Coagulation Abnormalities in Legg-Calvé-Perthes Disease

Vosmaer, A.; Pereira, R. Rodrigues; Koenderman, J. S.; Rosendaal, F. R.; Cannegieter, S. C.
January 2010
Journal of Bone & Joint Surgery, American Volume;Jan2010, Vol. 92-A Issue 1, p121
Academic Journal
Background: Legg-Calvé-Perthes disease is a pediatric disorder characterized by osteonecrosis of the proximal femoral epiphysis. The etiology probably involves successive vascular occlusions, in which hypercoagulable disorders may play a role. We evaluated the etiologic role of thrombophilia in Legg-Calvé-Perthes disease in a pediatric population. Methods: One hundred and sixty-nine consecutive patients who had been diagnosed with Legg-Calvé-Perthes disease at two centers in Rotterdam, the Netherlands, when they were between 1.5 and 13.5 years of age were identified between 2000 and 2003. The study also included two control groups: 474 subjects (16.3 to 73.1 years of age) from a population-based case-control study on the etiology of venous thrombosis as well as thirty-eight children (1.8 to 18.8 years of age) who were freated for asthma at one of the centers. We determined levels of protein C, protein S, factor VIII, and fibrinogen and tested for the factor V Leiden and prothrombin G20210A mutations. We calculated age and sex-adjusted odds ratios as measures of the relative risk of the development of Legg-Calvé-Perthes disease. Results: The incidence of Legg-Calvé-Perthes disease was increased in the presence of the factor V Leiden mutation (odds ratio, 3.3; 95% confidence interval, 1.6 to 6.7), in the presence of the prothrombin G20210A mutation (odds ratio, 2.6; 95% confidence interval, 1.0 to 6.3), in association with elevated levels of factor VIII (>150 IU/dL) (odds ratio, 7.5; 95% confidence interval, 2.2 to 25.2), and in association with protein S deficiency (<67 U/dL) (odds ratio, 2.8; 95% confidence interval, 0.7 to 10.8). Neither high levels of fibrinogen (>4.0 g/L) nor protein C deficiency (≤55 U/dL) had an apparent effect on the risk of Legg-Calvé-Perthes disease. (Odds ratios were adjusted for age and sex.) Overall, males had a 2.4 times higher risk of Legg-Calvé-Perthes disease developingthan did females. The effect of the factor V Leiden mutation, high levels of fibrinogen, and increasing levels of factor VIII was stronger in males than in females. The risk of Legg-Calvé-Perthes disease increased with an increasing number of coagulation abnormalities in males but not in females. Conclusions: There appears to be a thrombotic component in the etiology of Legg-Calvé-Perthes disease. Clinical Relevance: The findings of this study contribute to the understanding of the etiology of Legg-Calvé-Perthes disease and may thus have implications for its prevention or treatment.


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