Chronic anemia is present in all individuals with sickle cell disease. It is generally asymptomatic, though patients report chronic fatigue and exercise intolerance. Vaso-obstruction and pain are the major presenting symptoms of the disease. The precipitating cause of the vaso-occlusive crisis is often not clear but include the following :
Mandatory neonatal screening in the United States identifies new cases. Symptoms do not occur in the first 6 months of life because of the persistence of fetal hemoglobin (HbF). After 6 months of age as fetal hemoglobin levels decrease and the percentage of sickle hemoglobin increases, symptoms begin to appear. Hand and foot syndrome is often the presenting sign (6 mo.-5 yr.). The bone marrow of the small bones of the hands and feet is very active in infancy and early childhood. This activity level increases the risk of ischemia and infarct. It results in acute swelling, erythema, and severe pain of the hands and feet. Onset is sudden and duration short .
A complete history and review of symptoms should be completed at each visit. This should include the history of:
A comprehensive physical examination should pay particular attention to indicators of vaso-obstruction and infection, as well as evidence of complications of the disease.
Diagnosis of sickle cell disease is confirmed by the presence of homozygous HbS through hemoglobin electrophoresis. The presence of heterozygous HbS indicates a carrier of the sickle cell trait. Prenatal diagnosis may be made using DNA analysis with chorionic villus sampling at 8 to 12 weeks gestation or amniotic fluid testing at 6 weeks gestation.
Baseline blood studies should be done on all patients. Management of sickle cell disease should include regular routine blood work. The following schedule is suggested :
Other suggested testing:
Magnetic resonance imaging (MRI) is the best method for detecting early signs of osteonecrosis and osteomyelitis. It can distinguish between osteomyelitis and bony infarction and can detect changes in the bone marrow early. It can also identify the presence of silent cerebral infarcts, helpful for stroke prevention . An abdominal ultrasound should be used whenever patients present with abdominal pain to rule out cholecystitis, cholelithiasis, or ectopic pregnancy. Routinely the procedure can be used to measure and monitor spleen and liver size . Ultrasonography of the kidneys can detect causes of obstructive uropathy, nephrolithiasis, and papillary necrosis. Echocardiograms can identify pulmonary hypertension. Adults should be tested annually. Echocardiography should be performed on all patients with dyspnea .
The goal of treatment is two-fold; symptom control and prevention and management of complications. Treatment is aimed at :
Pneumococcal pneumonia vaccine is of greatest importance as pneumococcal pneumonia is a leading cause of morbidity and mortality in individuals with sickle cell disease. Recommended vaccines are:
Hydroxyurea therapy: Hydroxyurea is currently the only drug approved by the US Food and Drug Administration for the treatment of sickle cell disease. It increases the total fetal hemoglobin which retards the formation of polymers and sickling of red blood cells. It also reduces circulating leukocytes, decreasing inflammation . Hydroxyurea therapy has proven to decrease the frequency and severity of crises. It has been shown to reduce the number of hospitalizations and to limit the need for transfusions. Patients should be monitored for leukopenia and thrombocytopenia. Complications from long-term usage are not yet known. Efficacy in children has not been proven.
Other medications used in controlling symptoms include:
Vigorous hydration is needed to prevent acidosis, maintain circulating volume, and prevent venous stasis. This intervention decreases the incidence of sickling episodes. There are no dietary restrictions associated with the disease. However, a well-balanced diet is essential to maintaining health and preventing infection.
Oxygen therapy may be necessary during acute episodes to prevent hypoxia. It is not recommended for routine use to treat chronic anemia. It is imperative in acute chest syndrome, congestive heart failure and severe pneumonia. Incentive spirometry may be helpful in patients with respiratory complications or acute respiratory illness.
Transfusions are reserved for the treatment of sudden severe anemia due to acute splenic sequestration, para-virus B19 infection, hyper-hemolytic crises, and acute chest syndrome. They are also necessary peri-operatively and during pregnancy. Complications of transfusions include:
Erythrocytaphoresis is an automated red blood cell exchange procedure. The process exchanges blood containing HbS while replacing it with HbS free blood .
Alternative therapies that may be of help in the control of chronic pain include:
Bone marrow transplantation can be a cure for sickle cell disease. After the destruction of defective HbS bone marrow with radiation or chemotherapy, normal bone marrow replaces it. The use of this therapy is limited because it requires a matching sibling donor who is free of the disease or trait.
Stem cell transplantation is still experimental but has hopes of being a more realistic cure for the disease.
Sickle cell disease is a life–long progressive disorder marked by episodic vaso-obstructive crises resulting in chronic morbidity and early mortality. Morbidity varies from individual to individual. Symptomatology and complications increase with age. Life expectancy has been extended in the past twenty years and is now estimated to be >50 years. This change is due to the development of the vaccine for pneumococcal pneumonia, increasing use of Hydroxyurea therapy, and improved monitoring and control of complications .
Sickle cell disease originated in West Africa where it has the highest prevalence still. Through migration and dispersion, the genetic mutation spread and is now seen worldwide. The distribution is related to the collocation of endemic malaria and sickle cell disease. The heterozygous form (Sickle cell trait) seems to have Malaria inhibiting qualities. Individuals who carry the HbS trait have a lower incidence and severity of the disease.
The incidence rate for sickle cell disease in the United States is approximately 8,000 annually or 1 per 500 African American births . Prevalence is about 72,000 Americans. While 2 million people or 1 in 12 African Americans carry the sickle cell genetic trait.
Sickle cell disease arises from a gene mutation which substitutes thymine for adenine on the 6th beta-globin chain of the hemoglobin molecule (GAG to GTG) . The resulting sickle hemoglobin (HbS) forms a gel-like polymer when deoxygenated. This polymer gradually forms parallel filament strands which cause the red blood cells to sickle. Sickled cells have antigen-4 (VLA-4) on their surfaces which causes them to adhere to the vascular endothelium obstructing the microvasculature.
Vaso-obstruction is responsible for the symptoms and complications associated with the disease . Inflammation of the endothelium occurs secondary to ischemia. There is a sudden influx of leukocytes to the area causing swelling, narrowing and eventual obstruction of the microvasculature. Acute pain crises are a directed result of ischemia and infarct of tissues and organs following an acute vaso-obstructive episode. Deprived of oxygen, cells in the affected area are damaged. Inflammation, swelling, erythema, and eventually necrosis occur.
There are no guidelines for prevention of sickle cell disease.
Sickle cell disease is an autosomal recessive hemolytic anemia. It is a genetic disorder affecting primarily Africans (African Americans) . It is the most common genetic blood disorder in the United States. Sickle cell disease is caused by a mutation of the gene responsible for hemoglobin production. Red blood cells carrying the defective hemoglobin (HbS) change shape when deoxygenated forming the characteristic sickle shape. These cells become ridge and friable, leading to increased hemolysis. This alteration in the red blood cells is responsible for the major symptoms and complications of the disease.
The cardinal signs of sickle cell disease are :
What is sickle cell disease?
Sickle cell disease is an inherited/genetic disorder that affects the body’s red blood cells. It is passed from both parents who carry the sickle cell trait to their child. In this disease, defective hemoglobin, which carries oxygen in the blood, causes the red blood cells to change shape into the characteristic sickle shape.
Normal red blood cells are round and are able to move through small blood vessels in the body to deliver oxygen. The sickle-shaped cells are rigid and adhere to the walls of the small blood vessels. The defective red blood cells obstruct the vessels and clog the flow of blood and oxygen to the tissues and organs of the body.
Sickle cell disease is found most often in African-Americans and Africans. However, other ethnic groups can have sickle cell disease.
Sickle cell disease is diagnosed by hemoglobin electrophoresis, which determines the type of hemoglobin one has.
People who inherit only one sickle cell gene are carriers, but people who inherit two sickle cell genes have sickle cell disease.
What are the symptoms of sickle cell disease?
Newborn screening in the United States identifies babies with the disease at that time. In those individuals who have not been identified at birth, the following symptoms might indicate the need for testing for the disease.
What are the medical problems of sickle cell disease?
Medical problems associated with sickle cell disease include:
How is sickle cell disease treated?
Currently, there is no cure for sickle cell disease. Treatment of sickle cell disease depends upon the symptoms a person is experiencing. Some medicines that can be used to treat sickle cell disease-related pain include:
New treatments for sickle cell disease are improving life expectancy and quality of life.
What can you do to prevent complications of the disease?
If you or a member of your family has sickle cell disease you can go a long way toward preventing the complications associated with the disease. The following guidelines are important.