An indepth look at Thalassaemia

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( Started by caraiti on: July 22, 2008, 05:48:51 PM)

I have understood how thalassaemia affects my body but I don't yet understand how it affects me as a person, and the effect it has had on my body.
 Well, every person and every family is unique, and is affected by thalassaemia, reacts to it, and deals with it in unique ways. However, we do know a few things about individual and family development, that could help you understand matters a little better. We must start by talking a little about what possibly happened to you and your family when your thalassaemia was diagnosed.
 When two people decide to get married, they start out with the idea that they want to be with each other through good times and bad times. Of course, no one knows beforehand what these good times and bad times are going to be, but both partners believe that together they can work things through. The last thing they imagine is that when they decide to have a child, their child will be born with a chronic illness because they are carriers.
 In the beginning of their marriage the partners try to settle their ways of being with each other. They negotiate their differences, and establish common ways of being together. Some couples have difficulty in resolving disagreements and conflicts from the start. Sooner or later most couples decide to have children. They hope that this will help strengthen their mutual commitment, but of course most people do not know how the presence of children in their life will change them, or their relationship with their partner. When a child is born, it usually takes the couple some time to renegotiate their relationship and to fully adjust to the presence of a new family member.
The diagnosis of thalassaemia usually comes at an early and crucial time in the life of both the child and the couple.
Usually the parents do not even know what thalassaemia is. The result is normal and to be expected: the parents are shocked, disheartened and disappointed. They are in a state of despair because they do not know how to cope with such an unforseeable and tragic event in their life, and the life of their child. Often the presence of the illness brings the parents closer together, to help each other deal with the common misfortune in their life. However, it can push them apart, if the mother becomes completely preoccupied with the ill child, and leaves her partner and any other children further out from her consideration. No matter how each family, each mother, father, brother and sister deal with this unexpected event, it is obviously not an easy task. Parents need to be informed and understand what thalassaemia is. They need a lot of support and encouragement to learn how to deal with it in the most effective way, and in a way which will cause the least problems to their child. That is why help from a psychologist could be very useful at this time of crisis.

But how does thalassaemia affect my psychological development?
It can have a profound effect in your psychological development, both in childhood and in adult life. Erik Erikson, a prominent psychologist, has described how all human beings go through eight stages in life. Each stage has a positive, or desirable outcome, and a negative, or undesirable outcome. Whether the outcome of each stage will be positive and growth enhancing or not, depends on thousands of factors. The presence of thalassaemia can have an effect at every one of these stages.

What effect do you think thalassaemia has on childhood development?
There are four big steps in psychological development in childhood. Developingtrust, autonomy, initiative and industry. Let us look at each of these in turn, and the way thalassaemia can affect it.
    Year 1. The first thing we are called upon to learn in this life is how to TRUST. As infants we cannot survive on our own. We are completely dependent on the person who takes care of us. We hope and wish that this person (usually our mother) has the best possible intentions, but we can learn to trust her only by experiencing her consistent caring and affection. Her willingness and eagerness to be there for us is of utmost importance, especially during the first year of life.
The diagnosis of thalassaemia during this first year of life makes things more complicated both for the child and the parents. Parents are passing through a time of grieving and shock, and often they do not know how to deal with their infant. They feel guilty and they feel responsible. Often they also resent this sudden misfortune. This change in the parents, and in their behavior towards the child, combined with the beginning of painful treatments can make it very difficult for the young child to develop trust in other people. The child has no way of understanding what has suddenly happened, what it is that has changed its life so dramatically. The child feels the difference but has no way of explaining or understanding it. Although the child is far too young to understand the idea of a chronic hereditary disease, he/she is exceptionally capable of sensing when they are being really loved, and treated with honesty.
    Year 2. In order to become a mature, competent and independent adult a person needs to start developing a basic sense of AUTONOMY from the time when they enter toddlerhood. The so called "terrible two's is a difficult time for the parents (less of course than adolescence) because the child begins to say no and to have its own opinion. In addition the child begins to move around on its own. It can now move away and towards its mother and other people, and start exploring the world. If this newly developed autonomy and curiosity is thwarted by overprotective and fearful parents, the child develops shame, and doubt in its desires and abilities. Very often other people, as well as parents and medical professionals believe that a child who is ill is weak, vulnerable and in more need of protection and constant surveillance. However this attitude communicates the idea to the child that it is an inferior and less capable being. The fear that something may happen to the child or that the child will not be capable of making it on its own interferes with the development of autonomy. The autonomy of the child with thalassaemia is thwarted not only by the parents, but also by the medical treatments which increase dependence on the presence of adults and helplessness in their absence. This includes parents and doctors as well as blood donors. Thus, issues of autonomy, dependence, independence and trust in oneself and others are more complex, and more difficult to resolve, than they are for children without thalassaemia.
    Years 3 to 5-6. In the next stage the child begins to initiate its own activities, like playing with other children communicating with adults, etc. The development of INITIATIVE is important in order for the child to be prepared for school.
Fear, overprotectiveness, and the limiting factors of medical treatments (including Desferal treatment which usually begins about this time) may make the young child with thalassaemia feel doubtful of its abilities and guilty for attempting to do its own thing. It is very important for parents and health care providers to allow thalassaemic children to express themselves, and to participate in all activities appropriate for their age. Their physical disability must not be extended into an emotional or mental handicap, which does not exist.
    Years 6-7 to 12-13. When the child enters school the parents must deal with another important concern; presenting their child to the world. All parents are concerned about how their child will do at school. Whether the child is bright enough, competent enough, admirable enough, etc.

How will the teachers and the other children accept and judge the child?
These concerns are even more prominent for the parents of a thalassaemic child. The child has to develop INDUSTRIOUSNESS and must be encouraged to be competent both academically and socially, and not be made to feel inferior to and less competent than other children. It is of course true that many adults can be very prejudiced against an ill child, partly because of ignorance and partly because of their own fears of what it means to be ill. However, the most important thing is how the parents feel, and the message they transmit to the child and to the school system.
These four developmental stages can be resolved positively (i.e., the child develops trust, autonomy, initiative and industry) or negatively (i.e., the child develops mistrust, shame and doubt, guilt and inferiority). This is crucial for how well prepared the child will be for entering adolescence. Of course no one ever has such a perfect childhood that everything will be positive. But it is important to recognize the extent to which, for example, we are distrustful or guilt-ridden, and fearful of being our own person.

But why is adolescence always thought to be such a difficult time?
Adolescence is basically a preparatory stage for entering adulthood. Adulthood means leaving home, establishing intimate relationships outside the family, finishing one's education and entering the working world. The adolescent is becoming increasingly more aware of these tasks and has to start preparing her or himself. In order to do this, teenagers have to start forming their own IDENTITY. A number of things make adolescence difficult. At the beginning there are a lot of physical changes. Girls start to become women and boys men. This results in many emotional changes as well. In order to fully understand why it is so difficult to be a teenager, we must realize that adolescence also brings important mental changes. The teenager is able to think in a way that is very different from that of a child. Adolescents begin to wonder about their existence in more abstract and philosophical ways. Such questions as who am I? What do I want to do in my life? etc. become very important to them.
Having thalassaemia can make such questions more difficult since having a chronic illness is not something that can be easily accepted and integrated into one's identity. No one likes to think that they are ill, and especially that they have something which is a life long burden. Often added complications such as diabetes, hormonal and growth problems, and the fear of a shorter life can make matters worse. Questions about one's ability to be truly independent and self-sufficient are made more difficult because of the increased physical dependence due to the treatments, and the way other people view the thalassaemic teenager.
Generally speaking, teenagers tend to react against what they are told by "authority" figures, in order to declare their independence and their right to have their own views. Their effort, which is perfectly normal and appropriate, is to separate from their family, and from what adults in general think, and formulate their own opinion, their own being. Friends of the same age become a more important source of influence, and belonging to a "peer group" is crucial for their self-esteem. In the case of thalassaemia the rebellion can take the form of refusing, or poor "compliance" with, medical treatments, especially Desferal treatment which interferes the most with their increased social life. Although this may be a step towards emotional maturity, towards caring for your own well-being because this is what you want rather than what you are told to do, it may also be dangerous unless this stage is reached quickly. Support groups can be a great help for teenagers struggling with all these important concerns and considerations.

How about adult life? Now that thalassaemics grow to adulthood, what is it that I can know that will help me?
Love and work are the two important areas of life that an adult is called upon to fulfill and that give satisfaction. When we enter into adulthood, with some basic sense of who we are, of our sexual identity, and what we want to do in life, the most important and difficult task we have to achieve is forming intimate relationships. We should be able to trust and be open to a few people that we have carefully chosen to be our friends, so that we do not feel isolated and lonely. INTIMACY is the 6th step in emotional development. It can be difficult to achieve since in order to be able to have true friendships and a true partnership in life we must be willing and able to be very open with ourselves. This involves some risk because sometimes when we open up ourselves we get hurt. Emotional pain can be more serious than physical pain so we often protect ourselves by not being open towards others. However, true intimacy cannot be achieved when we hide ourselves.

But can I be open about myself and not get hurt?
How easily or how much we are hurt by other people depends on how important their opinion is to us. The more we like ourselves the less we are afraid to be open, because we feel we have fewer things to hide. We like ourselves, we feel good about ourselves. We care less about what everybody else will say, and more about what a few of our close friends think.

But can I like myself and can my friends like me since I have thalassaemia?
Having thalassaemia does not mean that you are not likable as a person. Everybody has to learn how to like and accept themselves as they are. There is nothing to be ashamed of, nothing that should make us feel bad about ourselves because we have thalassaemia. Everybody has strengths and weaknesses, good and bad sides. No one is all good or all bad, except in very rare cases. We all have to learn how to live with, accept, admire, and when possible or necessary, change what we have and who we are. Having thalassaemia is not something we can change, but we can change how we feel about having it. It is true, and perfectly normal, that we often feel that it is too much of a burden and it makes our life more difficult. It is normal at times to feel depressed and gloomy or angry and resentful. It is true that some people may be unable to think of sharing their lives, being friends with, or employing someone with a medical problem and consequently may turn us down. It is true that life is less carefree, and we often have to wonder how soon we will die and why we have to struggle so much. However, all these concerns and difficulties do not have to make us not like ourselves, or think of ourselves as less than other people. On the contrary, it takes a lot of strength and courage to face the challenges of dealing with thalassaemia.

What kind of work should I consider?
WORK is another important aspect of adult life. Whether we have thalassaemia or not, choosing a career or job is not an easy task. Often our inclinations are influenced by what other people, society and our parents, consider appropriate, respectable and desirable. When choosing a job we must consider a number of factors. Primarily, being employed is essential to being self-sufficient. Financial independence is an important aspect of self-sufficiency. In order to be able to do the things we want in life we must be able to afford them and not have to depend on others for their attainment. Secondly, however, we must also seriously consider what gives us fullfilment and satisfaction. Having a job that makes us feel bored, dissatisfied and unfulfilled, for the financial security it provides is a-big compromise. In adult life at least half of our time is spent at work, so having a job that makes us feel stagnant and unhappy instead of creative and productive can make our lives very miserable.
Part of the difficulty in choosing a satisfying and fulfilling job is that the choice is usually made in adolescence. At that time however, we may not know what we really want and what makes us happy, or how the ideal we have in our mind can be reached in real life. Quite often, later on in life, people feel they have made the wrong choice and would rather be doing something else. This may cause a great crisis especially for people with a family and children. Although it is risky to leave one's job and the things one knows how to do, a change can be a very growth promoting experience, and can lead to a more satisfying and fulfilled life.

But doesn't thalassaemia affect my career choice?
When choosing a career it is important to remember our limitations. For example, it would be unrealistic to decide to become a professional athlete. We must also remember that in order to have the career we want, we must have the best education available to us. Thalassaemia in itself does not influence how productive or creative we can be. However everybody has to struggle very hard to find a job that is satisfying and fulfilling, which also provides the necessary means for survival. We must not be afraid to go out in the job market and compete with other people for a position we want. We must make sure that we have the necessary skills and qualifications. We must also have the best medical treatment, provided at convenient times, so that our treatment does not interfere with our education or our job.
When we reach old age, or closer to our death, we will re-evaluate our life and we will think of all the things we have and have not done. Our eighth, and final developmental task is ending our life with a sense of INTEGRITY for a life well spent instead of a sense of DESPAIR for a life not well spent. Many people, however, do not have the wisdom, or the foresight to realize that life will not go on forever. They should start doing all the things they want to do, and that make them feel good about themselves and their lives, before it is too late.

But I have been thinking about the possibility of me dying sooner than most people and it scares me a great deal.
It is normal and natural that you have such thoughts. It is also normal and natural for such thoughts to make you sad and fearful. However, death is a part of life. Every being that has been born will die. Some live for only a few moments or days, some live for many yars. No one knows beforehand when thy will die, no matter how healthy they are.
The fact that one day we will die must not stop us from living today . Actually the idea of death can help us understand how important life is. It can help us appreciate life and all the things we have and it can make us work hard for acheiving what we want to acomplish before it is too late. The better we live today the less threatened we feel about the possibility of dying tomorrow.
What is most important to remember is, that since one day we will all die we must try to make each moment and each day of our life as beautiful, sutisfying and fulfilling, as we can. In order to do so, we must, at an early stage, develop an inner feeling and belief tthat we are capable of, and deserve, to have a happy life. Thalassaemia as such is not an obstacle for achieving this way of thinking. It is the way we vie it that can hinder our development.

Taken from www.thalassaemia.org.cy/books/what_is/table_contents.htm

[caraiti]

To view the complete article (11 pages) and images go to www.emedicine.com/PED/topic2229.htm

History
The history in patients with thalassemia varies significantly, depending on the severity of the condition and the age at the time of diagnosis.



In most patients with thalassemia traits, no unusual signs or symptoms are encountered.
Some patients, especially those with somewhat more severe forms of the disease, manifest some pallor and slight icteric discoloration of the sclerae with splenomegaly, leading to slight enlargement of the abdomen. An affected child's parents or caregivers may report these symptoms. However, some rare types of b thalassemia trait are caused by a unique mutation, resulting in truncated or elongated b chains, which combine abnormally with a chains, producing insoluble dimers or tetramers. The outcome of such insoluble products is a severe hemolytic process that needs to be managed like thalassemia intermedia or, in some cases, thalassemia major.
The diagnosis is usually suspected in children with an unexplained hypochromic and microcytic picture, especially those who belong to one of the ethnic groups at risk. For this reason, physicians should always inquire about the patient's ethnic background, family history of hematologic disorders, and dietary history.
Thalassemia should be considered in any child with hypochromic microcytic anemia that does not respond to iron supplementation.
In more severe forms, such as b thalassemia major, the symptoms vary from extremely debilitating in patients who are not receiving transfusions to mild and almost asymptomatic in those receiving regular transfusion regimens and closely monitored chelation therapy.
Children with b thalassemia major usually demonstrate none of the initial symptoms until the later part of the first year of life (when b chains are needed to pair with a chains to form Hb A, after g chains production is turned off). However, in occasional children younger than 3-5 years, the condition may not be recognized because of the delay in cessation of Hb F production.
Patients with Hb E/b thalassemia may present with severe symptoms and a clinical course identical to that of patients with b thalassemia major. Alternatively, patients with Hb E/b thalassemia may run a mild course similar to that of patients with thalassemia intermedia or minor. This difference in severity has been described among siblings from the same parents. Some of the variation in severity can be explained based on the different genotypes, such as the type of b thalassemia gene present (ie, b+ or b-0), the co-inheritance of an a thalassemia gene, the high level of Hb F, or the presence of a modifying gene.
Patients with heterozygous or homozygous Hb E are usually slightly anemic, with hypochromasia and microcytosis, and are usually asymptomatic.
If further studies are not performed, benign homozygous Hb E is usually misdiagnosed as Hb E/b thalassemia, a condition that is frequently severe.
In a thalassemia, the hematologic abnormalities are clearly evident in newborns with mild or moderate forms of the disease. Lethal clinical consequences and physical deformities encountered at the time of birth are the rule in severe homozygous a thalassemia.
In b thalassemia, symptoms of anemia start when the g chain production is switched off and the b chains fail to form in adequate numbers.
Manifestations of anemia include extreme pallor and enlarged abdomen due to hepatosplenomegaly.

Patients' typical reports may lead a physician who is not familiar with the condition to a first impression of acute leukemia.
This impression is supported by the large spleen, which leads to thrombocytopenia, and by the high WBC count and immature WBCs seen on the peripheral blood film due to the extreme activity of the marrow.
To support the impression of acute leukemia further, the elevated level of reticulocytes expected in all hemolytic anemias does not occur, despite the severe hemolysis; this anomaly is due to the massive splenomegaly and the ineffective erythropoiesis that prevents the release of the cells from the bone marrow. Evidence of hemolysis is usually present, with elevated indirect bilirubin level, high lactate dehydrogenase (LDH) level, and low level of haptoglobin.
Bony changes may be severe, resulting in a characteristic radiologic picture (see Imaging Studies, Image 9). These changes are caused by massive expansion of the bone due to the ineffective erythroid production.
The ineffective erythropoiesis also creates a state of hypermetabolism associated with fever and failure to thrive.
Occasionally, gout due to hyperuricemia may be encountered.
Iron overload is one of the major causes of morbidity in all patients with severe forms of thalassemia, regardless of whether they are regularly transfused.

In transfused patients, heavy iron turnover from transfused blood is usually the cause; in nontransfused patients, this complication is usually deferred until puberty (if the patient survives to that age).
Increased iron absorption is the cause in nontransfused patients, but the reason behind this phenomenon is not clear. Many believe that, despite the iron overload state in these patients and the increased iron deposits in the bone marrow, the requirement for iron to supply the overwhelming production of ineffective erythrocytes is tremendous, causing significant increases in GI absorption of iron.
Bleeding tendency, increased susceptibility to infection, and organ dysfunction are all associated with iron overload.
Poor growth in patients with thalassemia is due to multiple factors and affects patients with well-controlled disease as well as those with uncontrolled disease.
Patients may develop symptoms that suggest diabetes, thyroid disorder, or other endocrinopathy; these are rarely the presenting reports.

Physical

Patients with thalassemia minor rarely demonstrate any physical abnormalities. Because the anemia is never severe and, in most instances, the Hb level is not less than 9-10 g/dL, pallor and splenomegaly are rarely observed.
In patients with severe forms of thalassemia, the findings upon physical examination vary widely, depending on how well the disease is controlled.

Children who are not receiving transfusions have a physical appearance so characteristic that an expert examiner can often make a spot diagnosis.
In Cooley's original 4 patients, the stigmata of severe untreated b thalassemia major included the following:
Severe anemia, with an Hb level of 3-7g/dL
Massive hepatosplenomegaly
Severe growth retardation
Bony deformities
These stigmata are typically not observed; instead, patients look healthy. Any complication they develop is usually due to adverse effects of the treatment (transfusion or chelation).
Bony abnormalities, such as frontal bossing, prominent facial bones, and dental malocclusion, are usually striking.
Severe pallor, slight to moderately severe jaundice, and marked hepatosplenomegaly are almost always present.
Complications of severe anemia are manifested as intolerance to exercise, heart murmur, or even signs of heart failure.
Growth retardation is a common finding, even in patients whose disease is well controlled by chelation therapy.
Patients with signs of iron overload may also demonstrate signs of endocrinopathy caused by iron deposits. Diabetes and thyroid or adrenal disorders have been described in these patients.
In patients with severe anemia who are not receiving transfusion therapy, neuropathy or paralysis may result from compression of the spine or peripheral nerves by large extramedullary hematopoietic masses.

Causes
Thalassemias are inherited disorders caused by various gene mutations. The clinical expression and severity are subject to numerous factors that may either mask the condition or exaggerate the symptoms, leading to a more severe disease.

Other Problems to be Considered

The differential diagnoses of thalassemic states in general depend on the age of the child at the time of presentation, the type of thalassemia and its severity, and, in severe cases, whether it is treated and well controlled. Furthermore, the form of thalassemia then has to be identified once the thalassemic condition is suspected because of the numerous thalassemic conditions.

Congenital dyserythropoietic anemia is a condition that may mimic severe forms of thalassemia in children. A bone marrow examination, Hb electrophoresis, and other tests reveal the diagnosis. Diamond-Blackfan anemia may also resemble severe forms of thalassemia in young infants.

The a thalassemia trait is similar to the b thalassemia trait. Both traits should be differentiated from iron deficiency anemia, which is the most common cause of hypochromasia and microcytosis in children and should be excluded before considering thalassemia. A child with presumed iron deficiency anemia that has not responded to adequate iron treatment is a good candidate for thalassemia workup.

In b thalassemia, elevated levels of Hb A2, F, or both are usually helpful in confirming the diagnosis. However, in a thalassemia, the Hb electrophoresis results are usually normal; in this case, and in cases in which iron study results are also nondiagnostic, nonspecific tests may help to differentiate iron deficiency anemia or anemia of chronic inflammation from thalassemia. Free erythrocyte protoporphyrin (FEP) levels are usually elevated in patients with iron deficiency or anemia of chronic inflammation but not with thalassemia. The soluble transferrin receptors (sTfR) levels are high in patients with iron deficiency but not in those with anemia of chronic infection or thalassemia.

The process of differentiating thalassemia trait from iron deficiency anemia must include the patient's medical, developmental, nutritional, and family history and a review of the child's CBC, with emphasis on the RBC indices. Proper interpretation of the CBC may save the physician time and may save the patient from unnecessary further testing (see Lab Studies). The anemia in patients with thalassemia trait is usually mild; the Hb level is rarely, if ever, less than 9 g/dL, unless the cause of the anemia is multifactorial. The RBC count is almost always higher in patients with thalassemia than in those with iron deficiency anemia; in fact, it is frequently higher than the reported reference range for the age.

In thalassemia, the RBC indices, including the mean corpuscular volume (MCV) and mean corpuscular Hb (MCH), are both significantly low for an Hb level that is either normal or only slightly low. In addition, the RBC distribution width (RDW) is usually normal, reflecting the homogenous population of the RBCs in thalassemia (see Image 6), whereas iron deficiency anemia is known to be associated with anisocytosis (see Image . A faint basophilic stippling may be seen in the RBCs of patients with thalassemia but not typically in those of patients with iron deficiency.

Many formulae have been introduced to help in differentiating thalassemia trait from iron deficiency. The most practical and easiest to remember is the Mentzer index, which divides the patient's MCV by the RBC count (MCV/RBC). A result of less than 13 usually suggests thalassemia trait, while a result greater than 13 is indicative of iron deficiency.

Confirmation by Hb electrophoresis in b thalassemia is essential before the patient and the family are counseled. The Mentzer index loses its value if the patient has a combination of thalassemia and iron deficiency. In such patients, Hb electrophoresis results may also be inaccurate and misleading, since iron deficiency suppresses production of all Hbs, including Hb A2. For this reason, the Hb A2 level does not rise and is typically normal in these patients, masking the diagnosis of b thalassemia. In such cases, Hb electrophoresis should be repeated after the iron deficiency has been treated to obtain an accurate Hb A2 fraction.

When b and a thalassemia coexist, the elevated levels of Hb A2 and Hb F usually present in b thalassemia may also be lost. Furthermore, a thalassemia ameliorates the severity of b thalassemia since the decrease in a chains results in less inclusions and, hence, less hemolysis.

However, the confirmation of b thalassemia is easier than that of the a trait. The Hb electrophoresis result is usually normal, and DNA testing or globin chain synthesis enumeration are the only studies that confirm the diagnosis. A moderately severe form of a thalassemia, which some consider equivalent to b thalassemia intermedia, is termed Hb H disease. The disease is characterized by moderately severe anemia, splenomegaly, some jaundice, and, possibly, some bone changes due to marrow expansion. In this form, Hb electrophoresis is diagnostic in revealing the abnormal Hb, which is unstable and may be detected on the supra vital stain as inclusions in the RBCs (Heinz bodies).

The severity of Hb H disease depends on the inherited mutation. Seventy-five percent of Hb H mutations are caused by deletions on chromosome 16, which are usually associated with the milder forms of Hb H. Nondeletional forms are usually associated with severe Hb H and require transfusion. The diagnosis of Hb H may be difficult to establish, since it is unstable and may go undetected. The b tetramers of Hb H are replaced by g tetramers in the form of Hb Bart. Patients with Hb H disease usually have more than 20% Hb Bart at birth, a finding that has helped to identify 90% of the neonates with Hb H disease in the newborns screening program in California.

Hb Constant Spring (CS) is the most common nondeletional a thalassemia mutation associated with Hb H disease. The cells that contain Hb CS are usually overhydrated, which causes the loss of the traditional microcytosis seen in patients with thalassemia. Hb H/CS disease is more severe than Hb H disease, sometimes requiring splenectomy to improve the anemia, a procedure associated with a high rate of portal vein thrombosis.

Many clinical entities associated with splenomegaly and anemia, such as storage diseases, and other forms of chronic hemolytic anemias are to be considered in the differential diagnosis. The homozygous a thalassemia is not compatible with life (unless intrauterine blood transfusion is administered), and a baby with hydrops fetalis is usually delivered.

Other causes of immune and nonimmune hydrops fetalis are also to be differentiated from the hydrops fetalis of a thalassemia major, a condition that was rarely seen in the past since the mutation that predisposes to this condition is limited to the Southeast Asian population, not the African population.

Rare forms of a thalassemia are also described. Hb CS results from a specific mutation in the a thalassemia gene, leading to the production of elongated a chains. The clinical manifestations in the homozygous state are similar to those encountered in patients with Hb H disease; however, they differ in the electrophoretic pattern. g tetramers that consist of Hb Bart replace the b tetramers of Hb H.

Thalassemia may also interact with other globin structural variants, whether they involve b, a, or other chains. In the b variants, Bs, Bc, and Be are some of the globin chain's most common mutations. For instance, the interaction of Bs with b thalassemia produces a condition associated with sickle cell disease. Conversely, when Bs (sickle trait gene) interacts with an a thalassemia gene, less Hb S is present in the RBCs than when only Bs is present. Such interactions modify the severity of each separate condition.

The incidence of Hb E/b thalassemia has increased considerably in the United States in recent years due to the immigration of individuals from Southeast Asia, where the incidence of both Hg E and b thalassemia is high (see Frequency). Clinically, the severe forms of Hb E/b thalassemia are similar to the transfusion-dependent b thalassemia major. For this reason, the diagnosis Hb E/b thalassemia should be considered in patients of Southeast Asian descent.

Other rare thalassemia variants include Hb Lepore and hereditary persistence of fetal Hb (HPFH).