Procoagulants and osteonecrosis

Objective. To study the relationship between hypofibrinolysis, thrombophilia, and osteonecrosis. We evaluated the frequency of abnormal concentrations of 9 coagulation factors in patients diagnosed with osteonecrosis. Methods. Blood samples were drawn from 45 patients diagnosed with osteonecrosis. Etiologic associations included systemic lupus erythematosus (n = 9), inflammatory bowel disease (n = 1), corticosteroid therapy (n = 20), or history of heavy alcohol (n = 4) or tobacco (n = 3) use. No associated risk factors were identified in 5 patients; these individuals were labeled "idiopathic." The patient cohort was matched to a similarly studied cohort of 40 healthy individuals without documented osteonecrosis. The following factors were analyzed: plasminogen activator inhibitor (PAI-Fx), stimulated tissue plasminogen activator, lipoprotein (a), resistance to activated protein C, anticardiolipin antibodies (aCL IgG, IgM), protein C, protein S (free), and homocysteine. Results. Thirty-seven of the 45 patients (82.2%) with osteonecrosis were found to have at least one coagulopathy, versus 30% of controls (p < 0.0001). Twenty-one patients (46.7%) were identified with 2 or more abnormal test results versus 2.5% of controls (p < 0.0001). Patients were more likely than controls to have high levels of the hypofibrinolytic plasminogen activator inhibitor activity (42% vs 3%; p < 0.0001), and high anticardiolipin antibody IgG (34% vs 10%; p = 0.008). At least one coagulation factor abnormality was detected in all 5 idiopathic patients; elevated aCL IgG and PAI-Fx were evident in 4 patients. Conclusion. This study revealed a high incidence of thrombophilic and hypofibrinolytic coagulation abnormalities in patients with osteonecrosis. These findings have major implications for the diagnosis as well as the treatment of this disease. Since some of these abnormalities may be the result of autosomal dominant disorders, it may be possible to detect individuals at risk for development of this disease.