Defining sickle cell disease and its causes
What is sickle cell disease?
An autosomal recessive condition, sickle cell disease (SCD), also known as sickle cell anaemia, is characterised by a group of inherited red blood cell (RBCs) disorders. A person with the condition typically has two copies of the autosome gene (non-sex chromosome). Essentially, the normal function of red blood cells in the body is compromised and they aren’t able to carry a sufficient amount of oxygen throughout the body.
Normally, the body’s red blood cells are round in shape (like little discs) which enables them to travel easily throughout the body. The shape gives them enough movement flexibility to be carried through even the smallest blood vessels in the body.
A person with SCD does not have many round shaped red blood cells. Their RBCs are crescent-shaped, like that of the crescent-shaped blade known as a sickle (almost crescent moon or banana-shaped). This shape is not as flexible for the cells to perform their normal functions and thus makes them ‘sticky’ and more susceptible to becoming ‘trapped’ or ‘stuck’ as they move, particularly in smaller blood vessels. This in turn means that blood and the oxygen they carry is restricted from reaching various parts of the body that require it for normal function. The lack of sufficient blood flow and oxygen then results in tissue damage (organs, bones and muscles) and pain.
A person with SCD is also more susceptible to anaemia, infections and even stroke. As an inherited disease, the condition is managed with a daily treatment plan to alleviate symptoms and prevent as many complications as possible. As yet, there is no cure for sickle cell disease.
Causes of sickle cell disease
As an inherited blood disorder, sickle cell disease is passed from one generation to another (known as ‘autosomal recessive inheritance’). A mother and father must each pass on to their offspring a defective form of the gene (haemoglobin S gene) that normally produces healthy and red, iron-rich compounds (haemoglobin – the protein which carries oxygen in the blood) for SCD to occur.
It can happen that only one biological parent passes on this defective gene to their child. In this instance, a child may be diagnosed as having the sickle cell trait. This means that a child will have one defective form of the gene and one normal haemoglobin gene. This enables the body to produce a healthy supply of haemoglobin (with normal red blood cell function) as well as sickle cell haemoglobin (defective function causing damage to the body).
A person with the sickle cell trait may not have symptoms of pain as result of damage to the body, even though there is a presence of abnormally shaped RBCs. They will, however, be carriers of the disease, which means it is entirely possible to pass on the gene to their offspring.
Types of sickle cell disease
A haemoglobin molecule comprises of 4 polypeptide chains. Two of these are characterised as ‘alpha chains’ (containing 141 amino acid residues each) and the remaining two as ‘beta chains” (containing 146 amino acid residues each). These chains have differing amino acid sequences, but combine to form a three-dimensional structure (gene).
Different mutations in these genes (4 polypeptide chains) result in the four main types of sickle cell disease. These are:
- Haemoglobin SS disease: This is the most common variation of the disease and occurs when a child inherits two copies of the haemoglobin S gene (Hb SS) from both of their biological parents. This type is the most severe variation of the condition where the worst symptoms are experienced more frequently.
- Haemoglobin SC disease: The second most common variation of the disease occurs when a child inherits an Hb C gene from one biological parent, and the Hb S gene from the other. Symptoms of anaemia are less severe than those of the Hb SS variation, but a sufferer will display similar overall symptoms.
- Haemoglobin SB+ (beta) thalassemia: This variation of SCD affects the beta chain gene production by reducing the size of the RBC, and thus restricting the production of beta protein in the blood. A child will inherit the Hb S gene for this variation of the condition to occur but will not typically experience severe symptoms.
- Haemoglobin SB 0 (Beta-zero) thalassemia: This variation also affects the beta chain (globin) gene and displays similar symptoms to Hb SS anaemia, but often in a more severe capacity, and with a poorer outlook for treatment management.
Rarer types of sickle cell disease with less severe symptoms are:
- Haemoglobin SD
- Haemoglobin SE
- Haemoglobin SO
- Sickle cell trait
How does sickle cell disease affect the body?
Signs and symptoms
SCD as a condition is in constant movement, and thus symptoms vary in severity from one person to another and typically change over time too. It is difficult, even for medical professionals, to gauge when symptoms will start and how severe they are likely to be.
Common symptoms include:
- Pain: One of the primary results of a lack of sufficient blood flow and oxygen in the body is pain. Pain typically presents as ‘periodic episodes’ (known as sickle cell crisis) and is experienced as a result of restricted flow in the smaller blood vessels, particularly in the abdomen, chest, bones and joints. Pain (crisis) typically varies in intensity and can last anywhere between a few hours to several days at a time. Some sufferers will have a dozen or more crises in an annual period, and others will experience just a handful of episodes. Hospitalisation may be necessary in the case of a severe crisis episode. Chronic pain can lead to joint and bone damage, as well as ulcers (tissue damage). Pain in both the hands and feet is also known as hand-foot syndrome.
- Painful swelling: With reduced blood flow, the hands and feet in particular will be adversely affected. The result will be swelling in these areas which can be quite painful.
- Anaemia (chronic): The abnormal shape of sickle cells means that they are easily broken apart in the body. When this happens, they effectively ‘die’. This reduces the number of RBCs in the body even further, meaning that even less oxygen can be carried through the blood. Normally, RBCs are active for approximately 120 days before naturally being replaced in the body. Sickle cells die off within 10 to 20 days. A shortage of RBCs in the body is known as ‘anaemia’. A lack of oxygen throughout the body will result in symptoms of fatigue, low energy and lethargy. Babies suffering from the condition will also become quite fussy and irritable when tired.
- Infections: Organs that typically help fend off infections in the body, such as the spleen will incur a degree of damage over time. This makes a sufferer more prone to frequent infections such as pneumonia. Preventative measures (vaccinations and penicillin antibiotics) are therefore encouraged by medical professionals as a way to make a person (especially infants and young children) less vulnerable.
- Problems with vision: Damage to the retina occurs due to the lack of oxygen reaching the tiny blood vessels that support eye function. Normal visual image processes are impaired, causing problems with vision.
- Delayed growth: Oxygen carries essential nutrients to various areas of the body in order to maintain a healthy growth rate. When sickle cells become stuck, restricting blood flow, delayed growth occurs. This is of particular concern during the early stages of life – infancy and childhood – and delays the natural growth process of puberty (sexual maturation) during a person’s teenage years.
What other signs should you look out for?
Typically, signs will likely be picked up fairly quickly by a medical doctor in a new-born baby (between 4 and 6 months), but parents can also be on the look-out for other signs causing a little one great distress. In some instances, you may need to seek emergency care if any of the below are noted in a baby or young child:
- Episodes of severe pain which cannot be explained. Typical areas include the chest, abdomen, joints or bones.
- Swelling in the abdominal area, hands and feet. These areas will also be quite tender to the touch.
- Frequent infections with fever
- Yellowing of the skin and whites of the eyes (jaundice) or pale skin and nail beds
- Bed-wetting (associated with impaired kidney function)
- Shortness of breath (particularly when active)
- Signs of stroke (weakness in the facial area, arms, and legs, one-sided paralysis, inability to walk or talk, sudden problems with vision, confusion, unexplained numbness and headache). This is life-threatening and requires immediate medical assistance.
- Pulmonary hypertension (high blood pressure in the lungs) is a high risk of severe anaemia and can be life-threatening.
Risk factors and potential complications
Who is at higher risk of SCD?
Endemic malaria regions do appear to have a higher rate of sickle cell trait carriers due to the complex nature of both SCD and the infectious condition caused by the P. falciparum parasite. The two have a complex relationship, even though the red blood cells in the body are affected in different ways. Areas with a higher rate of carriers include Africa, India, Saudi Arabia and the Mediterranean.
One or more adults who carry the sickle cell trait place future biological children at risk of sickle cell disease. A blood test known as ‘haemoglobin electrophosresis’ can be performed to determine which type a parent may carry and likely pass on to a child.
What are the most common complications of SCD?
Complications can be severe and stem from the various parts of the body which are deprived of normal blood flow and oxygen.
- Chronic anaemia (severe anaemia)
- Hand-foot syndrome and leg (skin) ulcers
- Delayed growth during childhood (delayed puberty or sexual maturation)
- Splenic sequestration (a sudden and painful enlargement of the spleen – which can also shrink and cease to function at all - due to a blockage of the splenic vessels)
- Seizures, stroke, coma and other neurological complications
- Blindness and vision problems (retina damage)
- Heart problems (heart failure, heart attack and abnormal heart rhythms)
- Pulmonary hypertension and pulmonary fibrosis (scarring of the lungs) – lung disease
- Priapism (in males) – this is a painful, lingering erection (without sexual stimulation and not relieved by ejaculation) that occurs when blood vessels in the penis are blocked. A long-lasting erection can occur for several hours at a time and this condition is regarded as a urologic emergency in order to avoid complications such as impotence.
- Gallstones (due to high levels of bilirubin)
- Damage to nerves and organs – kidneys, spleen and liver
- Sickle chest syndrome (severe variation of sickle cell crisis) or acute chest syndrome – cough, mucus or sputum production, fever, low blood oxygen levels and shortness of breath are common signs other than severe pain in the chest area.
Another serious risk individuals with SCD should be aware of is the potential for the development of fifth disease (‘slapped cheek disease’), caused by the parvovirus (which is an airborne infection). Parvovirus can result in a temporary halt in the production of new red blood cells. For a person with sickle cell disease, this can become a life-threatening situation as it can lead to a severe case of anaemia (aplastic anaemia).
A person with SCD will need to be well aware of airborne infections and their contagious consequences, and do their utmost to reduce their exposure to these conditions so as to avoid serious complications that will arise if contracted.
Diagnosis and treatment procedures
How is sickle cell disease diagnosed?
Often, acute pain is a red flag and is commonly felt in the hands and feet. Other symptoms which will show signs include anaemia, respiratory infections, ulcers, heart problems and issues with delayed growth. If any of the aforementioned symptoms are mentioned to a doctor during an initial consultation, he or she is likely to recommend testing for SCD.
Once your doctor (general practitioner or paediatrician) feels they have a detailed enough medical history and a sufficient understanding of a patient’s symptoms, the following screening tests may be recommended:
- Blood tests: A doctor will check a patient’s blood count to assess whether there is an abnormal Hb level. Blood films will also show any irregularities with RBCs. A sickle solubility test using a blood sample will check for the presence of Hb S (haemoglobin S).
- Hb electrophoresis: This test is typically used to conclusively diagnose SCD by measuring all of the blood’s haemoglobin types.
If screening tests show the sickle cell gene, additional tests may be recommended to assess any obvious complications of the disease. This will also depend of what was discussed during the initial consultation.
Sometimes, prenatal testing can be done to check for the sickle cell gene in the amniotic fluid or placenta of a pregnant woman before a baby is born. This is highly recommended if one or both parents is aware that they have the disease or may be a sickle cell trait carrier. Genetic counselling is also advisable where the risk of passing on the gene is high or probable.
Prenatal testing involves:
- Amniocentesis: Amniotic fluid cells will be examined for the sickle cell gene. A needle is inserted through a woman’s belly and into her uterus, usually between weeks 15 and 20 of pregnancy. A sample of fluid is retrieved for analysis.
- Chorionic villus sampling (CVS): This test is performed at 10 to 12 weeks during pregnancy, making results available sooner than with an amniocentesis test. A sample of chorionic villus cells (tiny, finger-shaped growths situated in the placenta) are collected via a catheter (thin tube) inserted into a woman’s vagina. Samples can also be taken through a long needle inserted into a woman’s belly, using an ultrasound as a guide for locating the correct spot for retrieval.
Currently, there is no way to effectively cure SCD. Symptoms will need to be routinely monitored and treated as and when health complications arise. Tests will also become routine during a person’s lifetime. A medical professional will help to alleviate symptoms as best, ensuring that serious complications are avoided in any way possible.
For the parents of a child with SCD, a diagnosis will mark the beginning of a lifelong learning process for both you and your little one. Your doctor will want to work closely with you to help you recognise symptoms as they occur, how to go about caring for your child as they grow, as well as what to do in the event of a more serious concern requiring emergency intervention.
The treatment plan for children may involve:
- Routine vaccinations throughout childhood
- Penicillin antibiotics (to be taken daily between the ages of 2 months and 5 years when young children are at most risk of infection).
- Medications (hydroxyurea) that assist with changing the shape of RBCs and preventing sickle cell crisis, as well as reducing the need for blood transfusions and hospitalisations.
- Multivitamins (especially those with added iron which may be needed during infancy) and folic acid supplements.
- Protein supplements may also be needed to assist with gaining sufficient weight.
- Transcranial ultrasounds will be recommended on a routine basis from the age of 2. The screening will examine blood flow in the arteries of the head and neck. This test is useful for assessing the risk of stroke. If chances are high, a child may be given a blood transfusion to try and prevent this.
Routine tests a person will experience well into adulthood also include:
- CBC (complete blood count) tests
- Urine tests
- Organ function and vision function tests
- Hepatitis C tests (especially if a person receives frequent blood transfusions)
This will, unfortunately, be a chronic ailment for those living with SCD. A doctor or pain treatment specialist (physical therapist, chiropractor, rheumatologist, orthopaedic surgeon, acupuncturist, or osteopathic doctors) can help to alleviate any level of discomfort, as well as assist you with developing pain management skills.
A person with SCD will frequently experience painful crisis episodes and quite suddenly too (without too much warning). Pain also comes and goes unpredictably, and if not treated correctly can, in severe cases, become life-threatening. Pain is often difficult to treat in a SCD patient and frequently makes a person exhausted. It can be just as exhausting for a caregiver trying help alleviate pain and discomfort.
Dealing with chronic pain is challenging, but it can be effectively managed. Work closely with your health care providers and pain treatment specialists so that you can best target areas of the body taking severe strain sufficiently.
Men and young boys may struggle with priapism. This can also be quite painful, and as such should be assessed by a medical doctor for treatment. Likely treatment may involve oxygenation, hydration (plenty of fluids), a blood transfusion (if necessary), the administration of intravenous pain medication and possibly an assessment with a urologist.
Other necessary treatments for SCD may involve:
- Frequent red blood cell transfusions (improves the blood flow function of carrying oxygen and nutrients and increases the number of RBCs in circulation in the body). Packed red cells are removed from blood that is donated and then given intravenously to a person with SCD. A person does run the risk of increased infections and excess iron build-up with frequent transfusions – this can be damaging for organs in the body and as such should be closely monitored on a regular basis.
- Rehydration (intravenous fluids help to prevent dehydration which can cause RBCs to deform / ‘sickle’).
- Supplemental oxygen (administered via a mask) to improve breathing difficulties and increase oxygen levels in the blood.
- Pain medications may also be prescribed for crisis episodes. In severe cases, morphine may be necessary.
- Treatment for infections (medications may include penicillin antibiotics throughout adulthood).
- Vaccinations to prevent infections (particularly the flu shot or pneumococcal vaccine).
- A stem cell transplant or bone marrow transplant (children under the age of 16). A match donor is somewhat difficult to find and is usually a sibling. Where a match donor is not available stem cells taken from umbilical cord blood may be used for the transplant procedure. If a donor is available an SCD patient will need to undergo chemotherapy or radiation to reduce or kill off bone marrow stem cells. The healthy donor cells will then be intravenously injected into the bloodstream, allowing them to travel (migrate) to the bone marrow. The transplant aims to stimulate the production of new red blood cells. It is a risky procedure and requires a long stay in hospital. A patient will be monitored carefully following the procedure as the body may reject the newly transplanted stem cells. If this happens, it can be life-threatening.
- Surgeries to correct complications which arise may be necessary (for instance, removing the spleen or repairing problems with the eyes).
Coping with sickle cell disease at home
Any chronic condition that requires ongoing attention is stressful and can cause bouts of anxiety. When so much can go wrong so quickly, it is only human to be emotionally affected by a condition such as sickle cell disease. It can often feel as though your body is working against you, constantly.
There are things that you can do to improve your own quality of life:
- Maintain a healthy diet: It goes without saying, but what you put into your body influences your overall health. And it can go either way – improve your condition or make you unwell. An important consideration when it comes to your diet is folic acid. RBCs require a healthy dose of folic acid and other nutrients in order to stimulate production needed to consistently replenish the body. Your bone marrow needs folic acid in order to help with this process. Supplements, a variety of colourful fruits and veggies, and whole grains may become staples in your household.
- Keep hydrated: In addition to a nutritious diet you will also need plenty of fresh drinking water. People with SCD typically dehydrate easily, particularly when experiencing a crisis. It is strongly advisable to drink plenty of water throughout the day, and especially when exercising or travelling to destinations where the climate is hot and dry. Avoid alcohol consumption which can also cause you to easily dehydrate. Remaining hydrated is of the utmost importance if you have sickle cell disease as this slows the sickling process and helps to alleviate pain.
- Get moving: Exercise is good for you, but be mindful of overdoing it. Strenuous exercise can also cause dehydration, so ensure that you stay well hydrated when exercising and rest when your body is tired. You may need to take care with exercises that involve a change in body temperature, such as swimming. Changes in temperature can trigger your RBCs to sickle. Your doctor can advise on how much exercise may be good for you and how frequently you should engage in the activity. Too much of a good thing won’t help you in this instance. On the plus side, if your condition is a major source of stress for you, exercise will help alleviate this.
- Extreme heat or cold: Locations that experience extreme weather changes may not be good for a person with SCD. Exposure has been noted to increase risk for frequent crisis scenarios. Wherever possible, it may be recommended that you avoid these locations in the world. As mentioned, temperature changes can cause RBCs to sickle, so it is often easier to dress in layers which allow you to manage warming up when it is cold and cooling down in higher temperatures.
- Take care with medications: Over-the-counter medications also have side-effects and it is strongly advisable that you are cautious about what you take to help alleviate pain symptoms. Many can potentially have adverse effects on your kidneys. Check in with your medical doctor before taking anything other than what he or she has prescribed for you.
- Learn to manage your pain: Heating pads, massages, physical therapy and hot baths are some methods that can effectively reduce the effects of chronic pain in the body. Your pain management specialist is the best person to advise on techniques that will be most effective for you.
- Look after yourself: Go for routine eye exams and necessary vaccinations to prevent infections. Refrain from smoking or being in places where you are exposed to second-hand smoke as this will effectively reduce the amount of oxygen in your bloodstream. When you are tired, rest. Plenty of sleep can help to reduce symptoms of fatigue.
- Take care when it comes to air travel and high altitudes: The higher you go, the less oxygen. A lack of oxygen will cause RBCs to sickle and deform. If you are going to be exposed to high altitudes or travelling in an unpressurised airplane (or pressurised plane), plenty of water is necessary to help prevent dehydration. Shorter air travel times (4 to 6 hours) aren’t too problematic, as long as plenty of water is consumed.
- Seek support: Counselling can be beneficial for those suffering the disease, as well as for those around them (family in particular). Support groups for families are a good way to approach challenges, and receive assistance and learning tools that can help you cope emotionally.
- Be in-the-know, all the times: Ask questions. Try not to let this disease scare you. It is a serious condition, and as such much be taken seriously. But the more you learn about it, the more you will know. As you learn, the better you will be able to cope with and manage your condition. There is no ‘stupid question’. Your medical care team is there to assist you through everything and help you cope as best as is humanly possible every day.
Top tips for helping your child if he/she is diagnosed with sickle cell disease
Common symptoms of SCD will have an impact on a child’s daily functions and activities. It’s one thing to be able to control certain things that will have an impact in the home, it’s another challenge altogether when a child needs to go to school and interact socially (in environments not within your control).
Ways you can help manage the special needs your child will have at school include:
- Making your child’s teacher/s aware of how his or her condition will affect learning: Educating others who interact with your child about their condition can also help them, help your little one. Your child may frequently require time off from school because of the discomfort of their symptoms. As a result, they may fall behind their classmates. This can be foreseen in the sense that both sides can be more accommodating in helping a child keep up with their peers when they are well enough again. Extra tutoring classes may be required.
- Helping teachers/s and other school employees understand the nature of SCD symptoms: As part of the treatment and SCD management plan, children need to consume a considerable amount of water every day. This may mean that a child may need to use the bathroom more frequently that many of the other children. A teacher will need to be aware of this and the reasons why so as to be more accommodating, especially if the need to use the bathroom disrupts a normal classroom session. Helping teachers to understand the full spectrum of signs and symptoms is also highly beneficial. There may be times a crisis happens and a child will need urgent medical care. Recognising these types of signs can make all the difference. It is a good idea to perhaps have the signs written down, which school employees and teachers can easily reference if they notice that something about the child seems different, as well as who to call if there is an emergency situation.
What is the outlook for someone with sickle cell disease?
Once diagnosed, there is no way back. As a genetically inherited blood disorder, sickle cell disease is not a condition that can be prevented. The earlier it is diagnosed within the months following birth, or foreseen through prenatal testing, the better it can be managed.
If not sufficiently treated and severe complications occur as a result of crisis situations, it can happen that infants and young children lose their lives far too soon. Young children are at high risk of infections at this age and it can be fairly dangerous if they do contract something.
With sufficient and careful treatment, life expectancy is relatively good and an optimal quality of life can be achieved well into middle age (and beyond).