What is Sickle Cell Disease (SCD)?

Overview

Sickle cell disease (“SCD”) is an inherited genetic disorder caused by a mutation in the gene that encodes for hemoglobin, the protein in red blood cells that delivers oxygen throughout the body.

Red blood cells (“RBCs”) normally are disc-shaped, deformable and move easily through the microvasculature, using hemoglobin to carry oxygen from the lungs to the rest of the body (see below).

However, hemoglobin molecules in SCD patients stick together to form long fibers or rods. These fibers distort the shape of the RBCs, causing them to be less flexible and more likely to adhere to each other and to the walls of blood vessels, which severely impairs the flow of blood (see below). As a result, organs and tissues become deprived of oxygen, which can lead to severe pain, an accumulation of irreversible damage to organs, and an early death. Sickle cell disease is also an anemia since sickled RBCs are fragile and rupture more quickly than regular RBCs.

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Symptoms

What are the symptoms associated with SCD?

Signs and symptoms of sickle cell disease usually begin in early childhood. The hallmark of the disease is the recurring episodes of severe pain known as an acute crisis or vaso-occlusive crisis (“VOC”). VOC occurs when the proportion of sickled cells rises, leading to obstruction of small blood vessels and reduced blood flow to organs and bone marrow. This obstruction results in intense pain and tissue damage. Over a lifetime, the accumulated burden of damaged tissue leads to the loss of vital organ function and a greatly reduced lifespan. VOC is the leading cause for hospital admissions among SCD patients. The frequency, severity and duration of these acute crises can vary considerably from patient to patient and may range from once a year to more than monthly. Triggers for VOC episodes may include stress, dehydration, infection, or travel to a higher altitude, although the actual trigger is often unknown.

In addition to VOC, sickle-cell disease patients can suffer from many other complications, including:

    • Acute chest syndrome, a respiratory distress syndrome that may arise in the course VOC and the leading cause of death in SCD patients during vaso-occlusive crisis.
    • Stroke (including silent stroke), which can result from a progressive narrowing of blood vessels, preventing oxygen from reaching the brain.
    • Pulmonary hypertension and heart failure.
    • Kidney dysfunction and chronic renal failure.
    • Bone necrosis of the hip and other major joints.
    • Frequent infections due to loss of splenic function and decreased immune function.
    • Leg ulcers.
    • Blindness.
    • Increased rate of complications from pregnancy.
    • Chronic deep muscle and bone pain even in the absence of acute vaso-occlusive pain.

What Causes SCD?

SCD is an inherited genetic disease affecting millions of people worldwide.

In a healthy individual, two copies of the gene for normal hemoglobin are inherited. These individuals are designated as having hemoglobin AA. When an individual inherits one copy of the abnormal gene and one copy of the healthy gene, that individual is designated as having hemoglobin AS and is considered to have “sickle cell trait” (SCT). Individuals with SCT generally do not have any of the signs or symptoms of SCD; however, they can pass along the abnormal gene to their children. In individuals with SCD, both copies of the hemoglobin gene are abnormal (ss). In other words, these individuals do not have any copies of the normal hemoglobin A gene.

There are several genetic variants of SCD. The most common types are designated as hemoglobin SS (HbSS), hemoglobin SC (HbSC) and hemoglobin S Beta Thalassemia (HbSβthal). Individuals with HbSS have the most severe form of SCD and are responsible for the majority of hospitalizations. HbSC is generally a more mild form of SCD, although these individuals can still experience severe VOC. The severity of SCD in HbSβthal individuals depends on the severity of the co-inherited beta-thallasemia gene. When no beta globin is produced by the beta-thallasemia gene, the condition is very similar to that of individuals with HbSS.

Current Treatments

Crisis Management

Currently, there is no disease-modifying treatment for an ongoing vaso-occlusive crisis. Patients are treated symptomatically for pain using intravenous opioids until the crisis has settled, typically within 4 – 5 days, but crises may last a week or longer. Painful crises are also treated with hydration, and in some cases, blood transfusion. For crises not requiring hospitalization or for daily pain, patients can manage on non-steroidal anti-inflammatory drugs (“NSAIDs”) and other prescription oral medications.

Disease Management

Typically, disease management for SCD patients is focused on controlling complications and limiting the number and severity of painful crises.

The only drug that is FDA labeled for the treatment of sickle-cell anemia is hydroxyurea (“HU”). In controlled clinical trials the chronic administration of HU was associated with a decrease in the number and severity of VOC (Charache S, Terrin ML, Moore RD, et al., May 1995) and more recent studies suggest HU may also confer a longer term survival benefit (Steinberg MH, Barton F, Castro O, et al., April 2003, and; Voskaridou et al., Blood, March 2010).

Hydroxyurea is also used as a chemotherapy agent and there is some concern that long-term use may be harmful, but longitudinal studies suggest this risk is likely to be small and that the benefits of HU outweigh the risks.

Statistics

Sickle Cell Disease Statistics

    • Sickle cell disease affects approximately 10 million people worldwide.
    • Sickle cell disease is the most common inherited blood disorder in the United States.
    • The prevalence of sickle cell disease in the United States is estimated to affect approximately 90,000 – 100,000 people.
    • Sickle cell disease is estimated to occur in 1 of every 500 African American births and 1 of every 36,000 Hispanic American births.
    • Sickle cell disease may lead to shorter life expectancy.
    • The estimated annual cost of medical care for patients with SCD in the U.S. exceeds $1.0 billion.
    • Approximately 75% of sickle cell patients in the U.S. are covered by public health insurance.
    • It is estimated that undiscounted health care costs for a SCD patient reaching 45 years of age can total more than $950,000.
    • In the U.S., there are between 80,000 to 100,000 hospitalizations each year for vaso-occlusive crisis.
    • Episodes of sickle cell crisis typically last 4 – 5 days and may last a week or longer.
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