The Immunothrombotic Phenotype: Early Inflammatory and Hematologic Markers that Identify Children at Increased Risk of Avascular Necrosis Following Septic Arthritis.

Background: Avascular necrosis (AVN) is a devastating complication of pediatric septic arthritis (SA). While traditionally attributed to increased intra-articular pressure, emerging evidence suggests that the host's systemic response to infection may contribute to ischemic injury. We hypothesized that an immunocoagulopathic phenotype characterized by extreme inflammation and platelet consumption would identify children at the highest risk of developing AVN. Methods: Following institutional review board approval, children aged younger than 18 years diagnosed with SA between 2010 and 2016 were retrospectively identified from a multicenter database. The primary outcome was the development of AVN. Demographic, clinical, microbiologic, and early laboratory variables were collected. Multivariable logistic regression using Firth's penalized likelihood method was used to account for rare events. Subgroup-level predicted risks of AVN were calculated based on combinations of dichotomized laboratory markers. Results: Among 616 children with SA, 23 developed AVN (incidence, 3.7%). Patients with AVN demonstrated greater early inflammatory burden, including higher C-reactive protein (CRP) levels, lower platelet counts, and more frequent positive blood and tissue cultures. In multivariable analysis, extreme CRP elevation (>160 mg/L) and relative thrombocytopenia (<245 × 10 Conclusions: In this multicenter cohort, AVN occurred in 3.7% of children with SA. The development of AVN was strongly associated with an immunocoagulopathic phenotype, defined by extreme inflammation (CRP >160 mg/L) and coagulopathy (relative thrombocytopenia <245 × 10 Level of Evidence: Level IV, prognostic. See Instructions for Authors for a complete description of levels of evidence.