IHTC NEWS:

Sickle Cell Disease

• Acute Chest Syndrome
• Aplastic Crisis & Intervention
• Chronic Problems
• Fever Management
• Hydroxyurea
• Pain Management
• Pregnancy
• Simple Facts about Sickle Cell
• Splenic Sequestration
• Stroke Intervention
• Transfusion Therapy
• Clinics
• Emergencies
• Resources

Sickle Cell Disease

Sickle cell disease is the most common hereditary blood disorder in the world.  Early comprehensive treatment has changed sickle cell disease from a pediatric disease with high mortality to one in which patients live productive lives throughout adulthood.  It most commonly affects African Americans, as well as some persons of Mediterranean, East Indian or Latin American descent.  In the United States, it is estimated that 80,000 Americans of various ethnic backgrounds are affected with sickle cell disease.  About 8% othe African-American population carries the sickle cell trait.  Sickle cell disease affects approximately 1 in 400 African Americans.

Many patients never receive the information needed to make educated decisions about treatment. Many patients receive medical care outside of comprehensive centers. These patients and providers need information concerning new research into clinical symptoms including: anemia, bone infarctions, cerebrovascular events (stroke), cholelithiasis (gallstones), infections, leg ulcers, painful episodes, pregnancy, priapism (sustained erections), pulmonary hypertension, kidney disease, and problems of the eye.  They need information regarding transfusion therapy (simple and exchange transfusions), ongoing research studies, new chelation therapy, and bone marrow transplantation.

Patients can achieve a future including employment, marriage and children. To attain this, families and providers need information concerning psychological wellness, cultural issues and counseling for family planning and marriage. We hope to provide patients and their families with the necessary information to make informed decisions and achieve optimal quality of life. We hope to raise awareness for this disorder, and encourage people to get tested to see if they carry sickle cell trait.

Hemoglobinopathies
Sickle cell diseases are a group of hereditary hemoglobinopathies.  Hemoglobinopathies are a group of diseases caused by production of abnormal hemoglobin in the red blood cell.  Hemoglobin is the component of the red blood cell that transports oxygen from the lungs to body organs and tissues and returns carbon dioxide to the lungs.  Sickle cell anemia (hemoglobin SS) is but one type of sickle cell disease.  There are several other sickling disorders including:  hemoglobin SC disease, sickle cell beta thalassemia, hemoglobin SD disease, hemoglobin SE disease, and hemoglobin SOArab disease.  All of these disorders have defects in the hemoglobin causing red blood cells to distort into a sickle shape. 

In the normal adult, hemoglobin A (adult hemoglobin) is the most prevalent.  Hemoglobin A accounts for about 95% oall hemoglobin.  Hemoglobin A is composed of 2 alpha and 2 beta globins (22).  Two minor hemoglobins also occur in the normal adult.  They are hemoglobin A2 which accounts for 2-3.5% ohemoglobin.  Hemoglobin A2 is made of 2 alpha and 2 delta globins (22).  The other is hemoglobin F (fetal hemoglobin) which accounts for less than 2% ohemoglobin.  Hemoglobin F is composed of 2 alpha and 2 gamma globins (22). 

Hemoglobin F is produced by the fetus.  Hemoglobin F has a high affinity for oxygen and attracts oxygen from the mother’s blood to deliver it to the fetus while still in the uterus.  After birth, the production of adult hemoglobin rapidly increases and fetal hemoglobin production decreases.  By one year of age, the baby’s production of fetal hemoglobin is the same as that of an adult.

In a sickle cell patient, a single gene substitution that codes for the  chain of the hemoglobin molecule is responsible for the formation of hemoglobin S.  Persons with sickle cell disease inherit the gene for abnormal hemoglobin production from both parents.  There is no gene present to instruct the body to make normal adult hemoglobin (hemoglobin A).  Persons with these disorders have a prevalence of hemoglobin S in their cells.  Because of the distortion caused by the defective hemoglobin, the red blood cells become stiff and rigid, and can cause blockage or rupturing of small blood vessels that supply oxygen to the organs and tissues.  Sickle cell diseases can cause chronic anemia (low red blood cell counts), decreased resistance to infections, damage to the organs (particularly the lungs and kidneys), and are responsible for both acute and chronic pain.

Treatment
Early diagnosis of sickle cell disease is crucial so that children can receive proper medical care.  Proper care requires a comprehensive approach to treating the disease including therapy for infections, pain, other complications, and treatment of the psychological aspects of having a chronic disease.  Treatment for adults primarily consists of management of symptoms.  Antibiotics and vaccines are used to treat and prevent infections.  Folic acid should be taken on a daily basis to help with the anemia.  A variety of pain medications are used to treat the painful conditions associated with sickle cell disorders.  Patient need to drink large amounts of fluids to prevent dehydration. 

Sickle Cell Trait
People who carry the gene for sickle cell disease are said to have sickle cell trait (or a sickle cell carrier).  Sickle cell is a genetic disease.  That means that a person can only get sickle cell disease or trait by inheriting the genes from their parents.  Genes determine what we look like, such as hair or eye color, and are also responsible for many diseases.  Sickle cell disease cannot be ‘caught’ by another person, such as people ‘catch’ the cold or flu.  People with sickle cell disease and trait are born with it.  People born with sickle cell trait cannot develop into sickle cell disease.  In Indiana, all newborns are screened for the presence of sickle cell disease and sickle cell trait.

One in 10 persons of African decent carry the gene for sickle cell disease.  Individuals with sickle cell trait have some level of protection from Malaria.  Therefore, although sickle cell trait is found in all populations, it is most common in people from regions where Malaria occurs.  Most people who have sickle cell trait do not have any symptoms.  The only way to know if you have sickle cell trait is to have a special blood test called a hemoglobin electrophoresis.  Rarely, some persons with sickle cell trait may experience minor symptoms.  Special accommodations should be made for persons with sickle cell trait during extreme strenuous physical activity such as military training, or athletics at the collegiate or professional level.  If you have sickle cell trait and are involved in such activities, inform your medical staff or athletic trainers that you have sickle cell trait.

Adults with sickle cell trait can pass the abnormal hemoglobin gene to their children.  If two persons who carry the gene for sickle cell disease, or another hemoglobinopathy (hemoglobin C,  thalessemia, hemoglobin D, hemoglobin E, or hemoglobin SOArab) have a child, that child can have sickle cell disease.  If that child inherits both abnormal genes from both parents the child will have sickle cell disease.

With each pregnancy, there is a 50/50 chance that each parent who has sickle cell trait (or carries the gene for another hemoglobinopathy) will pass the sickle cell gene onto their children.  This inheritance happens purely by chance – there is nothing parents do, or do not do, that will cause their child to inherit the gene for sickle cell disease.  The defective gene must be inherited from each parent to have sickle cell disease.


Complications of Sickle Cell Disease
In a comprehensive approach to managing complications of sickle cell disease, patients should be seen in the clinic for a regular office visit at a time when they are not having pain crisis at least 2 times per year.  Early detection of organ damage is advantageous to begin treatments to prevent further damage.  Patients need to see an eye doctor at least once per year.  Patients with other chronic health issues will need to be seen by other doctors or specialists as well. 

Infection
Patients with sickle cell disease are more likely to have infections because their spleen doesn’t work properly.  This impacts both the clearance of bacteria from the circulation and impaired antibody synthesis.  Infections in adults tend to occur in the areas of the body damaged by recurrent sickling such as the lungs (pneumonia), kidneys (urinary tract infection), or bones.

We recommend routine vaccinations for all patients with sickle cell disease to decrease their risk of developing an infection.  All patients should receive the pneumonia vaccine every 3-5 years and the flu shot annually.  Other routine immunizations for hepatitis and tetanus should be administered as well.

Vaso-occlusion
Sickle cell painful episodes are caused by ischemic tissue injury from obstruction of blood flow by sickled red blood cells, called vaso-occlusion.  Lack of blood flow results in regional hypoxia (low oxygen levels) and acidosis, which perpetuate the sickling process.  Painful episodes usually last 4-7 days but can last longer.  Hypoxia, infection, dehydration, menstruation, sleep apnea, and exposure to cold temperatures can precipitate vaso-occlusive episodes.  Often, there is no precipitating factor identified.

Acute Chest Syndrome
This is a term used for a condition characterized by abnormal findings on a chest X-ray with chest pain, cough, fever, and low oxygen levels.  It can be caused by sickling in the blood vessels in the lungs, or by pneumonia.  Patients with acute chest syndrome must be admitted to the hospital and monitored very closely.

Splenic Sequestration
This is most common in children with sickle cell disease.  During splenic sequestration, large amounts of blood pool in the spleen.  The blood filled spleen may enlarge to the point of filling the entire abdomen.  There may be a very rapid and dramatic drop in blood counts resulting in hypovolemic shock.  These patients are hospitalized, as their condition can change very rapidly.  The treatment for splenic sequestration is volume expanders and blood transfusions as needed until the spleen returns to its normal size.  If patients have more than one episode of splenic sequestration, surgery to remove the spleen may be recommended.

Stroke
Stroke is an acute neurological syndrome caused by blockage of an artery or a hemorrhage with resultant ischemia and neurological signs and symptoms.  Stroke occurs in about 10% opatients with sickle cell disease under age 20.  Centers are identifying those children at greater risk for stroke with routine transcranial Doppler ultrasound.  This is the only predictive tool available to identify patients at increased risk of stroke.  Those with an increased risk of stroke should be offered chronic transfusion therapy.

Sickle Cell Eye Disease
Vaso-occlusion (blockage of blood flow) can occur in the blood vessels in the eyes.  Early stages often do not produce symptoms.  Yearly evaluation by an ophthalmologist is recommended for all patients with sickle cell disease.  Opthalmologists have specialized equipment to detect early damage in the eye and initiate treatment before symptoms worsen.  Untreated damage due to sickle cell disease can cause visual loss from bleeding and retinal detachment.

Sickle Cell Emergencies
Patients with sickle cell disease are taught to look for symptoms that could indicate an underlying emergency condition.  The presence of any symptoms requires immediate evaluation by a medical provider.  These include a fever greater than 100F, chest pain, cough, or shortness of breath.  Acute onset of anemia can cause weakness, shortness of breath, or dizziness.  Abdominal pain with nausea and vomiting may indicate an emergency involving the spleen.  Respiratory infection with a productive cough, symptoms of a urinary tract infection, or unusually severe headaches should all be evaluated by a health care provider.

Children may not be able to express these symptoms as clearly.  Therefore, it is extremely important that children with fever greater than 100F be evaluated by a medical provider, either in the clinic, or in the emergency room.  Other signs of a possible complication are chills, lethargy (excessive tiredness, or “droopy”), irritability, poor feeding, or vomiting.  These signs also warrant further evaluation by a medical provider.

Treatment
Treatment for adults primarily consists of management of symptoms.  Antibiotics and vaccines are used to treat and prevent infections.  A variety of pain medications are used to treat the painful conditions associated with sickle cell disorders.  Patient need to drink large amounts of fluids to prevent dehydration. 

Hydroxyurea
Hydroxyurea (Hydrea) is the only drug that has been approved by the US food and Drug Administration (FDA) to treat sickle cell disease.  Hydroxyurea causes the body to produce fetal hemoglobin.  Fetal hemoglobin is normally only found in children for a short time after birth before it is naturally replaced by adult hemoglobin.  Studies have found that persons with sickle cell disease who had a high concentration of fetal hemoglobin in their blood experience a milder disease.  Hydroxyurea holds a lot of promise for increasing the lifespan and lowering the complications of persons with sickle cell disorders.

Bone marrow transplation
At this time, the only true cure for sickle cell disease is bone marrow or stem cell transplantation. The bone marrow nurtures stem cells, which are early cells that mature into red and white blood cells and platelets. By destroying the sickle cell patient's diseased bone marrow and stem cells and transplanting healthy bone marrow from a genetically-matched donor, normal hemoglobin may be produced. Clinical studies using a few carefully selected patients have reported very successful results.  Unfortunately, only about 7% mt the criteria for transplantation, include those who:

• Are age 16 or younger
• Have severe symptoms but no long-term organ or neurologic damage
• Have a genetically matched brother or sister who will donate their marrow

Please discuss this with your medical providers if you have any questions

Prognosis
The prognosis in sickle cell disease has dramatically improved over the past 30 years.  The Cooperative Study of Sickle Cell Disease (CSSCD) published in the American Journal of Pediatric Hematology/Oncology in 1982 estimated a mean survival of 42 years for males and 48 years for females with hemoglobin SS disease.  The estimated mean survival for those with hemoglobin SC disease was 60 years for women and 68 years for men.  There are a significant number of persons living with sickle cell disease that are over age 50, and some are living into their 70’s and 80’s.  Our center’s oldest patient living with sickle cell disease is in his mid 60’s.

There are unique challenges for the aging adult with sickle cell disease.  Repetitive sickling over time causes damage in many organ systems in the body.  Diseases of the retina increase with age.  Damage to the kidneys and lungs compound over time as a result of repeated sickling episodes.  Leg ulcers and damage to the bones can occur causing chronic pain and disability.  It is imperative that adults with sickle cell disease see their health care providers on a regular basis for routine check-ups to evaluate for these complications early, so that treatment can be initiated early in the course of the disease.  Persons with sickle cell disease need to see their eye doctor at least once per year.  Persons with sickle cell disease can experience other common health problems that do not result from their sickle cell disease.  They also need routine screenings for hypertension, diabetes, coronary vascular disease, and age appropriate cancer screenings.

Research
The IHTC is involved a variety of research studies to better understand the complications of sickle cell disease.  It is our hope that this research will allow the medical community at large to develop treatments to prevent or minimize complications, prolong and improve the quality of life for those with sickle cell disease.  Through the IHTC, patients have access to national multicenter studies.

If you are interested in participating in a research study, please let a member of our heathcare team know.

Please check the website often, we will be enrolling patients for future studies soon!

Educational Materials

    About Sickle Cell Disease and Sickle Cell Trait (ISDH)
    Sickle Cell Anemia and Sickle Cell Trait (ASCAA)


Healthcare Provider Links
    Sickle Cell Disease Guidelines for Children and Adolescents (on CO website)
    Health Supervision for Children with Sickle Cell Disease
    Management of Patients with Sickle Cell Disease
    Grady Protocols