Sickle cell disease: Clinical

In sickle cell disease, also called sickle cell anemia, red blood cells take the shape of a crescent, or sickle, and that makes it easier for them to be destroyed, causing anemia.

Sickle cell disease is an autosomal recessive disorder caused by a mutated hemoglobin gene that encodes for an abnormal adult hemoglobin called hemoglobin S for sickle, or HbS for short.

A mutation in both copies of the gene is needed to get the disease. If the person has just one copy of the mutation and one normal hemoglobin A gene, or HbA for short, then they have sickle trait and they’re said to be a sickle cell carrier.

Having sickle trait typically doesn’t cause health problems unless a person is exposed to extreme conditions like high altitude or dehydration, where some sickle cell disease-like symptoms begin to crop up.

Now in individuals with sickle cell disease, when there’s acidosis, hypoxia, or dehydration, HbS changes its shape, and aggregates with other HbS proteins to form long chains that distort the red blood cell into a crescent shape, that looks like a sickle - which is the name of a blade used to cut grain.

Sickling leads to two important things - vaso-occlusion and hemolysis.

Hemolysis can be intravascular- meaning red blood cells are prematurely destroyed within the vasculature, or extravascular, meaning that they get engulfed by macrophages in the spleen and liver. These two processes are independent from each other, but usually, both are happening to some degree.

So, in intravascular hemolysis, hemoglobin and the enzyme lactate dehydrogenase, or LDH, spill out directly into the plasma. The hemoglobin gets bound by a protein called haptoglobin and gets recycled into unconjugated bilirubin.