH\/SSC\u2010BAT bleeding score (BS). A variety of metabolic and coagulation assays, including fibrin generation test derivatives, clotting time (CT) and clot lysis time (CLT), thromboelastometry (ROTEM), and PFA\u2010100 and Calibrated Automated Thrombogram (CAT), were used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients had mild\u2010to\u2010moderate renal insufficiency, and moderate bleeding tendency (BS 4) without spontaneous bleeds. Mild anaemia and thrombocytopenia occurred. Traditional clotting times were normal, but in contrast, CT in fibrin generation test, and especially ROTEM FIBTEM was abnormal. The patients showed impaired primary haemostasis in PFA, irrespective of normal von Willebrand factor activity, but together with lowered fibrinogen and FXIII. Thrombin generation (TG) was reduced in vitro, according to CAT\u2010derived endogenous thrombin potential, but in vivo TG was enhanced in the form of circulating prothrombin fragment 1 and 2 values. Very high D\u2010dimer and plasmin\u2010\u03b12\u2010antiplasmin (PAP) complex levels coincided with shortened CLT in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Defective primary haemostasis, coagulopathy, fibrin abnormality (FIBTEM, CT and CLT), low TG in vitro and clearly augmented fibrinolysis (PAP and D\u2010dimer) in vivo were all detected in LPI. Altered fibrin generation and hyperfibrinolysis were associated with the metabolic and renal defect, suggesting a pathogenetic link in LPI.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13543","type":"journal-article","created":{"date-parts":[[2018,8,4]],"date-time":"2018-08-04T22:28:55Z","timestamp":1533421735000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Abnormal coagulation and enhanced fibrinolysis due to lysinuric protein intolerance associates with bleeds and renal impairment"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2259-3244","authenticated-orcid":false,"given":"H. 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F.","family":"Kopatz","sequence":"additional","affiliation":[{"name":"Department of Experimental Vascular Medicine Academical Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Zuurveld","sequence":"additional","affiliation":[{"name":"Department of Plasma Proteins Sanquin Research  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. C. M.","family":"Meijers","sequence":"additional","affiliation":[{"name":"Department of Experimental Vascular Medicine Academical Medical Center University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Plasma Proteins Sanquin Research  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. J. M.","family":"Brinkman","sequence":"additional","affiliation":[{"name":"Department of Plasma Proteins Sanquin Research  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Lassila","sequence":"additional","affiliation":[{"name":"Coagulation Disorders Unit Department of Hematology Comprehensive Cancer Center University of Helsinki and Helsinki University Hospital  Helsinki Finland"},{"name":"Laboratory Services HUSLAB University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(65)92446-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1971.tb00280.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)91679-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1097\/MPG.0b013e318227b02d","article-title":"Early\u2010onset hepatic fibrosis in lysinuric protein intolerance","volume":"53","author":"Shinawi M","year":"2011","journal-title":"J Pediatr Gastroenterol 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