Review Question - QID 100098

This patient with homozygous sickle cell disease has a hemoglobin electrophoresis pattern marked by a single, thick band at the hemoglobin S level. Hemoglobin S is more positively charged than normal hemoglobin A.

Homozygous sickle cell disease is caused by an E6V mutation in both copies of the beta globin chain gene, HBB. Nearly all of her hemoglobin is composed of 2 alpha chains and two abnormal beta chains; the resulting hemoglobin is termed hemoglobin S (HbS). HbS is prone to aggregating into rigid polymers when deoxygenated; this leads to the formation of sickled red blood cells that can occlude microcirculatory flow. Such occlusions are responsible for the clinical manifestations of sickle cell disease. HbS is more positively charged than normal hemoglobin A (HbA), and so does not move as quickly toward the top of the positive electrode on gel electrophoresis (at the top of the image).

Wethers discusses the laboratory diagnosis and pathophysiology of sickle cell disease. She reviews the common variants of sickle cell disease (SS disease, SC disease, and sickle-beta-thalassemia), and notes that sickle cell disease can be diagnosed by a number of methodologies including hemoglobin electrophoresis, isoelectric focusing, high-performance liquid chromatography (HPLC), and DNA analysis.

Mirre et al. discuss the use of chronic transfusion to protect against stroke by maintaining HbS below a 30% level. Their retrospective study of 29 children receiving chronic transfusion found no cases of stroke in a primary prevention group (no prior history of stroke), and one case of stroke in a secondary prevention group (history of prior stroke).

Video V presents the pathophysiology and clinical manifestations of sickle cell disease. Illustration A shows a peripheral blood smear with numerous sickled red blood cells. Illustration B shows a scanning electron micrograph image of highly magnified sickled red blood cells among normal red blood cells.

Incorrect Answers:
Answer 1: Lane 2 shows a normal adult. There is a single large band at the HbA level.

Answer 2: Lane 3 shows a normal neonate. There is a band at the HbA level and another at the HbF level. This is because neonates have a significant amount of Hemoglobin F (composed of 2 alpha chains and 2 gamma chains) in addition to HbA.

Answer 4: Lane 6 shows a patient with sickle cell trait (a generally asymptomatic carrier state in which a patient is heterozygous for the HBB E6V mutation). Such patients generally have 50-60% HbA and 35-45% HbS, so bands can be seen at both of those levels.

Answer 5: Lane 7 shows an individual with sickle-hemoglobin C disease (SC disease). Such patients have approximately half HbS and half hemoglobin C (HbC). SC disease occurs in patients who are compound heterozygous for mutations in HBB: They have one copy of the E6V variant and one copy of an E6K mutation. Patients with SC disease have a phenotype that is more severe than those with sickle cell trait and less severe than those with homozygous sickle cell (SS) disease.