Approximately two-thirds of the patients experience exacerbation during febrile illnesses. During steady-state CAD, a majority of patients have low levels of complement proteins C3 and C4 because of a continuous consumption. These low levels, in particular low C4 availability, seem to be rate-limiting for hemolysis and prevent full-blown activation of the complement cascade with C5 cleavage and intravascular hemolysis. During acute phase reaction, C3 and C4 levels increase due to an enhanced production, resulting in exacerbation of hemolysis.