This algorithm is intended for use with additional UpToDate content on complement disorders.
CH50: total hemolytic complement; C4: complement component 4; C3: complement component 3; SLE: systemic lupus erythematosus; APS: antiphospholipid syndrome; HUS: hemolytic uremic syndrome; IgA: immunoglobulin A; C2: complement component 2. * All 9 complement components (C1 to C9) are required for a normal CH50. A normal CH50 value/titer ranges from 150 to 250 units/mL in a commonly employed functional assay system. Interpretation of a specific abnormal result should be based upon the reference range reported with that result. ¶ If improper specimen handling, C3 and C4 antigenic levels will be normal but lack functional activity, resulting in falsely low, very low, or undetectable CH50. Δ If there is a laboratory artifact due to cold activation, C4 and/or C3 antigenic levels will be moderately reduced or normal, in association with a very low, even 0, CH50 activity. Cold activation can occur in the presence of complement-activating immune complexes in a patient with inflammatory disease (eg, SLE, chronic viral hepatitis). ◊ C4 and/or C3 levels will be low in patients with some systemic autoimmune disorders. § If repeat CH50 is very low or undetectable, the next step is measurement of the quantity and then function of specific complement proteins, as well as genetic testing. C2 deficiency is the most common genetic cause of a complete deficiency in patients with a very low or undetectable CH50. When possible, the proband (affected family member) should be tested initially to determine the defect and relatives subsequently tested for the identified defect. If not possible, complement gene panel or whole exome sequencing may be advisable.
