Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg-Perthes disease.
Thirty-three (75 per cent) of forty-four unselected children who had Legg-Perthes disease were found to have coagulation abnormalities. Twenty-three children had thrombophilia (a deficiency in antithrombotic factor C or S, with an increased tendency toward thrombosis); nineteen of the twenty-three children had protein-C deficiency and four had protein-S deficiency. Seven children had a high level (0.25 gram per liter or more) of lipoprotein(a), a thrombogenic, atherogenic lipoprotein associated with osteonecrosis in adults. Three children had hypofibrinolysis (a reduced ability to lyse clots). The mean age of the children when the Legg-Perthes disease was first diagnosed was 5.8 +/- 2.7 years, and the mean age at the time of the present study was 10.1 +/- 4.4 years. At least one of the first-degree relatives of eleven of the nineteen probands who had a low protein-C level had a low protein-C level as well; all of these low levels represented previously undiagnosed familial protein-C deficiency. The eleven probands who had familial protein-C deficiency were more likely to have early onset of Legg-Perthes disease (at or before the age of five years) than the eleven children who had normal levels of protein C, protein S, and lipoprotein(a) as well as normal fibrinolytic activity (chi-square = 6.6; p = 0.01). At least one first-degree relative of one of the four probands who had a low protein-S level had a low protein-S level and previously undiagnosed familial protein-S deficiency. At least one first-degree relative of six of the seven probands who had a high level of lipoprotein(a) had a familial high level of lipoprotein(a). Six of the seven children who had a high level of lipoprotein(a) also had a low level of stimulated tissue-plasminogen activator activity, the major initiator of fibrinolysis. At least one first-degree relative of one of the three probands who had normal levels of protein C, protein S, and lipoprotein(a) but low stimulated tissue-plasminogen activator activity also had low stimulated tissue-plasminogen activator activity (familial hypofibrinolysis). Legg-Perthes disease, thrombophlebitis, premature myocardial infarction, and stroke, which are ramifications of the familial thrombophilic-hypofibrinolytic disorders, were common in the first and second-degree relatives of the thirty-three children with Legg-Perthes disease who also had thrombophilic-hypofibrinolytic disorders.
Glueck
C J
CJ
Cholesterol Center, Jewish Hospital, Cincinnati, Ohio 45229, USA.
Crawford
A
A
Roy
D
D
Freiberg
R
R
Glueck
H
H
Stroop
D
D
D000293:Adolescent; D000328:Adult; D001778:Blood Coagulation Disorders / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000235:genetics; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D005260:Female; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D007873:Legg-Calve-Perthes Disease / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics; D010375:Pedigree; D020151:Protein C Deficiency; D018455:Protein S Deficiency / Q000150:complications / Q000235:genetics; D013924:Thrombophlebitis / Q000235:genetics
D017270:Lipoprotein(a)