Sickle Cell Anemia

Sickle cell anemia is a common ailment in patients of African descent. This disorder is a very common reason for individuals to seek emergency medical treatment. Although we know a lot about the disorder and its treatment, it can still present in varied forms and present a diagnostic dilemma for the unwary emergency room physician. The condition can present with problems with any of the body systems. Sickle cell anemia is an inherited form of blood disorder which affects millions if individuals all over the world. In essence, the red blood cells which are designed to carry oxygen in the body are deformed and thus can no longer carry out their function. The red cells also develop a typical rigid sickle cell appearance. Not only do these cells function poorly but they also die prematurely and thus all individuals with sickle cell have a chronic shortage of red blood cells (anemia). Because of their abnormal structure, the red cells also tend to block and plug off the smaller blood vessels, thus depriving many tissues of oxygen. The blockage of the smaller blood vessels is what leads to the serious complications of sickle cell anemia. Today, more than 80-90% of individuals with sickle cell anemia make it to age 18. but this is not so in the rest of the World. It is believed that at least 8% of blacks in North America carry the gene for sickle cell disease. Estimates indicate that the disorder affects at least one in every 500 black American births. Today we have no cure and the treatment is generally supportive.

Sickle cell disease chiefly is a disorder limited to individuals of African descent and Hispanics of Caribbean ancestry. However, the disorder is also common in the middle east, Latin America and in the Mediterranean countries. Millions of individuals worldwide suffer complications from sickle cell disease. Data from the US indicate that at least 2 million African-Americans have the sickle cell trait. The disease affects both genders equally. Despite all the innovations in therapeutics, the majority of the affected individuals do not survive past the age of 50.

Sickle cell is caused by a defect in the hemoglobin molecule. Hemoglobin is the compound which binds to oxygen and when hemoglobin is deformed, sickle cell anemia can occur. Individual who have sickle cell have their hemoglobin named as Hb S. The disease is inherited genetically- each parent donates one gene. An individual must have two genes to have the disease and if there is only gene present, the individual is a carrier of the disease. In order for sickle cell to be passed to the next generation, both parents must pass the defective gene to the child. However, because the gene is recessive (not dominant), the chance of a child having sickle cell anemia is 25%, there is a 50% chance that the child may be a carrier and 25% chance that the child may be normal.

We now know that the defective hemoglobin gene that causes sickle cell anemia evolved centuries ago in Africa and the Middle East. In these parts of the world, malaria is very common and kills millions of individuals each year. The malaria vector requires a high concentration of oxygen in the body to survive. With changes in evolution, it is believed that the abnormal gene in hemoglobin occurred to prevent the survival of the mosquito vector in blood- due to the decreased oxygen. This resulted in increased survival of sickle cell individuals and avoiding malarial infections. Once the hemoglobin is deformed, it is no longer able to carry oxygen efficiently. In addition, the abnormal hemoglobin results in an abnormal shape of the red cells which creates difficulty in gliding through the small blood vessels. These sickle shaped cells plug up the small blood vessels in all parts of the body causing blockage of blood. Further, the red blood cells with defective hemoglobin become rigid and appear like a “sickle”. These deformed crescent-shaped cells are unable to pass through the small blood vessels and are responsible for the pain and organ damage that is so common in sickle cell anemia. The normal life span of red cell is about 120 days; sickle cell cells only live for 10-20 days. The body can't not replace them very fast and thus a condition called anemia results.

In most individuals with sickle cell anemia, the disease can be very unpredictable and variable in presentation. Some individuals have no problems but others have recurrent crises which requires hospital admissions. Sickle cell crises can be worsened or precipitated by the following: - cold weather (causing spasm in the blood vessels) - extreme hot weather (causing dehydration) - infection - alcohol intoxication - pregnancy - Stress

Not all individuals with sickle cell develop the disease. Those who have only one gene develop the sickle cell trait. These individuals have no signs or symptoms of the disease. Estimates indicate that 1 in 12 black African Americans may have the sickle cell trait. Only individuals with two genes develop the disease- one gene inherited from each parent. In most individuals, the first signs and symptoms will occur in early childhood (at around 4-9 months). The disease can be very variable in presentation- some have mild disease and in others the disease may be severe and life threatening. The typical presenting features of sickle cell anemia include:

 

Anemia: The red cells are distorted in shape and very fragile. These cells break up prematurely and thus the entire body remains short of oxygen. Because the red cells are in short supply, the individual develop a condition known as anemia. The symptoms of anemia may include constant fatigue, tiredness and even shortness of breath.

 

Pain: Sickle cell crises are known to produce pain. The pain is cyclical in nature and is a common presenting sign. The pain occurs when the abnormal sickle cells block blood supply to the organs. Usually the blood supply to the heart, bones and joints is blocked and the pain arises from these organs. The pain in most cases is pretty severe and most individuals require hospital admission. The pain may vary in intensity and can last for a few hours to a few weeks. Some individuals experience a few of these painful episodes a year; others who are not so fortunate may have these painful episodes once a month. The pain is generally severe enough to require intravenous narcotic infusions.

 

Hand-foot syndrome: Almost all individuals with sickle cell anemia develop swelling of their hands and foot. This swelling is much more common in the childhood stages and is due to lack of blood flow. In time, many of these individual lose the tips of their fingers and toes.

 

Jaundice: Yellowish discoloration of the skin and eyes is a common presenting feature in sicklers. The constant breakdown of the red cells results in the breakdown of hemoglobin which is further broken down in to a yellowish pigment.

 

Frequent infections: Sickle cell anemia destroys the spleen and thus these individuals are not able to fight off infections. Thus, a common presentation is infections of the lungs, skin and body.

 

Stunted growth: Because these individuals are deprived of oxygen and nutrients, the growth is stunted. The majority of these individuals have delayed puberty and severely stunted growth.

 

Vision problems: Because the abnormal cells plug up the small blood vessels in the eye, the majority of sickles will at some point in their life have visual problems, which are progressive.

 

Stroke: Because of sludging of the red cells, a stroke is a common occurrence in individuals with sickle cell anemia. The individual may present with weakness, inability to speak or swallow or have loss of consciousness. This is a common presentation in many emergency rooms but fortunately, most strokes are not of a severe nature.

 

Acute chest syndrome: Difficulty breathing, chest pain and shortness of breath is a typical presentation of sickle cell crises. The most common cause of an acute chest syndrome is a pneumonia. These individuals need urgent antibiotics, oxygen and even blood transfusion. Pain control is essential. For those who have recurrent chest attacks, the lung can become damaged over time.

 

Ulcers: The majority of individuals with sickle cell anemia develop ulcers on the leg. These painful ulcers are difficult to heal and are generally caused by lack of blood.

 

Gallstones: The increased breakdown of blood can result in formation of gall stones. Unlike the cholesterol gall stones seen in normal individuals, the gall stones in sicklers are pigmented and darkly colored.

 

Priapism: An unfortunate complication of sickle cell is priapism (painful erection). The prolonged and painful erections are due to blockage of the blood vessels in the penis. The penis stays rigid for prolonged times and is not associated with any desire for sexual activity-infact sex is the last thing on their minds. In some cases, surgery has to be performed to relieve the congestion in the penis.

The diagnosis of sickle cell anemia is straight forward. A simple blood test can determine the presence of hemoglobin S. In North America, this blood test is routinely done in all newborns. Once Hb S is identified, the presence of the sickle gene is determined. The diagnosis is then confirmed by looking for the sickle cell shaped cells underneath a microscope. In addition, other blood work may reveal a low red cell count (anemia). All newly diagnosed individuals are referred to a physician who is specialist in dealing with sickle cell anemia. Sickle cell anemia can even be detected by sampling the amniotic fluid during pregnancy. This test can determine if the unborn baby has the disease or is the carrier.

The essence of treatment is aimed towards prevention of the sickle cell crises. In order for this to work, all individuals with sickle cell anemia need to be regularly seen by a physician. The care of these individuals usually involves several specialists- who can monitor the disease and its progression. All women of childbearing age with sickle cell anemia should undergo genetic counseling. For those trying to prevent pregnancy, the intrauterine device should be avoided as it is prone to infection and can precipitate sickle cell crises. Females with sickle cell who do get pregnancy must be carefully monitored. Pregnancy in sicklers is known to be associated with an increase in blood pressure, premature births and infants who are very small in size- all of which leads to a high death rate. Pregnancy can also precipitate sickle cell crises. Close monitoring by physicians during pregnancy is a must. For those who have acute crises, hospital admission is very likely and if the disease is not managed properly, it is associated with numerous complications and even death. The basic care of any sickle cell crises involves:

Oxygen: this can relieve the pain and improve the crises. In some cases, the individual may even need to be placed on a mechanical ventilator to over come the crises.

Fluids: Intravenous fluids can help hydrate the individual and relieve the crises.

Pain control: No matter how simple or complicated the presentation of the sickle cell individual, pain is a constant feature and difficult to control. Part of the problem is that the physicians lack the expertise in dealing with pain and have a fear of patient addiction to narcotics. Most of these individuals require large amounts of narcotics to ease the pain. A consultation by a pain specialist is highly recommended.

Antibiotics: If an infection is suspected, antibiotics must be started immediately. In children with sickle cell anemia, it has been observed that taking penicillin since birth up to the age of 5 years helps prevent major infections.

Blood transfusions: When an individual with sickle cell crises is found to have a low red blood cell count, blood transfusions are essential. They relieve the anemia, improve breathing and pain. However frequent red blood cell transfusions also carry their own risks. Blood contains a lot of iron and frequent transfusions can result in iron build up in the body. This excess iron can damage the heart, liver, pancreas and kidney. In order to prevent this iron build up, sickle cell individuals have to take a drug which will bind the excess iron and excrete it. Last but least, blood transfusions are also associated with transmission of various infections including hepatitis and HIV.

Hydroxyurea: One drug which has been found to be very effective in the control of sickle cell crises is hydroxyurea. This drug when taken during sickle cell crises significantly reduces the duration of pain and also lessens the need for blood transfusions. It is believed to work by preventing the formation of the sickle cell hemoglobin. However, the drug can only be taken for a short while as there is concern that it may cause tumors such as leukemia. Numerous studies have shown that hydroxyurea decreases mortality and complications of sickle cell anemia. However, it is a toxic drug and it has to be monitored

The ultimate therapy for sickle cell patients is a bone marrow transplant. It is a cure but the procedure is extremely high risk and the results are not guaranteed. The problem is trying to find a suitable donor which is always a major stumbling block. Marrow transplants are done all over North America but the procedure is only for the most serious cases of sickle cell crises. The procedure is technically simple but fraught with complications. The sicklers own marrow is destroyed to kill all the bad red blood cells. One may use either chemotherapy or radiation to destroy the bone marrow. Following this, a matched donor’s healthy bone marrow is transfused. More often than not, the procedure fails. The hospital stay is always long and there is a life long need for chemotherapeutic drugs to prevent rejection.

Advances are constantly being made in medicine and newer treatments for sickle cell include: Gene therapy: Gene therapy is a futuristic concept. Research is currently being done to determine how to turn off the defective gene or perhaps activate another gene that prevents formation of the abnormal hemoglobin. This therapy is light years away from reality.

Butyric acid: Some studies have shown that this common food additive may increase the fetal hemoglobin levels and diminish the levels of HbS. Current trials are underway. Clotrimazole: This commonly used anti fungal drug has been shown to reduce formation of sickle cells. However, the clinical results are scant and conflicting and trials are needed to determine if it is really effective

Nitric oxide: It is well known that individuals with sickle cell anemia have low levels of nitric oxide. This gas is known to open up the blood vessels and decrease the stiffness of the red cells. However, the treatment requires hospital admission and is only effective for short periods. Administration of the gas is technically difficult and requires special machines. Various other chemicals are being investigated for their potential in the treatment of sickle cell anemia. These chemicals are anti oxidants and drugs which can prevent sludging of the red cells. Most recently, a few studies show that early bone marrow transplant (in childhood) may be a lot safer and offer a life long cure.

Unfortunately, we have no cure for this dreaded disease. But it can be prevented. For those who carry the sickle cell trait, genetic counseling may be helpful prior to conceiving a child. The genetic counselor can help determine the risk and probability of having a child with the disease. Advances in In-vitro fertilization have been suggested as a means of early detection- however the majority of these techniques are expensive and have a very high failure rate.

Sickle cell is a life long disease and it is essential to maintain good care. Diet and staying healthy is critical to preventing the crises of the disease. Some of the ways to maintain a good health is: - vaccination: make sure you are immunized against the annual common flu - take vitamins: folic acid helps replenish the red blood cells - keep well hydrated by drinking water - avoid extremes of temperature- both hot and cold can trigger sickle cell crises - Protecting yourself from infections can help prevent crises. - Relax and avoid stress - Fly in commercial airlines which are pressurized- anything which lowers oxygen can trigger sickle cell crises - Do not go climbing mountains or deep sea swimming- both are associated with lack of oxygen and can trigger sickle cell crises. - Avoid extremes of exercise

For those with a diagnosis of sickle cell anemia, it is quite traumatic and stressful. To help cope with the disease, there are numerous sickle cell centers and support groups. Coping systems may vary from massage, acupuncture, praying, family or friends support. If you or your child has sickle cell anemia, the best way to cope is to be more knowledgeable about it. This will help you seek the best health care available.