THALASSEMIA

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PRODI D-III ANALIS KESEHATANUNIVERSITAS MH. THAMRIN JAKARTACONTENTS

Definition .. 1History ... 2Prevalence Data .... 3Mechanism Of Disease . 4Symptoms .. 5Method And Equipment ... 6Lab Result .. 7Management Care 8Conclusion 9

DEFINITION

Thalassemia is a group of inherited blood disorders that affect the body's ability to produce hemoglobin and red blood cells - patients have a lower-than-normal number of red blood cells in their bodies and too little hemoglobin. In many cases the red blood cells are too small. Our red blood cells carry hemoglobin. Hemoglobin, a protein, carries the oxygen we breathe in through our lungs and transports it to the rest of the body. A spongy material inside some of our bones - bone marrow - uses iron that our body takes from food and makes hemoglobin.

The bone marrow of people with Thalassemia does not produce enough healthy hemoglobin or red blood cells, which causes anemia and fatigue, because the body is short of oxygen. In more severe Thalassemia cases, the patient's organs may be damaged, there is restricted growth, heart failure, liver damage, and even death. People with mild thalassemia may not require any treatment at all. In more severe forms of the disease, the patient may need regular blood transfusions. Doing plenty of exercises and eating a healthy diet can help some of the symptoms of thalassemia, especially fatigue.

Pathophysiology

Hemoglobin (Hb) is the molecule that carries and transports oxygen all through the body. Normal human hemoglobin is a tetramer formed by two pairs of globin chains attached to heme. The hemoglobin type is determined by the combination of tetra-globin chains (, , and chains). Each globin chain is structurally different and thus has different oxygen affinity, electrical charge, and electrophoretic mobility. Normal adult hemoglobins are expressed as A2, A and F (fetal). Ninety-five to ninety-eight percent of adult hemoglobin is A the major hemoglobin, which consists of two - and two -chains (2, 2). Hemoglobin A2 (2, 2), the remainder of hemoglobin in adults is a minor component (less than 3.3%), and 1% or less of F (2, 2) (Nathan & Oski, 1993.), the gamma hemoglobin (Hb-F) is the predominant hemoglobin found only during fetal development. The equal production of and non ( ) globin chains is necessary for normal red blood cell (RBC) function.

The failure in hemoglobin synthesis is a main cause of microcytosis and anemia in many population groups around the world. Hb variants are characterized by the gene mutation of the globin chains form hemoglobin (i.e., the replacement of different amino acids at a certain position). Thalassemia occurs when there is decreased or absent production of one of the types of globin chains (most commonly either or ), that cause insufficeient amount of normal structure globin chains. This results in an imbalance between - and -chains and causes the clinical features of thalassemia (Nathan & Gunn, 1966), it can be separated into two major types such as -thalassemia and - thalassemia.BASICS - 3 types of Hb

1. Hb A : 2 and 2 chains forming a tetramer 97% adult Hb Postnatal life Hb A replaces Hb F by 6 months

2. Fetal Hb : 2 and 2 chains 1% of adult Hb 70-90% at term. Falls to 25% by 1st month and progressively

3. Hb A2 : Consists of 2 and 2 chains 1.5 3.0% of adult Hb

Types of thalassemia

Thalassemia is classified on the basis of amino acid chains are exposed to 2 main types are:

1. Alpha Thalassemia

The alpha thalassemia patient's hemoglobin does not produce enough alpha protein. This type is commonly found in southern China, Southeast Asia, India, the Middle East, and Africa. To make alpha globin protein chains we need four genes, two on each chromosome 16. We get two from each parent. If at least one of these genes is missing, it produces alpha thalassemia. The severity of thalassemia depends on how many genes are faulty.

One faulty (mutated) gene - there are either no symptoms at all, or they are very mild. A person who is apparently "healthy" and has a child with symptoms of thalassemia is known as a Silent Carrier. This type is also known as alpha thalassemia minima, or 2 trait.

Two mutated genes - the patient will have mild anemia. Also known as alpha thalassemia minor, or 1 trait.

Three mutated genes - the patient will have hemoglobin H disease, i.e. chronic anemia. A person with hemoglobin H disease needs regular blood transfusions throughout his/her life.

Four genes are mutated - the patient has alpha thalassemia major, the severest form of this type of thalassemia. Fetuses with four mutated genes cannot produce normal hemoglobin and do not survive. Blood transfusions given to the fetus have a low success rate. This type of thalassemia is also known as hemoglobin Bart hydrops fetalis.

Alpha thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body. In people with the characteristic features of alpha thalassemia, a reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications.

Two types of alpha thalassemia can cause health problems :1. The more severe type is known as hemoglobin Bart hydrops fetalis syndrome or Hb Bart syndrome. The milder form is called 2. HbH disease.

Hb Bart syndrome is characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Additional signs and symptoms can include severe anemia, an enlarged liver and spleen (hepatosplenomegaly), heart defects, and abnormalities of the urinary system or genitalia. As a result of these serious health problems, most babies with this condition are stillborn or die soon after birth. Hb Bart syndrome can also cause serious complications for women during pregnancy, including dangerously high blood pressure with swelling (preeclampsia), premature delivery, and abnormal bleeding.

HbH disease causes mild to moderate anemia, hepatosplenomegaly, and yellowing of the eyes and skin (jaundice). Some affected individuals also have bone changes such as overgrowth of the upper jaw and an unusually prominent forehead. The features of HbH disease usually appear in early childhood, and affected individuals typically live into adulthood.

Beta Thalassemia We need two globin genes to make beta globin chains. We get one from each parent. If one or two of these genes are faulty, it produces beta thalassemia.Severity of beta thalassemia also depends on how many genes are mutated: If one globin gene is mutated - the patient may have Beta thalassemia minor. If both globin genes are mutated - the patient may have either moderate or severe symptoms (Colley's anemia). Beta thalassemia is much more common among people of Mediterranean ancestry, hence its other name, Mediterranean anemia. It is also more prevalent in North Africa and West Asia. Sixteen percent of the people in the Maldives, some islands in the Indian Ocean, are carriers. Beta thalassemias, ranges from very severe to having no effect on health. There are three kinds of beta thalassaemia Thalassemia Major Thalassemia Intermedia Thalassemia Minor

Thalassemia Major Thalassemia major is an inherited form of hemolytic anemia, characterized by red blood cell (hemoglobin) production abnormalities. This is the most severe form of anemia, and the oxygen depletion in the body becomes apparent within the first 6 months of life. If left untreated, death usually results within a few years. Note the small, pale (hypochromic), abnormally-shaped red blood cells associated with thalassemia major. The darker cells likely represent normal RBCs from a blood transfusion. (http://www.nlm.nih.gov/medlineplus/ency/imagepages/1498.htm)

Thalassemia Intermedia

Are associated with moderate anemia usually diagnosed after 3 years to 15 years of age. Normally they maintain heamoglobin level around 7gm without transfusion. They require occasional transfusion during puberty, infection, pregnancy etc.

Thalassemia minor

Thalassemia minor is an inherited form of hemolytic anemia that is less severe than thalassemia major. This blood smear from an individual with thalassemia shows small (microcytic), pale (hypochromic), variously-shaped (poikilocytosis) red blood cells. These small red blood cells (RBCs) are able to carry less oxygen than normal RBCs

http://www.nlm.nih.gov/medlineplus/ency/imagepages/1499.htm

HISTORY

In 1925 in the United States, the American pediatriciansCooleyandLeedescribed a disease, named Cooley's anaemia, in children of Italian and Greek immigrants, today known as thalassemia major orMediterranean anaemia. At about the same time, in Italy,Riettidescribed a disease having a symptomatology similar to the Cooley's anaemia but lighter, that became known as 'La Malattia di Rietti-Greppi-Micheli and today as thalassemia intermedia.

Ezio Silvestroni, Ida Bianco

In 1943 two known Italian haematolog ists,Ezio SilvestroniandIda Bianco, have described a hereditary anomaly, individualized in healthy subjects that has been named "microcitemia". Immediately after the microcitemia discovery, Silvestroni and Bianco noticed, with a long series of researches, that the Cooleys anaemia cames from the homozygous condition that results in asick child, and which is born only if both his parents transmit their microcitemica alteration.The hereditary transmission, according to the laws of Mendel, of the thalassaemias has been verified through the vast familiar case of histories picked up by Silvestroni and Bianco in more than 1100 families of heterozygotes and over 200 of homozygotes for the thalassaemia.

These studies have shown that in the families with one thalassaemic carrier parent and one normal is previewed at statistical level that: the 50% will be normal children and the 50% thal carriers. While in the families with both thal carriers, parents the 25% of their children will be normal, the 50% will be thal carriers and the 25% will be affected by the Mediterranean anaemia. These searches have been developed contemporarily to those of other American researchers and, independently the two groups of researchers have reached the same conclusion.

PREVALENCE DATADeputy Health Minister Ali Ghufron Mukti has warned that Indonesia is among a group of countries with a high risk of thalassemia, a genetic disease that disrupts hemoglobin production in red blood cells, leading to anemia. The prevalence for thalassemia carriers in Indonesia is about 3 percent to 8 percent, he said in a speech to mark the 25th anniversary of the Indonesian Thalassemia Foundation on Saturday. Ali said that in Indonesia, around 300,000 babies were born with thalassemia every year. A study in 2007 showed that national thalassemia prevalence stood at 0.1 percent. There are eight provinces that showed higher thalassemia prevalence compared to the national prevalence, the deputy minister said. Aceh has the highest prevalence, at 13.4 percent, followed by Jakarta at 12.3 percent, South Sumatra at 5.4 percent, Gorontalo at 3.1 percent and the Riau Islands at 3 percent. Ali said that of the 300,000 children born with thalassemia each year, 60,000 to 70,000 suffered from beta-thalassemia major, meaning they would rely on blood transfusions all their lives. People suffering from thalassemia spend about Rp 7 million to Rp 10 million [$750 to $1,100] per month on medical treatment, Ali said. To help people with thalassemia get medical treatment, the government has offered a guarantee of treatment. All thalassemia sufferers in the country get medical coverage under a scheme called Jampelthas, Ali said. He emphasized that thalassemia was a genetic disease and therefore not communicable. The red blood cells of thalassemia sufferers are easily damaged and since its age is shorter than normal blood cells, people with the disease suffer anemia, Ali said. Two other types of thalassemia are thalassemia minor, in which the carrier of the gene remains healthy but they can potentially pass it on to their offspring, and thalassemia intermedia, which may require sufferers to undergo occasional blood transfusions. Those sufferers can often reach adulthood. World Health Organization data in 1994 showed that 4.5 percent of people worldwide carried the thalassemia gene, but a 2001 estimate of carriers, also by the WHO, put it at 7 percent of the global population.Ismira LutfiaBy webadmin on 07:20 pm Jun 05, 2012 Persentase

MECHANISM OF DISEASE

1) Alpha Thalassemias You need four genes (two from each parent) to make enough alpha globin protein chains. If one or more of the genes is missing, you'll have alpha thalassemia trait or disease. This means that your body doesn't make enough alpha globin protein. If you're only missing one gene, you're a "silent" carrier. This means you won't have any signs of illness. If you're missing two genes, you have alpha thalassemia trait (also called alpha thalassemia minor). You may have mild anemia. If you're missing three genes, you likely have hemoglobin H disease (which a blood test can detect). This form of thalassemia causes moderate to severe anemia. Very rarely, a baby is missing all four genes. This condition is called alpha thalassemia major or hydrops fetalis. Babies who have hydrops fetalis usually die before or shortly after birth.Example of an Inheritance Pattern for Alpha Thalassemia

The picture shows one example of how alpha thalassemia is inherited. The alpha globin genes are located on chromosome 16. A child inherits four alpha globin genes (two from each parent). In this example, the father is missing two alpha globin genes and the mother is missing one alpha globin gene. Each child has a 25 percent chance of inheriting two missing genes and two normal genes (thalassemia trait), three missing genes and one normal gene (hemoglobin H disease), four normal genes (no anemia), or one missing gene and three normal genes (silent carrier).2) Beta ThalassemiasYou need two genes (one from each parent) to make enough beta globin protein chains. If one or both of these genes are altered, you'll have beta thalassemia. This means that your body wont make enough beta globin protein. If you have one altered gene, you're a carrier. This condition is called beta thalassemia trait or beta thalassemia minor. It causes mild anemia. If both genes are altered, you'll have beta thalassemia intermedia or beta thalassemia major (also called Cooley's anemia). The intermedia form of the disorder causes moderate anemia. The major form causes severe anemia.Example of an Inheritance Pattern for Beta Thalassemia

The picture shows one example of how beta thalassemia is inherited. The beta globin gene is located on chromosome 11. A child inherits two beta globin genes (one from each parent). In this example, each parent has one altered beta globin gene. Each child has a 25 percent chance of inheriting two normal genes (no anemia), a 50 percent chance of inheriting one altered gene and one normal gene (beta thalassemia trait), or a 25 percent chance of inheriting two altered genes (beta thalassemia major).

REACTION CHEMISTRY

Fe3+ + O2 Fe2+ + O2Fe2+ + H2O2 Fe3+ + OH+ OHOOO2+ H2O2 OHOO + OH+ O2

NET REACTION

These free radicals cause oxidative damage via lipid peroxidation, DNA hydroxylation, and protein oxidation (Schaible & Kaufmann 2004). Oxidative stress is another prominent mechanism of vasculopathy. In hemolytic disorders, the erythrocyte may be a major determinant of the global redox environment. The thalassemias have increased concentrations of ROS compared with normal red blood cells (Aslan & Freeman, 2004, Hebbel et al., 1982, Chakraborty & Bhattacharyya, 2001). Overproduction of ROS, such as superoxide, by both enzymatic (Xanthine oxidase, NADPH oxidase, uncoupled eNOS) and nonenzymatic pathways (Fenton chemistry), promotes intravascular oxidant stress that can likewise disrupt NO homeostasis and produce the highly oxidative peroxynitrite (Wood et al., 2008). Alters cell membrane lipids and abnormal erythrocyte phosphatidylserine (PS) exposure triggered in part by oxidative stress may also contribute to the early demise of the red blood cell in circulation, making them more vulnerable to enzymatic breakdown by secretory phospholipase A2, an important lipid mediator in inflammation. PS exposure also induces binding of red cells to endothelial cells, leading to sequestration of PS-exposing cells in peripheral blood vessels. This process can contribute to vascular dysfunction, hemolysis, and a pro-thrombotic state (Neidlinger et al., 2006).

In the alterations in glutathione buffering system common to these hemoglobinopathies (Chakraborty & Bhattacharyya, 2001, Chakraborty & Bhattacharyya, 2001, Reid et al., 2006) may render erythrocytes incapable of handing the increased oxidant burden, thereby predisposing them to hemolysis. Hydroxyl radical formed by iron catalyzed reactions reacts with a polyunsaturated fatty acid of a membrane lipid caused lipid peroxidation. The resulting lipid hydroperoxides can affect membrane fluidity and membrane protein function. A large number of lipid breakdown products are generated including malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE). In rat models of iron overload, lipid peroxidation has been found in whole liver and also in isolated cellular fractions including mitochondria, microsomes and lysosomes (Bacon et al., 1983, Britton et al., 1987). The reactive aldehydes (MDA and HNE) can react with proteins to form adducts. The MDA and HNE-lysine adducts have been found in hepatocytes and plasma from rats fed a diet containing carbonyl iron for 13 weeks (Houglum et al., 1990). Iron overload causes vitamin C to be oxidized at an increased rate, leading to vitamin C deficiency in these patients. Vitamin C in children 10 years at the time of DFO infusion may increase the chelatable iron available in the body, thus increasing the efficacy of chelation. However there is currently no evidence supporting the use of vitamin C supplements in patients on DFP, DFX or combination treatment. Vitamin C may increase iron absorption from the gut, labile iron and hence iron toxicity and may therefore be particularly harmful to patients who are not receiving DFO, as iron mobilized by the vitamin C will remain unbound, causing tissue damage. The effectiveness and safety of vitamin E supplementation in thalassemia major has not been formally assessed and it is not possible to give recommendations about its use at this time.

SYMPTOMS

Mild to Moderate Anemia and Other Signs and SymptomsPeople who have beta thalassemia intermedia have mild to moderate anemia. They also may have other health problems, such as: Slowed growth and delayed puberty. Anemia can slow down a child's growth and development. Bone problems. Thalassemia may cause bone marrow to expand. Bone marrow is the spongy substance inside bones that makes blood cells. When bone marrow expands, the bones become wider than normal. They may become brittle and break easily. An enlarged spleen. The spleen is an organ that helps your body fight infection and remove unwanted material. When a person has thalassemia, the spleen has to work very hard. As a result, the spleen becomes larger than normal. This makes anemia worse. If the spleen becomes too large, it must be removed. Severe Anemia and Other Signs and Symptoms People who have hemoglobin H disease or beta thalassemia major (also called Cooley's anemia) have severe thalassemia. Signs and symptoms occur within the first 2 years of life. They may include severe anemia and other health problems, such as: A pale and listless appearance Poor appetite Dark urine (a sign that red blood cells are breaking down) Slowed growth and delayed puberty Jaundice (a yellowish color of the skin or whites of the eyes) An enlarged spleen, liver, and heart Bone problems (especially bones in the face)

Complications of ThalassemiasBetter treatments now allow people who have moderate and severe thalassemias to live much longer. As a result, these people must cope with complications of these disorders that occur over time. Heart and Liver DiseasesRegular blood transfusions are a standard treatment for thalassemias. As a result, iron can build up in the blood (iron overload). This can damage organs and tissues, especially the heart and liver. Heart disease caused by iron overload is the main cause of death in people who have thalassemias. Heart disease includes heart failure, arrhythmias (irregular heartbeats), and heart attack. InfectionAmong people who have thalassemias, infections are a key cause of illness and the second most common cause of death. People who have had their spleens removed are at even higher risk because they no longer have this infection-fighting organ. OsteoporosisMany people who have thalassemias have bone problems, including osteoporosis (OS-te-o-po-RO-sis). This is a condition in which bones are weak and brittle and break easily.

METHOD AND EQUIPMENT

1. Screening of thalassemiaFollowing are the tests performed for screening of thalassemia : Complete blood count This is done to determine the level of hemoglobin and the grade of anemia. Also the morphology of the red blood cells is studied. Small red blood cells and other abnormalities of these cells are identified. Hemoglobin electrophoresis To know the type and the quantity of Hemoglobin Free erythropoietin Protoporphyrin estimation or serum ferritin levels: to assess the degree of iron overload. Screening for thalassemia can be undertaken in individuals who are chronically anemic, or in family members of affected individuals. It is recommended in high prevalence areas.2. Serum ferritinSerum ferritin levels in thalassemias and the effect of splenectomy.Iron overload is a constant and the more important complication in thalassemia. Serum ferritin concentration accurately reflects body iron stores. A total of 245 thalassemic patients aged 12-55 years were examined, 71 having Hb H disease and 174 beta-thalassemia/Hb E disease. The patients received minimal or no blood transfusions. 73 patients with beta-thalassemia/Hb E were studied 1-28 years after splenectomy. The serum ferritin levels in both Hb H and beta-thalassemia/Hb E patients were higher than normal. They were higher in beta-thalassemia/Hb E than Hb H disease. Most striking was the significantly higher serum ferritin levels in splenectomized patients with beta-thalassemia/Hb E disease than in the nonsplenectomized ones. The observation is compatible with previous observations that splenectomy in thalassemia is associated with increased iron deposition and increased transferrin iron saturation. The further increase in iron overload after splenectomy in thalassemia should be borne in considering removal of this organ.3. FE dan TIBC Serum iron is a medical laboratory test that measures the amount of circulating iron that is bound to transferrin. Clinicians order this laboratory test when they are concerned about iron deficiency, which can cause anemia and other problems.65% of the iron in the body is bound up in hemoglobin molecules in red blood cells. About 4% is bound up in myoglobin molecules. Around 30% of the iron in the body is stored as ferritin or hemosiderin in the spleen, the bone marrow and the liver. Small amounts of iron can be found in other molecules in cells throughout the body. None of this iron is directly accessible by testing the serum.However, some iron is circulating in the serum. Transferrin is a molecule produced by the liver that binds one or two iron(III) ions, i.e. ferric iron, Fe3+; transferrin is essential if stored iron is to be moved and used.Most of the time, about 30% of the available sites on the transferrin molecule are filled. The test for serum iron uses blood drawn from veins to measure the iron molecules that are bound to transferrin, and circulating in the blood.

Total iron-binding capacity (TIBC) is a medical laboratory test that measures the blood's capacity to bind iron with transferrin.[1] It is performed by drawing blood and measuring the maximum amount of iron that it can carry, which indirectly measures transferrin[2] since transferrin is the most dynamic carrier. TIBC is less expensive than a direct measurement of transferrin.[

LAB RESULT

MANAGEMENT CARE

Treatment for thalassemia depends on which type you have and how severe it is. Treatments for mild thalassemiaSigns and symptoms are usually mild with thalassemia minor and little, if any, treatment is needed. Occasionally, you may need a blood transfusion, particularly after surgery, after having a baby or to help manage thalassemia complications.Some people with beta-thalassemia intermedia may need treatment for iron overload. Although most people with this condition don't need the blood transfusions that often cause iron overload, people with beta-thalassemia intermedia may have increased digestive absorption of iron, leading to an excess of iron. An oral medication called deferasirox (Exjade) can help remove the excess iron.

Treatments for moderate to severe thalassemiaTreatments for moderate to severe thalassemia may include: Frequent blood transfusions. More-severe forms of thalassemia often require frequent blood transfusions, possibly every few weeks. Over time, blood transfusions cause a buildup of iron in your blood, which can damage your heart, liver and other organs. To help your body get rid of the extra iron, you may need to take medications that rid your body of extra iron.

Stem cell transplant. Also called a bone marrow transplant, a stem cell transplant may be used to treat severe thalassemia in select cases. Prior to a stem cell transplant, you receive very high doses of drugs or radiation to destroy your diseased bone marrow. Then you receive infusions of stem cells from a compatible donor. However, because these procedures have serious risks, including death, they're generally reserved for people with the most severe disease who have a well-matched donor available usually a sibling. Lifestyle and home remediesIf you have thalassemia, be sure to: Avoid excess iron. Unless your doctor recommends it, don't take vitamins or other supplements that contain iron. Eat a healthy diet. Eating a balanced diet that contains plenty of nutritious foods can help you feel better and boost your energy. Your doctor also may recommend you take a folic acid supplement to help your body make new red blood cells. Also, to keep your bones healthy, make sure your diet contains adequate calcium and vitamin D. Ask your doctor what the right amounts are for you and whether you need to take a supplement. Avoid infections. Protect yourself from infections with frequent hand-washing and by avoiding sick people. This is especially important if you've had to have your spleen removed. You'll also need an annual flu shot, as well as the meningitis, pneumococcal and hepatitis B vaccines to prevent infections. If you develop a fever or other signs and symptoms of an infection, see your doctor for treatment

http://www.medicalnewstoday.com/articles/263489.php

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