Familial idiopathic osteonecrosis mediated by familial hypofibrinolysis with high levels of plasminogen activator inhibitor.

Familial hypofibrinolysis with 3 generation, autosomal dominant, very high levels of plasminogen activator inhibitor activity (PAI-Fx) and antigen (PAI-Ag) was etiologically associated with bilateral idiopathic osteonecrosis in 2 brothers. They, their mother, 2 brothers, sister, and all 4 of her children (none of whom had yet developed osteonecrosis), all had very high PAI and could not elevate tissue plasminogen activator after 10 minutes of venous occlusion at 100 mmHg. Familial high PAI levels with concurrent hypofibrinolysis co-segregated with familial combined hyperlipidemia, both being independent risk factors for premature coronary heart disease. If thrombi block venous drainage in the femur, familial hypofibrinolysis mediated by familial high PAI with inability to lyse thrombi would contribute to venous hypertension of bone, bone anoxia, and bone death characteristic of osteonecrosis.