Sickling

The point mutation in the beta globin chain of sickle hemoglobin creates a hemoglobin molecule that will polymerize under low oxygen conditions.  Both polymerization and oxidant damage will lead to a dramatic reduction in the lifespan of the sickle cell and will cause damage to the circulation. Hemoglobin polymerization will lead to a change in the ability to deform as measured in the ektacytometer as the POS parameter.  

The RBC lab has developed a unique way to measure the morphology changes of sickle RBC exposed to low oxygen tension in time, providing insight in the kinetics of sickling.  The change in morphology under low oxygen is induced in vitro in the sicklomat, and quantified by image flowcytometry. These measures report on the kinetics of sickling, and the effect of as well as the effect of repeated cycles of oxygenation and de-oxygenation using the sickle cycler. Treatments that lower the rate of sickling or the formation of irreversible sickled cells (ISC) are used to improve the quality of life of sickle cell patients. These treatments include hydroxy urea,  compounds that increase oxygen affinity and gene therapy.