C4A and hereditary angioedema: As a result, in HAE with low or absent C1-INH, the early complement cascade (C1, C2, and C4) is unchecked and activated even before other inhibitors (C4-binding protein and factor I) can stop the pathway, which results in the consumption of the complement factors (C4) and increased production of anaphylatoxins (C3a, C5a), chemotaxins (C3b), and localized edema of the skin.