Thrombin, coagulation factors XIa, Xa, IXa and plasmin (Amara et al. 2010) can cleave C3 and C5 to generate C3a and C5a. Neutrophil elastase (ELANE) can cleave C5 generating an active C5a-like fragment (Vogt 2000).

Under normal conditions, thrombin cleavage of C5 may not be a physiologically significant reaction (Bagic et al. 2015) but the combined action of thrombin and convertases appears to enhance the efficiency of the lytic pathway (Krisinger et al. 2012). Clotting-induced production of thrombin leads to cleavage of C5 at the atypical site R947 in the CUB domain. C5a can be released from the atypical C5a fragment (termed C5aT) by conventional C5 convertases; the truncated C5b fragment, termed C5bT, can form a C5bT-9 membrane attack complex that has significantly increased lytic activity (Krisinger et al. 2012).