Diagnostic Utility of Complement Serology for Atypical Hemolytic Uremic Syndrome

Objective To investigate the clinical utility of a 9-analyte complement serology panel (COMS) covering complement function (CH50 and AH50), components (C3, C4), factor B (CFB), factor H, and activation markers (C4d, Bb, and soluble membrane attack complex) for the diagnosis of atypical hemolytic uremic syndrome (aHUS). Methods Physician orders for COMS from January 19, 2015, through November 4, 2016, were reviewed. Demographic characteristics, patient diagnosis, and laboratory parameters were recorded. Results There were 177 COMS orders for 147 patients. The median patient age was 44.9 years (range, 0.9-88.0 years). Common reasons for ordering COMS included monitoring and diagnosis of C3 glomerulopathy and renal dysfunction and differentiation of aHUS from other thrombotic microangiopathies (TMAs). Forty-four patients had COMS ordered for TMAs: 8 had aHUS and all had 1 or more abnormalities within the alternative pathway of complement. Although the sensitivity of this finding for the diagnosis of aHUS is 100%, the specificity is only 28%, with a positive likelihood ratio of 1.39. Patients with aHUS had lower CH50, C3, and CFB than did those with secondary non-aHUS TMA (all P<.01). A combined CFB of 20.9 mg/dL or less and CH50 of 56% or less led to sensitivity of 75% with increased specificity of 88.9% and a diagnostic odds ratio of 24. Conclusion A COMS abnormality should not be interpreted in isolation. In conjunction with clinical presentation, a decrease in both CFB and CH50 may be an important clue to support the diagnosis of aHUS.