Brief Summary
Sickle-cell anemia is a hereditary red blood cell disease where there are not enough healthy red blood cells in the body to hold oxygen. The versatile, circular red blood cells usually pass easily across blood vessels, but the red blood cell in sickle cell anemia is shaped like sickles or crescent moons and these stiff, adhesive cells can get trapped in tiny blood vessels which could slow down or obstruct the blood flow and oxygen to areas of the body.
Sickle-cell is normally inherited by the person from its parents. When the sickle cell gene is transmitted to the infant by only one parent, the child may have the sickle cell trait. People with the sickle cell phenotype develop both regular hemoglobin and sickle cell hemoglobin from one normal hemoglobin gene and one faulty type of the gene. However, the faulty form of the gene must be transmitted by both mother and father for a child to be affected by the disease. On the other hand, people whose one parent has sickle cell gene may have some sickle cells in their blood, but they don not normally show symptoms. They are carriers of the disease, which means they will transfer the gene on their offspring.
Frequency
It affects about 100,000 Americans, 1 in 1,000 to 16, 300 Hispanic Americans and 1 in 365 African Americans.
Inheritance
Sickle-cell anemia is inherited in an autosomal recessive manner.
SICKLE CELL ANEMIA
History of Disease
The origin of the sickle-cell gene mutation is derived from at least four separate mutational cases, three in Africa and one in either Saudi Arabia or Central India. Between 3,000 and 6,000 generations ago, about 70-150,000 years ago, these separate events happened. However, due to human migration, this gene was present all over the world in populations. Scientists claim that the sickle cell gene has appeared and vanished many times in the population, but after an especially vicious form of malaria in Asia, the Middle East, and Africa jumped from animals to humans, it became permanently known. There is a complex life cycle for the malaria parasite and it spends most of it in red blood cells. The presence of the malaria parasite in a sickle cell carrier induces premature rupture of the red blood cells with defective hemoglobin, rendering the Plasmodium parasite (the causative agent of malaria) unable to replicate. That's why the gene that causes sickle cell anemia is more prevalent in many parts of the globe because a single copy of it confers resistance to malaria. Balancing selection is the evolutionary force that seems to be responsible for preserving disease-related defects in our DNA, such as sickle cell anemia, since the detrimental consequences of the mutation may be compensated by its possible advantages in a biological way of thinking. The evolutionary connection between the sickle-cell trait and tolerance to malaria has shown that people can adapt and do so.
In Western medicine, the first known and recorded Sickle Cell event was when Walter Clement Noel traveled to the United States from Grenada in 1904 to begin studying at the Chicago College of Dental Surgery. A few months later, when he experienced extreme respiratory failure and a leg ulcer, both of which we now realize are signs of Sickle Cell, he was admitted to Presbyterian Hospital in Chicago. A routine blood examination and urinalysis for Noel was performed by Dr. Earnest E. Irons, the intern who was on duty that day and was the first to find these "pear-shaped, elongated" sickled blood cells. It was not until 1910 when in a case of extreme anemia, Dr. Herrick, Dr. Irons' superior, published his article about these "peculiar elongated and sickle-shaped red blood corpuscles."
However, prior to that, the first modern diagnosis of sickle cell anemia was in 1846 where the autopsy of an executed escaped slave was examined. The main findings of the report were the absence of the spleen. Moreover, African slaves reportedly displayed resistance to malaria in the United States but were susceptible to leg ulcers.
Pathogenesis
Achondroplasia is caused by a mutation in the FGF3 gene in chromosome 4 at 4p 16.3. This mutation causes a decreased production of fibroblast growth factor receptor 3 which is crucial in the conversion of cartilage into bone which is vital in the proper development of a person. This mutation is inherited in an autosomal dominant manner. More than 80 percent of people with achondroplasia have parents with normal characteristics and are born with achondroplasia due to a recent (de novo) gene modification (mutation).
Pathogenesis
Sickle-cell anemia is one of the sickle-cell diseases, which is a category of red blood cell disorders that are inherited. Healthy red blood cells are round and they travel to all areas of the body via small blood vessels to carry oxygen. The red blood cells become hard and sticky in someone who has sickle-cell anemia, and look like a C-shaped farm instrument called a "sickle." The sickle cells die early, causing a chronic shortage of red cells in the blood. Often they get trapped and clog the blood flow as they pass through narrow blood vessels. The mutations in the HBB gene are responsible for sickle cell disease. Instructions for making one component of hemoglobin are given by the HBB gene which is four protein subunits consist of, usually, two subunits called alpha-globin and two subunits called beta-globin, and different copies of beta-globin in the HBB gene arise from different mutations. At least one of the beta-globin subunits in hemoglobin is replaced with hemoglobin S in people with sickle cell disease, though, hemoglobin S replaces all beta-globin subunits in hemoglobin in sickle cell anemia (also called homozygous sickle cell disease), which is the most common type of sickle cell disease, it is the most prevalent form of sickle cell disease. Making the normal blood gene HBB into HbSS. Red blood cells may be twisted into a sickle form by irregular variants of beta-globin. The red blood cells that are sickle-shaped die prematurely, which can lead to anemia. In narrow blood vessels, the inflexible, sickle-shaped cells often get trapped and may cause severe medical complications. As the most extreme type of SCD, people with this form often encounter the worst effects at a greater rate.
Symptoms
1
Too much fatigue or irritability, caused by anemia
2
Bedwetting, from kidney disorders associated with
3
Swelling and stiffness of the hands and feet
4
In infants, fussiness
5
Chest, back, arm, or leg pain
6
Jaundice, which makes the eyes and skin yellow
7
Increased susceptibility to bacterial infections
Sickle cell anemia signs typically startup at an early age. They can appear as early as 4 months of age in infants but normally occur about the 6-month mark. Although there are different forms of SCD, they all have similar symptoms that differ in intensity.
Social Concerns
A cardinal feature of sickle cell disease is debilitating episodes or crises. Increased use of health care facilities, reduced social interactions and increased incidence of psychological distress have been correlated with sickle cell disease pain in infants, adolescents and adults with sickle cell disease. The incidence of pain is not consistent, and the period of pain ranges widely from a few hours to a few days. Moreover, the involvement of sicklers in the family is related to certain disruptions among family members, such as divorce, anxiety, emotional disturbances, and less group participation in social activities.
Stigmas around SCD exist in the United States that prevent individuals with SCD from accessing the appropriate treatment. According to the National Heart, Lung, and Blood Institute, these stigmas affect African Americans and Hispanics primarily. People with SCD feel the influence of disease stigmas on different aspects of life, including social and psychological aspects. Studies have shown that those with SCD often believe that to prevent prejudice in the workplace and even among peers in relationships, they must keep their diagnosis a secret.
Treatment
Normally, sickle cell disorder needs lifelong care. The only treatment for sickle cell disease is a stem cell or bone marrow transplants, but they aren't performed very often because of the major risks involved.
A significant symptom of sickle cell anemia is periodical episodes of pain, called pain crises. To minimize the risk of suffering a traumatic episode (sickle cell crisis), the main thing the patient can do is to try to eliminate potential causes. Drink lots of fluids to prevent dehydration, wear warm clothes to avoid the cold, and avoiding drastic increases in temperature, such as swimming in cold water are advisable. A medicine called hydroxycarbamide (hydroxyurea) may be recommended if the episode of pain continues. The number of other blood cells, such as white blood cells and platelets (clotting cells), can be decreased by hydroxycarbamide, so, typically, patients have daily blood tests to track their health.
Clinical Trials
Title:
A Phase II Trial of Regadenoson in Sickle Cell Anemia
Intervention:
Drug: Regadenoson
Phase:
Phase 2
Procedure:
Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.
Other Name: Lexiscan
Goal:
This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug called Regadenoson (or Lexiscan) to learn whether the drug works in treating a specific disease, in this case Sickle Cell Disease (SCD). Regadenoson (trade name Lexiscan) is a drug that may prevent this inflammation and injury caused by the sickle shaped cells. This drug is approved by the FDA to be used as a fast infusion during a heart stress test in people who are unable to exercise enough to put stress on their heart by making the heart beat faster. Regadenoson has been studied as a long infusion at this dose in adults, and no safety issues have been identified (ClinicalTrials.gov Identifier: NCT01085201). This is the first study to look at patient benefit with the long infusion of the drug. This drug has been used in laboratory experiments and information from those other research studies suggests that this drug may help to protect the body from damage caused by sickle-shaped cells in this research study.
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References
FOR INFORMATION
FOR IMAGES
[2]Novoa & Guzman (2010). Sickle Cell. Retrieved from https://slideplayer.com/slide/9763189/
[8] Ayurveda, S. (n.d.). Jaundice: Causes, Tips & Home Remedies. Sanyasi Ayurveda. https://www.sanyasiayurveda.com/diseases-jaundice.html