Familial heterozygous protein s deficiency: A pathophysiologic cause of osteonecrosis

Our specific aim was to evaluate the pathophysiologic association of familial heterozygous protein S deficiency with osteonecrosis (ON) in a 26 year old woman and her family. The otherwise healthy 26 year old propositus, without drugs {corticosteroids}, trauma, or diseases (sickle cell, Gaucher's, caisson's, etc) known to cause ON, developed bilateral ON of her hips (Ficat stage III), knees (stage I), and shoulders (stage II). Core decompression of all 6 areas was done. She was found to have low antigenic protein S (67, normal >70%), low free protein S (61%, normal >65%), low functional protein S (60%, normal >7Q%), and low C4B binding protein (71%, normal >85%). Her ON was the only evidence of venous thrombosis. Of 5 asymptomatic first degree family members, protein S and free protein S deficiency were found in 2, her 6 year old daughter ana her 28 year old sister. Protein S deficiency apparently causes ON by promoting thrombotic occlusion of venous drainage of bone with subsequent intramedullary hypertension, bone marrow edema, anoxia, and bone death. Coumadin (INR 2-2.5) has been given to the propositus for 8 weeks. We speculate that Coumadin therapy may ameliorate ON in patients with familial protein S deficiency.