In a patient with thalassemia, problems arise because there is a lack of healthy haemoglobin that the body requires for it to become properly oxygenated.
A patient with thalassemia, not only has lower levels of haemoglobin present in his or her bloodstream but also lacks good quality haemoglobin. Individuals with thalassemia can be treated according to the level of severity of their condition 2 , 4. The two main categories of thalassemia are alpha and beta thalassemia that are then divided into further subcategories 2 , 5.
The main cause behind thalassemia is always the defective synthesis of alpha or beta chains. Beta thalassemia occurs when one or both Beta globin genes are either abnormal or are absent 2 , 5. In most of the cases, mutations in the alpha or beta globin genes result in the development of thalassemia in the patient.
Some of these gene mutations result in mild versions of thalassemia while others result in extremely severe forms of thalassemia 1 , 2. In most cases, this can result in mild anaemia in an individual, which can also be mistaken for an iron deficiency 6. However, individuals who inherit this gene from their parents need to be very cautious when they have children of their own as the chances of their children inheriting more severe forms of thalassemia, increase significantly 7.
The three types of thalassemia minor include alpha plus thalassemia trait which involves one of the four alpha genes to be missing, alpha zero thalassemia trait which involves two missing alpha haemoglobin genes, and beta thalassemia trait which involves the absence of one out of two beta haemoglobin genes 2 , 3 , 5. However, there are a number of types of thalassemia that are more dangerous and severe than the aforementioned types. Firstly, there is beta thalassemia major BTM which basically involves the presence of two beta thalassemia genes in an individual 8.
However, despite the fact that this form of thalassemia is less severe than BTM, it still requires continuous monitoring for life 2 , 5 , 8. Hb H disease is another form of thalassemia where three of the four alpha haemoglobin genes are either missing completely or are abnormal 9.
Patients with this type of thalassemia are usually anaemic as well, and require regular blood transfusions for life 2 , 10 , This form of thalassemia is so severe that even before birth, no haemoglobin can be made, as a result of which, the baby with this form of thalassemia dies in the womb 9. A family history of thalassemia increases the chances of an individual being affected by the disease 5 , 10 , However, the severity of the disease depends on which type of gene mutation has taken place, since some gene mutations result in more severe forms of thalassemia than others 2 , It must be noted that individuals with certain ancestries are more likely to develop thalassemia than others.
Studies have revealed that African American individuals tend to have lower haemoglobin levels than whites in general as a result of which the incidence of thalassemia among these individuals is also likely to be higher In many cases, thalassemia is detectable six months after birth, if not during the pregnancy 2 , 10 , Alpha thalassemia major, however, can be identified during the pregnancy since Haemoglobin production in the foetus does not start.
In such cases, efforts can only be directed at taking the necessary precautions to avoid maternal complications that range from toxaemia to premature delivery and higher chances of delivery by caesarean sections 5 , 7.
The best option while dealing with thalassemia is to ensure that it is prevented, which can be done by checking both parents for the presence of any gene mutations before the couple decides to have a child 5 , 8. Patients with thalassemia usually experience a loss of appetite, jaundice, an enlarged spleen or liver and several bone problems 3.
This excess iron can then cause several heart problems for the individual including irregular heartbeats, heart attacks and even death by heart failure 2 , 6 , Spleen enlargement also causes individuals to have their spleens removed as a result of which they are left more prone to catching infections This is why patients with thalassemia are usually at a higher risk of infection, and death often results from these infections 2 , Finally, osteoporosis is another very common problem found in patients with thalassemia 16 — Osteoporosis causes the bones to become brittle, and can break easily as a result of which thalassemia patients can experience a lot of discomfort pertaining to the bones and teeth Patients with thalassemia can experience an enlargement of their upper jaw which is also known as the chipmunk face 19 , The chances of the migration and spacing of upper anterior teeth also increase, and there may be varying degrees of malocclusion in such patients too Other than that, the teeth of patients who have thalassemia might be discoloured and have short crowns and roots Individuals who have thalassemia have a higher rate of dental decay as compared to people who do not have thalassemia Thalassaemic patients also experience painful swelling of salivary glands and a dry mouth which leads to reduced salivary protection It has been seen from the previous studies that thalassaemic patients are prone to dental decay This, at times, happens because the patients do not tend to regular dental care or hesitate to go to a dentist thinking they will not understand their condition; there have also been cases where the thalassaemic patients are more concerned with the serious medical complications of thalassemia and their teeth get neglected in the process 20 , It is then that thalassaemic patients try to get dental services in emergency When patients start experiencing pain, this is when the dental decay has gone to an advanced stage.
At this stage, there is a higher risk of abscess and infection traveling and spreading further into the tissues of the neck and face. When a patient reaches this stage, the more likely treatment of this is to extract the teeth of patients rather than provide fillings. As a result, thalassaemic patients lose more teeth 10 , In general, thalassemia causes problems at varying levels depending on the severity of the form of thalassemia.
Patients with more serious forms of thalassemia experience a lot more difficulties with their daily lives as compared to those with milder forms of thalassemia 2. The important factor involved in pathophysiology of alpha thalassemia is the reduced or absent synthesis of alpha globin chains which leads to an accumulation of otherwise normal beta globin chains in adults and gamma chains in the foetus. These two homotetramers are susceptible to oxidant injury 23 , 25 , and are functionally useless as oxygen delivery pigments because their affinity for oxygen is at least 10 times greater than HbA; and the oxyhaemoglobin dissociation curve is not sigmoidal because there is no heme-heme interaction.
The degree of haemolysis is directly correlated with extra alpha globin chain Impaired deformability of RBCs alteration of affected RBCS surface, leads to removal of it by macrophages and oxidant injury to lipid and proteins of RBCs membrane by binding of oxidized alpha globin chains to the RBC membrane 29 , The two above-mentioned phenomena result in severe anaemia, marked erythroid hyperplasia in the bone marrow, resulting in bone marrow expansion, extramedullary haematopoiesis, hepatosplenomegaly.
The main difference in pathophysiology between alpha and beta thalassemia is that, the excess beta or gamma globin chains in the alpha thalassemias, can form partially soluble but ineffective haemoglobin homotetramers. These homotetramers do not precipitate extensively until they are exposed to damaging effects, mostly oxidant in nature, in the circulation.
Because of differences in the biochemical composition of aggregates between alpha globins and beta globins, the severity of the disease is less severe in alpha compared with beta thalassemia The main cause for oral manifestations of thalassemia is due to extreme compensatory hyperplasia of bone marrow, this in turn leads to expansion of marrow cavity.
Facial features and oral manifestations are illustrated in Tables 1. Before beginning the treatment, the following should be ascertained: 1 type of thalassemia: major, minor or intermedia, 2 present haemoglobin level of the patient, and 3 ddegree of iron overload in the body. Repeated transfusions increase the total body iron load resulting in complications, therefore assessment of iron overload should be done periodically: 1 elative organ involvement with iron, 2 chelators administered to the patient patients receiving regular transfusions need to be on chelation therapy to help excrete excess iron , 3 presence or absence of splenomegaly hypersplenism increases the need for blood transfusions.
If the hypersplenism is accompanied with leucopenia and thrombocytopenia, splenectomy may be the treatment of choice, 4 history of splenectomy, and 5 overall patient prognosis and life expectancy. There are also dental considerations for thalassemia. Any invasive procedure in thalassemia patients should be done under antibiotic cover and immediately after transfusion.
Liver function and coagulation tests should be done before dental procedures are carried out. Orofacial defects and malocclusions in less severe types of thalassemia can be treated surgically followed by orthodontic treatment for alignment of teeth.
Less severe malocclusions can be corrected by orthodontic treatment at an early age. Prescription of hepatotoxic drugs should be given cautiously. Tetracycline, metronidazole and erythromycin estolate should be avoided. Sedation or anaesthesia may be used during dental treatment of thalassemia patients for better control and cooperation.
Caution should be exercised in thalassemia patients due to complications related to compromised immunity, liver function, splenectomy and cardiovascular issues. Multidisciplinary approach involving dental surgeon, haematologist and orthodontist should be practiced. Conflict of Interest:. All authors contributed to this project and article equally. All authors read and approved the final manuscript. National Center for Biotechnology Information , U.
Journal List Electron Physician v. Electron Physician. Published online Mar Nawal Helmi 1 Ph. Iffat Mirza Ahmed 4 Ph. Author information Article notes Copyright and License information Disclaimer. Received Nov 21; Accepted Feb This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
This article has been cited by other articles in PMC. Abstract Thalassemia is a genetic disorder that involves abnormal haemoglobin formation. Keywords: Thalassemia, Abnormal haemoglobin, Thalassemia dental treatment.
Introduction Thalassemia is a genetic disorder that involves abnormal haemoglobin formation 1 — 3. Discussion 2. Pathophysiology 2. Pathophysiology of alpha thalassemia The important factor involved in pathophysiology of alpha thalassemia is the reduced or absent synthesis of alpha globin chains which leads to an accumulation of otherwise normal beta globin chains in adults and gamma chains in the foetus.
Clinical Manifestations and management of thalassemia 2. Clinical Manifestations The main cause for oral manifestations of thalassemia is due to extreme compensatory hyperplasia of bone marrow, this in turn leads to expansion of marrow cavity.
Table 1 Facial features and oral manifestations of thalassemia. Open in a separate window. Management of thalassaemic patients Before beginning the treatment, the following should be ascertained: 1 type of thalassemia: major, minor or intermedia, 2 present haemoglobin level of the patient, and 3 ddegree of iron overload in the body. Footnotes iThenticate screening: January 15, , English editing: March 01, , Quality control: March 06, Conflict of Interest: There is no conflict of interest to be declared.
Translate PDF. Medical College, Gwalior. Medical Officer, Blood Bank, G. Department of Biochemistry, Jiwaji University, Gwalior 4. Resident, Department of Pathology, G. One of the major complications in chronically transfused patients is development of irregular antibodies and in this situation; further transfusion of compatible red cell is difficult.
Hemoglobinopathies imply abnormalities in the globin proteins themselves. Health complications are mostly found in thalassemia major and intermediate patients. Signs and symptoms include severe anemia, poor growth and skeletal abnormalities during infancy. Untreated thalassemia major eventually leads to death, usually by heart failure. Diagnosis by hematologic tests, hemoglobin electrophoresis, and DNA analysis.
Individuals with severe thalassemia require blood transfusion, drug therapy i. Genetic studies DNA analysis to investigate deletions and mutations in the alpha- and beta-globin-producing gene help in correct diagnosis and improved management in thalassemic patients.
This topic will review the clinical features of thalassemia while focusing on pathophysiology, clinical features, complication, management, screening and diagnosis. In Europe, in patients of Italian origin [1, 2]. There are two main and Mediterranean Regions such as types, alpha and beta Thalassemia [4]. The Antalya, Adna, Mersin , in parts of Italy, severity of alpha and beta thalassemia particularly southern Italy and the lower depends on how many of four genes for Povalley.
The major Mediterranean islands alpha or two genes for beta globin are except Balearics such as Sicily, Sardinia, missing [5]. As the vicinity of the Mediterranean, also have of thalassemia occurs in about high rates of thalassemia, including the million people with 4. Far severe disease [7]. Diagnosis is typically population being in the Maldives [20, 21]. The accounting for the historic ability of Tharus aim of the transfusion therapy is to correct to survive in areas heavy malaria anemia and to maintain sufficient infestation, where other could not.
Palestinian descent , and Asians [24]. Even at a time when we Malaysia, and Pakistan [25,26,27,28]. Greece, Italy, Spain, and thalassemia major [18] but It is not possible others , and Portugal [25]. A bio- to manage and afford HSCT in each and geographic analysis with the aid of tools; every thalassemic patient in Indian such as Geographic Information System subcontinent. Ninety-five to ninety- are encoded by two closely linked genes on eight percent of adult hemoglobin is A, the chromosome 16 [31].
Thalassemia Syndromes, necessary for normal red blood cell RBC Genotypes, and clinical features are function. Laos, Cambodia, Thailand, Vietnam, These cells, which show a variety of Malaysia, the Philippines, and Indonesia abnormalities of membrane structure and [33].
The anemia acts as cause of transfusion-dependent a stimulus to erythropoietin production and thalassemia in the Gwalior and Chambal this causes expansion of the bone marrow, region of central India [34].
Because the is different to that of beta Thalassemia. These soluble tetramers do thalassemia major, thalassemia not precipitate in the bone marrow and intermediate and thalassemia minor. Unlike the deletion no signs or symptoms of the disorder. However, many caused by mutation on chromosome 11 that people with this type of thalassemia may be affect all aspect of beta globin production: asymptomatic or experience very few transcription, translation, and the stability symptoms.
Symptoms may be worse in of the beta globin production [36]. Symptoms may include: according to the type of mutation in the Fatigue. This may be the only symptom beta globin gene, may help to improve the that an individual with beta thalassemia compliance of beta thalassemic to chelation minor exhibits [39] Satwani et al.
Alpha have mild to moderate anemia. In the absence of their increased amount of bilirubin in the blood. Hence, two years of life. Affected infants fail to there is a variable degree of intramedullary thrive and gain weight normally and Sharma D. Feeding Heart Diseases, such as congestive heart problems, diarrhea, irritability, fever and failure and abnormal heart rhythms, may be progressive enlargement of the abdomen associated with severe Thalassemia [47].
Signs and symptoms occur of amniotic fluid [49]. The step in the within the first 2 years of life. They may diagnosis of the different forms of include severe anemia and other serious thalassemia include the initial recognition health problems, such as: Pale and listless of the disease as thalassemic disorder and appearance, Poor appetite, Dark urine. The its differentiation from other congenital Hydrops Fetalis Syndrome is recognized and acquired disorder of hemoglobin by the finding of a hydropic infant with a synthesis which can mimic the thalassemia severe anemia, a thalassemic blood picture, syndromes [39].
Slight hypochromia and deformities, enlarged spleen, and slow microcytosis may be evident by growth rate and heart problems. People microscopic evaluation. This is more Hb Barts on hemoglobin especially true if the spleen has been electrophoresis [40].
The homozygous for removed [43]. Thalassemia can make the the severe form of beta thalassemia are bone marrow expand, which causes bones easily recognized by the hematological to widen. This can result in abnormal bone change with very high level of Hb F; Hb A2 Medico Research Chronicles, structure, especially in the face and skull.
The heterozygous states are Bone marrow expansion also makes bones recognized by microcytic hypochromic red thin and brittle, increasing the risk of cells and elevated level of Hb A2 [41].
The spleen aids in DNA analysis tests are used to help fighting infection and filters unwanted confirm mutations in the alpha and beta material, such as old or damaged blood globin-producing genes.
DNA testing is cells. Splenomegaly can make anemia not routinely done but can be used to help worse, and it can reduce the life of diagnose thalassemia and to transfused red blood cells. Severe determine carrier status, if indicated.
More enlargement of the spleen may necessitate than mutations have been associated its removal [45]. Anemia can cause a with beta thalassemia, though some cause child's growth to slow. Puberty also may be no signs or symptoms. However, others delayed in children with Thalassemia [46]. Each person has Presently, till today the Bone Marrow two copies of each of these genes, Transplant BMT is still remains the only called alleles, in their cells, one from their definitive cure available for patients with mother and one from their father.
These Thalassemia. First successful BMT was or more of alpha genes, alpha thalassemia done in s by Prof. Guido Lucarelli. In occurs. This is The drawback is that this curative method especially important if both parents likely required an HLA Human leukocyte carry a mutation because that increases the Antigen -matched compatible donor [60].
They may want mother to child mismatched donor , in to consider genetic counseling, however, which donor is the mother. It was invented because they may pass the mutant gene on in by Doctor Pietro Sodani. The to their children [51]. BMT treatment for They can live relatively normal lives but thalassemia is still not available for all will require regular monitoring and may patients in Indian perspective, at our center occasionally need blood transfusion.
Folic out of patients only one patient has acid supplementation is often given, but gone for successful bone marrow transplant iron supplementation is not recommended. Attempts at intrauterine effective chelating therapy and transfusions, after early prenatal detection management of complications of iron with Doppler ultra-sonography of this overload [16]. The aim of the transfusion condition, have been conducted, but most therapy is to correct anemia and to maintain survivors experienced a high prevalence of circulating level of hemoglobin Hb congenital malformations [53, 54] and sufficient to suppress endogenous attempts should be discouraged until more erythropoiesis [15].
In transfusion effective therapies e. As symptomatic anemia, was first recognized Sharma D. Prevalence of transfusion program aimed at monitoring a Alloimmunization at our center was 3.
Author s has also used other blood hypoxia [63, 64]. A unit processed from damage and bone deformities, allowing ml of donor blood contains approximately normal activity and quality of life, and is mg of iron, or 0. In patients accumulation [65]. The amount of blood to with thalassemia who do not receive any be transfused depends on several factors transfusion, iron absorption increases including the weight of the patient, and the several-fold.
It has been estimated that iron target increase in Hb level. Appropriate absorption exceeds iron loss when graphs and formulae to calculate the expansion of red cell precursors in the bone amount of blood to be transfused are marrow exceeds five times that of healthy available [66, 67].
In general, the amount individuals [72]. The iron status of multi-transfused Characteristics of blood products for patients can be assessed by several transfusion: Careful selection of healthy methods. Serum ferritin has in general been Medico Research Chronicles, voluntary donors is a prerequisite for found to correlate with body iron stores obtaining safe blood units for patients with [73].
In recent years, nuclear magnetic thalassemia. To avoid transfusion reactions resonance imaging MRI techniques for from anti-leukocyte and anti-platelet assessing iron loading in the liver and heart antibodies and transmission of viral agents have been introduced []. As the body present in leukocytes such as has no effective means for removing iron, cytomegalovirus, patients with thalassemia the only way to remove excess iron is to use should receive leukoreduced packed red iron binders chelator , which allow iron cells [68, 69].
As plasma proteins washed red cells may be a general rule, patients should start iron beneficial. Sharma D. After approximately one iron overload was deferoxamine DFO , an year of transfusions, iron begins to be hexadentate iron chelator that is not orally deposited in parenchymal tissues [83]. Second and cirrhosis [85]. Endocrine abnormalities drug deferiprone DFP , orphan drug is an related to iron overload include diabetes orally active iron chelator which has mellitus and impaired glucose tolerance, emerged from an extensive search for new adrenal insufficiency, hypothyroidism, treatment of iron overload.
Comparative osteoporosis, hypoparathyroidism and studies have shown that this chelator, at hypogonadism [85]. Third drug, Deferasirox DFX is a thalassemia, particularly those with once-daily, orally administered iron hypogonadism. Osteopenia may be related chelator that a large program of clinical to marrow expansion, even in patients who trials has shown to be effective in adults receive transfusions, [86] or to iron induced and children [79, 80].
It received European osteoblast dysfunction, diabetes, Union marketing authorization as an hypoparathyroidism, or hypogonadism orphan drug from the EMEA in and [87]. Indications for splenectomy are was authorized for marketing in most symptoms of splenic enlargement, countries in To prevent thalassemia has high severity, presented by alloimmunization extended blood grouping mild to severe anemia. Treatment of Patients maintained on a regular Individuals with severe anemia is via transfusion regimen progressively develop regular blood transfusion, iron chelation, clinical manifestations of iron overload: splenectomy, and bone marrow transplant.
Iron overload of tissue with was for death by age five from infections or without transfusion is fatal, which is the and cachexia. Bone 7. Global Burden of Disease Study Gene therapy 8. Genetic studies DNA Global regional and national age- analysis to investigate deletions and sex specific all cause and cause-specific mutations in the alpha- and beta-globin- mortality for causes of death, producing gene help in correct diagnosis a systematic analysis for the and improved management in thalassemic Global Burden of Disease Study patients.
Methods in Ped. Jaypee Brothers The authors are thankful to Prof. Medical College, Gwalior for his close How Are Thalassemia Diagnosed? July 3, Retrieved 5 review study would have not been possible. September The authors are also thankful to Mrs.
Mala Bhadoriya and management of patients with Mr. Dharmendra Singh, senior laboratory thalassemia major. Hospital for —97 their kind cooperation in this work. Results and prospective. J References Paediatr — 1. Cooley TB, Lee P. A series of cases of Proter JB Practical splenomegaly in children with anemia management of iron overload.
Curr and peculiar bone changes. Bradford W. British J Hematology — 4. July Hollan SR Transfusion 3, Retrieved 5 September associated iron overload. Curr Opin 5. Hematol — July 3, Retrieved 5 September Angelucci E. Hematopoietic stem John NL. Cappellini MD et al editors. Guidelines for the management of Sharma D. Stem Cell.
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