The role of protein C, protein S, and resistance to activated protein C in Legg-Perthes disease.
OBJECTIVE
It has been hypothesized that Legg-Perthes disease is caused by repeated vascular interruptions of the blood supply to the proximal femur, which are precipitated by coagulation system abnormalities. To test this theory, we conducted a case-control study among 57 patients with Legg-Perthes disease and an equal number of community controls. We measured protein C and protein S and resistance to activated protein C (APC-R) from plasma.


METHODS
Participants were placed into 1 of 3 mutually exclusive categories based on the control distribution: 1) normal, defined as either above or within 1 standard deviation below the expected mean; 2) low normal, defined as between 1 and 2 standard deviations below the expected mean; and 3) low, defined as >2 standard deviations below the expected mean. DNA was analyzed to determine the presence of a point mutation in the factor V gene that causes APC-R.


RESULTS
We observed a statistically significant increased risk of Legg-Perthes disease with decreasing levels of protein C and a nearly significant increased risk with decreasing levels of protein S. The factor V gene defect was present in 5 (9%) of 55 cases and 3 (5%) of 56 controls (odds ratio 1.8, 95% confidence interval: 0.4-7.7), but the mean level on the APC-R plasma test was similar for cases and controls. Nine cases and 1 control had 2 low normal or low test results (odds ratio 13.0, 95% confidence interval: 2.2-75).


CONCLUSIONS
Our results support the belief that abnormalities of the coagulation system leading to a thrombophilic state play a role in Legg-Perthes disease; however, larger studies are needed before definitive recommendations for coagulation testing can be made.
Eldridge
J
J
Department of Orthopedics and Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Dilley
A
A
Austin
H
H
EL-Jamil
M
M
Wolstein
L
L
Doris
J
J
Hooper
W C
WC
Meehan
P L
PL
Evatt
B
B
D020016:Activated Protein C Resistance / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000235:genetics; D005260:Female; D006801:Humans; D007873:Legg-Calve-Perthes Disease / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D017354:Point Mutation / Q000235:genetics; D011486:Protein C / Q000032:analysis* / Q000502:physiology; D017293:Protein S / Q000032:analysis* / Q000502:physiology; D012307:Risk Factors
D011486:Protein C; D017293:Protein S; D005165:Factor V