The Syndromes of Thrombotic Microangiopathy: A Critical Appraisal on Complement Dysregulation

Sjoerd A. M. E. G. Timmermans*, Pieter van Paassen

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

7 Citations (Web of Science)

Abstract

Thrombotic microangiopathy (TMA) is a rare and potentially life-threatening condition that can be caused by a heterogeneous group of diseases, often affecting the brain and kidneys. TMAs should be classified according to etiology to indicate targets for treatment. Complement dysregulation is an important cause of TMA that defines cases not related to coexisting conditions, that is, primary atypical hemolytic uremic syndrome (HUS). Ever since the approval of therapeutic complement inhibition, the approach of TMA has focused on the recognition of primary atypical HUS. Recent advances, however, demonstrated the pivotal role of complement dysregulation in specific subtypes of patients considered to have secondary atypical HUS. This is particularly the case in patients presenting with coexisting hypertensive emergency, pregnancy, and kidney transplantation, shifting the paradigm of disease. In contrast, complement dysregulation is uncommon in patients with other coexisting conditions, such as bacterial infection, drug use, cancer, and autoimmunity, among other disorders. In this review, we performed a critical appraisal on complement dysregulation and the use of therapeutic complement inhibition in TMAs associated with coexisting conditions and outline a pragmatic approach to diagnosis and treatment. For future studies, we advocate the term complement-mediated TMA as opposed to the traditional atypical HUS-type classification.

Original languageEnglish
Article number3034
Number of pages19
JournalJournal of Clinical Medicine
Volume10
Issue number14
DOIs
Publication statusPublished - Jul 2021

Keywords

  • thrombotic microangiopathy
  • atypical hemolytic uremic syndrome
  • complement
  • hypertensive emergency
  • pregnancy
  • kidney transplantation
  • eculizumab
  • HEMOLYTIC-UREMIC SYNDROME
  • FACTOR-H AUTOANTIBODIES
  • THROMBOCYTOPENIC PURPURA
  • RENAL-TRANSPLANTATION
  • INHIBITOR ECULIZUMAB
  • ALTERNATIVE PATHWAY
  • LUPUS NEPHRITIS
  • GENE-MUTATIONS
  • RISK-FACTORS
  • STEC-HUS

Cite this