The present paper aims at studying the pathophysiology of anemias based on the case of J.L. The patient is a 12-year-old male with an ongoing diagnosis of sickle cell anemia. When attending the clinic for his routine 6-month follow-up visit, the physician noticed that J.L. has jaundiced sclera. The patient has a history of gout with an affected left ankle. He also underwent a splenectomy three years before the visit. The paper will discuss hemoglobinopathy blood disorders in terms of their prevalence, population, diagnostic criteria, pathophysiology, and genetics. It will also compare and contrast different anemias in terms of signs, symptoms, laboratory values, and other diagnostic tests.
Hemoglobinopathy Blood Disorders: Sickle Cell Disease
Sickle cell disease (SCD) is a term utilized to define a group of inherited disorders. Such disorders are caused by mutations in the gene encoding the hemoglobin subunit β (Kato et al., 2018). SCD is diagnosed in 300,000 – 400,000 newborns every year globally (Kato et al., 2018). Around 75% of all patients diagnosed with the condition live in sub-Saharan Africa, where the 5-year survival rate of neonates varies between 10 and 50 percent (Kato et al., 2018). In other countries, however, the survival rate is much higher, as median life expectancy grew to 67 years (Kato et al., 2018). Modern medicine achieved higher survival rates due to effective screening, early diagnosis, and treatment innovations.
Before turning to the diagnosis, it is crucial to understand the pathophysiology of the disease. Even SCD is associated with several changes in the body of the patient, HbS polymerization is the primary pathophysiological occurrence (Sundd et al., 2019). The process is associated with changing the shape and physical properties of the erythrocytes, which causes the blockage of smaller blood vessels. Such changes often lead to a vaso-occlusive pain crisis (Sundd et al., 2019). The disease can be diagnosed during four overlapping periods, including preconception, prenatal, neonatal, and post-neonatal (Kato et al., 2018). The diagnosis requires obtaining a DNA sample for identifying mutation in erythrocytes (Kato et al., 2018). Early diagnosis is crucial for improving the survival rates of patients.
Thalassemia
Thalassemia is a genetic condition associated with changes in hemoglobin cells. There are two types of thalassemia: alpha-thalassemia and beta-thalassemia. There are four types of alpha-thalassemia, depending on how many genes α-globin genes are deleted or inactive (Tamary & Dgany, 2020). Studies demonstrate that up to 5% of the global population may carry the disease; however, only 1 in 1,000,000 people have a severe form of the condition (National Organization of Rare Diseases, 2017). The most frequent type of α-thalassemia is hemoglobin H disease, which is caused by the deletion/inactivation of three out of four genes (Tamary & Dgany, 2020). This type of disease may be associated with enlargement of the spleen, mild jaundice, and bone changes (Tamary & Dgany, 2020). The most dangerous type of α-thalassemia is the Hb Bart syndrome, which is caused by the deletion/inactivation of all four Hb genes (Tamary & Dgany, 2020). This condition leads to the prenatal onset of generalized edema and pleural and pericardial effusions, which causes severe anemia (Tamary & Dgany, 2020). Both types of diseases are diagnosed using molecular genetic testing (Tamary & Dgany, 2020).
Beta-thalassemia is another rare condition that occurs in infants. The condition is caused by reduced or absent synthesis of the β-globin chains in red blood cells (Origa, 2017). The condition is classified into three types depending on the severity, which are carrier state, thalassemia intermedia, and thalassemia major (Origa, 2017). The severity depends on the degree of α-globin chain excess, which causes mechanic and oxidative damages. Around 68,000 children are diagnosed with thalassemia major every year around the globe (Origa, 2017). The condition is usually diagnosed in children aged between 6 and 24 months (Origa, 2017). Such patients usually have severe microcytic anemia, mild jaundice, and hepatosplenomegaly (Origa, 2017). Beta-thalassemia patients also have reduced Hb level, corpuscular volume, and corpuscular Hb (Origa, 2017). In summary, both types of thalassemia are usually found in children with anemia and jaundice and diagnosed using molecular genetic testing.
Genetics and Pathophysiology of Hemoglobinopathies
Genetics play a crucial role in the development of hemoglobinopathies. In particular, the symptoms of these diseases are caused by severe changes in genes of red blood cells, as it was described above. The changes in genes are inherited from parents, which implies that these conditions are not contagious (Sabath, 2017). For instance, in J.L.’s case, sickle cell disease was caused by the fact that the infant inherited one copy of the sickle cell gene from each parent (Hodge, 2020). Such genetics caused all the symptoms that can be seen in J.L. However, if the patient inherited a sickle cell gene from one parent only, it would result in him having both normal and sickle-shaped hemoglobin (Hodge, 2020). Such a condition is called sickle cell trait, which rarely has any clinical symptoms. Traits of hemoglobinopathies can be revealed using molecular genetic testing (Sabath, 2017). Since people with hemoglobinopathy traits can have children that can develop the disease (they have 50% of passing the gene), it is crucial to screen for the changes in blood cells (Hodge, 2020). In short, genetics is crucial for the development of symptoms and the possibility of passing the condition.
Spleen, Jaundice, Effect on Development, and Environmental Factors
The pathophysiological process associated with SCD affects different organs. Spleen is one of the organs, which is affected early by the disease. Sickle-shaped blood cells may be trapped and destroyed in the spleen, which can damage and enlarge the organ (Owusu-Ofori & Remmington, 2017). Such processes often lead to splenic sequestration crises associated with severe abdominal pain and increased heart rate (Owusu-Ofori & Remmington, 2017). Such crises can be fatal, which is why splenectomy is used after the first onset to prevent reoccurrence (Owusu-Ofori & Remmington, 2017). Thus, the condition of the spleen should be monitored in patients with SCD.
Sickle-shaped cells have a shorter life in comparison with normal blood cells, which often leads to the liver’s inability to filter them (Kato et al., 2018). This often leads to the development of jaundice, as bilirubin from the broken cells remains in the system longer than usual. Apart from jaundice, SCD can lead to long-term anemia, pain crises, stroke, increase the chance of infections, and priapism (Kato et al., 2018). SCD may lead to delayed growth and development and damage of any organ, which implies that J.L. is at high risk of leg ulcers, bone damage, eye damage, and multiple organ failure (Kato et al., 2018). J.L. will also need to control environmental factors, such as exposure to extreme temperatures and atmospheric pressures (Piel et al., 2017). Additionally, environmental pollution affects the severity of SCD crises; however, the reason for the influence of these factors have a complex nature (Piel et al., 2017).
Role of Bone Marrow
The only known cure for SCD is bone marrow transplant (Ashorobi & Bhatt, 2019). Bone marrow plays a crucial role in the development of SCD, as its stem cells produce all the blood cells for the body. Replacing these stem cells helps the body to start generating normal hemoglobin cells and gradually replace all the sickle-shaped ones (Ashorobi & Bhatt, 2019). Bone marrow transplant, however, is associated with significant toxicity (Ashorobi & Bhatt, 2019). Therefore, only patients with severe symptoms are recommended to undergo the operation.
Anemias in Primary Care Settings
There are several types of anemia that can be seen in primary settings. These types include iron deficiency anemia, vitamin deficiency anemia, aplastic anemia, sickle cell anemia, and thalassemia. Common symptoms include fatigue, weakness, pale skin, chest pain, arrythmia, headaches, dizziness, cold extremities, and shortness of breath (National Institute of Health [NIH], 2011). The type of anemia is identified using a wide variety of diagnostic procedures.
Hemophilia
Common inherited blood disorders include SCD, thalassemia, and hemophilia. While SCD is associated with anemia, hemophilia is associated with extensive bleeding due to the inability of blood to clot (CDC, 2020). The disease is caused by mutation or absence of genes responsible for clotting (CDC, 2020). Common symptoms include bleeding into joints and skin, bleeding of the mouth and gums, blood in urine, extensive bleeding after surgeries and injections (CDC, 2020). This disease occurs in 1 out of 5,000 men, while women are very unlikely to be affected. The disease is diagnosed by measuring the clotting factor.
Comparing and Contrasting Anemias
The most common type of anemia is caused by iron deficiency, which may develop due to a variety of factors (NIH, 2011). Common reasons for such anemia are significant blood loss, unhealthy diet, inability to absorb iron and pregnancy. Usually, blood deficiency anemia is treated with diet correction and iron supplements (NIH, 2011). However, in severe cases, iron injections or blood transfusion may be necessary (NIH, 2011). Additionally, if anemia is caused by an inability to absorb iron, the underlying cause, such as celiac disease, should be treated (NIH, 2011). Iron deficiency anemia is diagnosed using complete blood count and evaluation of serum ferritin, iron, total iron-binding capacity, and transferrin if needed.
Iron deficiency anemia can be easily distinguished from SCD by clinical tests. However, before ordering expensive tests for SCD, it is beneficial to examine the history of the patient and associated symptoms. SCD is usually accompanied by severe abdominal pain, swelling of hands and feet, delayed development, frequent infection, jaundice, and vision problems (Kato et al., 2018). Moreover, SCD may be considered if the patient has a family history of the disorder. Lab tests of iron deficiency anemia usually show low hemoglobin (Hg), hematocrit (Hct), mean cellular volume, and ferritin found during evaluation of complete blood count (NIH, 2011). SCD is diagnosed using molecular genetic testing, which is expected to demonstrate changes in the form of the hemoglobin cells (Kato et al., 2018). It is appropriate to test for iron deficiency anemia first, as it is the most common type of anemia.
Conclusion
The present paper described inherited blood conditions and different types of anemia in the form of a case study. The results demonstrated that J.L. has common symptoms of SCD, which will affect its development in the future and become a significant risk factor for infections, organ failure, bone damage, and eyesight problems. The only cure for the disorder is bone marrow transfusion, which is associated with significant toxicity. However, the analysis demonstrated that J.L.’s form of anemia is rare, as iron deficiency anemia is most prevalent in all populations.
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