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Sickle cell disease is a blood disorder wherein there is a single amino acid substitution in the hemoglobin protein of the red blood cells, which causes these cells to assume a sickle shape, especially when under low oxygen tension.Sickling and sickle cell disease also confer some resistance to malaria parasitization of red blood cells, so that individuals with sickle-cell trait (heterozygotes) have a selective advantage in environments where malaria is present. Taubenberger of the National Institutes of Health discovered the earliest proof of sickle-cell disease while looking for the virus of the 1918 flu during the autopsy of an African-American soldier.A person with sickle cell trait inherits one normal allele and one abnormal allele encoding hemoglobin S (hemoglobin genotype AS).The sickle cell trait can be used to demonstrate the concepts of co-dominance and incomplete dominance.The inflammation and leakage of intracellular material resulting from muscle cell necrosis releases a particular protein, myoglobin, into the blood stream.While necessary in muscle tissue to bind iron and oxygen, myoglobin circulating through the bloodstream can break down into smaller compounds that damage kidney cells, leading to various complications, such as those seen in sickle cell trait athletes during high levels of physical exertion.

The abnormal hemoglobin can cause the body to destroy red blood cells, essentially causing anemia.

In order to determine the deformability of erythrocytes multiple factors including blood and plasma viscosity and hematocrit (a calculation of the percent of red blood cells present in the blood) are measured.

Alpha-thalassemia, like sickle cell trait, is typically inherited in areas with increased exposure to malaria.

Because of the microcirculatory distress, a telltale sign or symptom of a potential sickling collapse is cramping.

Specifically to sickle cell trait, cramping occurs in the lower extremities and back in athletes undergoing intense physical activity or exertion.

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