Legg-Calve-Perthes disease and thrombophilia.
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.


METHODS
Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence.
Balasa
Vinod V
VV
Hemophilia and Thrombosis Center, Hematology/Oncology Division, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. vinod.balasa@cchmc.org
Gruppo
Ralph A
RA
Glueck
Charles J
CJ
Wang
Ping
P
Roy
Dennis R
DR
Wall
Eric J
EJ
Mehlman
Charles T
CT
Crawford
Alvin H
AH
D000293:Adolescent; D017153:Antibodies, Anticardiolipin / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007873:Legg-Calve-Perthes Disease / Q000097:blood / Q000209:etiology*; D008297:Male; D017354:Point Mutation; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications* / Q000175:diagnosis
D017153:Antibodies, Anticardiolipin; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C095381:factor V Leiden; D005165:Factor V