about thalassemia

Thalassemia is a hereditary blood disease in which the body produces an irregular hemoglobin type. The protein hemoglobin is found in red blood cells and is responsible for oxygen delivery. Hemoglobin is made up of three parts: heme, alpha-globin, and beta-globin. Thalassemia affects either the alpha or beta globin portions of the blood, depending on the type. Anemia is caused by this disease's excessive loss of erythrocytes (Muncie, Herbert, and Campbell 339).

Thalassemia is a quantitative hemoglobin disease, according to Muncie, Herbert, and Campbell (339), since it either reduces or stops hemoglobin activity. We group thalassemia disorders into two primary groups: alpha thalassemia and beta-thalassemia, with each subtyped as either thalassemia major or thalassemia minor. These thalassemia conditions cause anemia of varying degrees that range from almost insignificant to life-threatening.

Symptoms

Muncie, Herbert, and Campbell (340) argue that the symptoms of thalassemia depend on the type, and they vary from no signs to very severe symptoms. Unaffected carriers of all the kinds of thalassemia traits do not experience any health problems. The thalassemia trait is protective against malaria. Theories have it that the mutations that cause thalassemia increase the likelihood of carriers surviving malaria infection. These malaria survivors give the variation to generations and pass the trait throughout endemic malaria regions. These mutations have been spread throughout the globe as people migrate.

According to Muncie, Herbert, and Campbell (341-342), one of the most affected body systems is the reticuloendothelial system. The liver and the spleen enlarge severely due to extra-medullary hemopoiesis, excessive red cell destruction, and later iron overload due to inevitable repeat transfusions. Extra-medullary hemopoiesis results as the spleen and the liver attempt to compensate for the increased demand for red cells and hemoglobin. The bone marrow is unable to keep up with the increased demand hence the help from the extra-medullary organs. An enlarged spleen causes increase erythrocyte destruction, cause pooling, and cause expansion of plasma volume increasing blood requirements. It becomes a cycle as the erythrocyte demand increases splenic activity and the rises splenic activity leads to the destruction of more red cells.

Muncie, Herbert, and Campbell (342) argue that The above constellation of activities lead to anemic symptoms like shortness of breath, chest pain, drowsiness and fatigue, rapid heartbeat, cold hands and feet, leg cramps, dizziness, and faintness and headaches. Destruction of the liver may also cause yellowness and itchiness of the skin and sclera and poor feeding.

Increased bone marrow hyperplasia in an attempt to solve the abnormal bone marrow problem expands the bones which cause the thalassemic face appearance. Increased bone marrow activity also causes the cortex of many bones to thin, increase the tendency of these bones to fracture, and lead to skull bossing with an X-ray “hair on end” appearance (Cao, Antonio, and Renzo 62)

Cao, Antonio, and Renzo (63) argue that if we do splenectomy without prophylactic penicillin, the patients, especially children become more susceptible to infections. One can also transmit diseases through infected blood. Some patients, therefore, present with symptoms of infections like fever, chills. Patients with the thalassemia trait have an average life expectancy. However, patients with thalassemia major can have a fatal condition and poor prognosis due to heart complications before age thirty years. The primary cause of these heart complications is Iron overload due to multiple transfusions.

Etiology

Thalassemia is an inherited disorder which means at least one of the parents must be a carrier for the offspring to inherit this disease. If both the parents are thalassemia carriers, then one has an increased chance of contracting a more severe form of the disorder. Either a deletion of specific vital fragments of genes or a genetic mutation cause thalassemia. Mutations in the HBB gene cause beta thalassemia while mutations in the HBA1 and HBA2 regions cause alpha thalassemia. There are two types of thalassemia, beta-thalassemia and alpha-thalassemia each having their subtypes thalassemia major and thalassemia major (Musallam, Khaled et al. S16).

Musallam, Khaled et al. (S20) argue that usually, there are four copies of genes of the alpha type. If the hemoglobin loses the four copies, this suppresses the alpha chain synthesis which leads to hydrops fetalis which is incompatible with life as the alpha chain is critical in both fetal and adult hemoglobin. Deletion of three alpha genes causes a moderately severe microcytic hypochromic anemia and splenomegaly. The loss of one or two genes causes alpha thalassemia trait which is not associated with anemia although MCV and MCH are low and red cell count high. We categorize alpha-thalassemia into alpha-thalassemia-major and hemoglobin H disease.

According to Musallam, Khaled et al. (S21), beta-thalassemia is the most well-known thalassemia and is also called Cooley’s anemia. Beta-thalassemia-major occurs if both parents are carriers of the beta-thalassemia trait. It is either the hemoglobin synthesizes no beta chains, or the hemoglobin incorporates small amounts of the beta globin. Excess alpha chains cause ineffective erythrocyte production and hemolysis. Majority of the genetic lesions in beta thalassemia are point mutations rather than the gene deletions in alpha thalassemia. These variations are either in the promoter region, the enhancer region or within the gene complex.

Other than the genetic risk factors for thalassemia, there are other risk factors like race. Alpha-thalassemia mostly occurs in people from the Middle East, China, Africa, and those of Southeast Asian descent. Beta-thalassemia mainly occurs in persons of Mediterranean origin. Beta thalassemia also happens to a lesser extent in African Americans, Chinese and other Asians (Muncie, Herbert, and Campbell 343).

Clinical Tests

The primary tests for thalassemia are complete blood count (CBC) and peripheral blood film (PBF). CBC will determine the number of erythrocytes present and the amount of hemoglobin in them. A PBF will evaluate the red cell indices that include the size and shape of red cells. In a PBF, there is a severe microcytic hypochromic anemia, the percentage of the reticulocyte is high, and there are normoblasts in the film. The red cells in thalassemia patients are microcytic with a low mean corpuscular volume (MCV). There are other inclusions in the thalassemia patient’s blood film which include target cells, nucleated red blood cells, and basophilic stipplings (Musallam, Khaled et al. S18).

According to Musallam, Khaled et al. (S19), another standard test for hemoglobinopathies is the iron tests which include the iron levels, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), ferritin, and ferritin saturation. The iron study measures various aspects of the body’s iron usage and storage, and from this study, we can tell if it is iron deficiency causing the anemia. Erythrocyte porphyrin tests are also performed to differentiate the diagnosis of an unclear beta-thalassemia minor from lead poisoning or iron deficiency anemia. Individuals with iron deficiency anemia and lead poisoning will have elevated levels of porphyrin. Thalassemia patients, however, will have standard porphyrin levels.

Hemoglobin electrophoresis assesses the amount and type of hemoglobin present in the red cells. In adults, hemoglobin A (Hb A) that is composed of alpha and beta globin makes up 95% to 98% of hemoglobin. Hemoglobin A2 (Hb A2) makes 2% to 3% while hemoglobin F accounts for about 2% of hemoglobin. Thalassemia increases the minor hemoglobin components, and electrophoresis shows almost all circulating hemoglobin as hemoglobin F (Hb F) and nearly complete absence if not the lack of Hb A (Galanello, Renzo, and Raffaella 11).

According to Galanello, Renzo, and Raffaella (11), we could also perform high liquid chromatography as the first line method to test the synthesis of alpha and beta globin chain and the alpha-beta ratio. DNA Analysis helps to confirm the mutations in the genes producing the alpha and beta globin and detect the allelic defects. To get a high-quality hemoglobinopathy diagnosis, we can perform a molecular identification test of causative mutations where we do PCR amplification for genomic DNA.

According to Galanello, Renzo, and Raffaella (11) argue that if health practitioners deem it necessary, they can do family studies to evaluate the types of mutations and the carrier status in other family members. These family studies are essential because relatives who carry thalassemia mutations increase the likelihood of another family member having a similar mutant gene. Practitioners can also perform genetic testing of the amniotic fluid to fetuses at an increased risk for contracting thalassemia although rarely. Amniotic fluid genetic testing is especially important when both parents are likely carriers of a mutation. A child of such parents is expected to inherit combined abnormal genes that cause a very severe variant of thalassemia.

Treatment and Prevention

Transfusion with 2-3 units of blood in every 4-6 weeks maintains hemoglobin above 10g/dl. We transfuse with fresh blood that has been filtered to remove leukocytes as it has the fewest reactions and has the best red cell survival. If the diet is inadequate, we give 5mg of folic acid per day. At the beginning of the transfusion programme, the patients are first genotyped red cell antibodies develop against the transfused red cells. (Finotti, Alessia, et al. 69).

Finotti, Alessia, et al. (69) argue that we treat iron overload with iron chelation therapy. Deferiprone is an oral iron chelator that predominantly causes urine iron excretion. Deferiprone is either used alone or used combined with deferoxamine. Deferasirox is a new oral chelator that causes fecal iron excretion, and we give it once daily. Vitamin C, when combined with deferoxamine accelerates the deferoxamine iron excretion effect.

According to Finotti, Alessia et al. (69), it may require splenectomy but only for patients above six years as it has a high risk of dangerous infections after splenectomy. We do splenectomy to reduce the blood requirements followed by vaccination and antibiotics. Iron overload causes end-organ failure hence the need for endocrine therapy if puberty is delayed to stimulate the pituitary. We treat patients with osteoporosis using vitamin D, calcium, and bisphosphonate and diabetic patients with insulin.

There is a prospect of permanent cure with allogeneic transplantation of bone marrow. The success rate of bone marrow transplantation in younger patients who are well chelated and without hepatomegaly and liver cirrhosis is over 80%. The bone marrow donor is usually a family member or unrelated donor matching the patient’s human leukocyte antigen (HLA). Transplant failure occurs due to recurrence of thalassemia or a severe chronic graft-versus-host disease. We can prevent thalassemia through genetic screening and counselling of spouses (Musallam, Khaled et al. S19).

Works Cited

Cao, Antonio, and Renzo Galanello. "Beta-thalassemia." Genetics in Medicine 12.2 (2010): 61-

76.

Galanello, Renzo, and Raffaella Origa. "Beta-thalassemia." Orphanet journal of rare diseases 5.1

(2010): 11.

Finotti, Alessia, et al. "Recent trends in the gene therapy of β-thalassemia." Journal of Blood

Medicine 6 (2015): 69.

Muncie Jr, Herbert L., and J. Campbell. "Alpha and beta thalassemia." American family

physician 80.4 (2009): 339-344.

Musallam, Khaled M., et al. "Iron overload in non-transfusion-dependent thalassemia: a clinical

perspective." Blood reviews 26 (2012): S16-S19.