Reticulocytes in Sickle Cell Disease Contain Hemoglobin S Detectable by Standard Testing
Yes, reticulocytes in sickle cell disease contain hemoglobin S that can be detected by electrophoresis, HPLC, and point-of-care tests, because reticulocytes are young red blood cells that have already completed hemoglobin synthesis and contain the same abnormal hemoglobin composition as mature erythrocytes. 1
Hemoglobin Composition in Reticulocytes
Reticulocytes in SCD patients contain HbS in the same proportions as mature red cells because hemoglobin synthesis is completed before the cell loses its nucleus and becomes a reticulocyte. 2
In HbSS disease, reticulocytes will contain 80-95% HbS with no HbA, matching the composition of mature sickled cells. 3
The abnormal β-globin gene mutation (glutamic acid to valine at position 6) produces hemoglobin S in all red cell precursors during erythropoiesis, meaning reticulocytes emerge from the bone marrow already containing HbS. 1, 4
Detection Methods
Standard hemoglobin electrophoresis, HPLC, and point-of-care testing measure total hemoglobin composition from whole blood samples, which include both reticulocytes and mature erythrocytes—all containing HbS in SCD patients. 3
The chronic hemolytic anemia characteristic of SCD results in elevated reticulocyte counts (reticulocytosis), but these young cells contain the same pathological HbS that polymerizes under deoxygenated conditions. 1, 2
Clinical Significance of Reticulocytes in SCD
Reticulocytes in SCD are less dense than mature sickled cells but have increased adhesive properties, contributing to vaso-occlusive events despite their younger age. 2
The reticulocyte count may assist in predicting disease severity, with higher counts reflecting more severe hemolysis, but the HbS within these cells remains fully detectable and pathogenic. 2
Under deoxygenated conditions, HbS in reticulocytes polymerizes just as it does in mature cells, though reticulocytes may have slightly different sickling kinetics due to their unique membrane properties. 1, 2
Important Caveats
Fetal hemoglobin (HbF) levels above 8% reduce HbS polymerization and disease severity, but this protective effect applies to both reticulocytes and mature cells, not selectively to one population. 3
Newborn screening relies on detecting HbS in cord blood, which contains predominantly young red cells and reticulocytes—confirming that HbS is present and detectable from the earliest stages of red cell development. 3