Prevalence of Annexin A5 Resistance in Children and Adolescents with Rheumatic Diseases

Objective. The underlying mechanism(s) by which antiphospholipid antibodies (aPL) result in thrombosis remains poorly understood. A significant body of evidence has evolved to support the hypothesis that antibody-mediated disruption of an annexin A5 anticoagulant shield may play a role in the pathogenesis; this proposed mechanism has not been previously studied in children. Methods. We investigated the association between aPL and resistance to annexin A5 anticoagulant activity in 90 children with a variety of rheumatic diseases using a novel mechanistic assay, the annexin AS resistance assay (A5R). Results. Patients with a diagnosis of primary aPL syndrome, systemic lupus erythematosus, and mixed connective tissue disease demonstrated lower mean A5R levels (p = 0.030), higher prevalence of positive aPL (p < 0.001), and more thrombotic events (p = 0.014) compared to those with other diagnoses. Patients with persistently positive aPL had significantly lower mean A5R compared to patients with no aPL (mean A5R = 203% +/- 44% vs 247% +/- 35%; p < 0.001), whereas patients with transient aPL did not. Patients with thrombosis had lower A5R levels compared to those without thrombosis (mean A5R = 207% +/- 36% vs 237% +/- 46%; p = 0.048). Conclusion. Children and adolescents with rheumatic diseases and persistent aPL have reduced annexin AS anticoagulant activity, whereas transient, nonpathogenic aPL have less effect on annexin A5 activity. (First Release Dec 15 2011; J Rheumatol 2012;39:382-8; doi:10.3899/jrheum.110768)