Complement-Mediated Thrombotic Microangiopathies

Complement testing has acquired considerable clinical popularity in recent times. As the medical industry gains a better understanding of its role in infectious, autoimmune, and inflammatory diseases, complement testing is progressively being recognized as a potential target for therapeutics. An overview of the complement system, pre-analytical challenges, and modern laboratory testing will be presented in this webinar.

There are genetic and acquired causes for complement dysfunction and an increasing recognition of the role of complement beyond infection to several disorders, including thrombotic microangiopathies. With the advent of eculizumab (Soliris®) and other complement inhibitors being used as therapeutic options to treat complement-mediated disorders, proper complement testing for diagnosis and also monitoring the impact of therapy are needed. This requires new considerations for complement testing. An overview of the complement system will be discussed, with a list of biomarkers for complement deficiency and activation/consumption, including targets such as antibodies against the C3 convertase and Factors H.

Pre-analytical diligence is critical for accurate results in complement testing, as complement factors tend to be unstable at room temperature. Careful pre-analytic practices are highly recommended, especially when testing is sent out to be performed at a reference laboratory. The lack of standardization in complement testing across laboratories is a significant drawback; most analytes are not regulated, and a wide range of assays is available. There are a number of assay formats to test complement, including manual hemolytic assays, radial immunodiffusion, and nephelometry (some of these techniques have been in place for decades). Standardization groups have been formed to homogenize tests and provide a performance comparison across laboratories from different countries.

Video length: 54 minutes


Ronald Go, M.D.
Consultant, Division of Hematology
Associate Professor of Medicine
Mayo Clinic College of Medicine and Science
Mayo Clinic, Rochester, Minnesota

Maria Alice Willrich, Ph.D.
Consultant, Division of Clinical Biochemistry
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
Mayo Clinic, Rochester, Minnesota

Learning Objectives

  • Determine the major types of thrombotic microangiopathies according to underlying pathophysiology.
  • Identify risk factors and triggers.
  • Discuss how to systematically perform initial evaluation and treatment.
  • Describe the complement system pathways.
  • Define challenges of clinical testing for the complement system.
  • Identify the most-used biomarkers and their pattern to assess complement dysfunction in thrombotic microangiopathies.

Target Audience

This webinar is designed for hematologists, health care providers (including physicians, physician assistants, and nurse practitioners), pathologists, hematopathologists, genetic counselors, laboratory technologists, and laboratory support staff.

Mayo Medical Laboratories is not an applicable manufacturer or applicable group purchasing organization. (GPOs per the Centers for Medicare & Medicaid Services, and this program, do not trigger any reporting requirements pursuant to Open Payments [Sunshine Act] legislation.)

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This post was developed by our Education and Technical Publications Team.