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Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg-Perthes disease
C J Glueck1, A Crawford, D Roy
1Cholesterol Center, Jewish Hospital, Cincinnati, Ohio 45229, USA.
Insights
Children with Legg-Perthes disease often have coagulation abnormalities, including protein C or S deficiency and high lipoprotein(a) levels. These thrombophilic conditions are frequently inherited and linked to early disease onset.
Area of Science:
- Pediatrics
- Hematology
- Genetics
Background:
- Legg-Perthes disease is a childhood hip condition.
- Coagulation abnormalities are increasingly recognized in pediatric diseases.
- Genetic predispositions can influence disease development.
Purpose of the Study:
- To investigate the prevalence of coagulation abnormalities in children with Legg-Perthes disease.
- To identify specific thrombophilic and hypofibrinolytic factors associated with the condition.
- To explore the familial inheritance patterns of these abnormalities.
Main Methods:
- Coagulation screening was performed on 44 children diagnosed with Legg-Perthes disease.
- Assays included tests for protein C, protein S, lipoprotein(a), and fibrinolytic activity.
- Family history and genetic analysis were conducted for probands with identified abnormalities.
Main Results:
- 75% of children with Legg-Perthes disease exhibited coagulation abnormalities.
- Thrombophilia (protein C or S deficiency) was found in 23 children.
- High lipoprotein(a) levels and hypofibrinolysis were observed in 7 and 3 children, respectively.
- Familial inheritance was confirmed for protein C deficiency, protein S deficiency, high lipoprotein(a), and hypofibrinolysis.
- Familial protein C deficiency was associated with earlier onset of Legg-Perthes disease (p=0.01).
Conclusions:
- Coagulation abnormalities, particularly thrombophilia and hypofibrinolysis, are common in children with Legg-Perthes disease.
- These disorders often have a familial component and may contribute to disease pathogenesis.
- Screening for coagulation factors and family history is crucial in managing Legg-Perthes disease.
Abstract:
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.