The Intern At Work: Internal Medicine
May 31, 2026 · 20 min · 10 segments
Send us Fan Mail In this episode, we discuss how to identify and manage the acute complications of sickle cell disease. Written by Dr. Yi Hui Luo (Internal Medicine Resident). Reviewed by Dr…
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Yi Hui LuoHost
Let's start with the hemoglobin, the protein that carries oxygen inside our red blood cells.
Each hemoglobin molecule is a tetramer composed of four globin subunits, of which there are a few types, notably alpha, beta, delta, and gamma globin.
In a newborn child, the most abundant form of hemoglobin is fetal hemoglobin, or hemoglobin F, which is composed of two alpha globin subunits and two gamma globin subunits.
A gradual shift in globin synthesis occurs such that from the age of six months onward, the most abundant form of hemoglobin becomes adult hemoglobin, or hemoglobin A, which is composed of two alpha globin and two beta globin subunits.
Remember that sickle cell disease is an autosomal recessive inherited disorder of hemoglobin.
Hemoglobin molecules that incorporate these abnormal beta globin subunits are called hemoglobin S.
Under deoxygenated conditions, circulating red blood cells carrying hemoglobin S tend to adopt a sickle shape, hence the name sickle cell disease.
Patients with a single mutated beta globin gene have sickle cell trait, which is virtually asymptomatic and is relatively protective against malaria.
Patients with two mutated beta globin genes have hemoglobin SS genotype and have sickle cell disease.
Of note, patients may have the hemoglobin S mutation in one beta globin gene and a different mutation on the other copy, such as beta thalassemia or hemoglobin C mutation.
These hybrid genotypes all result in sickle cell disease, but with different degrees of severity.
Sickled red blood cells can cause harm via two mechanisms, vaso-occlusion and hemolysis.
Firstly, sickled red blood cells can adhere and cause vascular occlusions in any organ, which leads to ischemia and painful episodes known as vaso-occlusive crises.
Secondly, chronic hemolysis of fragile sickled red blood cells causes anemia and hyperbilirubinemia, but also disrupts endothelial homeostasis, which leads to complications such as pulmonary hypertension and chronic leg ulcers, among others.
While healthy adults produce virtually no fetal hemoglobin, some patients with sickle cell disease maintain a higher level of fetal hemoglobin production well into adulthood.
Indeed, fetal hemoglobin inhibits sickling and protects many against complications of sickle cell disease.
Therefore, many therapies for sickle cell disease aim to increase the percentage of fetal hemoglobin.
Let's start with the hemoglobin, the protein that carries oxygen inside our red blood cells.
Each hemoglobin molecule is a tetramer composed of four globin subunits, of which there are a few types, notably alpha, beta, delta, and gamma globin.
In a newborn child, the most abundant form of hemoglobin is fetal hemoglobin, or hemoglobin F, which is composed of two alpha globin subunits and two gamma globin subunits.
A gradual shift in globin synthesis occurs such that from the age of six months onward, the most abundant form of hemoglobin becomes adult hemoglobin, or hemoglobin A, which is composed of two alpha globin and two beta globin subunits.
Remember that sickle cell disease is an autosomal recessive inherited disorder of hemoglobin.
Hemoglobin molecules that incorporate these abnormal beta globin subunits are called hemoglobin S.
Under deoxygenated conditions, circulating red blood cells carrying hemoglobin S tend to adopt a sickle shape, hence the name sickle cell disease.
Patients with a single mutated beta globin gene have sickle cell trait, which is virtually asymptomatic and is relatively protective against malaria.
Patients with two mutated beta globin genes have hemoglobin SS genotype and have sickle cell disease.
Of note, patients may have the hemoglobin S mutation in one beta globin gene and a different mutation on the other copy, such as beta thalassemia or hemoglobin C mutation.
These hybrid genotypes all result in sickle cell disease, but with different degrees of severity.
Sickled red blood cells can cause harm via two mechanisms, vaso-occlusion and hemolysis.
Firstly, sickled red blood cells can adhere and cause vascular occlusions in any organ, which leads to ischemia and painful episodes known as vaso-occlusive crises.
Secondly, chronic hemolysis of fragile sickled red blood cells causes anemia and hyperbilirubinemia, but also disrupts endothelial homeostasis, which leads to complications such as pulmonary hypertension and chronic leg ulcers, among others.
While healthy adults produce virtually no fetal hemoglobin, some patients with sickle cell disease maintain a higher level of fetal hemoglobin production well into adulthood.
Indeed, fetal hemoglobin inhibits sickling and protects many against complications of sickle cell disease.
Therefore, many therapies for sickle cell disease aim to increase the percentage of fetal hemoglobin.
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