Sickle Cell Disease (SCD) is a major public health concern in Nigeria. It is a complex disease that causes several complications and limits the lifespan of those affected. Approximately 25% of the population carry the sickle cell trait, and about 150,000 children are born with SCD each year. As a nation, Nigeria has the highest SCD population and trait carriers in the world. With no universal newborn screening available, most children are diagnosed once they present to the healthcare setting with suspicious symptoms that prompt the test for SCD. At this point, many of them already have complications from the disease process.
WHAT IS SICKLE CELL DISEASE?
Sickle Cell Disease (SCD) is a group of hemoglobin disorders caused by the inheritance of two alleles carrying the sickle cell mutation from both parents who have the sickle cell trait. The result is the formation of Hemoglobin S (HbS) or other forms of sickling hemoglobin including HbC, HbSC, HbSD, and HbSO. The disease is characterized by anemia and acute pain in the setting of reduced oxygen. The frequency of these two systems and the way in which they are managed is often a reflection of the level of disease control and risk of mortality for affected individuals.
Anemia is caused by the decreased lifespan of sickled red blood cells, leading to low blood counts. Acute pain on the other hand occurs when blood cells become sickled and are not able to flow freely through blood vessels. They therefore become stagnant and occlude blood supply to several organs. The disruption of blood supply to target organs prevents oxygen from being delivered to those organs, thereby causing tissue injury and organ damage, which manifest as pain in several parts of the body.
There are several systems and organs severely affected by sickle cell disease. These include:
| SYSTEMS | EFFECTS OF SICKLE CELL DISEASE | MANAGEMENT |
| Neurologic (Brain) | Sickled cells obstruct blood flow to parts of the brain and can cause strokes especially in childhood. Approximately 10% of children with sickle cell will develop strokes, and 50% of these may have recurrent strokes. Adults with sickle cell tend to have brain hemorrhage. | Transfusions
Hydroxycarbamide |
| Cardiovascular (Heart) | Frequent sickling of red blood cells lead to early cell death, causing anemia. Chronic anemia causes the heart to work harder just to meet the body’s demand for oxygen delivery. With time, the muscle tissue of the heart becomes enlarged, resulting in restriction in how much blood can fill the heart. This whole process causes the heart to malfunction over time.
Chest pain is also another symptom experienced when there is obstruction of blood flow to heart muscles, or when the patient has severe anemia. |
Transfusions
Hydroxycarbamide |
| Pulmonary (Lungs) | People with sickle cell disease have an increased risk of developing pneumonia and restrictive lung disease which presents as difficulty breathing. | Bronchodilators
Transfusions Hydroxycarbamide |
| Spleen | When sickle cell crisis occurs, blood becomes stagnant in the spleen and blood cells are rapidly destroyed. Parts of the spleen also become infarcted (tissue death) due to lack of oxygen caused by obstructed blood flow. These factors cause the spleen to become enlarged and non-functional over time. This condition is known as functional asplenia and predisposes affected individuals to infections. | Splenectomy (surgical removal of the spleen) |
| Liver | Frequent transfusions and rapid death of red blood cells results in increased bilirubin which causes jaundice.
These patients also develop gallstones, and enlarged liver from sickling and occlusion of blood supply to the liver. |
Cholecystectomy (removal of the gallbladder) |
| Kidneys | Sickle cell nephropathy starts in childhood; parts of kidney function is lost and it becomes less able to concentrate urine. The kidney at this point hyperfiltrates proteins, leading to further damage to the structures of the kidneys, and eventually end-stage renal disease. | Angiotensin Converting Enzyme Inhibitors (ACE-I) have been shown to work on the kidneys to reduce protein excretion which in turn preserves kidney function.
Other options include dialysis, kidney transplant, and hydroxycarbamide to reduce the frequency of sickling |
| Bones and Skin | Sickle cell causes decreased blood supply to bones resulting in the death of bone tissue; a condition known as avascular necrosis.
Patients also develop leg ulcers from tissue death because of decreased blood supply. |
Wound care, supportive therapy, surgery if necessary |
| Eyes | Sickle cell causes damage to blood vessels of the eye and lead to vision loss. This condition is known as retinopathy. | May be treated with laser therapy |
| Penis | Sickle cell causes impotence and infertility.
Male patients also experience priapism, which is a state where the penis is engorged and painful because of pooling of blood in the penis. |
Surgery if necessary |
MANAGEMENT OF SICKLE CELL DISEASE
Management is primarily focused on optimizing well being by preventing frequent sickle cell crisis, maintaining health, preventing infections and prolonged anemia. SCD requires management with several therapies including blood transfusions and Hydroxycarbamide
Transfusions: patients with sickle cell experience chronic anemia because of rapid destruction of red blood cells that are sickled. Therefore, transfusions are a mainstay of therapy, and the goal is to increase the oxygen carrying capacity of blood, replenish sickled and rigid blood cells, and reduce the risk of organ damage. Frequent transfusion carries its own risk including exposures to blood-borne infections such as HIV, hepatitis B and C, sensitization to antigens from donors’ blood resulting in life threatening transfusion reactions, and iron overload with deposits in tissues. Red blood cells have high iron stores, so frequent transfusions lead to a buildup of body iron stores at a rate that is faster than the body’s ability to clear it. This can be treated with chelation therapy.
Preventing Infections: most people with SCD do not have functional spleens because it is damaged in early childhood from frequent sickle cell crisis. This phenomenon is known as functional asplenia and results in increased susceptibility to infections. The spleen is an organ responsible for filtering the blood, removing some infections, storing platelets and white blood cells. The spleen therefore is a very important aspect of the immune system, and once it loses its function, the affected person becomes very susceptible to life threatening infections. People with SCD need immunization against infections such as invasive pneumococcal infections and meningitis etc. In addition, the world health organization recommends prophylactic continuous antibiotic coverage for children with sickle cell up to the age of 5. The recommended antibiotic is penicillin; other options can be used in patients with allergy to penicillin. Several studies have also shown evidence of benefits with prophylactic anti-malarial treatment as malarial infections are known to induce sickle cell crisis and increase the risk of death in children with SCD.
Hydroxycarbamide/Hydroxyurea therapy: these drugs have been a mainstay in the management of SCD for many years. They work by inducing the availability of fetal hemoglobin (HbF) which is necessary to inhibit the sickling of HbS. The therapy is well tolerated by most patients, but the cost of long-term management and availability of these drugs in low-income settings is still unclear. However, one could assume that given the healthcare system in Nigeria where patients pay out-of-pocket before receiving treatment, most may not be able to afford it, even if it was widely available.
Stem Cell Transplant/Bone Marrow Transplant: this is the only cure for SCD because it completely replaces abnormal blood forming cells with normal cells which can produce normal red blood cells. However, the therapy has several challenges including finding a matching donor, and surviving the ablative phase which is carried out to eradicate all the original blood cells prior to the infusion of new progenitor cells. The person is also high risk for bone marrow rejection and other complications which can be life threatening.
Healthy Lifestyle and Stress Management: stress management is an important aspect of disease control because physical or emotional stress can trigger crisis. Therefore, individuals with sickle cell must understand their bodies very well and their trigger points. They must hydrate well, avoid infections and promptly treat it once suspected. They must also follow-up with timely immunizations, and learn more about the disease so they can better manage themselves and be a resource to others with similar conditions. Above all, they have look to maximize well-being, happiness, and quality of life.
THE FUTURE OF SICKLE CELL DISEASE IN NIGERIA
Nigeria has the highest prevalence of SCD in the world, and there will be more cases with increasing population growth, because 1 in 4 persons carry the sickle cell trait. Therefore, it is important for the Ministry of Health to address the sickle cell epidemic by raising awareness, providing counseling, screening of newborn babies, and providing resources for management of those already affected by the disease. In addition, we must join the world in researching for therapeutic options to treat the disease and improve the quality of life for those affected.
Raising Awareness and Counseling: public health officials and healthcare providers must raise awareness about SCD, therapeutic options, complications, and the resources available to help manage the disease. Couples who plan to marry should know their status and find out if they carry the sickle cell trait, as this puts the risk of having a child with SCD at about 25% for each pregnancy when both parents are carriers. It is important to inform them of options such as invitro fertilization which can allow for the selection of normal embryos should the carrier couples decide to proceed and marry each other. Moreover, due to improved management of SCD, some individuals live into the 4th and 5th decade of life. With this comes a rise in the number of women with sickle cell who get pregnant and bear children. These women need special consideration because they have an increased risk of sickle cell crisis, infections, maternal, and perinatal death. Sometimes they have intrauterine growth restriction because of decreased blood flow to the babies. In normal pregnancies, the blood volume increases by about 50% to meet the needs of the growing baby, but women with sickle cell disease may not have as much increase in blood volume. Therefore, their babies are at a higher risk for intrauterine growth restriction and death. These are very high risk pregnancies and should be handled by a specialist.
Screening: universal screening of all newborn babies for SCD is available in most parts of the world. Unfortunately, despite having the largest population of individuals with sickle cell trait and SCD, Nigeria does not have universal screening. The benefits of newborn screening cannot be understated. Sickle cell symptoms do not usually appear in babies until after the third month. At that time, the fetal hemoglobin (HbF) which inhibits the sickling of HbS has diminished, so these babies begin to have symptoms of sickle cell, and tend to be diagnosed after their first crisis when they present to the hospital with swollen hands and feet. Unfortunately, if the babies were not screened prior to this incidence, some parents may opt to manage the baby at home because they are not aware that the child is experiencing a life-threatening phenomenon known as sickle cell crisis. Therefore, universal screening of all babies born in Nigeria is necessary, and database must be created to keep counts of the incidence and prevalence of SCD in Nigeria. Screening programs should be funded by the government, and will go a long way to reduce the incidence of babies who die from sickle cell because of lack of awareness and poor management.
Resources for Management of Chronic Patients: the cost of managing SCD is astronomical. Frequent transfusions and repeated hospitalizations can make the average family bankrupt in a healthcare system where funding is out-of-pocket. Therefore, the government must look to subsidize some aspects of healthcare management for this sub-population by funding newborn screening, penicillin prophylaxis for those under 5 years, and immunizations etc. These factors can go a long way to reduce morbidity and mortality in this population. There is also need for increased federal and state funding for specialty centers that manage the sickle cell population in Nigeria.
Written by Dr. Idongesit Udoh
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