Hemoglobinopathies
Now that we have a better understanding of hemoglobin, we can dig into the hemoglobinopathies.
A hemoglobinopathy is defined as a hereditary condition involving an abnormality in the structure of hemoglobin (not the quantity). The most common structural mutations involve the beta chain. Let’s go through a few examples.
Hemoglobin S:
Hemoglobin S has a valine amino acid in place of a glutamic acid amino acid in the 6th position of the beta gene on chromosome 11.
Hemoglobin C:
Hemoglobin C has a lysine amino acid in place of a glutamic acid amino acid in the 6th position of the beta gene on chromosome 11.
A single base pair change can cause hemoglobin to be drastically different and this can cause RBCs to have a physically different shape as well. However, the final RBC phenotype is determined by both copies of the globin chain genes. Let’s use hemoglobin S as an example.
If a person has one copy of hemoglobin S and one regular copy of the beta globin chain, this person is heterozygous for hemoglobin S and has sickle cell trait. If a person has two copies of hemoglobin S, this person is homozygous for hemoglobin S and has sickle cell disease. Sickle cell trait tends to be asymptomatic; whereas, sickle cell disease can cause numerous problems including autosplenectomy (a damaged spleen due to filtering the misshapen sickle cells), and intracorpuscular RBC defects (defects in the RBC). However, an important thing to remember is sickle cell disease will present with normocytic, normochromic blood values. Some patients with sickle cell disease will also have slightly increased levels of hemoglobin F.
The combinations don’t stop there and there’s a near endless amount of combinations. Hemoglobin SC (one copy of Hgb S and one copy of Hgb C) is the second most common hemoglobinopathy behind sickle cell disease. Hemoglobin SC disease can present with crystals in the peripheral blood smear. Some say these crystals appear to look like the “Washington Monument.” I’ve seen the Washington monument and I’m not seeing the resemblance but be aware of the association.
Crystals on the peripheral smear can also be seen in cases of hemoglobin C. They appear more bar shaped and more symmetrical in appearance. They have been compared to “gold bars.”
How does the clinical lab figure out what types of hemoglobin people have?
Different types of hemoglobinopathies and diseases can be detected by hemoglobin electrophoresis. This test can determine which types and what percentage of hemoglobin a person has by charge separation. There are two methods which are very similar but slightly different, and it’s very important to know the differences of each test.
Cellulose acetate hemoglobin electrophoresis, pH 8.6:
Hemoglobin flows from cathode (-) to anode (+)
Memory Trick
What’s an easy way to remember these groups? For the group that includes hemoglobin A2, C, E, O-Arab, and C-Harlem use the mnemonic “A₂CE Of Clubs,” for the group with hemoglobin S use “Sad Dogs Get Love.” For the overall flow on cellulose acetate use the mnemonic Cultural Society of Filipino Americans. This will give you CSFA.
Citrate agar hemoglobin electrophoresis, pH 6.2:
The blood sample is placed in the middle of this gel in this test and some hemoglobin will flow toward the anode (+) and some will flow toward the cathode (-). Not all hemoglobin will flow in the same direction in this test.
Memory Trick
To remember this sequence use the mnemonic “Florida Association of Smelly Cats.” Florida is associated with citrus (citrate agar), and the o in “of” is where the sample originates. If you remember both the cellulose acetate and citrate agar in this fashion, they both have the positive charge on the right.