Rabu, 08 Juli 2009

THALASEMIA

THALASEMIA

DEFINISI
Thalassemia adalah sekelompok penyakit keturunan yang merupakan akibat dari ketidakseimbangan pembuatan salah satu dari keempat rantai asam amino yang membentuk hemoglobin.

PENYEBAB
Ketidakseimbangan dalam rantai protein globin alfa dan beta, yang diperlukan dalam pembentukan hemoglobin, disebabkan oleh sebuah gen cacat yang diturunkan.
Untuk menderita penyakit ini, seseorang harus memiliki 2 gen dari kedua orang tuanya.
Jika hanya 1 gen yang diturunkan, maka orang tersebut hanya menjadi pembawa tetapi tidak menunjukkan gejala-gejala dari penyakit ini.
Thalasemia digolongkan bedasarkan rantai asam amino yang terkena.
2 jenis yang utama adalah Alfa-thalassemia (melibatkan rantai alfa) dan Beta-thalassemia (melibatkan rantai beta).
Thalassemia juga digolongkan berdasarkan apakah seseorang memiliki 1 gen cacat (Thalassemia minor) atau 2 gen cacat (Thalassemia mayor).
Alfa-thalassemia paling sering ditemukan pada orang kulit hitam (25% minimal membawa 1 gen), dan beta-thalassemia pada orang di daerah Mediterania dan Asia Tenggara.
1 gen untuk beta-thalassemia menyebabkan anemia ringan sampai sedang tanpa menimbulkan gejala; 2 gen menyebabkan anemia berat disertai gejala-gejala.
Sekitar 10% orang yang memiliki paling tidak 1 gen untuk alfa-thalassemia juga menderita anemia ringan.

GEJALA
Semua thalassemia memiliki gejala yang mirip, tetapi beratnya bervariasi.
Sebagian besar penderita mengalami anemia yang ringan.
Pada bentuk yang lebih berat, misalnya beta-thalassemia mayor, bisa terjadi sakit kuning (jaundice), luka terbuka di kulit (ulkus, borok), batu empedu dan pembesaran limpa.
Sumsum tulang yang terlalu aktif bisa menyebabkan penebalan dan pembesaran tulang, terutama tulang kepala dan wajah.
Tulang-tulang panjang menjadi lemah dan mudah patah.
Anak-anak yang menderita thalassemia akan tumbuh lebih lambat dan mencapai masa pubertas lebih lambat dibandingkan anak lainnya yang normal.
Karena penyerapan zat besi meningkat dan seringnya menjalani transfusi, maka kelebihan zat besi bisa terkumpul dan mengendap dalam otot jantung, yang pada akhirnya bisa menyebabkan gagal jantung.

DIAGNOSA
Thalassemia lebih sulit didiagnosis dibandingkan penyakit hemoglobin lainnya.
Hitung jenis darah komplit menunjukkan adanya anemia dan rendahnya MCV (mean corpuscular volume). Elektroforesa bisa membantu, tetapi tidak pasti, terutama untuk alfa-thalassemia. Karena itu diagnosis biasanya berdasarkan kepada pola herediter dan pemeriksaan hemoglobin khusus.
Pada thalassemia yang berat diperlukan transfusi darah rutin dan pemberian tambahan asam folat. Penderita yang menjalani transfusi, harus menghindari tambahan zat besi dan obat-obat yang bersifat oksidatif (misalnya sulfonamid), karena zat besi yang berlebihan bisa menyebabkan keracunan.

PENGOBATAN
Pada bentuk yang sangat berat, mungkin diperlukan pencangkokan sumsum tulang.
Terapi genetik masih dalam tahap penelitian.

PENCEGAHAN
Pada keluarga dengan riwayat thalassemia perlu dilakukan penyuluhan genetik untuk menentukan resiko memiliki anak yang menderita thalassemia.
www.medicastore.com/med/detail_pyk.php?idktg=12&
Thalassemia is an inherited blood disorder that causes mild or severe anemia (uh-NEE-me-uh). The anemia is due to reduced hemoglobin (HEE-muh-glow-bin) and fewer red blood cells than normal. Hemoglobin is the protein in red blood cells that carries oxygen to all parts of the body.
In people with thalassemia, the genes that code for hemoglobin are missing or variant (different than the normal genes). Severe forms of thalassemia are usually diagnosed in early childhood and are lifelong conditions.
The two main types of thalassemia, alpha and beta, are named for the two protein chains that make up normal hemoglobin. The genes for each type of thalassemia are passed from parents to their children. Alpha and beta thalassemias have both mild and severe forms.
Alpha thalassemia occurs when one or more of the four genes needed for making the alpha globin chain of hemoglobin are variant or missing. Moderate to severe anemia results when more than two genes are affected. The most severe form of alpha thalassemia is known as alpha thalassemia major. It can result in miscarriage.
Beta thalassemia occurs when one or both of the two genes needed for making the beta globin chain of hemoglobin are variant. The severity of illness depends on whether one or both genes are affected and the nature of the abnormality. If both genes are affected, anemia can range from moderate to severe. The severe form of beta thalassemia is also known as Cooley’s anemia. Cooley’s anemia is the most common severe form of thalassemia in the United States.www.medicastore.com/med/detail_pyk.php?idktg=12&
Ahttp://www.nhlbi.nih.gov/health/dci/Diseases/Thalassemia/Thalassemia_WhatIs.h Basic Description

Thalassemia is the name of a group of genetic blood disorders. To understand how thalassemia affects the human body, you must first understand a little about how blood is made.

Hemoglobin is the oxygen-carrying component of the red blood cells. It consists of two different proteins, an alpha and a beta. If the body doesn't produce enough of either of these two proteins, the red blood cells do not form properly and cannot carry sufficient oxygen. The result is anemia that begins in early childhood and lasts throughout life.

Since thalassemia is not a single disorder but a group of related disorders that affect the human body in similar ways, it is important to understand the differences between the various types of thalassemia.


Alpha Thalassemia

People whose hemoglobin does not produce enough alpha protein have alpha thalassemia. It is commonly found in Africa, the Middle East, India, Southeast Asia, southern China, and occasionally the Mediterranean region.

There are four types of alpha thalassemia that range from mild to severe in their effect on the body.

Silent Carrier State. This condition generally causes no health problems because the lack of alpha protein is so small that the hemoglobin functions normally. It is called "silent carrier" because of how difficult it is to detect. Silent carrier state is "diagnosed" by deduction when an apparently normal individual has a child with hemoglobin H disease or alpha thalassemia trait.

Hemoglobin Constant Spring. This is an unusual form of Silent Carrier state that is caused by a mutation of the alpha globin. It is called Constant Spring after the region of Jamaica in which it was discovered. As in silent carrier state, an individual with this condition usually experiences no related health problems.

Alpha Thalassemia Trait or Mild Alpha Thalassemia. In this condition, the lack of alpha protein is somewhat greater. Patients with this condition have smaller red blood cells and a mild anemia, although many patients do not experience symptoms. However, physicians often mistake mild alpha thalassemia for iron deficiency anemia and prescribe iron supplements that have no effect on the anemia.

Hemoglobin H Disease. In this condition, the lack of alpha protein is great enough to cause severe anemia and serious health problems such as an enlarged spleen, bone deformities and fatigue. It is named for the abnormal hemoglobin H (created by the remaining beta globin) that destroys red blood cells.

Hemoglobin H-Constant Spring. This condition is more severe than hemoglobin H disease. Individuals with this condition tend to have a more severe anemia and suffer more frequently from enlargement of the spleen and viral infections.

Homozygous Constant Spring. This condition is a variation of hemoglobin H-Constant Spring that occurs when two Constant Spring carriers pass their genes on to their child (as opposed to hemoglobin H Constant Spring, in which one parent is a Constant Spring Carrier and the other a carrier of alpha thalassemia trait). This condition is generally less severe than hemoglobin H Constant Spring and more similar to hemoglobin H disease.

Hydrops Fetalis or Alpha Thalassemia Major. In this condition, there are no alpha genes in the individual's DNA, which causes the gamma globins produced by the fetus to form an abnormal hemoglobin called hemoglobin Barts. Most individuals with this condition die before or shortly after birth. In some extremely rare cases where the condition is discovered before birth, in utero blood transfusions have allowed the birth of children with hydrops fetalis who then require lifelong blood transfusions and medical care.


Beta Thalassemia

People whose hemoglobin does not produce enough beta protein have beta thalassemia. It is found in people of Mediterranean descent, such as Italians and Greeks, and is also found in the Arabian Peninsula, Iran, Africa, Southeast Asia and southern China.

There are three types of beta thalassemia that also range from mild to severe in their effect on the body.

Thalassemia Minor or Thalassemia Trait. In this condition, the lack of beta protein is not great enough to cause problems in the normal functioning of the hemoglobin. A person with this condition simply carries the genetic trait for thalassemia and will usually experience no health problems other than a possible mild anemia. As in mild alpha thalassemia, physicians often mistake the small red blood cells of the person with beta thalassemia minor as a sign of iron-deficiency anemia and incorrectly prescribe iron supplements.

Thalassemia Intermedia. In this condition the lack of beta protein in the hemoglobin is great enough to cause a moderately severe anemia and significant health problems, including bone deformities and enlargement of the spleen. However, there is a wide range in the clinical severity of this condition, and the borderline between thalassemia intermedia and the most severe form, thalassemia major, can be confusing. The deciding factor seems to be the amount of blood transfusions required by the patient. The more dependent the patient is on blood transfusions, the more likely he or she is to be classified as thalassemia major. Generally speaking, patients with thalassemia intermedia need blood transfusions to improve their quality of life, but not in order to survive.

Thalassemia Major or Cooley's Anemia. This is the most severe form of beta thalassemia in which the complete lack of beta protein in the hemoglobin causes a life-threatening anemia that requires regular blood transfusions and extensive ongoing medical care. These extensive, lifelong blood transfusions lead to iron-overload which must be treated with chelation therapy to prevent early death from organ failure.


Other Forms of Thalassemia

In addition to the alpha and beta thalassemias, there are other related disorders that occur when the gene for alpha or beta thalassemia combines with an abnormal or mutant gene.

E Beta Thalassemia. Hemoglobin E is one of the most common abnormal hemoglobins. It is usually found in people of Southeast Asian ancestry, such as Cambodians, Vietnamese and Thai. When combined with beta thalassemia, hemoglobin E produces E beta thalassemia, a moderately severe anemia which is similar in symptoms to beta thalassemia intermedia.

Sickle Beta Thalassemia. This condition is caused by a combination of beta thalassemia and hemoglobin S, the abnormal hemoglobin found in people with sickle cell disease. It is commonly found in people of Mediterranean ancestry, such as Italians, Greeks and Turks. The condition varies according to the amount of normal beta globin produced by the beta gene. When no beta globin is produced by the beta gene, the condition is almost identical with sickle cell disease. The more beta globin produced by the beta gene, the less severe the condition.


Treatment of Thalassemia

Blood Transfusions

The most common treatment for all major forms of thalassemia is red blood cell transfusions. These transfusions are necessary to provide the patient with a temporary supply of healthy red blood cells with normal hemoglobin capable of carrying the oxygen that the patient's body needs.

While thalassemia patients were given infrequent transfusions in the past, clinical research led to a more frequent program of regular blood cell transfusions that has greatly improved the patients' quality of life. Today, most patients with a major form of thalassemia receive red blood cell transfusions every two to three weeks, amounting to as much as 52 pints of blood a year.

Iron Overload

Because there is no natural way for the body to eliminate iron, the iron in the transfused blood cells builds up in a condition known as "iron overload" and becomes toxic to tissues and organs, particularly the liver and heart. Iron overload typically results in the patient's early death from organ failure.

Chelation Therapy

To help remove excess iron, patients undergo "iron chelation therapy," in which a drug is introduce dinto the body which binds with excess iron and removes it through the urine or stool. For many years, the only FDA-approved iron chelator was Desferal, which has to be administered through a painful and difficult infusion process. When using Desferal, a needle is attached to a small battery-operated infusion pump and worn under the skin of the stomach or legs five to seven times a week for up to twelve hours.

In November 2005, the FDA approved an oral chelator, Exjade. This is a pill which is dissolved in water or juice and drunk, once a day. Many patients now have an option in terms of chelators, and it is hoped that more options will become available in the coming years.

The Compliance Problem

Compliance with chelation therapy is vital to the thalassemia patient's long term survival. However, many patients find the administration of Desferal so difficult that they do not keep up with it or abandon treatment altogether. If they do not have access to another chelating option, this is extremely dangerous. Lack of compliance with chelation therapy leads to accelerated health problems and early death.
http://www.thalassemia.org/sections.php?sec=1


Thalassemia

Thalassemia is a general name for a group of inherited blood diseases. They involve abnormalities in hemoglobin, the oxygen-carrying part of the red blood cells. Hemoglobin is mainly made up of two kinds of protein, called alpha and beta globin. Individuals with thalassemia do not produce enough of one (or occasionally both) of these proteins. As a result, their red blood cells may be abnormal and unable to carry enough oxygen throughout the body.
The two main types of thalassemia are called alpha and beta thalassemia. Individuals with alpha thalassemia do not produce enough alpha globin, and those with beta thalassemia lack sufficient beta globin. There are a number of different forms of alpha and beta thalassemias, with symptoms ranging from mild to severe.
Thalassemia is among the most common inherited disorders caused by a single abnormal gene. More than 100,000 babies worldwide are born each year with severe forms of thalassemia, according to the National Academy of Sciences (1). Thalassemia occurs most frequently in people of Italian, Greek, Middle Eastern, Southern Asian and African ancestry.
What is alpha thalassemia?
There are at least five main types of alpha thalassemia. These are most common in people of Southeast Asian, Indian, southern Chinese, Middle Eastern, and African ancestry (2). There are four genes that control the production of alpha globin. The severity of the condition is determined by how many of these genes are missing or abnormal.
● Silent carrier, the mildest form, has one alpha globin gene missing or abnormal. Affected individuals generally have no symptoms, but they can pass on the genetic abnormality to their children.
● Alpha thalassemia minor, in which two alpha globin genes are missing or abnormal, usually does not cause major health problems. However, affected individuals may have mild anemia and can pass the condition on to their children.
● Hemoglobin H disease is caused by having only one normal alpha globin gene. The condition results in abnormalities in the red blood cells and rapid destruction of these cells. Most affected individuals have mild to moderate anemia and can live fairly normal lives. The anemia may temporarily worsen when the individual has a viral infection or when they are treated with certain medications (such as sulfa drugs) (3). Some affected individuals eventually develop complications, such as an enlarged spleen and gallstones (3). Individuals with hemoglobin H disease should receive regular medical care to detect and treat these complications. Some may need occasional blood transfusions (4).
● Hemoglobin H-Constant Spring is a more severe form of hemoglobin H disease. Affected individuals have one normal alpha globin gene, plus one abnormal one that carries a specific mutation (change) called Constant Spring. Those with this condition generally have moderate to severe anemia and often develop complications, such as an enlarged spleen. Some need blood transfusions from time to time, such as when they develop an illness with a fever, while others need more frequent transfusions (3, 4).
● Alpha thalassemia major, the most severe form, results from having no genes for the production of alpha globin. Affected fetuses suffer from severe anemia, heart failure and fluid buildup. They usually are stillborn, but some die in the first hours after birth. In rare cases, babies diagnosed and treated before birth with blood transfusions have survived. These babies require lifelong blood transfusions (4).
What is beta thalassemia?
There are three main forms of beta thalassemia, which range from having no effect on health to having severe health effects. These are most likely to affect people of Greek, Italian, Middle Eastern, Southeast Asian, southern Chinese and African descent (2). Two genes control the production of beta globin, and mutations (changes) on one or both of them can cause the disorder.
● Thalassemia minor (also called thalassemia trait) usually causes no symptoms, but mild anemia and other changes in the blood do occur.
● Thalassemia intermedia usually results in a mild to moderate anemia, though severity varies greatly (5). Affected children may develop some of the complications seen in thalassemia major, including poor growth and bone abnormalities (including fractures). Many affected individuals require occasional or more frequent blood transfusions to reduce complications (2, 5)
● Thalassemia major is the most severe form. It also is called Cooley's anemia, named after the doctor who first described it in 1925. Most affected children appear healthy at birth. However, during the first year or two of life, they become pale and fussy and have a poor appetite. They grow slowly and often develop jaundice (yellowing of the eyes and skin). Without treatment, they develop an enlarged spleen and liver, thinning bones that break easily, abnormal facial bones, frequent infections, and heart problems, and they die in the first decade of life. Affected children require regular blood transfusions beginning in infancy, which allows normal growth and development (5).
Other forms of thalassemia related to beta thalassemia are E-beta thalassemia and Hb S/beta thalassemia. E-beta thalassemia is most common in people from Cambodia, Vietnam, Thailand and Laos (4). Individuals with E-beta thalassemia produce a variant form of hemoglobin called hemoglobin E. Individuals who produce hemoglobin E generally are healthy or have only a mild anemia, unless they also have a form of beta thalassemia. They are then said to have E-beta thalassemia. This condition results in mild to severe anemia. Some affected individuals have symptoms resembling beta thalassemia intermedia, while others have more severe symptoms resembling beta thalassemia major (4).
Individuals with Hb S/beta thalassemia inherit one gene for beta thalassemia and one gene for sickle cell disease, another inherited anemia. Symptoms generally resemble those of sickle cell disease, including varying degrees of anemia, serious infections, pain and damage to vital organs. Often, symptoms are milder than for sickle cell disease, though severity varies.

What is the treatment for thalassemia?
Blood transfusions are used to treat severe forms of thalassemia. Children and adults with beta thalassemia major require regular transfusions. Some individuals with beta thalassemia intermedia, E-beta thalassemia, and hemoglobin H-Constant Spring require tranfusions from time to time, or sometimes more frequently. Some may need a transfusion if they develop a viral illness or other infection, which may cause anemia to become more severe. More frequent transfusions may be recommended if these individuals develop complications.
Children with severe thalassemia, such as beta thalassemia major, generally receive a transfusion every 2 to 3 weeks (2). Regular transfusions help keep hemoglobin levels near normal and help prevent many of the complications of thalassemia. This treatment improves the child's growth and well-being and usually prevents heart failure and bone deformities.
Unfortunately, repeated blood transfusions lead to a buildup of iron in the body. Iron buildup can damage the heart, liver and other organs. To help prevent organ damage, children and adults who receive regular transfusions are treated with a type of drug called an iron chelator. This drug binds to iron and helps the body get rid of excess iron.
Until recently, the only drug approved in the United States to prevent iron buildup was deferoxamine (Desferal or DFO). Individuals usually receive this drug over 6 to 8 hours, often while they are sleeping, five to seven nights a week. The drug is delivered by a pump under the skin (2). In November 2005, the U.S. Food and Drug Administration (FDA) approved the first oral iron chelating drug (Exjade or deferasirox) (6). This oral drug, used alone or in combination with deferoxamine, may simplify treatment for affected children and adults.
Individuals with beta thalassemia major who are treated with regular blood transfusions and iron chelation often live 40 years or longer (1). The most common cause of death in these individuals is heart complications caused by iron buildup (1).
Children and adults with thalassemia must undergo tests to measure the level of iron in their bodies. Blood tests are used to measure the amount of iron in the blood. Unfortunately, blood tests are not very accurate in measuring the levels of iron in the heart and liver. Doctors may recommend a yearly liver biopsy, a surgical procedure in which a small amount of liver tissue is removed and tested. A few medical centers have begun to use new noninvasive imaging tests called SQUID and T2* to measure iron levels in the liver and heart (1, 2, 5). For more information on where these tests are available, contact the Cooley's Anemia Foundation
Some children with thalassemia can be cured with a bone marrow transplant. However, this form of treatment is most successful when a donor who is an exact genetic match is available (2, 7). Generally, a sibling or other family member is most likely to be an exact match. The procedure can cure about 80 percent of children who have a fully matched family donor (7). However, only about 20 to 30 percent of children with thalassemia have a family member who is a suitable donor (7). The procedure is risky and can result in death. Scientists are evaluating whether a transplant using umbilical cord blood (which, like bone marrow, contains unspecialized cells called stem cells that produce all other blood cells) from a newborn sibling may be as effective as a bone marrow transplant, while posing fewer risks.
How is the disease transmitted?
All forms of thalassemia are inherited. The disease cannot be caught from another person who has it. Thalassemia is passed on through parents who carry the thalassemia genes in their cells.
When both parents carry alpha thalassemia genes, any child that they have is at risk for inheriting a more severe form of this condition. Individuals who know they have one of these disorders, those with family histories of these disorders, and those from countries where they are common should consider consulting a genetic counselor to find out whether their children could be at risk. (Health care providers can provide referrals to genetic counselors, or individuals can find them by contacting a major medical center.)
When two individuals with beta thalassemia trait have children together, there is a 25 percent chance (1 in 4) that any child they have will inherit a thalassemia gene from each parent and have a severe form of the disease. There is a 50 percent (2 in 4) chance that the child will inherit one of each kind of gene and have the trait like its parents; and a 25 percent (1 in 4) chance that the child will inherit two normal genes and be completely free of the disease. The odds are the same for each pregnancy when both parents have the beta thalassemia trait.
Women with milder forms of thalassemia usually have healthy pregnancies. Until recently, pregnancy was rare in women with beta thalassemia major. Several recent studies suggest that pregnancy appears safe for a woman with well-treated beta thalassemia major who does not have heart problems (8). As long as her partner does not carry a gene for thalassemia, her children will not be at risk for thalassemia, although all will be carriers (thalassemia minor).
Is there a test for thalassemia?
Yes. Blood tests and family genetic studies can show whether an individual has any form of thalassemia or thalassemia trait. Newborn screening tests now identify many babies with thalassemia. In addition, prenatal testing using chorionic villus sampling (CVS) or amniocentesis can detect or rule out thalassemia in the fetus. Researchers are seeking to develop noninvasive prenatal tests the look at fetal DNA (genetic material) in the mother's blood.
What research on thalassemia is taking place?
Scientists are working on better ways to remove excess iron from the body to prevent or delay iron overload. They are developing and testing new oral iron-chelating drugs and looking at whether combining one of these drugs with deferoxamine may be more effective than either treatment alone (1, 5).
Researchers are studying the effectiveness of certain drugs (including hydroxyurea, a drug used to treat another inherited anemia called sickle cell disease) in reactivating the patient's genes for fetal hemoglobin. All humans produce a fetal form of hemoglobin before birth. After birth, natural genetic switches "turn off" production of fetal hemoglobin and "turn on" production of adult hemoglobin. Scientists are seeking ways to activate these genetic switches so that they can make the blood cells of patients with beta thalassemia produce more fetal hemoglobin to make up for their deficiency of adult hemoglobin. Studies to date suggest that treatment with these drugs may be helpful for some patients with beta thalassemia intermedia (1).
Researchers also are exploring the possibility that dietary treatments, such as with vitamin E, may help reduce organ damage from iron buildup (4, 5). Others continue to improve bone marrow transplantation methods that may offer a cure to more children with thalassemia.
March of Dimes grantees have been among the many scientists seeking to develop an effective form of gene therapy that may offer a cure for thalassemia. Gene therapy may involve inserting a normal alpha or beta globin gene into the patient's stem cells, possibly allowing these immature blood cells to produce normal red blood cells.
http://www.marchofdimes.com/pnhec/4439_1229.asp
Thalasemia
BATASAN
Thalassemia adalah suatu kelompok anemia hemolitik kongenital herediter yang diturunkan secara autosomal, disebabkan oleh kekurangan sintesis rantai polipeptid yang menyusun molekul globin dalam hemoglobin.
PATOFISIOLOGI
Molekul globin terdiri atas sepasang rantai-a dan sepasang rantai lain yang menentukan jenis Hb. Pada orang normal terdapat 3 jenis Hb, yaitu Hb A (merupakan > 96% dari Hb total, tersusun dari 2 rantai-a dan 2 rantai-b = a2b2), Hb F(< 2% = a2g2) dan HbA2 (< 3% = a2d2). Kelainan produksi dapat terjadi pada ranta-a (a-thalassemia), rantai-b (b-thalassemia), rantai-g (g-thalassemia), rantai-d (d-thalassemia), maupun kombinasi kelainan rantai-d dan rantai-b (bd-thalassemia).
Pada thalassemia-b, kekurangan produksi rantai beta menyebabkan kekurangan pembentukan a2b2 (Hb A); kelebihan rantai-a akan berikatan dengan rantai-g yang secara kompensatoir Hb F meningkat; sisanya dalam jumlah besar diendapkan pada membran eritrosit sebagai Heinz bodies dengan akibat eritrosit mudah rusak (ineffective erythropoesis).
EPIDEMIOLOGI
Frekuensi gen thalassemia di Indonesia berkisar 3-10%. Berdasarkan angka ini, diperkirakan lebih 2000 penderita baru dilahirkan setiap tahunnya di Indonesia.
DIAGNOSIS
I. Anamnesis
● Keluhan timbul karena anemia: pucat, gangguan nafsu makan, gangguan tumbuh kembang dan perut membesar karena pembesaran lien dan hati. Pada umumnya keluh kesah ini mulai timbul pada usia 6 bulan.
II. Pemeriksaan fisis
● Pucat
● Bentuk muka mongoloid (facies Cooley)
● Dapat ditemukan ikterus
● Gangguan pertumbuhan
● Splenomegali dan hepatomegali yang menyebabkan perut membesar
III. Pemeriksaan penunjang
1. Darah tepi :
● Hb rendah dapat sampai 2-3 g%
● Gambaran morfologi eritrosit : mikrositik hipokromik, sel target, anisositosis berat dengan makroovalositosis, mikrosferosit, polikromasi, basophilic stippling, benda Howell-Jolly, poikilositosis dan sel target. Gambaran ini lebih kurang khas.
● Retikulosit meningkat.
2. Sumsum tulang (tidak menentukan diagnosis) :
● Hiperplasi sistem eritropoesis dengan normoblas terbanyak dari jenis asidofil.
● Granula Fe (dengan pengecatan Prussian biru) meningkat.
3. Pemeriksaan khusus :
● Hb F meningkat : 20%-90% Hb total
● Elektroforesis Hb : hemoglobinopati lain dan mengukur kadar Hb F.
● Pemeriksaan pedigree: kedua orangtua pasien thalassemia mayor merupakan trait (carrier) dengan Hb A2 meningkat (> 3,5% dari Hb total).
4. Pemeriksaan lain :
● Foto Ro tulang kepala : gambaran hair on end, korteks menipis, diploe melebar dengan trabekula tegak lurus pada korteks.
● Foto tulang pipih dan ujung tulang panjang : perluasan sumsum tulang sehingga trabekula tampak jelas.
DIAGNOSIS BANDING
Thalasemia minor :
● anemia kurang besi
● anemia karena infeksi menahun
● anemia pada keracunan timah hitam (Pb)
● anemia sideroblastik
PENATALAKSANAAN
I. Medikamentosa
● Pemberian iron chelating agent (desferoxamine): diberikan setelah kadar feritin serum sudah mencapai 1000 mg/l atau saturasi transferin lebih 50%, atau sekitar 10-20 kali transfusi darah. Desferoxamine, dosis 25-50 mg/kg berat badan/hari subkutan melalui pompa infus dalam waktu 8-12 jam dengan minimal selama 5 hari berturut setiap selesai transfusi darah.
● Vitamin C 100-250 mg/hari selama pemberian kelasi besi, untuk meningkatkan efek kelasi besi.
● Asam folat 2-5 mg/hari untuk memenuhi kebutuhan yang meningkat.
● Vitamin E 200-400 IU setiap hari sebagai antioksidan dapat memperpanjang umur sel darah merah.
II. Bedah
Splenektomi, dengan indikasi:
● limpa yang terlalu besar, sehingga membatasi gerak penderita, menimbulkan peningkatan tekanan intraabdominal dan bahaya terjadinya ruptur
● hipersplenisme ditandai dengan peningkatan kebutuhan transfusi darah atau kebutuhan suspensi eritrosit (PRC) melebihi 250 ml/kg berat badan dalam satu tahun.
III.Suportif
Transfusi darah :
Hb penderita dipertahankan antara 8 g/dl sampai 9,5 g/dl. Dengan kedaan ini akan memberikan supresi sumsum tualang yang adekuat, menurunkan tingkat akumulasi besi, dan dapat mempertahankan pertumbuhan dan perkembangan penderita. Pemberian darah dalam bentuk PRC (packed red cell), 3 ml/kg BB untuk setiap kenaikan Hb 1 g/dl.
IV.Lain-lain (rujukan subspesialis, rujukan spesialisasi lainnya dll)
Tumbuh kembang, kardiologi, Gizi, endokrinologi, radiologi, Gigi
PEMANTAUAN
I. Terapi
● Pemeriksaan kadar feritin setiap 1-3 bulan, karena kecenderungan kelebihan besi sebagai akibat absorbsi besi meningkat dan transfusi darah berulang.
● Efek samping kelasi besi yang dipantau: demam, sakit perut, sakit kepala, gatal, sukar bernapas. Bila hal ini terjadi kelasi besi dihentikan.
II.Tumbuh Kembang
Anemia kronis memberikan dampak pada proses tumbuh kembang, karenanya diperlukan perhatian dan pemantauan tumbuh kembang penderita.
III. Gangguan jantung, hepar dan endokrin
Anemia kronis dan kelebihan zat besi dapat menimbulkan gangguan fungsi jantung (gagal jantung), hepar (gagal hepar), gangguan endokrin (diabetes melitus, hipoparatiroid) dan fraktur patologis.

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