Sickle Cell Disease: Symptoms, Diagnosis, and Treatment

Sickle cell disease is caused by an inherited change in the red blood pigment (hemoglobin). It takes its name from the crescent-shaped red blood cells

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Sickle Cell Disease - Briefly Explained

  • Sickle cell disease is a hereditary change in the red blood pigment (hemoglobin), the so-called sickle cell hemoglobin (HbS).
  • More than 50 percent of those affected have the altered sickle cell hemoglobin. After the release of oxygen, the red blood cells change and take on a sickle shape, which can lead to vascular occlusions, recurring pain crises and even shock symptoms due to the blood sinking into the spleen. Other organs can also be affected by vascular occlusions.
  • Newborn screening for sickle cell disease has been in place in many countries for years. The diagnosis is so far an incidental finding in Germany. Doctors should consider sickle cell disease if a child has frequent bone pain or haemolytic anemia - a form of anemia in which red blood cells break down prematurely.
  • To confirm the diagnosis, specialized laboratories carry out a hemoglobin analysis and a test for the solubility of the hemoglobin.
  • Therapy is based on the prevailing symptoms. A cure is only possible through a stem cell transplant or gene therapy.

What is sickle cell disease (sickle cell disease)?

In sickle cell disease, genetic errors (mutations) lead to changes in hemoglobin. Those affected produce abnormal hemoglobin - sickle cell hemoglobin (HbS). This is only considered sickle cell disease when more than half of the blood pigment (hemoglobin) is present as sickle hemoglobin.

As soon as the HbS has given up its oxygen, it clumps and creates a sickle shape in the red blood cells. They are no longer elastic and can therefore get stuck in small and very small blood vessels and block them. This leads to symptoms due to reduced blood flow to organs and anemia, as the changed blood cells increasingly break down (hemolytic anemia).

People from Central and West Africa, the Eastern Mediterranean, the Middle East, India, the Caribbean, North and South America are particularly affected. The HbS sponsorship, but not sickle cell disease, protects against the most severe form of malaria, malaria tropica. Sickle cell disease also occurs in Germany. This affects around 3,000 people nationwide (as of 2019).

The sickle shape of some blood cells can be clearly seen on the blood smear

© Getty Images / Photoresearchers

What is hemoglobin?

Hemoglobin (Hb) is the red pigment in the blood. It sits in the red blood cells and can bind oxygen for transport through the bloodstream. The red blood cells are usually in the shape of a disk that is thinner in the middle. Due to their elastic structure, they can move easily through even the smallest blood vessels. In adults, hemoglobin consists of 98 percent HbA1 and two percent HbA2. In newborns there is still hemoglobin F (HbF), which accounts for up to 87 percent of hemoglobin. Up to the age of about six months, HbF is increasingly being replaced by adult HbA.

Causes: How does sickle cell disease come about?

Sickle cell disease is a hereditary disease. Some people carry a healthy gene and a sick gene (HbAS) - they are so-called heterozygous carriers of the genetic make-up for sickle cell disease (see also the background information below). These people produce over 50 percent normal red blood pigment (HbA) and also the altered blood pigment HbS. Heterozygous carriers have no symptoms, but can pass the system on to their children.

However, if an affected person has two diseased genes (HbSS), then he only produces the changed blood pigment HbS and not normal HbA. This homozygous form of HbSS leads to sickle cell disease (previously called sickle cell anemia).

In addition to HbS, there are other hereditary changes in hemoglobin: beta thalassemia, HbC, HbD, Hb Lepore, Hb OArab. In combination with HbS, they can lead to sickle cell disease. They are then called sickle cell disease Sß + / ß ° Thal, sickle cell disease SC, sickle cell disease SD, sickle cell disease SLepore or sickle cell disease SOArab. These gene combinations occur when one parent is a carrier of the sickle cell gene and the other parent is a carrier of another hemoblobin disease, such as beta thalassemia

© W & B / Astrid Zacharias

HbAA: healthy genes

HbAS: heterozygous carrier, the gene can be passed on to children

HbSS: homozygous patient with sickle cell disease

How sickle cell disease can be inherited

In our example, both parents have a healthy gene (HbA) and a sickle cell gene (HbS). They are heterozygous carriers. Since each gene from the mother (A or S) and a gene is inherited from the father (A or S), this results in the following distribution options for your children: HbA.A - manS.A - manA.S - manS.S. The statistical probability of having a healthy child is 25 percent. The likelihood that the child is a heterozygous carrier is 50 percent. The probability that the child will suffer from sickle cell disease is again 25 percent. Based on this hereditary distribution, it can be seen that there can be healthy and sick children as well as carriers of the disease within families.

Further hereditary constellations

If both parents are sick (HbSS), 100 percent of the children also get sickle cell disease. If both parents have normal hemoglobin (HbAA), the children are healthy too. If only one parent is a carrier of an HbS gene (HbAS) and the other parent is healthy (HbAA), there is a 50 percent chance that a child is a heterozygous carrier. Sickle cell disease (HbSS) is then not possible.

Symptoms: what symptoms does sickle cell disease cause?

Most severely affected are people with the homozygous (HbSS) form and HbSß ° thalassemia. You can develop severe symptoms from the fourth to sixth month of life.

  • Anemia

Since the sickle cells disintegrate more quickly, chronic anemia (hemolytic anemia) occurs. However, the anemia is tolerated more easily, as HbS releases oxygen much more easily than HbA. An exception with regard to anemia are patients with the HbSC form. Their red blood cells also break down (hemolysis), but their hemoglobin levels after puberty are rather high compared to other sickle cell diseases (over 10 g / dl). This makes the blood thicker and those affected suffer from diffuse pain as well as changes in the inner ear and the fundus in adulthood.

  • Pain crises

The main symptom is pain in the skeletal system. They are caused by vascular occlusions and insufficient blood flow to the bone marrow. The bone marrow reacts with swelling, which leads to irritation of the pain nerves and to pressure on the periosteum (periosteum) surrounding the bone. The blood-forming bone marrow (red bone marrow) is found in adults mainly in the ribs, vertebrae, sternum and the thigh bone near the trunk. In small children, on the other hand, red marrow is still found in all bones. A pain crisis (around the age of three) is therefore often caused by vascular occlusions in the metacarpal and foot bones. There is painful swelling of the hands or feet. The children then no longer want to run or reach for something.

  • Organ damage

The sickle-shaped blood cells can clog not only the vessels in the bone marrow, but also other blood vessels. Depending on the region, organs such as the spleen, liver, lungs, kidneys, brain, eyes and inner ear can also be affected and cause acute and chronic organ damage. Vascular occlusions can also lead to the development of femoral head or femoral head necrosis. This means that the bone dies due to the lack of blood supply.

  • Increased susceptibility to infection

The spleen, whose main task is to filter dangerous bacteria such as pneumococci from the bloodstream, loses its function in the first years of life due to vascular occlusions. This makes those affected susceptible to certain bacterial infections.

An infection with rubella, which is harmless to most people, can cause life-threatening anemia (aplastic crisis).

  • Spleen sequestration

So-called spleen sequestration is particularly possible in infants and toddlers. A large part of the blood sinks into the vascular bed of the spleen and leads to a threatening lack of volume. Therefore, a blood transfusion is usually necessary here. If there are multiple events, the spleen should be removed (splenectomy).

  • Possible symptoms in heterozygous carriers (HbAS)

Carriers (heterozygous form; HbAS) usually have no symptoms. You do not suffer from pain crises or vascular occlusions. Anemia does not occur either. However, if you stay at high altitude (from 2500 meters above sea level), HbS carriers can have a splenic infarction. This is expressed by severe pain in the left upper abdomen. Around four percent of HbS carriers have episodes of painless macrohematuria (blood in the urine) due to dead kidney papillae (papillary necrosis). The very rare medullary renal carcinoma affects younger (10 to 40 years) male HbS carriers with an above-average rate.

Diagnosis: how is sickle cell disease recognized?

A prenatal diagnosis using a so-called chorionic villus sampling is possible. It comes into question, for example, if both parents are carriers of a disease-causing hemoglobin variant.

Newborn screening for sickle cell disease is common in some countries in Europe and the United States. It is to be introduced in Germany in 2021.

The doctor should listen carefully if children often complain of bone pain and a reduction in red blood cells is found in the laboratory. A large, palpable spleen and other complications such as a stroke should also make you think of sickle cell disease in this context. Since no screening examinations on newborns (search test for certain genetic diseases) for sickle cell disease have been carried out in Germany so far, it is more of an incidental finding. However, if the suspicion is confirmed based on the symptoms, a hemoglobin analysis (hemoglobin electrophoresis) provides information about the disease and also about the composition of the red blood pigment.

If a child is diagnosed with sickle cell disease, a hemoglobin analysis should also be performed for the rest of the family members.

Therapy: How can you treat sickle cell disease?

Depending on the time of diagnosis, a distinction can be made between preventive measures and the actual treatment of the disease.

Preventive measures

  • Preventive antibiotic administration and vaccinations

Once the diagnosis has been made, experts recommend preventive antibiotics (penicillin) up to the age of five. They also advise vaccination against pneumococci. Both are important measures to protect against life-threatening blood poisoning (sepsis) by pneumococci.

  • Hydration

In addition, sickle cell patients have to drink plenty of fluids. In sickle cell patients, the kidney cannot concentrate the urine. This means that much more pale-colored urine is excreted than in healthy people. Tap water or unsweetened teas are best suited here.

  • Spleen examination

As early as possible, parents of affected children should be shown how to examine their child's spleen themselves. This technique is best used every time you swaddle. If the spleen is palpable under the costal arch, there is a strong suspicion of splenic sequestration. The child then has to go straight to the hospital for treatment (usually a blood transfusion).

  • Imaging procedures

From the age of two, an annual ultrasound examination of the vessels supplying the brain is important (transcranial Doppler sonography, TCDS). It allows the children who are at high risk of stroke to be identified and treated accordingly.

  • Laboratory tests

In order to detect kidney damage at an early stage and to be able to treat it, an annual examination of the urine for protein is necessary in all sickle cell patients from the age of six.

  • Medication

The cytostatic drug hydroxycarbamide (also called hydroxyurea) affects red blood cells. It increases the fluid content of the red blood cells and reduces the "stickiness" of the red blood cells so that they do not stick to the vessel walls as easily. Furthermore, it leads to an increased formation of HbF (see also section on hemoglobin), which reduces sickling. Hydroxycarbamide can reduce the number and extent of pain crises in many people affected.

If the kidneys excrete more than 300 milligrams of protein in 24 hours, patients need a drug that protects the kidney (ACE inhibitor).

  • Further measures

To prevent crises of pain, those affected should not swim in cold water and must avoid fluid loss, smoking and alcohol.

treatment

  • Hydration

If acute pain occurs due to vascular occlusion, the therapy consists in the supply of fluids - preferably by drinking enough according to the instructions of the medical professional, if necessary also by infusions.

  • Painkiller

All sickle cell patients should have the following pain medication at home: acetaminophen, metamizole sodium, or ibuprofen. If the pain is severe, a morphine preparation can be given via an infusion in the clinic.

  • Further measures

In certain situations, antibiotics, removal of the spleen or gallbladder, and for some patients regular transfusions (blood transfusions) are necessary. In sickle cell disease SC there is usually an increased number of red blood cells, which is why bloodletting is also used here if necessary.

A stem cell transplant can cure the disease. However, since this therapy method involves risks, the advantages and possible disadvantages must be carefully weighed. Stem cell transplantation is an option in severe cases, for example after strokes and in severe and frequent pain crises that do not respond to hydroxycarbamide. However, a suitable family donor must be available, as there is still little experience with third-party donor transplants.

So far there are relatively few sickle cell patients in Germany (around 3000). That is why it is difficult for doctors in this country to gain sufficient personal experience. Mostly they rely on information from experts - for example in the form of guidelines or through contact with specialized institutions. The best possible medical care can have a positive influence on the course of the disease.

Dr. Roswitha Dickerhoff

© W & B / private

Consulting expert:

Dr. med. Roswitha Dickerhoff is a specialist in pediatric and adolescent medicine with a focus on pediatric hematology and oncology. Until 2018 she was in charge of a special outpatient clinic for rare anemia at the University Clinic in Düsseldorf and, among other things, is the founder of the self-help group "Sickle Cell Disease and Thalassemia Association". She has been working in the practice of Prof. Dr. Boar in Munich.

Swell:

  • "Sickle Cell Disease Information Website for Patients, Parents, and Physicians" and "Sickle Cell Patient Care Guide". Online: http://www.sichelzellkrankheit.de (accessed on February 11, 2020)
  • Interest group sickle cell disease and thalassemia e.V, "sickle cell disease (formerly sickle cell disease)". Online: http://www.ist-ev.org/sichelzellanaemie-krankheit/ (accessed on February 11, 2020)
  • Onkopedia, "Sickle Cell Disease", as of 2010 (being updated). Online: https://www.onkopedia.com/de/onkopedia/guidelines/sichelzellkrankheiten/@@guideline/html/index.html (accessed on February 11, 2020)

Important NOTE:
This article contains general information only and should not be used for self-diagnosis or self-treatment. It cannot replace a visit to the medical practice. To answer individual questions, contact [email protected]

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