Surely you have ever heard of hemoglobin . Hemoglobin is a blood protein that is found inside the red blood cells (also called red blood cells or erythrocytes), of a characteristic red color (that is why the blood is red), which is responsible for transporting the oxygen that reaches our torrent. blood to every corner (tissue) of our body. In addition, it also transports the CO2 that is released from these tissues, as a waste molecule (product of metabolism), to the lungs. Thus, an exchange between oxygen and CO2 occurs, using hemoglobin as a bridge.
Hemoglobin and anemias
Now it’s easy to understand that if we didn’t have enough hemoglobin, we would suffocate, because we wouldn’t have enough oxygen where we needed it. The lack of hemoglobin is usually called anemia . Thus, anemia is one of the causes of shortness of breath, for example.
What you may not have known is that a person can have anemia for various reasons. Let me explain: a hemoglobin molecule is formed, broadly speaking, by a protein part, the “ globin ”, and a “ heme ” part (formed by protoporphyrin and ferrous -Fe++-), responsible for the color.
As you may know, proteins can be complex structures, with many parts or “ chains ” making them up (like a LEGO puzzle, where each piece is a protein and all together they are a larger protein).
In this aspect, globin is a protein made up of chains that we call alpha, beta, delta, and gamma . 97% of our hemoglobin is made up of 2 alpha chains and 2 beta chains .
Understanding this so technical is relevant to understand that any condition that affects the alpha, beta chains, the heme group or its formation, could result in anemia, since it is not possible to have hemoglobin that works normally. For example, the lack of iron means that the “heme” part cannot be formed. This type of anemia is known as iron deficiency anemia (due to lack of iron). As this part is responsible for the color, it is easy to understand that in the most serious cases, people are pale.
Thalassemias
Well, if the condition in question affects the alpha chains, we speak of alpha-thalassemias . If it affects beta chains, beta-thalassemias . But why can the chains that make up hemoglobin be affected? Mainly because of genetics.
Thalassemia is an inherited disorder, meaning it is passed down through the genes of carrier parents to their children. As you can imagine, if hemoglobin is one of the bricks that make up red blood cells, the alteration in the formation of hemoglobin leads to an alteration in the structure of the red blood cell. In addition, with fewer “bricks”, smaller red blood cells are built, capable of holding less hemoglobin than usual. This is why, in people with thalassemia, we find red blood cells that are smaller ( microcytic ) and “less red” ( hypochromic ). Some altered red blood cells with insufficient levels of hemoglobin lead to less oxygenation of the organs and tissues of our body. Thus, thalassemia patients can suffer from severe or mild forms of anemia.
And if we talk about numbers? Approximately 5% of the world population has some genetic alteration that affects hemoglobin (hemoglobinopathy), the most frequent condition being thalassemia. In addition, each year around 300,000 children are born with thalassemia worldwide, which means that 4.4 out of 10,000 live births are affected by this disorder.
Types of thalassemia
We can find different classifications of thalassemia depending on the specific altered component and the severity of the disease.
As we mentioned, depending on the affected chains, we can distinguish between alpha and beta thalassemia . It is worth mentioning that alpha is more frequent throughout the world, but rare in our environment. It is more common, for example, in people of African descent (25% of the population has an altered gene), while beta is more common in people from the Mediterranean and Asian areas.
As for the severity of the condition , it depends almost strictly on the degree of genetic inheritance . We are facing an autosomal recessive inheritance disease, which means that, for a person to suffer from a condition, both parents must be carriers of the gene and have inherited both altered genes. But the case of thalassemia is particular .
Affection by alpha-thalassemia can vary from being an asymptomatic carrier ( silent trait ) without any symptoms (when only an altered gene affects one of the alpha chains), to incompatibility with life (intrauterine death occurs or shortly after birth ), when genes from both parents affect both alpha chains. In other words, it is the absolute absence of alpha chains (Bart’s hemoglobin) . Between these two extremes we find alpha-thalassemia minor (or alpha-thalassemia trait), which consists of the absence of two of the four genes on which the alpha chains depend, or hemoglobinopathy H (absence of three of the four genes of alpha chains).
Regarding beta-thalassemia , we differentiate between beta-thalassemia minor or thalassemia trait ( heterozygous ), if you only inherit the alteration in one of the beta chains from one parent, and beta-thalassemia major (also known as Cooley’s anemia). or homozygous ), in case of inheriting altered genes from both parents in both chains, which makes the disease more serious (we are talking about an absolute absence of beta chains).
In short, if a person inherits an alpha-thalassemia trait from the father and normal alpha-hemoglobin components from the mother, then that person will suffer from the alpha-thalassemia minor trait, but if they inherit a beta-thalassemia trait from both the father and from the mother, then that person will have beta thalassemia major.
What are the symptoms?
All kinds of thalassemia have similar symptoms (fatigue, shortness of breath, paleness, weakness,…), which vary only on a scale of severity. Since thalassemia is characterized by reduced levels of red blood cells, affected individuals may have symptoms of anemia or low blood counts.
The lack of red blood cells can also trigger associated conditions and their symptoms. When the red blood cell count is low, the body overworks to make more. Red blood cells are produced primarily in the bone marrow, the soft, dark section inside the bones. As the marrow works overtime to produce more red blood cells, it tends to increase in size, and as a result, bones tend to enlarge and expand , making them brittle, thinner, and prone to fracture easily.
The spleen is another organ where red blood cells are made, but it also performs additional functions, such as filtering blood and checking for and fighting underlying infections. In patients with thalassemia, the spleen is also enlarged , and since it spends all its time and effort producing red blood cells, it is not as effective at filtering the blood and fighting infection. As a result, patients with thalassemia are said to be “immunocompromised”, meaning that their body is unable to defend itself against infection. Therefore, they are at a higher risk of developing infections.
How is it diagnosed?
Patients with severe or moderate types of thalassemia are usually diagnosed with the disease during childhood , as they begin to show symptoms of anemia at a very young age. Patients with mild forms of thalassemia may discover (often later in life) the underlying blood disorder when they start showing symptoms of anemia. The disease can also be suspected after a blood test . In that case, the next step will be to put that blood under the microscope and observe the morphology of the red blood cells (if “bricks” -chains- are missing in their structure, the shape is abnormal, and that is why they are also smaller than normal red blood cells). usual).
Since the blood disorder is passed down through families, the disease tends to run in families, so some people may be diagnosed with thalassemia because of a family history of the disease. Even so, it can occur if the parents are asymptomatic carriers without knowing it.
In addition to genetic background, ancestry also plays a role. The disorder is most often diagnosed in people of Greek, Turkish, Middle Eastern, Mediterranean, African, and Asian descent. Both women and men have a similar rate of getting the disease.
Being an inherited disease, it is very difficult to prevent the development of thalassemia. However, couples who have relatives with the disease, or who are from the regions mentioned, can seek genetic counseling before trying to become pregnant.
Thalassemia Treatment and Prognosis
Thalassemia is treated depending on the severity of the disease. In severe thalassemia, the red blood cell count is very low, leading to severe anemia, which can be treated by increasing the red blood cell count. This can be done through regular blood transfusions , although this is not all beneficial, as too many blood transfusions can lead to iron overload. The accumulation of iron in vital organs such as the brain, liver and heart negatively affects their function. For this reason, patients can also undergo chelation therapy to prevent further accumulation of iron in the body.
In the case where the spleen is affected (hypersplenism), it must be removed ( splenectomy ).
It is also attempted to induce the synthesis of red blood cells. For example, there are drugs (anti -sickling ) that increase the synthesis of gamma chains. Bone marrow transplant is also an option to consider.
Because patients with thalassemia may be immunocompromised, they need additional protection against disease and infection . Flu shots and other types of vaccines can offer that protection, so they’re especially important in these people.
Folic acid needs increase in some patients, so your doctor may prescribe supplementation with folic acid and/or vitamin B (these 2 elements are related).
In select cases, allogeneic stem cell transplantation may be helpful and may even be a curative option. It involves the replacement of damaged or destroyed stem cells in the bone marrow with healthy cells from a donor. The prefix “alo” means “other,” meaning that the healthy cells are taken from a person other than your child.
Regarding life expectancy , patients with thalassemia trait usually have a normal life expectancy, while people with thalassemia major usually have an average life of 17 years and succumb to the disease before the age of 30.
References:
Braunstein, EM (2021). Talasemias. Manual MSD. https://www.msdmanuals.com/es/hogar/trastornos-de-la-sangre/anemia/talasemias?query=talasemia
Mensah, C., & Sheth, S. (2021). Optimal strategies for carrier screening and prenatal diagnosis of α- and β-thalassemia. Hematology. American Society of Hematology. Education Program, 2021(1), 607–613. https://doi.org/10.1182/hematology.2021000296
Sheth, S., Thein, S., Kaushansky, K., Prchal, J. T., Burns, L. J., Lichtman, M. A.,et.al. (2021). Thalassemia: a disorder of globin synthesis. Williams Hematology. 10th ed. McGraw-Hill.
Taher, A. T., Weatherall, D. J., & Cappellini, M. D. (2018). Thalassaemia. Lancet (London, England), 391(10116), 155–167. https://doi.org/10.1016/S0140-6736(17)31822-6
What Are Thalassemias (2022). National Institutes of Health (NIH): National Heart, Lung and Blood Institute (NHLBI). https://www.nhlbi.nih.gov/health/thalassemias
