The emerging role of complement inhibitory approaches in the treatment of acute sickle cell disease complications.

INTRODUCTION: Sickle cell disease (SCD) is a common and life-threatening hematological disorder that affects almost 100,000 people in the United States and millions worldwide. The wide phenotypic variability of SCD results from a complex pathophysiology involving coagulation, inflammation, leukocyte and endothelial cell activation, and other cellular and humoral mechanisms. To improve the prognosis of SCD patients, we must gain a better understanding of the underlying molecular pathogenesis and offer new therapies.

AREAS COVERED: In SCD and other hemolytic disorders, continual red blood cell breakdown generates free plasma hemoglobin and free heme. Plasma free heme directly activates the complement cascade, resulting in further hemolysis. Complement pathway activation has been linked to SCD; however, the exact mechanism and role of this activation in the pathophysiology of SCD are still being studied. We performed a literature review identifying studies describing complement activation or the impact of complement inhibition in SCD.

EXPERT OPINION: Emerging preclinical and clinical data support the role of complement in SCD. Thorough and careful investigation of the efficacy and safety of proximal and distal complement inhibitors in SCD is warranted. This novel pathway has a tremendous potential to pave the way for innovative therapies to prevent and treat SCD complications.