Sickle cell anemia is an inherited disorder that is caused by a mutation in the gene encoding for hemoglobin, which is the protein in red blood cells that carries oxygen. The altered form of hemoglobin in patients with this condition is called hemoglobin S or sickle hemoglobin.

Sickle cell anemia patients often experience episodes of acute pain that are caused by vaso-occlusive crisis (VOC). VOC is the most common complication of sickle cell anemia and a frequent reason for emergency department visits and hospitalization.

What is VOC?

Hemoglobin is a protein inside red blood cells and is responsible for transporting oxygen. Hemoglobin S molecules tend to stick together and form aggregates. These aggregates distort the shape of red blood cells, resulting in so-called sickle-shaped red blood cells. Hemoglobin S also damages the membrane of red blood cells, which makes them sticky. As a result, the cells tend to adhere to the inner lining of blood vessels. Sickle red blood cells also are stiffer than normal blood cells. The combination of these two characteristics is thought to promote the blockage of small blood vessels, which prevents oxygen supply to tissues and causes injury,known as VOC.

Patients with sickle cell anemia may experience VOC several times per year. The triggers of VOC are not entirely understood. The cell aggregates that cause VOC consist not only of red blood cells, but also of inflammatory cells. Inflammation, therefore, seems to play a role in the development of VOC and might be promoted by infections. Dehydration and cold weather also are possible VOC triggers.

Legs, arms, back, chest, and abdomen often are involved in VOC. VOC might cause leg ulcers, stroke, kidney insufficiency, and spontaneous abortion.

The acute management of VOC

VOC can be extremely painful and is considered a medical emergency. However, the pain is not always adequately addressed in sickle cell anemia patients, and pain management guidelines have been put in place to improve the occurrence. Moderate-to-severe pain may be controlled with opioids.

If the patient is dehydrated, rehydration is recommended. If possible, the patient should be rehydrated orally, or alternatively by infusion.

If the patient has low levels of oxygen in the blood (hypoxemia), the problem should be addressed with oxygen therapy. This also might help reduce the pain.

Because hemoglobin levels often decrease during VOC, a red blood cell transfusion may be necessary in some cases to help to restore hemoglobin levels to the patient’s baseline levels.

Prevention and long-term management of VOC

One approach to inhibit VOC is to increase levels of fetal hemoglobin (HbF) in the patient’s body. HbF is abundant during the early stages of development and has a high affinity for oxygen. Hydroxyurea is one agent that increases the levels of HbF. It not only improves anemia, but also decreases the number and severity of VOC episodes.

High levels of oxidative stress are thought to be involved in the increased stiffness of sickle red blood cells. So, antioxidant therapy is one approach to decrease this stiffness. Endari (L-glutamine) is a medicine with antioxidant properties and has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of sickle cell anemia in individuals 5 and older.

Further therapies for the treatment of VOC are in clinical development. They include targeting inflammation and the adhesion, or “stickiness,” of sickle red blood cells.

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