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 CME 4: October, November, December 2004
Pediatrics Test 6: Topics in Pediatric Orthopaedic Surgery
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The Journal of Bone and Joint Surgery (American). 2004;86:2642-2647
© 2004 The Journal of Bone and Joint Surgery, Inc.

Legg-Calvé-Perthes Disease and Thrombophilia

Vinod V. Balasa, MD, MBBS1, Ralph A. Gruppo, MD1, Charles J. Glueck, MD2, Ping Wang, PHD2, Dennis R. Roy, MD3, Eric J. Wall, MD1, Charles T. Mehlman, DO, MD1 and Alvin H. Crawford, MD1

1 Hemophilia and Thrombosis Center, Hematology/Oncology Division (V.V.B. and R.A.G.) and Department of Orthopedics (E.J.W., C.T.M., and A.H.C.), Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229. E-mail address for V.V. Balasa: vinod.balasa{at}cchmc.org
2 Cholesterol Center, Health Alliance of Greater Cincinnati, ABC Building, 3200 Burnet Avenue, Cincinnati, OH 45229
3 Shriner's Hospital for Children, 3101 S.W. Sam Jackson Park Road, Portland, OR 97239

Investigation performed at the Hemophilia and Thrombosis Center, Hematology/Oncology Division, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: Thrombophilia has previously been identified as a potential etiologic factor in Legg-Calvé-Perthes disease. We prospectively studied the association between Legg-Calvé-Perthes disease and coagulation abnormalities by comparing seventy-two children who had the disease with 197 healthy controls.

Methods: A nonselected, consecutive series of seventy-two patients with Legg-Calvé-Perthes disease (mean age [and standard deviation], 6.6 ± 2.6 years) was studied in their order of referral and compared with 197 healthy controls (mean age, 7.6 ± 5.1 years). Assays were done for factor-V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase C677T, and plasminogen activator inhibitor-1 4G/5G gene mutations. Levels of anticardiolipin antibodies immunoglobulin G and M (IgG and IgM), homocysteine, protein C, protein S, antithrombin III, and plasminogen activator inhibitor-1 were also measured.

Results: The factor-V Leiden mutation was more common in the patients (eight of seventy-two) than in the controls (seven of 197) (chi-square = 5.7, p = 0.017). After we controlled for the false-discovery rate, the case-control difference remained significant (p = 0.017). The odds ratio for the development of Legg-Calvé-Perthes disease in the presence of the factor-V Leiden mutation was 3.39 with a 95% confidence interval of 1.18 to 9.73. A high level of anticardiolipin antibodies (IgG and/or IgM) was found in nineteen of the seventy-two patients compared with twenty-two of the 197 controls (chi-square = 9.5, p = 0.002). After we controlled for the false-discovery rate, the case-control difference remained significant (p = 0.002). The odds ratio of patients with Legg-Calvé-Perthes disease having one or more abnormalities in factor V, anticardiolipin antibody IgG, or anticardiolipin antibody IgM as opposed to normal values for all three variables was 3.29 (95% confidence interval, 1.73 to 6.24; p = 0.0003).

Conclusions: Two thrombophilic risk factors, the factor-V Leiden mutation and anticardiolipin antibodies, are associated with Legg-Calvé-Perthes disease, an association that may reflect causality.

Level of Evidence: Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence.


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