When to order complement levels?

From the Guidelines

Complement levels, specifically C4, should be ordered in patients with recurrent angioedema without urticaria to evaluate for C1INH deficiency, as a normal C4 level during an angioedema attack strongly suggests an alternative diagnosis. When evaluating patients with suspected complement deficiencies or certain infections, such as hereditary angioedema, start with ordering C3, C4, and CH50 (total hemolytic complement) 1. More specific complement component testing (C1q, C1 inhibitor, factor B, factor H) should be ordered based on initial results and clinical presentation.

• Key considerations for ordering complement levels include:
  • Recurrent angioedema without urticaria
  • Suspected hereditary angioedema
  • Evaluation of C1INH deficiency
  • Normal C4 level during an angioedema attack suggests an alternative diagnosis
  • Measurement of C4 level is an excellent screening tool for C1INH deficiency states
• The most recent and highest quality study, from 2013, provides guidance on the diagnostic algorithm for hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema 1.
• Other studies, such as those from 2014,2015, and 2016, provide additional information on the use of meningococcal vaccines, practice parameters for the diagnosis and management of primary immunodeficiency, and vaccination of the immunocompromised host 1. However, these studies are not directly relevant to the question of when to order complement levels.
• In clinical practice, complement levels should be ordered when evaluating patients with suspected complement deficiencies or certain infections, and the results should be interpreted in the context of the patient's clinical presentation and medical history.

From the Research

Compliment Levels Ordering

• Compliment levels, such as CH50, C3, and C4, are useful to measure in patients with immune-mediated diseases 2.
• Decreased levels of CH50 in combination with normal or decreased levels of C3 and C4 are associated with specific immune-mediated diseases 2.
• Measurement of C3 and C4 can be useful in diagnosis, prognosis, and therapeutic monitoring of immune complex disease 3.
• Complement measurements can be beneficial in clinical practice, particularly in diseases such as atypical hemolytic uremic syndrome (aHUS), autoimmune diseases, and C3 glomerulopathies (C3GN) 4.

Specific Conditions

• In systemic lupus erythematosus (SLE), complement levels can be useful in diagnosis and monitoring of disease activity 5.
• SLE patients with atypical hemolytic uremic syndrome (aHUS) may benefit from complement-directed therapies, such as eculizumab 6.
• Complement system abnormalities, including low C3 and C4 levels, are common in SLE patients with aHUS 6.

Laboratory Tests

• Measurement of CH50, C3, and C4 can be used to evaluate the complement system 2.
• Immune complex assays, such as those that measure cryoglobulins and serum viscosity, can also be useful in evaluating immune complex disease 3.
• Complement-related biomarkers can be used to decipher the role of complement in pathology and to optimize treatment efficacy versus toxicity 4.