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Updated: Aug 13, 2026
Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
Published on: September 9, 2012
Legg-Calve-Perthes disease and thrombophilia
Vinod V Balasa1, Ralph A Gruppo, Charles J Glueck
1Hemophilia and Thrombosis Center, Hematology/Oncology Division, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. vinod.balasa@cchmc.org
Insights
Children with Legg-Calve-Perthes disease show higher rates of factor-V Leiden mutation and anticardiolipin antibodies. These thrombophilic risk factors may contribute to the development of Legg-Calve-Perthes disease.
Area of Science:
- Pediatric Orthopedics
- Hematology
- Genetics
Background:
- Thrombophilia is a suspected factor in Legg-Calve-Perthes disease (LCPD).
- This study investigated the link between coagulation abnormalities and LCPD in children.
Purpose of the Study:
- To prospectively examine the association between LCPD and specific thrombophilic risk factors.
- To compare the prevalence of genetic mutations and antibody levels in LCPD patients versus healthy controls.
Main Methods:
- A prospective case-control study involving 72 children with LCPD and 197 healthy controls.
- Genetic assays for factor-V Leiden, prothrombin G20210A, MTHFR C677T, and PAI-1 4G/5G.
- Measurement of anticardiolipin antibodies (IgG/IgM), homocysteine, protein C, protein S, and PAI-1 levels.
Main Results:
- Factor-V Leiden mutation was significantly more common in LCPD patients (p=0.017), with an odds ratio of 3.39.
- Elevated anticardiolipin antibodies (IgG/IgM) were also more prevalent in LCPD patients (p=0.002), odds ratio 3.29.
- A combined analysis showed a significant association between LCPD and abnormalities in factor V, anticardiolipin IgG, or anticardiolipin IgM (p=0.0003).
Conclusions:
- Factor-V Leiden mutation and anticardiolipin antibodies are identified as thrombophilic risk factors associated with Legg-Calve-Perthes disease.
- The observed association suggests a potential causal link between these thrombophilic factors and LCPD development.
Background:
Thrombophilia has previously been identified as a potential etiologic factor in Legg-Calve-Perthes disease. We prospectively studied the association between Legg-Calve-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-Calve-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-Calve-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-Calve-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-Calve-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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