Splenic filtration of red blood cells in physiology, malaria and sickle cell disease.

PURPOSE OF REVIEW The human spleen clears the blood from circulating microorganisms and red blood cells (RBCs) displaying alterations. This review analyzes how generic mechanisms by which the spleen senses RBC, such pitting, trapping and erythrophagocytosis, impact the pathogenesis of twos major spleen-related diseases, malaria and sickle cell disease (SCD). RECENT FINDINGS Scintigraphy, functional histology, comparison of circulating and splenic RBC, ex-vivo perfusion of human spleens and in-silico modeling enable relevant exploration of how the spleen retains and processes RBC in health and disease. Iterative cross-validations between medical observations, in-vitro experiments and in-silico modeling point to mechanical sensing of RBC as a central event in both conditions. Spleen congestion is a common pathogenic process explaining anemia and splenomegaly, the latter carrying a risk of severe complications such as acute splenic sequestration crisis and hypersplenism in SCD. Sickling of hemoglobin S-containing RBC may contribute but not trigger these complications. SUMMARY Ongoing progress in the exploration and understanding of spleen-related complications in malaria and SCD open the way to optimized prognosis evaluation and therapeutic applications.