THALASSEMIA

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Acah Wulandari
Jen Retno Utaminingsih
Nina Nirmala
Panji Wuryanto
Risma Anggriani
Samsul Arifin
Siti Bunamah
Wiwit Handayani

PRODI D-III ANALIS KESEHATAN

UNIVERSITAS MH. THAMRIN
JAKARTA

CONTENTS

Definition .. 1
History ... 2
Prevalence Data .... 3
Mechanism Of Disease . 4
Symptoms .. 5
Method And Equipment ... 6
Lab Result .. 7
Management Care 8
Conclusion 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), abnormallyshaped 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 pediatricians Cooley and Lee described
a disease, named Cooley's anaemia, in children of Italian and Greek immigrants, today
known as thalassemia major or Mediterranean anaemia. At about the same time, in
Italy, Rietti described 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 Silvestroni and Ida 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 a sick 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 DATA
Deputy 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 Lutfia
By webadmin on 07:20 pm Jun 05, 2012

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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 Thalassemias
You 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+ + O2
Fe2+ + H2O2 Fe3+ + OH+ OHOO
O2+ 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 and 100 mg >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 Symptoms

People 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 Thalassemias
Better 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 Diseases

Regular 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.

Infection

Among 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.

Osteoporosis

Many people who have thalassemias have bone problems, including osteoporosis (OS-te-opo-RO-sis). This is a condition in which bones are weak and brittle and break easily.

METHOD
EQUIPMENT

AND

1. Screening of thalassemia
Following 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 ferritin
Serum 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 betathalassemia/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 betathalassemia/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 thalassemia
Signs 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 thalassemia

Treatments 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 remedies

If 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

http://www.thirdage.com/hc/c/what-is-thalassemia
http://www.medicalnewstoday.com/articles/263489.php
http://www.thejakartaglobe.com/archive/indonesia-at-high-risk-of-genetic-diseasethat-can-lead-to-anemia-health-official/
http://emedicine.medscape.com/article/959122
http://www.mayoclinic.org/diseases-conditions/thalassemia/basics/copingsupport/con-20030316