In eight patients with
Legg-Perthes disease, we assessed the etiologic roles of
thrombophilia caused by
protein C and
protein S deficiency and hypofibrinolysis mediated by low levels of
tissue plasminogen activator activity. We speculated that
thrombosis or hypofibrinolysis were common causes of
Legg-Perthes disease. Three of the eight patients had
protein C deficiency; they came from kindreds with previously undiagnosed
protein C deficiency. In one of these three kindreds there were six
protein C-deficient family members (beyond the proband child), four of whom had thrombotic events as adults. One of the eight patients had
protein S deficiency, as did his brother who had sustained mesenteric vein
thrombosis at age 43. One of the eight patients who had normal
proteins C, S, and
antithrombin III had hypofibrinolysis, failing to elevate
tissue plasminogen activator activity after 10 min of venous occlusion at 100 mm Hg.
Plasminogen activator inhibitor, alpha 2-antiplasmin, and
fibrinogen values were normal in all eight patients. Beyond their
Legg-Perthes disease, none of the eight patients had evidence for
venous thrombosis. Of the eight patients, four had
thrombophilia and one had hypofibrinolysis, disorders that we believe contributed to thrombotic venous occlusion of the femur with subsequent venous
hypertension and bone death that characterize
Legg-Perthes disease.