Complement activation during intravascular hemolysis: Implication for sickle cell disease and hemolytic transfusion reactions

Abstract

Intravascular hemolysis is a hallmark of a large spectrum of diseases, including the sickle cell disease (SCD), and is characterized by liberation of red blood cell (RBC) degradation products in the circulation. Released Hb, heme, RBC fragments and microvesicles (MVs) exert pro-inflammatory, pro-oxidative and cytotoxic effects and contribute to vascular and tissue damage. The innate immune complement system not only contributes to the RBC lysis, but it is also itself activated by heme, RBC MVs and the hypoxia-altered endothelium, amplifying thus the cell and tissue damage. This review focuses on the implication of the complement system in hemolysis and hemolysis-mediated injuries in SCD and in cases of delayed hemolytic transfusion reactions (DHTR). We summarize the evidences for presence of biomarkers of complement activation in patients with SCD and the mechanisms of complement activation in DHTR. We discuss the role of antibodies-dependent activation of the classical complement pathway as well as the heme-dependent activation of the alternative pathway. Finally, we describe the available evidences for the efficacy of therapeutic blockade of complement in cases of DHTR. In conclusion, complement blockade is holding promises but future prospective studies are required to introduce Eculizumab or another upcoming complement therapeutic for DHTR and even in SCD.

Keywords: Complement; Complément; Drépanocytose; Hemolytic transfusion reaction; Hémolyse intravasculaire; Hémolyse post-transfusionnelle; Intravascular hemolysis; Sickle cell disease.