SCD can be diagnosed in several ways; through a neonatal screening test (heel prick test), genetic tests (prenatal or family), or through a blood test of the patient. Symptoms that are consistent with SCD include anemia and regular painful limbs, abdominal pain, or pain in other body parts. Especially when the country of origin or ancestry makes SCD likely or when a family member has SCD, SCD should be considered as a diagnosis.

A diagnosis of SCD can concern different forms of hemoglobinopathy. SCD will, for example, be diagnosed in cases of:

• HbSS (homozygote SCD or sickle cell anemia), diagnosed in roughly 70% of SCD patients
• HbSC disease (compound heterozygote sickle cell anemia), diagnosed in
  roughly 25% of patients,
• a different kind of compound heterozygote sickle cell anemia (such as HbS/beta-thalassemia, HbS/D Punjab, HbS/O Arab) jointly in roughly 5% of patients.

In the Netherlands, all newborns are screened for sickle cell disease only a few days after birth, using the neonatal screening test, which is also known as the heel prick test. A blood sample taken from the baby’s heel is screened for various diseases. Since January 2007, SCD is one of these diseases. Since newborns still mainly have fetal hemoglobin (HbF), they will not have any SCD symptoms when the neonatal screening test is conducted. Newborns do, however, already produce small quantities of HbS. The neonatal screening test will reveal HbS production and this will lead to the diagnosis of SCD. Over the first months of a child’s life, HbS production will increase, topping out between the 4th and the 6th month. From that moment onward, SCD symptoms may start to occur.

If diagnosed early, antibiotics can be administered on time to prevent infections, which course will be more severe as SCD causes the spleen to start to fail. Aside from that, early diagnosis will provide time for the parents to be informed better and more comprehensively, so that they will be able to recognize the symptoms of a sickle cell crisis or severe anemia.

General blood test:
With SCD, there are various changes in the blood that can be measured, in the following items:

• Complete blood count (consisting of):
  • Hemoglobin (Hb): Hb levels show how much hemoglobin protein you have available for oxygen transport.
  • Hematocrit (Ht): this is the ratio of the amount of red blood cells to the total blood volume. The higher your Ht levels, the more viscous (thicker) your blood.
  • Leukocytes (L): these are the white blood cells, which can be counted. An increase or decrease in the white blood cell count can point to an infection. Further microscopical examination can subsequently be used to differentiate between the different types of white blood cells, which is called a differential blood count. Differentiation of the white blood cells will show which type of white blood cell has increased or decreased to provide a better picture of the underlying problem. For example: is an infection probably caused by bacteria or a virus?
  • Thrombocytes (T): these are the platelets, which can also be counted. The platelet count shows to what extent your blood is able to clot. A low platelet count may lead to diminished clotting, meaning that bleeding may go on longer, while a high platelet count may make blood clot too quickly.
  • Erythrocytes: these are the red blood cells, which can be counted. Their size and shape can also be determined, which happens through so-called erythrocyte indices. The shape is described as sickle-shaped, large or oval, etc.
• Reticulocyte count: the volume of young red blood cells (recently produced) says something about how active the bone marrow is in terms of red blood cell production. In cases of anemia, there is a greater need for red blood cells and red blood cell production will therefore be stepped up. This means that the volume of young, recently produced, red blood cells (reticulocytes) should then also be greater. If it is not, or if it has decreased, despite the anemia, this points to a problem in bone marrow function. The problem can be a (viral) infection or a shortage of substances needed to produce red blood cells (iron, folic acid, vitamin B12). Or there may a different underlying cause, such as a malignancy or leukemia. The reticulocyte count is expressed as a percentage, which is the ratio of the number of reticulocytes to the total number of red blood cells.
• Substances that point to increased breakdown of red blood cells: one substance that is produced as red blood cells are broken down is bilirubin. The bilirubin count will increase both in cases of sickle cell disease and in cases of thalassemia, for example. The bilirubin count can also increase due to reduced liver and gallbladder function. Haptoglobin (a protein that is produced by the liver) binds the iron released as red blood cells are broken down. As a result, all diseases that come with increased red blood cell breakdown, such as SCD and thalassemia, lead to a lower haptoglobin count. In young children, the liver produces insufficient haptoglobin, and a low haptoglobin count can therefore not be considered a sign of increased red blood cell breakdown. LDH (lactate dehydrogenase) is an enzyme that is produced in greater volumes in cases of increased red blood cell breakdown.

Specific blood tests:
Sickle cell test:There are two possible tests that can be used to determine the presence of HbS. The first one uses a compound called sodium bisulfite, which is added to the blood that has been drawn by a venepuncture. If there is HbS in the blood, sickle cells will form after thirty minutes, which can be seen under a microscope. This test does not say anything about the volume of HbS in the blood. In other words, the test will be positive when you have sickle cell disease, but also when you are a carrier. This test can be done on people of all ages.

The second test can be done only on children of over six months old. Before six months, the HbS volume will be too low, and the test requires HbS levels of at least 20% to produce a conclusive test result. A positive test means that the test result is abnormal. The test result will be negative when the abnormal result is not produced. This test involves addition of a substance to the blood that has been drawn by a venipuncture, that together with HbS forms an insoluble crystal. If such a crystal is indeed formed, the fluid in the tube will go turbid, which means that there is HbS in the blood. Like the first test, this test says nothing about the volume of HbS in the blood, meaning that it will be positive for both SCD patients and sickle cell carriers.

Transition of SCD care from pediatric hematologist to hematologist for adults:

The pediatric hematologist and your parents or carers have been caring for you since the day you were born. As the years pass, you find out more and more things yourself and get more responsibility. You also get to know your body better. After you have turned eighteen, you will be treated by a hematologist for adults and become fully responsible for managing your disease. This transition from child to adult is a gradual one. The pediatric hematologist and sickle cell nurse will be actively involved in guiding you through this transition. You will probably also want to know more about your disease and how it will affect your life. You may have questions about heredity, the chances of your children getting the disease, the risk during pregnancy when you have SCD, but also about when to get in contact with the Sickle Cell Center.

If you have questions about heredity, you can turn to the Sickle Cell Center’s clinical geneticist (heredity expert). It is important that you and your future partner, with whom you decide to have children, seek expert advice. A clinical geneticist can also tell you about what tests you could consider before or during a possible pregnancy (pre-implantation genetic diagnosis, prenatal diagnosis based on chorionic villus sampling or an amniocentesis test). If you have SCD and you want to get pregnant, it is important to let your hematologist know and make an appointment with a gynecologist at an early stage. As an SCD patient, you will be monitored intensively by various medical specialists during pregnancy.

Pregnancy:

While pregnant, a woman’s body undergoes some major changes. Your body basically has to perform at the top of its ability. To supply adequate levels of nutrients and fuels to the baby, your blood volume, among other things, will increase. Hemoglobin levels will drop, as is normal in any pregnancy. If you have SCD and are pregnant, you are more likely to develop severe anemia because you are already anemic going into the pregnancy. Aside from that, sickle cell crises will be more severe and more frequent. Your body already has a long history of SCD by then and you are likely to already have problems in several organs (heart, kidneys, liver). To recap, the pregnancy will compound the existing SCD problems and can be a difficult period, with intensive monitoring and a higher risk of lots of symptoms and complications. SCD patients have a greater chance of early and late miscarriage, premature birth, growth restriction of the child, and the negative side effects of medication.

Prenatal genetic screening test:

Prior to the birth, you can have so-called chorionic villus sampling done around the tenth week of pregnancy. The sample of cells (from the placenta) contains the fetus’ DNA, which can be examined. In cases of SCD, the test will specifically check for the presence of the point mutation (which is responsible for HbS production). This prenatal test is done if the parents are carriers. Since carriers of HbS and HbC have a unique point mutation, the test can be specifically targeted on finding that point mutation. This is harder for carriers of beta thalassemia, because these have over 200 different possible mutations. To be able to screen the fetus’ DNA for a specific mutation in cases involving beta thalassemia carrier parents, it is essential to know which mutations the test needs to look for.

Future and life expectancy:

If you have SCD, important organs such as your brain, heart, kidneys, and liver may be damaged over time, and the treatment of your disease sometimes also causes damage. This differs from one patient to the next. Although homozygote HbSS SCD and HbS beta 0 thalassemia SCD are often the most severe forms, there are also major differences in the symptoms and complications within these groups. In some patients, the disease develops less severely than in others. Generally, the life expectancy of people with SCD is shorter than that of people who do not have the disease. In the Netherlands, at this moment life expectancy of patients with homozygote HbSS SCD is between 40 and 50 years. For patients with a compound heterozygote form, life expectancy is 20 years higher, lying between 60 and 70 years. The expectation is, however, that early diagnosis through neonatal screening, increased knowledge and guidance on the disease, regular and careful monitoring by (pediatric) hematologists who specialize in SCD, and good results of medication will lead to a clear rise in life expectancy over the coming years.