Familial Thrombophilia Is Associated With Primary Multifocal Osteonecrosis: A Case-Control Study of 40 Patients

Abstract

To characterize pathoetiologic associations of heritable thrombophilia-hypofibrinolysis with idiopathic (primary) multifocal osteonecrosis (ON) (≥3 ON anatomic sites), we prospectively studied 28 women and 12 men with primary multifocal ON compared with 27 women and 24 men with primary nonmultifocal ON (<3 sites) and 110 healthy controls without ON. The 40 cases with primary multifocal ON differed from controls for 3 familial thrombophilias: Factor V Leiden heterozygosity (6 of 40 [15%] vs 2 of 109 [2%], P =.002), G20210A prothrombin gene heterozygosity (6 of 40 [15%] vs 3 of 110 [3%], P =.011), and high (>150%) Factor VIII (8 of 40 [20%] vs 7 of 103 [7%], P =.031). These case-control familial coagulation differences paralleled those in 51 concurrently evaluated cases with primary nonmulti-focal ON, 7 of 51 (14%) of whom had Factor V Leiden heterozygosity vs 2% of controls ( P =.005) and 14 of 44 (32%) of whom had high Factor VIII vs 7 of 103 (7%) of controls ( P =.0002). Recognition of familial thrombophilia as a common pathoetiology of primary multifocal ON provides an opportunity for early anticoagulation (before joint collapse), allowing both prophylaxis and therapy aimed at relieving pain and slowing or stopping progression of the disease to joint collapse. [ Orthopedics . 2023;46(3):164–168.]