PAPER 006: THROMBOPHILIA AND HYPOFIBRINOLYSIS, REVERSIBLE PATHOETIOLOGIES OF OSTEONECROSIS OF THE FEMORAL HEAD

Abstract

Purpose: We hypothesized that thrombophilia-hypofibrinolysis are risk factors for femoral head osteonecrosis. Separately, we hypothesized that when Enoxaparin is started at Ficat stages I or II in patients with idiopathic osteonecrosis and thrombophilia-hypofibrinolysis, progression of osteonecrosis can be stopped.

Method: We compared measures of thrombophilia and hypofibrinolysis in 71 adults with idiopathic osteonecrosis, in 62 with corticosteroid-associated secondary osteonecrosis, and in gender-race matched healthy controls. In a prospective Enoxaparin treatment study, 16 patients (25 hips)with one or more thrombophilic-hypofibrinolytic disorders and Ficat Stages I–II idiopathic ON of the hip(s). Enoxaparin (60 mg/day) was given for the first 12 weeks of the study. Yearly X-rays were taken for 5–7 years follow-up (average 6 years). Maintenance of Ficat Stages I-II versus progression to Stages III–IV or total hip replacement was the study outcome.

Results: Patients with idiopathic osteonecrosis were more likely than controls to have high (> 150%) levels of heritable thrombophilic Factor VIII (19/71 [27%] vs 3/66 [5%], p =.0004), and to have inherited high levels of hypofibrinolytic lipoprotein(a) (25/69 [36%] vs 12/67 [18%], p =.016). Patients with secondary osteonecrosis were more likely than controls to have high (> 150%) levels of Factor VIII (16/62 [26%] vs 5/60 [8%], p =.011), to be heterozygous for the Factor V Leiden mutation (6/61 [10%] vs 0/61 [0%], p =.028), and to have heritable thrombophilic resistance to activated protein C (8/51[16%] vs 2/59[3%], p =.042). After 3 months on Enoxaparin, based on intent to treat, 17 of 25 hips (68%) have remained Ficat Stages I–II at 6-year follow-up versus approximately 20% 2-year hip survival in untreated historical controls. This suggests that the original 12 week Enoxaparin thromboprophylaxis produced lasting benefit.

Conclusion: Inherited thrombophilia-hypofibrinolysis are risk factors for both idiopathic and secondary osteonecrosis of the head of the femur. The importance of the diagnosis of thrombophilia-hypofibrinolysis lies in the potential to stop the progression of osteonecrosis when Enoxaparin is started at Ficat stages I–II. Enoxaparin seemingly prevents progression of idiopathic hip ON, causing a decrease in the incidence of total hip replacement at 6 years follow-up.