Overview of Sickle Cell Disease

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ORIGIN AND HISTORY OF SICKLE CELL DISEASE

Origin of Sickle Cell Disease

The origin of sickle cell disease (SCD) is from West Africa, with the highest prevalence. However, the prevalence of SCD was also on the higher side in the Mediterranean and Indian regions.

The single mutation idea about sickle cell disease was first proposed, implying that a single mutation happened in Neolithic times on the then-fertile Arabian Peninsula. Later, with the change in climatic conditions and the area became a desert, people who could have possessed the gene migrated to India, Eastern Saudi Arabia, and Equatorial Africa

Early History of Sickle Cell Disease

For at least 5,000 years, SCD has been prevalent in Africa and is referred to by different names in various tribal languages. However, it was not in Africa, but in the United States, it was “discovered” in 1910. A dentistry student named Walter Clement Noel from Grenada studying in Chicago went to Dr. James B. Herrick with anemic symptoms and pain episodes.

Because Herrick, a cardiologist, showed no concern, that’s why he handed over Noel’s case to a resident, Dr. Ernest Irons. Irons studied Noel’s blood under a microscope and noticed red blood cells he termed as “sickle-shaped.” After that, Herrick was surprised and involved when he saw this in the diagram because he thought it might be a new, unknown condition. After that, he used the term “sickle-shaped cells” in a report published in one of the medical journals.

In 1911, a 25 years old female patient also reported the symptoms of sickle cell diseases after Herrick’s discovery. She had been getting medical treatment for many years but was formally diagnosed with a rare type of pernicious anemia. This female patient had a blood film that indicated the morphology of sickle hemoglobin cells, identical to Herrick’s case.

After each passing year, an increasing number of cases of sickle cell disease began to be reported. With the increase in SCD cases, the improvement was seen in the medical knowledge about the disease. During that period, disease terminology emerged, such as the “active” and “latent” versions of the disease, eventually revealed to be inherited in heterozygous and homozygous patterns, respectively.

Later on, researchers discovered a link between the sickle cell trait and more excellent resistance to falciparum malaria. Electrophoresis revealed for the first time in 1949 that sickle hemoglobin traveled at a different rate than normal hemoglobin, indicating a molecular alteration in the aberrant cell.

When hemoglobin electrophoresis became commonly accessible in 1954, it became feasible to distinguish between different types of SCD. As a result, the disease was divided into subcategories, as we know them now.

Progress about Sickle Cell Disease Based on History

Currently, there are many such conditions known, but SCD was the first in 1951. Dr. Vernon Ingram figured out the facts of the anomaly in 1956. More information about how this aberrant structure impacts red blood cells was disclosed in the 1970s, and better diagnostics for illness identification were created. In addition, new and improved means of treating sickle cell patients and prospective medicines emerged in recent years.

Patients’ life expectancy and quality of life increased with recent treatments. In addition, genetic counseling became a popular method for educating people about the dangers of having sickle-cell children. However, physicians and scientists are still working to understand the condition better and find novel ways to treat it in the future. Although the objective of a complete cure for sickle cell disease has not been achieved, significant progress has been made.

Learn more about the origin and history of SCD

INHERITANCE OF SICKLE-CELL DISEASE

SCD is a genetic disease, however, it affects primarily people of color. For a child to be born with sickle cell disease both parents must be carriers of the sickle cell gene (HbAS) also known as sickle cell trait, or another trait form such as HbC, HbD, HbE, HbO or beta thalassemia.

Individuals who have the sickle cell trait are unlikely to show any of the disease symptoms, however, if their partner is a carrier their child is likely to have the disease.

There is a 25% chance of an child being born with sickle cell disease
50% chance of a child being born with a copy of the sickle cell gene
25% chance of a child not carrying the sickle cell gene

DIFFERENT GENOTYPES OF SICKLE CELL DISEASE

SCD belongs to the class of hemoglobinopathies with a wide range of clinical symptoms. The most severe type is sickle cell anemia (SCA), while SC hemoglobinopathy (Hb SC) is milder.

The mutation in the β-globin gene HBB is the primary reason for sickle cell disease. Different genotypes of SCD are distributed in different areas of the world. Like people in the United States, United Kingdom, and African countries represent (Hb SS). On the other hand, people of India and Greece have Hb Sβ-thalassemia, and Burkina Faso represent (Hb SC).

Hb SS, Hb SC, Hb S+-thalassemia, and Hb S0-thalassemia are the most common genotypes that cause SCD. Hemoglobin SD and hemoglobin SE are two relatively uncommon types. The three latest multicenter studies provide the pattern of these genotypes among SCD patients of primarily African descent in the Americas and the United Kingdom.

Hemoglobin SS disease

The most common type of sickle cell disease is hemoglobin SS. It happens when a person gets copies of the hemoglobin S gene from both parents. This results in Hb SS hemoglobin. Patients with the severe type of SCD also suffer the most severe symptoms at a greater rate. This kind of SCD is caused by the inheritance of two sickle cell genes (“S”), one from each parent. It is also known as sickle cell anemia, and it is the most severe type of the condition.

HbSC disease

The second most prevalent kind of sickle cell disease is hemoglobin SC illness. HbSC is a milder type of SCD. People with this type of SCD receive a sickle cell gene (“S”) from one parent and a gene for aberrant hemoglobin called “C” from the other. Hemoglobin is a protein found in red blood cells that helps them to transport oxygen throughout the body.

The symptoms of Hb SC patients are almost identical to the symptoms of Hb SS patients. But, on the other hand, the severity of anemia is less.

HbS/b-0 thalassemia

It is also an inherited disorder. In HbS/b-0 thalassemia, abnormal hemoglobin is present in red blood cells, known as hemoglobin S, with another condition called thalassemia. In the body, it makes hemoglobin, or red blood cells, a sickle shape and moves more slowly through the blood vessels. This can lead to a variety of issues. The “zero” signifies that there is no normal hemoglobin in the blood. This is distinct from sickle beta + thalassemia, in which a person’s average hemoglobin level is lower than usual.

Hb SB+ (beta) thalassemia

The development of the beta-globin gene is affected by Hemoglobin SB+ (beta) thalassemia. The size of red blood cells decreases due to the low amount of beta protein. Hemoglobin S beta-thalassemia is caused by inheriting the Hb S gene. However, its symptoms are not severe.

HbS/hereditary persistence of fetal Hb (S/HPHP)

A rare disorder called Hereditary Persistence of Fetal Hemoglobin (HPFH) in which hemoglobin F (fetal hemoglobin) is present in higher amounts in red blood cells than usual. The HPFH carrier (trait) condition affects roughly one in a thousand African-Americans, compared to about one in every twelve who has sickle cell trait.

HbF is the most significant regulator of sickle cell anemia’s clinical and hematologic characteristics (described as homozygosity for glu6val in the -globin gene or HBB). The exclusion of fetal hemoglobin (HbF) from the sickle hemoglobin polymer is the critical genetic modulator of sickle cell disease’s hematologic and clinical characteristics. The level of HbF and its distribution among sickle erythrocytes are very changeable, and fetal hemoglobin genes are genetically regulated.

HbS/HbE disease

Hb E trait and Hb EE are both minor hemoglobinopathies. A sickle cell disease syndrome comparable to sickle beta(+) thalassemia is caused by the combination of Hb E and Hb S (Hb SE). Due to the significant differences in clinical presentation among genotypes, it is critical to identify Hb E diseases through proper diagnosis.

HbS/HbD disease

First case of Sickle cell HbSD was reported in Iranian male. Sickle Cell hemoglobin SD diagnosed by solubility tests, agarose gel electrophoresis and Hb electrophoresis. In case of HbSD variation both the beta chains affected leading to cause severe hemolytic anemia. Due to interaction of the HbD and HbS In Africa and America Hb-SD syndrome is caused. For HbSD peripheral blood film compares to the less hectic type of HbSS syndrome. HbSD and HbSS have two different clinical features that are being differentiated. Treatment of patients that are suffering from SCD is quite similar to the HbSD and in accordance to the clinical situations severity treatment is administered.

HbS/HbO disease

HbSO is a rare heterozygous hemoglobinopathy that is characterized by presence of a beta globin variant chains. It is inferred from various searches that Hb O is a severe disease and clinically identified similar to the homozygous sickle cell anemia.

HbSD, and HbSO are the rare subtypes that are caused or person get affected by rare syndromes when he or she inherits defective gene (Hb O or Hb D ) from one parent and the sickle gene from the other parent. The severity or mildness syndrome varies

Learn more about the different genotypes of SCD

Clinical Manifestations or Complications of Sickle Cell Disease

Sickle cell disease affects the ability of your body to produce red blood cells, which carry oxygen throughout your body. Red blood cells are flat and flexible disc-shaped cells that are vital for the functioning of the body. When you have sickle cell disease, the body produces abnormal red blood cells having distorted shapes. These abnormal cells are stiff and shaped like a crescent or sickle. This abnormal shape makes it hard for these cells to travel in the blood vessels.

Consequently, it leads to major health problems. Here are some of the important clinical manifestations and complications of sickle cell disease:

1. Pain

It’s the most common clinical manifestation of sickle cell disease (SCD). Pain starts when the sickle-shaped cells get stuck and block small blood vessels. The pain usually spreads to the arms, chest, belly, lower back, and legs. It can appear in sudden, severe attacks, called a crisis or an episode. Older teens and adults can suffer from long-term pain due to this disease.

Over-the-counter (OTC9 painkillers like aspirin or naproxen can ease pain during a crisis. However, it is recommended that individuals younger than 19 should avoid aspirin. If simple painkillers don’t resolve the pain, you can get powerful medications like opioids prescribed by doctors. Some people may need a visit to the hospital for the management of their pain. Your doctor will recommend additional ways to relieve or prevent a pain crisis such as:

Drinking enough water
Avoiding extreme heat or cold
Avoiding spending time at high altitudes

One particular drug, called hydroxyurea, can decrease the frequency of pain episodes in children and adults.

2. Anemia

The deficiency of blood and particularly red blood cells is called anemia. It’s another common complication of sickle cell disease. Anemia develops when sickled blood cells start dying faster than your body can replace them. It happens because these cells get trapped in organs such as the spleen which destroys them due to their abnormal shape. The deficiency of red blood cells makes it harder for your body to get oxygen. Oxygen is necessary for the performance of each and every function of the body. So, if sufficient oxygen is not available, we start feeling tired, weak, and dizzy. In addition to this, anemia can also lead you to have a fast heartbeat and trouble breathing. It also restricts the growth of children.

Blood transfusions are needed if anemia is severe. Contrarily, too many transfusions can also be problematic. It can end up with too much accumulation of iron in your blood. This accumulated iron can affect your heart, liver, or pancreas. You’ll have to be in touch with your doctor to help you manage your iron levels. Hydroxyurea may also be helpful for anemia in adults.

3. Infections

People with sickle cell disease, especially kids, are at an increased risk of developing infections. That’s because of damage to the spleen caused by these diseases. The spleen is an important organ of the body that helps your body clean bacteria out of your blood.

Doctors prescribe antibiotics for the treatment of infections. It’s important to get yourself checked up timely to keep minor infections from turning into more serious ones. If you or a child has a high fever, it is time to rush to the emergency room right away.

4. Splenic Sequestration

Children are especially at risk of developing this complication, which happens when sickle cells get trapped and block blood flow through the spleen. That leads the spleen to swell painfully. A child with splenic sequestration will feel weak, have pale skin or lips, feel sleepy or lazy, have pain in the left side of the belly, and have a fast heartbeat. These symptoms may not appear in some children.

Splenic sequestration is a life-threatening emergency condition. Therefore, if you or your child has symptoms, visit the nearby hospital right away. Splenic sequestrations require blood transfusions in many cases.

5. Acute Chest Syndrome

This complication occurs when abnormal red blood cells block blood flow in the lungs. It’s also very serious and needs immediate medical attention if symptoms such as fever, trouble breathing, chest pain, and cough appear.

Doctors may give you oxygen, antibiotics, medicines to improve your breathing, and you may have a blood transfusion. The drug hydroxyurea also has some role in preventing acute chest syndrome.

Other Complications

When sickle cells block the blood supply to the major bones of the body, it can cause bone tissue to die. This is termed as avascular necrosis, and it mainly damages the hip joints of teenagers and adults having sickle cell disease. Pain medication can help, but surgery may ultimately be needed to repair the damage.

People with sickle cell disease are also at more risk of developing eye, heart, liver, and kidney problems. They are also prone to blood clots and strokes.

Can You Prevent Complications?

Many clinical manifestations of sickle cell disease have to be managed as they happen. But you can also adopt certain preventive protocols to make them less likely.

Some medicines help some individuals prevent complications or decrease their severity. It’s always the best idea to consult your doctor when you or your child are having symptoms of sickle cell disease. Currently, there are few drugs commonly prescribed in adults and children to decrease the episodes of pain crises and acute chest syndrome. These drugs are:

Hydroxyurea
L-glutamine
Adekevo
Oxybryta

Other helpful strategies are moderate exercises and deep breathing. They can also help prevent complications but be sure not to overburden yourself. Discuss with your doctor and physiotherapist the safest ways to work out. It’s also important to consume a healthy and nutritious diet.

To prevent infections, wash your hands with soap and water regularly. Learn about safe food cooking to avoid germs in food. Children should be vaccinated thoroughly.

Is there a treatment for SCD?

People who have severe sickle cell disease symptoms may want to undergo a bone marrow transplant. It’s a delicate procedure in which bone marrow cells that produce crescent or sickle-shaped red blood cells are replaced with healthy bone marrow cells. As a result, your body will start producing normal and healthy red blood cells, curing this condition ultimately.

However, a bone marrow transplant doesn’t work for anyone. It’s a risky procedure and requires long hospital stays. There are always long discussions between family and the doctors from different specialties about the feasibility of this procedure for a person before going for it.

Learn more about the clinical manifestations of SCD