Understand Childhood Cancers and Blood Disorders
Sickle Cell Disease (SCD)
Sickle cell disease is an inherited disorder characterized by abnormally shaped red blood cells resembling crescents, or half moons, instead of the usual donut configuration. The disorder occurs most frequently in people of African ancestry but can be found in other populations as well (e.g., Mediterranean and Middle Eastern descent). There are about 70,000 Americans with sickle cell anemia. About 2 million Americans (one in every 12 African Americans) - have sickle cell trait, a carrier state that does not cause symptoms but can affect children. Until about 40 years ago the average life span of a patient with SCD was about 15 years, but today, owing to advanced treatments, early detection methods, blood transfusions, and infection prevention, the average life span of such patients has increased to 50 years of age, with many exceeding that age.
Sickle cells are more sticky and rigid than normal cells, and will lead to numerous complications related to obstruction of blood flow. These abnormal cells cannot flow through small blood vessels, and instead clog them. The result of the obstruction is that tissues cannot get the oxygen and nutrients they need, resulting both in acute crises, as well as chronic organ damage. Unlike normal red blood cells that survive about 4 months in the bloodstream, sickle cells hemolyze (break down) within about 10 to 20 days, resulting in anemia.
Vaso-occlusive syndrome ("painful crisis") - this is the most common complication in SCD patients. It can present as early as 6 months of age as a painful swelling of the feet and hands (called dactylitis or Hand-Foot Syndrome). These crises vary in severity, frequency, and duration. Whereas one person may have only one sickle cell crisis a year, another may experience them more frequently. Painful crises may be brief lasting just hours, or may be prolonged, lasting days or even weeks. Symptoms can develop in any body organ or tissue, and include aching arms, legs, hips, back, and shoulders. Most patients tend to have the same sort of crisis each time, affecting the same region of the body, but on occasion will have pain in other areas. The frequency of painful crises also may change with age. The mainstay of treatment of such crises is vigorous hydration and pain medication. The treatment of pain must be customized, with some patients managing with oral medications, while others with more severe crises require intravenous medications, sometimes self administered by the patients with PCA (patient-controlled analgesia) pumps.
There are ways to try to avoid or minimize the occurrence of painful crises -
- Drinking plenty of fluids (at least 6 glasses of water a day, especially during warm weather or when exercising).
- Avoiding exposure to extreme cold temperatures (wear warm clothes outside in cold weather and inside in air-conditioned rooms during hot weather). Also, avoid swimming in cold water.
- Avoid potentiating factors, such as alcohol and smoking.
- If you are pregnant or plan a pregnancy, get early prenatal care and notify your hematologist.
- Tell the doctor if you think your child might have a sleep problem, such as snoring, or if he or she sometimes stops breathing for short periods of time during sleep (called "sleep apnea").
- Treat any infection as soon as it occurs. Notify the doctor of any fever over 100.4�F.
- Air travel is safe in modern commercial airplanes because they are properly pressurized. Avoid any flights in unpressurized airplanes.
- Reduce or avoid stress. Job, school, or family problems can contribute to exacerbations of SSD.
- If a child has another medical condition, like diabetes, it, too, must be treated and controlled.
- Exercising regularly is great but not so much that the child gets very fatigued.
- Quite often, your child's mild painful crisis pain can be treated at home with pain medicines and plenty of fluids. If the medicines fail to resolve your child's pain, contact your hematologist's office or bring your child to the emergency room. If the pain still cannot be controlled or your child has other problems, he or she may end up being admitted to the hospital for more comprehensive care.
Acute Chest Syndrome (ACS)
This is the second most common cause of hospitalization for SCD patients. ACS is unpredictable - it can start quite suddenly and with varying degrees of severity. Typical signs and symptoms include fever, chest pain, cough, and difficulty breathing. Many of the preventative measures mentioned above for painful crisis would hold true for ACS. These patients are nearly always admitted to the hospital for observation and blood transfusions or exchange blood transfusions (where a patient's blood is removed in small amounts and replaced with fresh donor blood).
Priapism is a prolonged and painful erection of the penis that can last from several hours to a few days. This type of erection is NOT associated with sexual thoughts or sexual activity. What happens is that blood flows into the penis, but is unable to drain as it would in a normally flaccid penis; it can cause permanent erectile dysfunction. The treatment includes lots of fluids and painkillers, sometimes blood transfusions, and on occasion may require surgical drainage by a urologic surgeon.
About 10-15% of patients may suffer strokes, where an area of the brain is deprived of oxygen by a blocked blood vessel, resulting in an area of brain damage. This most commonly occurs when child is between the ages of 4-6 years old. The most common symptoms are severe headaches, weakness or a sudden limp, a sudden drooping of the face, seizures, or severe lethargy. However, there are also small, so-called "silent" strokes that can occur in SSD patients and are usually diagnosed serendipitously on scans done for other reasons. Strokes are best diagnosed using magnetic resonance imagining (MRI). The treatment includes both immediate and prolonged blood transfusion programs in order to prevent a recurrence. During the last decade a nonpainful procedure called transcranial doppler (TCD) has enabled physicians to accurately identify patients who are at risk for developing major strokes.
This is when the bone marrow temporarily slows its production of red blood cells due to infection (most commonly by a virus called parvovirus B19) or another cause (especially medications). Signs include paleness and fatigue. Treatment usually includes red blood cell transfusions and waiting until the virus is cleared by the body's immune system.
The spleen becomes rapidly enlarged by trapping (pooling or sequestering) the abnormal red blood cells. This leads to fewer red blood cells in the general circulation and a dramatic fall in blood pressure. This is considered an emergency and your child must be brought to the clinic or the emergency room as soon as possible. Early signs include sudden paleness, weakness, sleepiness, an enlarged spleen, and pain in the abdomen. Treatment includes red blood cell transfusions, intravenous fluids and on occasion, emergency surgical removal of the spleen. If this sequestration crisis recurs more than once, it becomes necessary to consider an elective surgical removal of the spleen.
Chronic organ damage occurs as children grow to adult age and can be both prevented and better treated if they are detected early. Examples of chronic damages include the following -
- Splenic dysfunction - In children with SCD, the spleen is frequently dysfunctional after six to nine months of age. That unfortunately means that young children are predisposed to certain serious bacterial infections. The doctor will start the patient on penicillin for the first 5-6 years of life to try and protect the child from those infections, in addition to administering special vaccines. Because of the risk of infection, any fever of over 100.4�F should be called in to the doctor. Sometimes the doctor will choose to place your child on oral antibiotic, at other times, a single intravenous antibiotic could be given with follow-up the next day, and at times, the child may have to be admitted to the hospital for intravenous antibiotics and observation.
- Eyes - retinopathy (disease of the retina in the eye), detachment of the retina and blindness can occur. That is why children must have a comprehensive eye examination by an ophthalmologist yearly.
- Heart - enlargement of the heart due to anemia, pulmonary artery hypertension (increase in blood pressure in the pulmonary artery or lung vasculature resulting in markedly decreased exercise tolerance and right-sided heart failure). Every SCD patient must be examined by a cardiologist yearly and have two tests
- Echocardiogram or echo (a type of ultrasound test that picks up echoes of sound waves as they bounce off the different parts of the heart. These echoes are turned into moving pictures of the heart and give a good idea of how well the heart is functioning).
- Electrocardiogram (ECG or EKG which records the electrical voltage in the heart and the heart rhythm in the form of a graph on a strip of paper).
- Lungs - Sickle Cell chronic lung disease manifests as radiographic lung abnormalities, impaired lung functions (as measured by a test called PFT or pulmonary function test), and, in its most severe form, by the evidence of pulmonary artery hypertension (as discussed above).
- Bone - vertebral flattening with a �fishmouth' shape (hence the name "codfish vertebrae"), Avascular (or aseptic) necrosis (death) of the ends of large bones (humeral or femoral heads). The main symptoms are limping and pain. The diagnosis is by x-ray or MRI. Few treatments have proven useful and unfortunately many patients eventually require joint replacement surgery.
- Skin - these ulcers start occurring in adolescents or adults in rare cases.
- Gallbladder disease - patients with SCD have a high level of bilirubin (bilirubin is the waste product that results from the breakdown of hemoglobin molecules from broken down sickled red blood cells. Ordinarily, bilirubin leaves the body in the form of bile. Excessive levels of bilirubin stain the white of the eye yellow).
- addition gallstones are common in SCD patients (12-15% of young children and up to 40% of adults), but usually do not cause symptoms.
- Kidney - the main complications are hematuria (blood in the urine), hyposthenuria (the inability of the kidney to retain extra water, thus placing the child at risk for dehydration), nephrotic syndrome (high level of protein in the urine, low level of protein in the blood and swelling feet or legs from buildup of salt and water), and uremia (also called azotemia or kidney failure) indicates the kidneys lost their ability to rid the body of waste products.
Kidney complications are uncommon in children but each child with SCD should have his/her urine checked at least yearly.
Various forms of Sickle Cell Disease
There are several variant forms of SCD. Both parents do not have to be carriers of the sickle abnormality to have a child with this condition. A situation that combines the hemoglobin S molecule with another defective hemoglobin molecule - such as hemoglobin C, O, or beta-thalassemia disease - will result in a form of sickle cell disease. The doctor will discuss the differences, if any, between these variant forms of SCD and the usual SCD, when needed. In general, however, it can be said that hemoglobin SC disease tends to have a milder course compared to SCD and hemoglobin S-Beta thalassemia disease runs a course that is largely indistinguishable from SCD.
It should be noted that sickle cell trait is not a disease. Individuals with the trait can pass it on to their children. It is therefore important to seek genetic counseling when both spouses have the trait because in such a marriage, there is 25% chance to have a child with sickle cell disease with each pregnancy. Prenatal diagnosis of SSD is available either by chorionic villus sampling (CVS) or, later in the pregnancy, by amniocentesis. After birth, the diagnosis of SCD is made through the neonatal screening.
- Prevention - avoiding complications is always the best tactic. That is why it is important to ensure your child is well hydrated at all times, particularly on hot days and when they actively play. Avoiding cold temperatures is also important. Fevers should be reported to the doctor. It is also important to take your child to the pediatrician (for all routine vaccinations, yearly flu vaccination, and general care) as well as the hematologist. Make sure your child is screened periodically with the following tests:
- Yearly complete eye examination
- Yearly echocardiogram and EKG
- Yearly transcranial doppler (TCD)
- Liver tests twice yearly
- Kidney tests twice yearly
- Hydroxyurea - this is a medication that has been used safely in patients with SCD for several years with some success. It is a medication that was initially used as mild chemotherapy but was found to increase the levels of hemoglobin F (or fetal hemoglobin, the hemoglobin that is found in fetuses and young infants). Hemoglobin F makes it difficult for the abnormal sickle hemoglobin molecules to stick together. As a result, many patients experience fewer and less severe crises. Hydroxyurea does not cure sickle cell disease, but it can improve the daily life of the child and help him or her attend school regularly. The doctor will have to monitor your child's blood counts when he or she is taking hydroxyurea.
- Blood transfusions - red blood cell transfusions are sometimes given to patients during very severe painful crises (vaso-occlusive syndrome) or acute chest syndrome. Some patients end up receiving chronic transfusions as treatment for strokes or other complications. The risks of many blood transfusions include allergic reactions, accumulation of too much iron in the body, and the rare (but possible) transmission of viruses through the blood (e.g., hepatitis C, HIV, etc).
- Bone marrow transplantation (BMT) - this is a treatment whereby the doctors replace the child's old bone marrow (or blood producing factory) with a new one from a donor without sickle cell disease. There are several limitations to this treatment at this time:
- Only 1 in 5 patients has a healthy family donor who is identically matched
- There is a risk of complications and even a risk of death due to bone marrow transplantation. Some of the complications of transplant can be chronic and significant - therefore, those risks must be carefully weighed against the benefits of that procedure.
- In the future, we hope to be able to treat patients with gene therapy. Their own cells would be altered such that normal hemoglobin is produced (instead of the abnormal sickled hemoglobin). This research is still in its infancy
Pregnancy in Patients with Sickle Cell Disease
In the past, only few women with SCD carried pregnancies to term without major complications. Modern medical and obstetrical developments have enabled more and more pregnancies to result in healthy newborns. However, pregnant women with SCD still have increased risks for miscarriage, preeclampsia, premature labor, ruptured membranes, and more. In addition, there is a relatively higher risk for prematurity and babies who are too small in size.
- To prevent pregnancies, oral and intramuscular contraceptives are suitable choices. Intrauterine devices (IUD) should always be avoided.
- Early prenatal care for a pregnant patient is essential in order to recognize and prevent complications, such as pregnancy-induced hypertension or diabetes.
- Consultation with the hematologist is imperative in order to decide about blood transfusions.
- Crises can still happen during pregnancy and should be managed early before the pain is completely out of control.