Cells containing hemoglobin S have a decreased capacity to maintain normal levels of potassium (K+). As K+ leaves the cell, water follows.
Two mechanisms are responsible for maintaining intracellular ion levels, the Gardos channel and the K+-Cl- channel. Both channels are abnormally activated in patients with sickle cell disease. The resulting loss of water from the cell increases the hemoglobin concentration and the chances for sickling.