In order to understand sickle cell anemia (SCA) we have to first understand the basic structure of the hemoglobin molecule. Hemoglobin is composed of 4 protein molecules: 2 identical α-globin chains and 2 identical β-globin chains.
Sickle cell disease is caused by a mutation in the gene that encodes for the β-globin chain of hemoglobin. The exact mutation results in a glutamate being substituted for a valine in the protein molecule. This substitution causes the hemoglobin molecules in a red blood cell to polymerize (ie: bind together) under conditions of low oxygen. This polymerization gives the red blood cells their characteristic sickle shape under the microscope.
Of interest, only patients who are homozygous for the mutation (ie: they inherit the mutation from mom and dad) show signs of the disease. The reason the mutation exists at such a high frequency in African American populations is because heterozygotes (ie: those containing only one mutated copy of the gene) have a decreased risk of malaria infection, which in sub-Saharan Africa is a tremendous survival advantage.
Patients with sickle cell anemia rarely present with symptoms before six months of age. This is because fetal hemoglobin has not yet been eliminated from the patient's circulation. At approximately six months of age people begin making adult type hemoglobin (ie: 2α/2β hemoglobin) and the symptoms of sickle cell start to appear if mutated copies of the beta globulin are present.
Patients with sickle cell anemia are at an increased risk of several complications. One complication occurs when patients are exposed to parvovirus B19 (the same virus that causes "slapped cheek measles"). Exposure to this virus can cause patients to have an aplastic crisis in which their bone marrow creates no new red blood cells. This can cause a profound anemia.
In addition, sickling of the red blood cells causes them to get "clogged" in the tiniest blood vessels of the body (ie: microvasculature). This clogging causes vaso-occlusive crises, which can be extremely painful. If severe enough death of tissue (aka: infarction) can occur.
This commonly occurs in the femoral head of the leg where it is called avascular necrosis. This is why many people with sickle cell disease have bilateral hip replacements.
If the clogging occurs in the kidney it can cause papillary necrosis and kidney dysfunction.
In addition, most patients with sickle cell disease have infarcted their spleen by adolescence. This puts them at increased risk for infection with encapsulated organisms like streptococcus pneumonia (can cause pneumonia and meningitis) and haemophilus influenzae (can cause bacteremia, pneumonia, and meningitis).
If microvasculature clogging occurs in the brain it can cause a stroke. Priapism (erection lasting for hours) is another complication of microvascular clogging and is extremely painful.
Vaso-occlusive crisis can also occur in the lung in a complication known as acute chest syndrome. This syndrome is characterized by fever, chest pain, shortness of breath, and an infiltrate seen on chest x-ray. It is commonly caused by an underlying pneumonia. Finally clogging in the small blood vessels in the hands/feet can cause dactylitis.
Gold standard diagnosis of sickle cell disease is based of seeing the characteristic sickled red blood cells on a peripheral blood smear sample. Hemoglobin electrophoresis can also clench the diagnosis.
A complete blood count (CBC) will show anemia, usually in the 6 to 8 g/dL range. In addition, the reticulocyte count (a measure of "young" red blood cells) is often elevated. This is indicative of the bone marrow appropriately pumping out more red blood cells to compensate for the anemia.
All vaso-occlusive disorders should be treated with oxygen, lots of intravenous fluids, and analgesics. Anemia, if severe, often requires transfusion of packed red blood cells. In addition to these basic treatments, more specific guidelines are followed depending on which complication the patient is having.
Stoke, perhaps the most feared complication of sickle cell disease, should be treated with immediate exchange blood transfusion to ensure a sickle cell hemoglobin concentration of less than 30% and an overall hemoglobin concentration of at least 10 g/dL. The risk of recurrent stroke is high and monthly scheduled exchange blood transfusion is often instituted after the first episode of stroke to prevent recurrence.
Patients with acute chest syndrome should be placed on antibiotics to treat any underlying infection. Acute chest syndrome also requires exchange blood transfusion to ensure a hemoglobin of at least 10 g/dL.
Avascular necrosis of the hip may warrant orthopedic surgery to replace the affected femoral heads.
Priapism is often treated with needle drainage and injection of an alpha agonist such as phenylephrine into the penile tissue (ouch!).
Preventing complications of sickle cell disease is an important aspect of management. As discussed above, patients are at an increased risk of infection with encapsulated organisms since their spleens auto-infarct. Therefore, all sickle cell patients should be vaccinated with the pneumococcal vaccine.
Since the red blood cells are destroyed faster than normal, many patients burn through their folate supply (an essential vitamin in the production of red blood cells). Because of this, folate supplementation is often prescribed.
Finally a medication known as hydroxyurea is used to prevent painful crises.
Sickle cell disease is caused by a mutation in the β-globin gene. This causes an abnormal hemoglobin molecule that polymerizes under conditions of low oxygen. Symptoms include painful vaso-occlusive crises that can lead to stroke, bone infarction, priapism, dactylitis; aplastic anemia can also occur after parvovirus infection. Diagnosis is made off of a peripheral blood smear and hemoglobin electrophoresis. Treatment is decreasing the frequency of attacks with exchange transfusions and hydroxyurea; folate supplementation should also be given. Acute treatment of pain crises involves IV fluids, pain control, and oxygen, as well as etiology specific treatment (ie: antibiotics for acute chest syndrome).
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