What blood tests are used to diagnose Angioedema?

Blood Tests for Angioedema Diagnosis

The most important initial blood test for diagnosing angioedema is serum complement C4 level, which serves as an excellent screening test for C1 inhibitor deficiency, with low levels present in 95% of patients between attacks and nearly 100% during attacks. 1, 2

Initial Laboratory Evaluation

• Serum C4 level - the best initial screening test for hereditary angioedema (HAE) and acquired C1 inhibitor deficiency 1, 2
• C1 inhibitor (C1-INH) antigenic level - measures the amount of C1-INH protein 1
• C1 inhibitor functional level - measures how well C1-INH works (particularly important for diagnosing Type II HAE) 1, 2

Diagnostic Patterns for Different Types of Angioedema

Hereditary Angioedema with C1-INH Deficiency

• Type I HAE:

  • Low C4 level
  • Low C1-INH antigenic level
  • Low C1-INH functional level
  • Normal C1q level 1, 3

• Type II HAE:

  • Low C4 level
  • Normal or elevated C1-INH antigenic level
  • Low C1-INH functional level
  • Normal C1q level 1, 3

Acquired C1-INH Deficiency

• Type I Acquired Angioedema:

  • Low C4 level
  • Low C1-INH antigenic level
  • Low C1-INH functional level
  • Low C1q level (key differentiator from hereditary forms) 1

• Type II Acquired Angioedema:

  • Low C4 level
  • Low C1-INH antigenic level
  • Low C1-INH functional level
  • Low C1q level
  • Presence of autoantibodies against C1-INH 1, 3

Additional Tests for Specific Scenarios

• C1q level - helps differentiate between hereditary and acquired C1-INH deficiency (normal in HAE, decreased in acquired forms) 1, 4
• Anti-C1-INH antibodies - useful for diagnosing acquired C1-INH deficiency type II 3
• Genetic testing:
  • SERPING1 gene sequencing - for confirming HAE types I and II, especially in patients >40 years to distinguish from acquired forms 1, 5
  • F12 gene sequencing - for diagnosing HAE with normal C1-INH (HAE-FXII) 1
  • Other gene sequencing (KNG1, PLG, ANGPT1, etc.) - for diagnosing other rare forms of HAE with normal C1-INH 5, 6

Testing Algorithm for Angioedema

1. Measure serum C4 level as initial screening test 1, 2
2. If C4 is low, measure C1-INH antigenic and functional levels 1
3. If both C1-INH antigenic and functional levels are low, HAE type I or acquired angioedema is likely 1, 3
4. If C1-INH antigenic level is normal but functional level is low, HAE type II is likely 1, 3
5. If C1-INH levels are normal but strong clinical suspicion of HAE exists, consider testing for HAE with normal C1-INH through genetic testing 1
6. If acquired C1-INH deficiency is suspected (especially in patients >40 years with no family history), measure C1q level and anti-C1-INH antibodies 1, 4

Important Considerations

• C4 levels can be normal in patients already receiving treatment for HAE 1
• C4 should be repeated during an attack if initially normal, as it should be low during attacks in HAE 1
• Functional C1-INH assays should be less than 50-60% of the lower limit of normal to be compatible with HAE 1
• Chromogenic functional C1-INH assays (used in Europe) appear superior to ELISA-based assays commonly used in the US 1
• Samples for C4 and C1-INH function should be processed promptly to avoid degradation and false low results 1
• No specific laboratory tests exist for ACE inhibitor-induced angioedema; diagnosis is confirmed by symptom resolution after medication discontinuation 2

By following this systematic approach to laboratory testing, clinicians can accurately diagnose the various forms of angioedema and implement appropriate treatment strategies.