Secondary thrombotic microangiopathy in children-a central role for the glycocalyx

Thrombotic microangiopathy (TMA) is classically defined by the triad of hemolytic anemia, thrombocytopenia, and organ injury, most notably kidney involvement. Secondary TMA, which arises in association with specific diseases or external triggers, is more common than primary or complement-mediated TMA. Current evidence supports an important role for complement activation in the pathogenesis of secondary TMA, and emerging data highlight the contribution of the endothelial glycocalyx to complement dysregulation at the endothelial surface. The endothelial glycocalyx is an integrated matrix lining the luminal aspect of endothelial cells and plays a central role in maintaining endothelial homeostasis and preventing thrombosis. Its unique structure may represent a missing mechanistic link in several forms of secondary TMA that are relevant to children, including pneumococcal-associated TMA, Shiga toxin-producing Escherichia coli hemolytic uremic syndrome, calcineurin inhibitor-associated TMA, and hypertension-associated TMA. This mini review summarizes current evidence and understanding of the central role of the endothelial glycocalyx in these conditions and discusses the implications for future therapeutic innovation.