{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T18:30:34Z","timestamp":1780425034404,"version":"3.54.1"},"reference-count":25,"publisher":"American Academy of Pediatrics (AAP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,6,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives.<\/jats:title>\n                  <jats:p>It has been hypothesized that Legg-Perthes disease is caused by repeated vascular interruptions of the blood supply to the proximal femur, which are precipitated by coagulation system abnormalities. To test this theory, we conducted a case-control study among 57 patients with Legg-Perthes disease and an equal number of community controls. We measured protein C and protein S and resistance to activated protein C (APC-R) from plasma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study Design.<\/jats:title>\n                  <jats:p>Participants were placed into 1 of 3 mutually exclusive categories based on the control distribution: 1) normal, defined as either above or within 1 standard deviation below the expected mean; 2) low normal, defined as between 1 and 2 standard deviations below the expected mean; and 3) low, defined as &amp;gt;2 standard deviations below the expected mean. DNA was analyzed to determine the presence of a point mutation in the factor V gene that causes APC-R.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results.<\/jats:title>\n                  <jats:p>We observed a statistically significant increased risk of Legg-Perthes disease with decreasing levels of protein C and a nearly significant increased risk with decreasing levels of protein S. The factor V gene defect was present in 5 (9%) of 55 cases and 3 (5%) of 56 controls (odds ratio 1.8, 95% confidence interval: 0.4\u20137.7), but the mean level on the APC-R plasma test was similar for cases and controls. Nine cases and 1 control had 2 low normal or low test results (odds ratio 13.0, 95% confidence interval: 2.2\u201375).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions.<\/jats:title>\n                  <jats:p>Our results support the belief that abnormalities of the coagulation system leading to a thrombophilic state play a role in Legg-Perthes disease; however, larger studies are needed before definitive recommendations for coagulation testing can be made.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1542\/peds.107.6.1329","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:55:51Z","timestamp":1092441351000},"page":"1329-1334","source":"Crossref","is-referenced-by-count":47,"title":["The Role of Protein C, Protein S, and Resistance to  Activated Protein C in Legg-Perthes Disease"],"prefix":"10.1542","volume":"107","author":[{"given":"John","family":"Eldridge","sequence":"first","affiliation":[{"name":"From the Department of Orthopedics and Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Dilley","sequence":"additional","affiliation":[{"name":"Hematologic Diseases Branch, Division of AIDS, STD, and Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harland","family":"Austin","sequence":"additional","affiliation":[{"name":"Hematologic Diseases Branch, Division of AIDS, STD, and Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, Georgia;"},{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhydine","family":"EL-Jamil","sequence":"additional","affiliation":[{"name":"Hematologic Diseases Branch, Division of AIDS, STD, and Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, Georgia;"},{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Wolstein","sequence":"additional","affiliation":[{"name":"Hematologic Diseases Branch, Division of AIDS, STD, and Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, Georgia;"},{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Doris","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Atlanta, Georgia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Craig","family":"Hooper","sequence":"additional","affiliation":[{"name":"Hematologic Diseases Branch, Division of AIDS, STD, and Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Meehan","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Atlanta, Georgia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Evatt","sequence":"additional","affiliation":[{"name":"Hematologic Diseases Branch, Division of AIDS, STD, and Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2001,6,1]]},"reference":[{"key":"2021121009525024500_B1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0268-0890(88)90027-8","article-title":"Perthes disease.","volume":"2","author":"Weinstein","year":"1988","journal-title":"Curr Orthop"},{"key":"2021121009525024500_B2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.2106\/00004623-197355020-00009","article-title":"Experimental stimulation of the blood supply to the capital epiphysis in the puppy.","volume":"55A","author":"Sanchis","year":"1973","journal-title":"J Bone Joint Surg"},{"key":"2021121009525024500_B3"},{"key":"2021121009525024500_B4","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1073\/pnas.90.3.1004","article-title":"Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a 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