The microangiopathic haemolytic anaemias (MAHAs) share a common picture of mechanical red-cell fragmentation, thrombocytopenia, and small-vessel thrombosis, but their treatment depends entirely on the mechanism. The subset driven by dysregulated complement — atypical haemolytic uraemic syndrome (aHUS) and related complement-mediated TMAs — has been transformed by complement inhibition. (Thrombotic thrombocytopenic purpura, driven instead by ADAMTS13 deficiency, is a distinct MAHA treated with plasma exchange, caplacizumab, and recombinant ADAMTS13.)
The terminal complement C5 inhibitors eculizumab and the longer-acting ravulizumab are the mainstays for complement-mediated TMA, blocking formation of the membrane attack complex and dramatically improving outcomes in aHUS; ravulizumab's eight-weekly dosing eases the treatment burden, and meningococcal vaccination is mandatory for both. The toolkit is now broadening beyond terminal blockade toward proximal and pathway-selective complement inhibition — C3 inhibitors (pegcetacoplan), factor B inhibitors (iptacopan), factor D inhibitors, and lectin-pathway (MASP-2) inhibition — offering oral options and more targeted control for different complement-driven disorders.
Further reading: complement-mediated TMA management (Musalem, BMC Nephrology 2025); complement inhibition in haematologic disease (Gavriilaki et al., Blood 2022); interventions for aHUS (Cochrane 2021).