How many of the symptoms you will experience differs from one person to the next. This is because the symptoms depend on various factors, such as the type of SCD, the severity of your anemia or the breakdown of red blood cells, how often you suffer sickle cell crises or infections, and how severe these are.

Common symptoms and problems:

• Anemia: symptoms depend on the extent of the anemia. Common symptoms include tiredness, feeling weak, shortness of breath, dizziness, heart palpitations, sweating, headache.
• Sickle cell crisis: an episode where small blood vessels get clogged up, potentially leading to a lack of oxygen in body tissue, which is referred to as infarction. Infarction can occur in many places in the body and do temporary or lasting damage. Examples include brain, renal, or bone infarctions.
• A sickle cell crisis is often very painful. The extent of the pain is determined by the location of the crisis. A bone crisis, for example, is very painful, while splenic infarction can go entirely unnoticed due to the absence of pain.
• Infections: if your spleen is not working properly, or not at all, you will be more prone to infections with, among other things, encapsulated bacteria such as streptococci, meningococci, and Hemophilus influenza. Symptoms include fever, not feeling well, loss of appetite, and pain (such as a sore throat or headache). Due to reduced splenic function, bacteria are not adequately eliminated, allowing the infection to spread through the body quickly and easily. This may lead to more serious and severe infections, like sepsis or meningitis. The infections, in turn, trigger a sickle cell crisis that leads to further organ damage.

Organ-related problems:

• Brain: after some time, sickle cell disease can lead to a narrowing of the blood vessels in the brain. If this leads to a blocking of blood flow, the arteries will not be able to supply blood and oxygen to surrounding parts of the brain tissue, which leads to damage. This is called a brain, or cerebral, infarction. Since this can happen almost unnoticed, it is sometimes referred to as a silent infarction. To monitor blood flow in the brain, children who have SCD have a brain scan once or twice a year. In the Netherlands, for children with HbSS and HbS- beta thalassemia, brain scans are done every six months from age 2, and every year from age 10. Due to blood flow abnormalities, children who have SCD are consequently more prone to develop learning difficulties and concentration problems, as well as emotional and behavioral issues. Needless to say, this is partly also down to the regular check-ups in hospital and possible hospital admissions.
• Heart: the heart is a muscle with four cavities in the center, two atria (a left atrium and a right atrium), and two ventricles (a left ventricle and a right ventricle). The ventricles are basically blood pumps. The left ventricle pumps blood into the aorta and through the entire body and the right ventricle pumps blood into arteries towards the lungs. Due to the severe anemia associated with SCD, the heart has to work a lot harder to supply the required amount of oxygen to the body. Consequently the left ventricle of an SCD patient develops a thickening, or hypertrophy, of the heart muscle tissue which ultimately leads to a widening of the left ventricle (left ventricle dilatation). Pulmonary hypertension, in turn, potentially leads to a thickening of the right ventricle wall (i.e. right ventricle hypertrophy).
• Lungs: the breakdown of sickle cells leads to more nitric oxide (NO) being bound to the increased amount of free hemoglobin in the bloodstream. This means you will have less active NO in your system. Normally, NO relaxes the wall of blood vessels, widening them to allow more blood to flow through. If NO levels are low, you could develop high blood pressure in the lungs, because the blood vessels in the lungs are unable to relax properly, leading to reduced blood flow through the lungs. This is called pulmonary hypertension. Other processes are also affected by NO shortage, causing extra complications in SCD patients.
• The term acute chest syndrome refers to a sickle cell crisis in the lungs, which is generally triggered by an infection in the airways. Acute chest syndrome can be life threatening. It may come with the following symptoms: fever, coughing, difficulties breathing, and oxygen deficiency. Due to this crisis the lung tissue will be damaged and destroyed, as a result lung function may be reduced permanently (restrictive lung function).
• Kidneys: kidneys are highly sensitive to changes in blood flow. One important function of your kidneys is the concentrating ability. They control the fluid balance in your body, by regulating secretion and reabsorption. Kidney tissue will be damaged when the sickle cells get stuck in the narrow arteries in the kidneys, which can have serious consequences and lead to kidney damage in the long run. For example, the kidneys’ ability to control fluid levels can diminish, this reduces your body’s ability to reabsorb fluid. As a result, you will dehydrate because you urinate a lot. When you are dehydrated, the amount of fluid in your blood is diminished, your blood will get thicker. This, in turn, makes it more likely that you will suffer a sickle cell crisis.
  
  This is why it is extra important to drink enough. As the kidneys’ ability to regulate fluid balance diminishes, your body will lose a lot of water, causing you to urinate a lot and often, also at night. This can lead to you waking up at night to go to the bathroom, or if you do not wake up, wetting your bed. It is important that you, after every time you urinate (also at night), drink a little water to top up your fluid level.
• Bones: reduced blood flow can lead to bone tissue damage and destruction, which is sometimes referred to as a bone infarction or avascular necrosis. This is very painful and means that you will not be able to use the affected limb as normal. Upper legs and arms, as well as vertebrae, are particularly susceptible to it.
  During an aplastic crisis, the bone marrow temporarily stops producing new blood cells, like red and white blood cells and blood platelets. This kind of crisis leads to aplastic anemia, i.e. anemia of all blood cells. This is almost always caused by a Parvovirus B19 infection.
• Gallbladder and bile ducts: the breakdown of red blood cells leads to the formation of gallstones due to the high amount of bilirubine as a waste product of this breakdown. These gallstones can end up in the bile ducts and obstruct the gallbladder passage, which can cause severe (colic) abdominal pain.
• Spleen: sickle cell disease can lead to obstruction of small blood vessels (vaso-occlusion) in the spleen. This starts very early on in a newborn’s life, after only a few months. Vaso-occlusion does not produce pain, meaning that it goes by unnoticed. But with every occurrence of vaso-occlusion, the spleen tissue is damaged and tissue is lost, which ultimately leads to spleen failure. The spleen then loses the ability to properly filter bacteria out of the blood, and the spleen's B lymphocytes can no longer do their job. In the end, this seriously undermines defenses against encapsulated bacteria in particular. This makes you more prone to infections with these kinds of bacteria, while such and other infections will also be far more severe than if you did not have SCD.
• Growth and puberty: when you have a chronic condition that involves severe anemia, conditions are simply far from ideal for your body. This has an inhibiting effect on growth. It also often leads to delayed puberty development. Children with SCD tend to start puberty two years later than peers who do not have SCD.
• Eyes: the retina can sustain damage due to frequent periods of vaso-occlusion and oxygen deficiency. This is a trigger for the production of new blood vessels in the retina. And these new blood vessels lead to additional complications such as retinal detachment and vitreous hemorrhage, which ultimately leads to reduced eyesight. These kinds of ophthalmologic problems arise from halfway into a child’s teenage years and are more common with HbSC SCD. They can get more severe later in life. This process is also referred to as proliferative sickle cell retinopathy (PSR). It is therefore important to have regular eye examinations and vision tests from age 4 onward.
• Skin: SCD also affects wound healing, at all ages. Wounds take longer to heal or do not heal properly. In adults, open infections can occur on the lower legs (ulcer or ulcis cruris), which take longer to heal or do not heal properly. The reasons for that include reduced blood flow around the wound, causing red blood cells to sickle faster and obstructing other healing cells in reaching the wound. The sickling of the red blood cells leads to oxygen deficiency, as well as reduced NO levels, narrowing of blood vessels and activation of endothelial cells, which further constricts blood vessels, reducing the chance of healing.

Unusual appetite (pica):

when you have an appetite for unusual things that are not really edible, you are suffering from a disorder that is called pica. Things you may want to eat include paper, earth, hair, etc. Sometimes children with SCD or people with anemia have this disorder. It is possibly caused by a shortage of certain nutrients or because you are sick and do not feel well. Pica can cause abdominal pain and be bad for your teeth. The things you end up eating can also be unhealthy. It is therefore important that you talk about an urge to eat unusual things, so that you can be counseled.