Effect of Red Blood Cell Transfusion on Inflammatory and Angiogenic Pathways in Patients With Sickle Cell Disease

Sickle cell disease (SCD) is a chronic inflammatory state, characterized by increased plasma values of inflammatory and angiogenic proteins. Although red blood cell (RBC) transfusion is known to have immunomodulatory effects in other conditions, its potential effects on the inflammatory state in SCD remain largely unknown. This study aimed to explore the longitudinal effects of RBC transfusion on plasma inflammatory and angiogenic proteins in chronically transfused patients with SCD. Plasma samples were collected from SCD patients treated with either exchange ( N  = 12) or top‐up ( N  = 12) transfusion prior to transfusion and 1 h, 24–72 h, 1 and 2 weeks post‐transfusion. Proximity Extension Assay technology was used to measure plasma values of 21 proteins at each of these timepoints. Exchange transfusion resulted in decreased values of proteins released during inflammasome activation (IL‐1β, IL‐18), B cell survival and activation (TNFRSF13B/TACI, TNFRSF13C/BAFFR, TNFSF13/APRIL), angiogenesis (ANGPT2, VEGFA, KDR, CXCL12), and neutrophil differentiation, recruitment and activation (G‐CSF, G‐CSFR, CXCL1, CXCL5, CXCL6), at 1 h post‐transfusion, returning gradually to values comparable to pre‐transfusion values during 2 weeks post‐transfusion. In contrast, top‐up transfusion resulted in increased values of EPO and ANGPT1. While exchange transfusion seems to reduce the activation of pro‐inflammatory and pro‐angiogenic pathways, top‐up transfusion might result in reduced hypoxia and increased vascular stability as suggested by the increased values of EPO and ANGPT1. These results enhance our understanding of the effects of RBC transfusion on inflammatory and angiogenic pathways and suggest that exchange transfusion has a stronger effect on these pathways in SCD patients compared to top‐up transfusion.