Wednesday, May 22, 2024

Sickle Cell Disease Prevention

Overview of Sickle Cell Anemia Prevention

Sickle cell anemia, or sometimes referred to as “Sickle cell disease” is an inherited type of anemia where red blood cells (which are responsible for carrying oxygen from the lungs to the rest of the body) are sickle shaped.

Sickle cells contain abnormal hemoglobin called sickle hemoglobin or hemoglobin S. Sickle hemoglobin causes the cells to develop a sickle shape.

These sickle shaped red blood cells can possibly clog sections of blood vessels which means oxygen cannot be carried properly to the rest of the organs, thus, causing episodes of severe pain. Abnormal sickle-shaped red blood cells have a shorter life-span compared to regular round shaped red blood cells and they usually die in about 10-20 days, and unfortunately they cannot be quickly replaced with new ones. This causes a shortage of red blood cells until the new ones are produced, causing anemia.

The symptoms of the disease usually begin in early childhood and symptoms of sickle cell anemia are, low count of red blood cells, shortness of breath, developmental growth and delay in children and high blood pressure. Treatment of sickle cell anemia involves measures to reduce the severity and frequency of episodes of sickle cell crises.

Sickle cell disorder is caused by the HBB gene mutation. Sickle-cell anemia is caused by a mutation in the ß-globin chain of hemoglobin, caused by an amino acid substitution of Glu to Val at the sixth amino acid position in the beta-chain hemoglobin protein. The substitution causes a mutation (abnormality) which causes the hemoglobin to distort the red blood cells into a sickle shape.

Pattern of inheritance is autosomal recessive, which means, in order to have sickle cell anemia, the patient will need to acquire the mutation carrying gene allele from both parents. If both male and female patients have the sickle cell carrying gene allele, then there is a very high risk of exposing their offspring to this disease.

If a person only acquires one allele from a single parent (whereas the other parent is not a carrier and is free of sickle cell disease), the person remains a carrier of the disease. A carrier is not at any risk. However, if both parents are carriers of the sickle cell mutant gene, then there is a 25% chance of passing it down to the offspring. In other words, having the sickle cell trait itself is not likely to cause a person to develop sickle cell disease. But if two people with the trait are going to conceive a child then there is a one in four chance that child will be born with sickle cell anemia.

Sickle cell trait is different from sickle cell anemia. Sickle cell trait indicates that a person is a carrier. Person who is a carrier will run the risk of passing this genetic mutation down to his/her child if he/she conceives a child with another carrier. However, a carrier will not have any of the symptoms of sickle cell anemia. Sickle cell anemia is most common in African and Mediterranean populations but it can also be seen in people from Caribbean, Middle East and Central America and it estimated to occur in 1 in 500 Africans.

The red cells that contain the globin are unable to deliver oxygen as effectively as other red blood cells. Due to inefficient transport of oxygen, the body tries to compensate by producing additional hemoglobin, therefore, additional bone marrow. This causes the bones to be more fragile. The inefficiency of oxygen transport also causes the heart to enlarge in an attempt to improve the transport of oxygen by increasing the blood pumping rate. The abnormal sickle cells are collected in the spleen, causing it to enlarge and become fibrotic. More importantly, sickle-shaped blood cells clog the capillaries and further restrict blood flow, which causes additional symptoms. People with sickle cell disease will have signs of the disease as early as six months old. The symptoms of this disease can range from very mild to very severe and it affects different people differently. Symptoms include:

  • – Painful swelling of the hands and feet, known as dactylitis
  • – Fatigue or fussiness due to anemia
  • – A yellowish skin color, referred to as jaundice, or whites of the eyes, referred to as icteris, occurring due to the hemolysis of a large number of red blood cells.

Baby or fetal hemoglobin has the ability of preventing red blood cells from sickling. This is the main reason why the onset of symptoms is not at birth, but rather around 6 months old when the baby or fetal hemoglobin is replaced by sickle hemoglobin and the cells begin to sickle.

At this point, one can ask themselves, can sickle cell disease be treated? Or at least prevented? Luckily, with advancements in technology and medicine, it is possible to completely avoid passing sickle cell anemia down to your children! Pre-Implantation Genetic Diagnosis allows us to screen embryos for majority of genetic disorders as well as single gene disorders such as the sickle cell anemia. With this technology, we are able to biopsy each and every embryo prior to pregnancy and we are able to determine which embryo has the gene mutation for sickle cell disease. This allows us to eliminate the embryos with mutation altogether and only transfer the healthy embryos into the uterus for pregnancy.

PGD technique is offered as part of an IVF treatment program. Therefore, if you are at risk of passing sickle cell down to your offspring, IVF treatment will be required in order to prevent the next generation from sickle cell disease. Using PGD technologies will also allow us to screen for many other genetic disorders as well as the gender of your child. While preventing your child from sickle cell anemia, it is also possible to choose the gender of your child for family balancing purposes.

How to Get Started?

Even though sickle cell anemia is caused by a specific mutation on a specific gene, we will still need to obtain your blood samples from both partners in order to be able to design the PGD probe for embryo screening. This means that a couple who would like to undergo PGD treatment for sickle cell anemia prevention will need to give us their blood samples before we can proceed with treatment. This can be done in two ways:

-Couple can come to Cyprus to provide us with their blood samples and return back home until the probe design has been finalized and then come back for the second time in about two months time for the actual treatment. This means coming to Cyprus twice.
-Couple can send their blood samples in appropriate tubes so that they don’t have to come to Cyprus twice. They will be required to come to Cyprus only once later for treatment. If you are sending your blood sample in tubes, the samples should be placed in K3 Edta tubes with the purple cap. These are the only tubes that are appropriate to place your blood sample for sickle cell screening purposes. Please keep in mind that the blood samples must be with us within 36 hours, which eliminates DHL as an option, so you would  either need to organize a courier company or have someone fly out to Cyprus to bring the blood samples.

It is up to the patients how they would like to provide their blood sample. However, some patients find it more advantageous to come to Cyprus to give their blood samples as that enables them to have an initial consultation with us and possibly have their initial testing at our clinic. This also allows patients to purchase their medication at lower costs in Cyprus.

Processing the blood samples take about two months. Once we have finished designing the PGD probe, then we will contact you to prepare you for your treatment. Within the two month period, we will ask that you have your hormone testing and semen analysis so that we can identify the right medication dosage for your treatment. Once we have this information, we will be able to prepare you for your treatment.

The initial parts of the treatment are very similar to standard IVF/ICSI treatment where the female patient uses medication to stimulate her ovaries in order to produce multiple eggs. Having multiples eggs is essential for success in IVF treatments because the higher the egg count and the higher the quality of these eggs, the more likely it is to have good quality embryos later on for transferring into the uterus. Once the couple is ready, the eggs are collected via a minor surgical procedure at our clinic so that they can be fused with the sperm cells to create embryos. These embryos, in turn, are screened for sickle cell anemia so that the healthy ones can be chosen and transferred into the uterus o generate pregnancy.

Preliminary Testing

As mentioned above, treatment which will be offered for sickle cell disease prevention is an IVF treatment. At least the initial parts of the treatment are very much like an IVF treatment. The only difference is, your embryos will be screened for sickle cell anemia before they are transferred into the uterus. Therefore, the steps of IVF treatment outlined in our IVF/ICSI treatment page will also apply here. The following is a basic summary of events which will be followed:

-Initial testing before IVF treatment so that we can make an assessment of your fertility level and design the most optimal treatment protocol in order to maximize your chances of success with treatment. Given that we are carrying this treatment for a genetic disease prevention purpose, it is important that we get as many embryos as possible so that once the diseased embryos are eliminated, we are still left with a good number of healthy embryos to transfer.

-While you are having the initial testing, we will be doing the field work and getting started on your probe design with the blood samples that have been provided previously.

-Once the probe design has been finalizesd, you will follow our IVF treatment program that has been designed for you and come to Cyprus so that both your IVF treatment and embryo screening can be finalized.

For patients over the age of 35, due to their lowered ovarian reserves, we recommend that they consider having two IVF cycles so that we can combine two sets of embryos obtained from both cycles. Having more embryos to screen will allow us to offer you a higher number of healthy embryos to transfer, which is something that keeps your chance of success high with this procedure. If you decide to have two cycles, then the first cycle can be organized around the time when you come to provide us with your blood samples, so that the whole treatment can still be finalized in two trips to Cyprus.

Cost of Sickle Cell Disease Prevention with PGD

Sickle cell disease prevention is offered as part of an IVF treatment which involves Pre-Implantation Genetic Diagnosis (PGD) on the embryos which will be created in-vitro after the IVF protocol. The cost of treatment includes processing of blood samples for field work, designing a PGD probe to successfully screen your embryos, all your IVF procedures and a final embryo transfer. We are able to offer you this service at 6,500 Euros. However, your medication, initial local testing, airfare and hotel accommodation are not included in this treatment cost. For more information about accommodation and travel, please see our “Accommodation” section.