{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:02:02Z","timestamp":1787162522809,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,7,11]],"date-time":"2006-07-11T00:00:00Z","timestamp":1152576000000},"content-version":"vor","delay-in-days":4543,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[1994,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In 30 patients with osteonecrosis of the hip (12 idiopathic, 18 secondary), we assessed the role of hypofibrinolysis mediated by high levels of piasminogen activator inhibitor (PAI). We evaluated hypofibrinoiysis as a common, potentially reversible, pathophysiologic cause of idiopathic osteonecrosis. In all 18 patients with secondary osteonecrosis. PAI was normal, as was the ability to activate fibrinoiysis. Nine of the 12 patients with idiopathic osteonecrosis had exceptionally high PA1 levels and could not normally elevate tissue piasminogen activator (tPA\u2010Fx), the major stimulator of fibrinolysis, after 10 min of venous occlusion at 100 mm Hg. The group of 12 patients with idiopathic osteonecrosis, compared to the 18 with secondary osteonecrosis, had low mean stimulated tPA\u2010Fx (1.92 vs. 7.6 IU\/mi,\n                    <jats:italic>P<\/jats:italic>\n                    .001) and very high stimulated PAI\u2010Fx (70 vs. 7.6 U\/mi,\n                    <jats:italic>P<\/jats:italic>\n                    \u2a7d .01). Three of the 12 patients with idiopathic osteonecrosis had both normal PAI and normal Stimulated tPA\u2010Fx. These three patients and 14 of the 18 with secondary osteonecrosis had high lipoprotein (a) [Lp(a)] (&gt;20 mg\/dI). Mean Lp(a) was much higher (60 mg\/dI) in the patients with secondary osteonecrosis than Lp(a) (16 mg\/dI,\n                    <jats:italic>P<\/jats:italic>\n                    \u2a7d .001) in the 12 patients with idiopathic osteonecrosis. These findings suggest that hypofibrinoiysis mediated by high PAI is a common cause of idiopathic osteonecrosis, whereas high Lp(a) may play an etiologic role in secondary osteonecrosis. Prospective studies of patients with high PA1 and\/or high Lp(a) should be carried out to assess further their apparently causal roles in osteonecrosis. \u00a9 1994 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ajh.2830450212","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T08:49:32Z","timestamp":1172047772000},"page":"156-166","source":"Crossref","is-referenced-by-count":106,"title":["Hypofibrinolysis: A common, major cause of osteonecrosis"],"prefix":"10.1002","volume":"45","author":[{"given":"Charles J.","family":"Glueck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Freiberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen J.","family":"Glueck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clyde","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Welch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trent","family":"Tracy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davis","family":"Stroop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Hamer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Sosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,11]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199205283262206"},{"key":"e_1_2_1_3_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/00003086-199204000-00006","article-title":"Intravascular coagulation and osteonecrosis","volume":"277","author":"Jones JP","year":"1992","journal-title":"Clin Orthop Rel Res"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00959552"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/00003086-198909000-00028","article-title":"A microangiographic study of idiopathic osteonecrosis of the femoral head","volume":"246","author":"Atsumi T","year":"1989","journal-title":"Clin Orthop"},{"key":"e_1_2_1_6_2","first-page":"1545","volume-title":"Arthritis and Allied Conditions: A Textbook of Rheumatology","author":"Jones JP","year":"1989"},{"key":"e_1_2_1_7_2","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1055\/s-0038-1651633","article-title":"Familial high plasminogen activator inhibitor with hypofibrinolysis, a new pathophysiologic cause of osteonecrosis?","volume":"69","author":"Glueck CJ","year":"1993","journal-title":"Thromb Haemostas"},{"key":"e_1_2_1_8_2","first-page":"309A","article-title":"High plasmin\u2010ogen activator inhibitor activity and antigen and hypofibrinolysis, a cause of osteonecrosis?","volume":"41","author":"Glueck CJ","year":"1993","journal-title":"Clin Res"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0954-6820.1961.tb07838.x"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(93)90042-M"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1987.tb02261.x"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0268-9499(92)90066-Q"},{"key":"e_1_2_1_13_2","first-page":"273","volume-title":"Clinical Aspects of Fibrinolysis and Thrombolysis","author":"Nilsson IM","year":"1983"},{"key":"e_1_2_1_14_2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1001\/archinte.1986.00360130226030","article-title":"Release of tissue plasminogen activator and its fast\u2010acting inhibitor in defective fibrinolysis","volume":"146","author":"Pizzo SV","year":"1986","journal-title":"Arch Intern Med"},{"key":"e_1_2_1_15_2","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1055\/s-0038-1646881","article-title":"Elevated plasminogen activator inhibitor (PAI), a cause of thrombophilia? 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