The role of protein C, protein S, and resistance to activated protein C inLegg-Perthes disease

Objectives. 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 t heory, we conducted a case-control study among 57 patients with Legg-Perthe s 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. Study Design. Participants were placed into 1 of 3 mutually exclusive categ ories based on the control distribution: 1) normal, defined as either above or within 1 standard deviation below the expected mean; 2) low normal, def ined 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 an alyzed to determine the presence of a point mutation in the factor V gene t hat causes APC-R. Results. We observed a statistically significant increased risk of Legg-Per thes disease with decreasing levels of protein C and a nearly significant i ncreased 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 plasm a test was similar for cases and controls. Nine cases and 1 control had 2 l ow 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 coagu lation system leading to a thrombophilic state play a role in Legg-Perthes disease; however, larger studies are needed before definitive recommendatio ns for coagulation testing can be made.