Consequentially, Xa, IIa, and plasmin produces C5a (anaphylatoxin) from the C5 complement by the complement cascade-independent manner, and induces histamine release from basophils and skin mast cells via the C5aR, resulting in the release of a large amount of histamine and the development of urticaria (Figure 1 and Figure 2) [44,54]. This evidence concerns the gene C5AR1 and urticaria.