There is no cure for SCD, which means that it is a lifelong condition. Some physical problems come on in the very short term, while others take some time to occur, often in different organs. As a result, it is important to have regular check-ups by your attending (pediatric) hematologist at a specialized hospital (in the Netherlands, a Sickle Cell Center), possibly together with a pediatrician from a regional hospital. At the Sickle Cell Center, you will find a range of different people who can help you, such as a (pediatric) hematologist, a specialist nurse, a clinical genetic consultant, a social worker, a (pediatric) psychologist, and various other medical specialists. The (pediatric) hematologist will diagnose possible complications at an early stage, so that you can get the medical treatment you need (medication, blood transfusion) and the right specialists can be brought in. These specialists will also examine your brain, heart, lungs, and eyes. In acute situations or with complicated symptoms, the pediatrician from a regional hospital can always consult with the pediatric hematologist at the Sickle Cell Center.

Besides the treatment options specified below, it is important to have a healthy lifestyle, especially when you have sickle cell disease. Living a healthy life will enable your body to stay in good shape. Healthy food, lots of fluid, going to bed on time, and exercise will all help you stay in good condition. Aside from that, you could try to avoid stress for your body to reduce the chance of a sickle cell crisis. Drinking alcohol, partying all night long, or going to bed late every day are examples of things you should not be doing.

Medication:

• Antibiotics: given SCD patients’ increased chance of developing serious infections due to spleen failure, children aged up to 12 are given antibiotics twice a day in the Netherlands, generally Phenethicillin (Broxil). This is particularly important during childhood, due to the greater susceptibility to infections. Severe infections with encapsulated bacteria in particular (which are bacteria with a capsule around them, such as pneumococci, meningococci, and hemophilus influenza) can largely be prevented by these antibiotics.
  
  To SCD patients from age 12 onward, antibiotics are prescribed only in cases of fever or sickness, although doctors will be quick to prescribe antibiotics to prevent problems. As a general rule, you should start taking antibiotics if you have had a fever for over 24 hours or if you are quite sick. Such a course of antibiotics will then have to last at least a week (often Augmentin or Amoxicillin).
• Pain relief: a sickle cell crisis is very painful. Given that a sickle cell crisis is perpetuated when the pain is not treated properly, pain treatment is very important. This means not only that you must take lots of fluid (by drinking or intravenously) during a sickle cell crisis, but also that you must take painkillers or even need morphine. The most commonly used painkillers are paracetamol and NSAIDs (such as ibuprofen, diclofenac). If these do not work, a medical specialist can administer opiate medications (such as morphine).
  
  It is important that you take painkillers regularly, at fixed times (as prescribed by your doctor), so as to ensure steady effective levels of the medicine in your blood. If you both take paracetamol and an NSAIDs, make sure you alternate them. When you need pain medication, it is very important to, together with your doctor, make a clear schedule of when to take which medication.
• Taking folic acid will support the increased production of red blood cells in the bone marrow. This will prevent anemia caused by a shortage of folic acid. Increased red blood cell production in the bone marrow will cause folic acid reserves to deplete rapidly. Folic acid will be administered from the moment a baby switches to solids.
• Hydroxycarbamide (Hydrea© or Siklos©): this medication is prescribed in cases of frequent sickle cell crises or severe complications of the disease.
  
  This medication intervenes in the production of blood cells in the bone marrow. As blood production in the bone marrow is suppressed, the bone marrow creates HbF (fetal hemoglobin) again instead of HbS. When HbF levels rise, the HbSS red blood cell percentage drops, which often leads to the disease being less severe. Aside from that, it also inhibits the production of white blood cells and platelets, causing the number of cells in the bloodstream to fall, which means less chance of sickle cell crises. It also makes red blood cells less quick to clot together or stick to the vascular wall.
  
  This medication is mostly prescribed when a patient frequently has painful crises (more than 3 per year), after acute chest syndrome, or other complications, or in cases of very severe anemia. It is important, however, to take note of the side effects, which include nausea, headache, and hair loss. The bone marrow might also be inhibited too much, which would see white blood cell production drop to an insufficient level. Close monitoring by a specialist is therefore important. During pregnancy, hydroxycarbamide may be harmful to the fetus. Using this medication during pregnancy or while trying to get pregnant is therefore advised against. In men, hydroxycarbamide has a (temporary) impact on sperm cell production.
• Medication in case of iron overload:
  • Desferal, Desferal, also known as deferoxamine or DFO, can be administered subcutaneously or intravenously. Subcutaneous administration is the most common form of administration for this drug, which involves inserting a small needle just under the skin and attaching it to a small infusion system. Deferoxamine can have side effects such as nausea, headache, hair loss, and sometimes also pancytopenia (shortage of red and white blood cells and platelets), fever, pneumonia, and ankle joint ulcers. It does, however, ensure highly effective removal of overload iron (which is called iron chelation), although the impact on the patient can be big. Deferoxamine is contraindicated in pregnancy or when trying to get pregnant because it can cause birth defects. And in men, it reduces sperm cell production.
  • Ferriprox, which is also known as deferiprone or L1, is used when Desferal is insufficiently effective or in cases of severe iron overload in the heart. This medication comes in tablet form, meaning that it can be taken orally. Deferiprone can produce side effects such as nausea, vomiting, abdominal pain, zinc deficiency, increased susceptibility to infections, painful joints, reduced kidney and liver functions, and an accelerated heart rate.
  • Exjade, which is also known as deferasirox or ICL670, is medication that binds iron, so that it can be discharged from the body. This medication comes in tablet form, meaning that it can be taken orally. Deferasirox can produce side effects such as nausea, vomiting, abdominal pain, constipation, bloating, rash, and headache. It may also affect kidney functions.

If your sickle cell disease is acting up a lot or you have a severe (acute) complication, your (pediatric) hematologist may decide to treat you with a blood transfusion or an exchange transfusion, or perhaps even several transfusions. A blood transfusion or an exchange transfusion will (temporarily) reduce the HbSS red blood cell count (or other kind of sickle cell red blood cell). And it will (temporarily) boost the blood’s ability to transport oxygen through the healthy red blood cells introduced into your bloodstream by the blood transfusion. Blood transfusions or exchange transfusions are indicated only in cases of severe symptoms. This is because of several reasons: blood transfusions can spark immune reactions and lead to hyperviscosity (increased blood cell count), and they can lead to iron overload in the long run, which will require treatment with medication. Iron overload can produce severe symptoms in the long run.

Treatment with blood transfusion is only indicated when you have severe symptoms, such as when you need intensive care on an ICU, in cases of severe anemia with physical problems, acute chest syndrome, a liver crisis, a prolonged painful sickle cell crisis, priapism, or a cerebral infarction (or one in history).

As donor blood comes from another body, a blood transfusion may spark an immune reaction. Despite careful treatment and screening of the donor blood, it may contain proteins that your body considers to be foreign, which will prompt your body to produce antibodies. The next time you have a transfusion, you may get very sick, as it provokes a transfusion reaction (or rejecting immune reaction).

An exchange transfusion (erythrocytapheresis)

An exchange transfusion (erythrocytapheresis is a special kind of blood transfusion. The advantage of an exchange transfusion is that while you receive red blood cells from the donor blood, your own HbSS red blood cells are filtered out of your blood. As a result, an exchange transfusion will provide relief for longer than a normal blood transfusion, the blood cell count in the bloodstream will not increase so much (meaning that the blood will be less thick), and there will be less iron overload. Still, the downsides are that creating a venous access may be difficult with young children and an exchange transfusion requires a larger volume of blood.

Antibiotic protection and vaccinations:

Antibiotics and vaccinations are very important given the spleen failure that plagues SCD patients. One of the spleen’s primary purposes is to protect you against infections, as it filters bacteria, and encapsulated bacteria in particular, out of the bloodstream. Due to the fact that blood vessels in the spleen tend to get blocked by the sickle cells (vaso-occlusion), the spleen will ultimately damage, stop working and die off. This damaging process starts as early as a few months after birth, requiring antibiotics from this very young age.

Vaccinations:

in the Netherlands, all children are eligible for vaccination through the Rijks Vaccinatie Programma (RVP, or National Vaccination Program). The first vaccination is given as soon as two months after birth. Protection against diseases is extremely important for children with SCD. Besides the standard vaccinations of the National Vaccination Program, the following vaccinations are also recommended: a pneumococcal vaccination (type: unconjugated 23-valent vaccine) at the age of 2, repeated every five years. In case of regular blood transfusions: a hepatitis B vaccination (only for children who were born before October 2011, because for children born after October 2011 this vaccine is part of the standard vaccinations of the National Vaccination Program). Influenza vaccination from age 2, repeated annually. If you have not been vaccinated through the National Vaccination Program (because you lived in another country): Hib and Meningococcal vaccination. And when traveling to the tropics, special vaccinations against infections that are specific to tropical areas and prophylaxis for malaria.

Stem cell and bone marrow transplantation:

Sickle cell disease is a hereditary condition that can only be cured by replacing a patient’s bone marrow with donor bone marrow. This is called a stem cell or bone marrow transplant, which is an intensive and complex procedure that replaces the patient’s entire red blood cell production infrastructure with that of a donor. The new produced red blood cells will not have hemoglobin with an abnormal beta globin chain, but instead have normal beta globin chains, which means that normal hemoglobin A1 will be produced. In the Netherlands, there is considerable experience with this kind of transplant. However, this option is rarely used in cases of SCD, because the adverse effects and risks still outweigh the benefits.

Future treatment options:

Despite widespread research into gene therapy, it is a long way off from being a treatment option in cases of SCD. Gene therapy consists in introducing a healthy gene into the hemoglobin-producing (stem) blood cells through a (retro)virus. The virus penetrates cells and deposits genetic material. In theory, this enables the bone marrow to create red blood cells with normal hemoglobin.

Support:

SCD can also lead to social and emotional problems, as well as behavioral problems. To deal with these kinds of problems, a social worker and a (pediatric) psychologist can be involved in the treatment. Early identification and support, as well as getting the school actively involved, are very important. Absence from school due to frequent hospital admissions or check-ups must be avoided as much as possible.

Special circumstances that can trigger a sickle cell crisis:

• Very cold and/or humid conditions (wear warm clothes and whenever you get a chill, make sure you get warm again quickly)
• Dehydration (drink plenty of fluids, especially in hot weather or during exercise, or in situations of excessive fluid loss, ie. while having a fever, vomiting and/or diarrhea, or alcohol consumption)
• Stress (not enough sleep, under too much strain, etc.)
• Infections
• Excessive alcohol consumption
• Menstruation (due to abdominal pain and physical stress)

Special circumstances that can trigger a sickle cell crisis:

• Very cold and/or humid conditions (wear warm clothes and whenever you get a chill, make sure you get warm again quickly)
• Dehydration (drink plenty of fluids, especially in hot weather or during exercise, or in situations of excessive fluid loss, vomiting and/or diarrhea or alcohol consumption)
• Stress (not enough sleep, under too much strain, etc.)
• Infections
• Excessive alcohol consumption
• Menstruation (due to abdominal pain and physical stress)

Special measures to prevent a sickle cell crisis :

• Drink lots of water or get fluids administered intravenously
• Pain relief
• Stay warm
• Fever suppression, by the use of paracetamol or NSAIDs
• Take antibiotics or other medication to fight an infection
• Oxygen
• Blood transfusion
• Exchange transfusion

Possible access to the venous bloodstream:

Fluid or blood is administered intravenously directly into your vein (a blood vessel that flows towards your heart). With small children, it is often harder to insert the needle with intravenous (IV) tube into the vein, plus their vessels are more vulnerable. And, if you have had an IV on several occasions, scar tissue may have formed on the vein due to the tiny damage done by prior insertions. Here are a few examples of how your venous bloodstream can be accessed:

• Peripheral venous catheter: this is a small flexible plastic tube that is fitted around a needle. Once the needle has properly pierced the vessel, the catheter can be moved down on the needle and into the vessel. After that, the needle is removed and the infusion system can be hooked up. The inserted catheter must be stabilized well using tape, and the hand, arm, or foot in question is often put in a splint for extra stability.
• Central venous catheter or line: this is a needle with a larger, flexible silicon tube. In the case of children, this is often inserted into a large vein below the collarbone under anesthetics. The tube is mostly tunneled under the skin,meaning that it is good fixated. Due to the fact that the line has a direct connection to your blood for a long time, there is increased risk of infection. Connecting and disconnecting a central intravenous line must therefore always be done very carefully and hygienically to minimize the risk of infection.
• Port-a-cath: this is a small hollow device or box that is placed under the skin under anesthetics. The device is attached to a silicon line that is inserted into a large vein (such as the vein below the collarbone). The device itself is implanted on the thorax under the patient’s skin. The top of the device is covered by a membrane, so that a needle can be inserted into it. As a result, a needle can be inserted into it from the outside through the skin to create a conduit between the needle and the vein, through the device and its line. This also comes with a risk of infection due to the direct connection with the blood. Connecting and disconnecting a port-a-cath must therefore always be done very carefully and hygienically to minimize the risk of infection.