Case studies and expert opinion on the management of complement-mediated and secondary thrombotic microangiopathy in Singapore

Complement-mediated thrombotic microangiopathy (C-TMA), previously referred to as atypical haemolytic uraemic syndrome, is a rare cause of thrombotic microangiopathy (TMA). Secondary TMAs are heterogeneous conditions associated with established triggers (e.g. drugs, infection, pregnancy), some of which may be driven by complement activation. Differentiating between C-TMA and secondary TMA can be difficult, as there may be considerable overlap between the conditions. The authors describe 3 cases of TMA potentially involving complement activation as examples of a multidisciplinary approach to diagnosis and management in Singapore. Complement component 5 (C5) inhibition is central to the treatment of C-TMA, but lack of access to therapy remains a major challenge in the region, as illustrated by Case 1 (probable C-TMA). Case 2 (gemcitabine-associated TMA) and Case 3 (lupus nephritis-associated TMA) explore the emerging role of C5 inhibitors in secondary TMAs. Short-duration C5 inhibitor treatment is feasible for some patients without pathogenic gene variants but should be undertaken only with appropriate monitoring.