Sickle Cell Disease

Source: Wikipedia and University of Maryland's "Sickle Cell Anemia"

Sickle-cell disease, is a general term to describe a variety of genetic disorders caused by sickle hemoglobin (Hgb S or Hb S) to red blood cells. In sickle cells, there is a single amino acid mutation (at position 6 Glutamate becomes Valine). This is a substantial change in terms of the properties of the amino acids (because Glutamate is hydrophillic and Valine is hydrophobic, a hydrophobic patch on the surface of the protein is exposed).

In many forms of the disease the red blood cell changes form into a crescent-shape, or a sickle shape. The danger lies in the tendency for the sickle-shaped red blood cells to clog together and get stuck in vessels. This deprives the downstream tissues of oxygen and causes ischemia (reduction of blood flow to an organ, thus damaging tissues) or infarction (necrosis caused by arterial deprivation).

*It is important to note that "sickle-cell anemia" is the proper name of a specific type of "sickle-cell disease", and that "sickle-cell disease" is a non-specific term.

Sickle cell anemia: The person has most or all of the normal hemoglobin (HbA) replaced with the sickle hemoglobin (HbS). This is referred to as HbSS. It is the most common and most severe form of the sickle cell variations. These persons suffer from a variety of complications due to the shape and thickness of the sickled cells. Severe and chronic anemia is also a common characteristic for children with HbSS.

The allele responsible for sickle cell anemia is autosomal recessive. A person who receives the defective gene from both father and mother develops the disease; a person who receives one defective and one healthy allele remains healthy, but can pass on the disease and is known as a carrier. If two parents who are carriers have a child, there is a 1-in-4 chance of their child developing the illness and a 1-in-2 chance of their child just being a carrier.

Sickle cell RBC's contain long fibres of protein which give rise to the strange shapes of the cell. Since there are fewer cells and the cells that exist have abnormalities, the gas carrying capacity of the cells is greatly altered.

Symptoms

Patients with sickle cell anemia have a part varies in severity, with typical hemoglobin levels of 6-9 g/dl. Reticulocyte counts are elevated, reflecting new red blood cells replacing the rapidly destroyed older cells - red blood cell life span is markedly reduced in this disease. Often, the white blood cell and platelet counts are elevated, and these cells may contribute to vaso-occlusion.

The following is a list of symptoms and complications associated with sickle cell disease. However, each individual may experience symptoms differently. Symptoms and complications may include, but are not limited to, the following:

anemia - the most common symptom of all the sickle cell diseases. In sickle cell disease, red blood cells are produced but then become deformed into the sickle shape, which causes red blood cells to lose their oxygen carrying capacity. The body subsequently becomes dehydrated, or with a fever. This sickle shape makes the cells stiff and sticky causing them to become stuck in the vessels, destroyed by the spleen, or simply die because of their abnormal function. The decrease in red blood cells causes anemia. Severe anemia can make a person pale and tired, and makes the person's ability to carry oxygen to the tissues more difficult. Healing and normal growth and development may be delayed because of chronic anemia.

pain crisis, or sickle crisis - when the flow of blood is blocked to an area because the sickled cells have become stuck in the blood vessel. These are also called "vasoocclusive crises." The pain can occur anywhere, but most often occurs in the chest, arms, and legs. Painful swelling of the fingers and toes, called dactylitis, can occur in infants and children under 3 years of age. Priapism is a painful sickling that occurs in the penis. Any interruption in blood flow to the body can result in pain, swelling, and possible death of the surrounding tissue not receiving adequate blood and oxygen.

acute chest syndrome - when sickling is in the chest. This can be a life-threatening complication of sickle cell disease. It often occurs suddenly, when the body is under stress from infection, fever, or dehydration. The sickled cells stick together and block the flow of oxygen in the tiny vessels in the lungs. It resembles pneumonia and can include fever, pain, and a violent cough. Multiple episodes of acute chest syndrome can cause permanent lung damage.

splenic sequestration (pooling) - crises are a result of sickle cells pooling in the spleen. This can cause a sudden drop in hemoglobin and can be life threatening if not treated promptly. The spleen can also become enlarged and painful from the increase in blood volume. After repeated episodes of splenic sequestration, the spleen becomes scarred, and permanently damaged. Most children, by the age of 8 years old, do not have a functioning spleen either from surgical removal, or from repeated episodes of splenic sequestration. The risk of infection is a major concern of children without a functioning spleen. Infection is the major cause of death in children under the age of 5 years in this population.

stroke - another sudden and severe complication of persons with sickle cell disease. The misshapen cells can block the major blood vessels that supply the brain with oxygen. Any interruption in the flow of blood and oxygen to the brain can result in devastating neurological impairment. Having had one stroke, a person is 60 percent more likely to have a second and third stroke.

jaundice, or yellowing of the skin, eyes, and mouth - a common sign and symptom of sickle disease. Sickle cells do not live as long as normal red blood cells and, therefore they are dying more rapidly than the liver can filter them out. Bilirubin (which causes the yellow color) from these broken down cells builds up in the system causing jaundice.

Any and all major organs are affected by sickle cell disease. The liver, heart, kidneys, gallstone, eyes, bones, and joints can suffer damage from the abnormal function of the sickle cells and their inability to flow through the small blood vessels correctly. Problems may include the following:

- increased infections
- leg ulcers
- bone damage
- early gallstones
- kidney damage and loss of body water in the urine
- eye damage

The symptoms of sickle cell disease may resemble other blood disorders or medical problems. Always consult your physician for a diagnosis.
How is sickle cell disease diagnosed?

Treatment

Most patients with sickle cell disease have intensely painful episodes called vaso-occlusive crises. The frequency, severity, and duration of these crises vary tremendously, however. Painful crises are treated symptomatically with analgesics; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises a subgroup of patients manage on NSAIDs (such as diclofenac or naproxen). For more severe crises most patients require inpatient management for intravenous opioids; patient-controlled analgesia (PCA) devices are commonly used in this setting. Diphenhydramine is effective for the itching associated with the opioid use. Gene therapy is under investigation.

Other treatments offered:

- drinking plenty of water daily (eight to 10 glasses) or receiving fluid intravenously (to prevent and treat pain crises)

- blood transfusions: for anemia and to prevent stroke, blood transfusions may be used. Transfusions are also used to dilute the HbS with normal hemoglobin to treat chronic pain, acute chest syndrome, splenic sequestration, and other emergencies.

- penicillin (to prevent infections)

- folic acid (to help prevent severe anemia)

- hydroxyurea: Hydroxyurea is a medication that has recently been developed that may help reduce the frequency of pain crises and acute chest syndrome. It may also help decrease the need for frequent blood transfusions. The long-term effects of the medication, however, are unknown.

- bone marrow transplant: Bone marrow transplant has been effective in curing some persons with sickle cell disease; the decision to undergo this procedure is based on the severity of the disease and ability to find a suitable bone marrow donor. These decisions need to be discussed with your physician.