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Review

What is the role of complement in bystander hemolysis? Old concept, new insights

, , &
Pages 107-116 | Received 07 Jan 2024, Accepted 24 Apr 2024, Published online: 06 May 2024
 

ABSTRACT

Introduction

Bystander hemolysis occurs when antigen-negative red blood cells (RBCs) are lysed by the complement system. Many clinical entities including passenger lymphocyte syndrome, hyperhemolysis following blood transfusion, and paroxysmal nocturnal hemoglobinuria are complicated by bystander hemolysis.

Areas covered

The review provides data about the role of the complement system in the pathogenesis of bystander hemolysis. Moreover, future perspectives on the understanding and management of this syndrome are described.

Expert opinion

Complement system can be activated via classical, alternative, and lectin pathways. Classical pathway activation is mediated by antigen-antibody (autoantibodies and alloantibodies against autologous RBCs, infectious agents) complexes. Alternative pathway initiation is triggered by heme, RBC microvesicles, and endothelial injury that is a result of intravascular hemolysis. Thus, C5b is formed, binds with C6-C9 compomers, and MAC (C5b-9) is formulated in bystander RBCs membranes, leading to cell lysis. Intravascular hemolysis, results in activation of the alternative pathway, establishing a vicious cycle between complement activation and bystander hemolysis. C5 inhibitors have been used effectively in patients with hyperhemolysis syndrome and other entities characterized by bystander hemolysis.

Article highlights

  • Bystander hemolysis occurs when antigen-negative red blood cells (RBCs) are lysed by the complement system.

  • Several clinical entities are complicated by bystander hemolysis: passenger lymphocyte syndrome, post-transfusion hemolysis, delayed hemolytic transfusion reactions (DHTRs), paroxysmal nocturnal hemoglobinuria, and hemolysis complicating infectious diseases.

  • Complement system activation is implemented in the pathogenesis of this syndrome.

  • Activation of both classical and alternative pathways has been identified.

  • C5b-9 formulation in bystander RBCs membrane is crucial for cell lysis.

  • Intravascular hemolysis leads to activation of alternative pathway.

  • C5 inhibition has been used for the treatment of bystander hemolysis in patients with hyperhemolysis syndrome and other entities characterized by bystander hemolysis.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.

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