Not all red cells sickle the same: Contributions of the reticulocyte to disease pathology in sickle cell anemia

Abstract

Sickle cell anemia (SCA) is associated with morbidity and early death. While the switch from fetal to sickle hemoglobin during the first months of life results in hemolytic anemia with reticulocytosis, the role of the reticulocyte in the pathophysiology and prognosis of SCA is not well-defined. Reticulocytes have unique cytoskeletal and membrane components that allow them to be distinguished from mature sickle erythrocytes in the circulation. Reticulocytes in patients with SCA are less dense than more mature and 'sickled' erythrocytes, and have increased adhesive properties. The circulating reticulocyte number in peripheral blood may assist in predicting disease severity in SCA; characterization of patient-specific reticulocyte properties during infancy and childhood may assist in predicting therapeutic response to therapies. Here, we review the biological and clinical data regarding reticulocytes and their potential impact on SCA pathophysiology and disease severity.

Keywords: Adhesion; Reticulocyte; Severity; Sickle cell anemia; Vaso-occlusion.

Figure 1.

Circulating reticulocytes in sickle cell anemia can be identified by the unique presence of cytoplasmic RNA and cell-surface adhesion molecules compared to the more mature erythrocyte. (LW=Landsteiner-Weiner blood group (ICAM-4); PS=phosphatidylserine; GPA=glycophorin-A) (© 2019 Indiana Hemophilia & Thrombosis Center, Inc.)

Figure 2.

Reticulocytes can be enriched by osmotic density gradient and over-represent the least dense red blood cells among patients with sickle cell anemia. (© 2019 Indiana Hemophilia & Thrombosis Center, Inc.)