title: High prevalence of prothrombotic abnormalities in multifocal osteonecrosis: description of a series and review of the literature.
abstract: Multifocal or multiple osteonecrosis (ON), defined by the involvement of 3 or more anatomic sites, is unusual, being observed in only 3%-10% of patients diagnosed with ON. We report the clinical characteristics of a cohort of 29 patients with multifocal ON from a single center and evaluate the prevalence of associated prothrombotic abnormalities in 26 of these patients. We conducted a retrospective study of all patients diagnosed with multifocal ON evaluated in our institution during the last 20 years. We recorded clinical manifestations and underlying diagnoses. A wide thrombophilic profile was performed, including antithrombin, protein C, protein S, lupus anticoagulant, anticardiolipin antibodies, activated protein C resistance, factor V Leiden, mutation G-20210-A of the prothrombin gene, and factor VIII. Coagulation test results were compared with those in a healthy control group and a group of patients with history of lower-extremity deep venous thrombosis. The mean age of the patients was 49.2 ± 15 years (range, 28-81 yr). The mean number of ON localizations per patient was 5.2 ± 2.3 (range, 3-11). Hips were the most commonly affected joint (82%), followed by knees (58%), shoulders (37%), and ankles (13%). Most patients had an underlying disease process, and 12 of 25 (48%) patients had coagulation test abnormalities. The most common alterations were high factor VIII levels and antiphospholipid antibody (aPL) positivity in 24% and 20% of cases, respectively. These abnormalities were more prevalent in patients with multifocal ON compared with patients in the control groups. Sixty-one percent of patients had a history of corticosteroid treatment. Patients with coagulation abnormalities had a higher number of ON localizations per patient (6.5 ± 2.7 vs. 3.88 ± 0.8; p = 0.002) and a higher prevalence of atypical ON localizations (25% vs. 0%; p = 0.05). In conclusion, in the present cohort of patients with multifocal ON, 48% of the patients had at least 1 prothrombotic factor, especially high levels of factor VIII and aPL. These findings have major implications for the diagnosis and treatment of multifocal ON and clearly indicate the need to perform a thrombophilic profile in these patients.
authors.affiliation: From the Department of Rheumatology (JAG-P, PP, AM-F, AM, NG), CIBERehd; and Hemotherapy and Haemostasis Service (JCR, JM, DT), Hospital Clínic, Barcelona; Department of Autoimmune Diseases (GE), Hospital Clínic, University of Barcelona, Barcelona, Spain; and Division of Rheumatology, Immunology and Allergy (JAG-P), Brigham and Women's Hospital, Boston, Massachusetts, United States.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Gómez-Puerta
authors.forename: Pilar
authors.initials: P
authors.lastname: Peris
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Reverter
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.forename: Angeles
authors.initials: A
authors.lastname: Martinez-Ferrer
authors.forename: Ana
authors.initials: A
authors.lastname: Monegal
authors.forename: Juan
authors.initials: J
authors.lastname: Monteagudo
authors.forename: Dolors
authors.initials: D
authors.lastname: Tàssies
authors.forename: Nuria
authors.initials: N
authors.lastname: Guañabens
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001778:Blood Coagulation Disorders / Q000097:blood / Q000150:complications / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010020:Osteonecrosis / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D015995:Prevalence; D012189:Retrospective Studies; D013927:Thrombosis / Q000097:blood / Q000150:complications / Q000453:epidemiology