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click here for freelancing tutoring sitesCASE REPORTPresenter : Sasikala B.

Yeoh Shu TIngDay/Date : Wednesday, 28th of August 2013Supervisor : dr. Tina Christina. L. Tobing , Sp.A(K)

CHAPTER I

INTRODUCTION1.1. Background

The term “thalassemia” is derived from the Greek words “Thalassa” (sea) and “Haema” (blood) and refers to disorders associated with defective synthesis of alpha- or beta-globin subunits of hemoglobin (Hb)A(alpha2; beta2), inherited as

pathologic alleles of one or more of the globin genes located on chromosomes 11 (beta) and 16 (alpha). More than 200 deletions or point mutations that impair transcription, processing, or translation of _- or _-globin mRNA have been identified. The clinical manifestations are diverse, ranging from absence of symptoms to profound fatal anemias in utero, or, if untreated, in early childhood.

Thalassemias are genetic disorders in globin chain production, inherited autosomal recessive blood disease. In thalassemia, the genetic defect results in reduced rate of synthesis of one of the globin chains that make up hemoglobin. Reduced synthesis of one of the globin chains causes the formation of abnormal hemoglobin molecules, and this in turn causes the anemia which is the characteristic presenting symptom of the thalassemias.1,2

Thalassemia was first defined in 1925 when Dr. Thomas B. Cooley described five young children with severe anemia, splenomegaly, and unusual bone abnormalities and called the disorder erythroblastic or Mediterranean anemia because of circulating nucleated red blood cells and because all of his patients were of Italian or Greek ethnicity. In 1932 Whipple and Bradford coined the term thalassemia from the Greek word thalassa, which means the sea (Mediterranean) to describe this entity. Somewhat later, a mild microcytic anemia was described in families of Cooley anemia patients, and it was soon realized that this disorder was caused by heterozygous inheritance of abnormal genes that, when homozygous, produced severe Cooley anemia.2,3

In Europe, Riette described Italian children with unexplained mild hypochromic and microcytic anemia in the same year Cooley reported the severe form of anemia later named after him. In addition, Wintrobe and coworkers in the United States reported a mild anemia in both parents of a child with Cooley anemia. This anemia was similar to the one that Riette described in Italy. Only then was Cooley's severe anemia recognized as the homozygous form of the mild hypochromic and microcytic anemia that Riette and Wintrobe described. This severe form was then labeled as thalassemia major and the mild form as thalassemia minor. These initial patients are now recognized to have been afflicted with β thalassemia. In the following few years, different types of thalassemia that involved polypeptide chains other than β chains were recognized and

described in detail. In recent years, the molecular biology and genetics of the thalassemia syndromes have been described in detail, revealing the wide range of mutations encountered in each type of thalassemia.2,4

Pericardial effusion is a common finding in everyday clinical practice. The

first challenge to the clinician is to try to establish an etiologic diagnosis.

Sometimes, the pericardial effusion can be easily related to a known underlying

disease, such as acute myocardial infarction, cardiac surgery, end-stage renal

disease or widespread metastatic neoplasm. When no obvious cause is apparent,

some clinical findings can be useful to establish a diagnosis of probability.

The presence of acute inflammatory signs (chest pain, fever, pericardial

friction rub) is predictive for acute idiopathic pericarditis irrespective of the size

of the effusion or the presence or absence of tamponade. Severe effusion with

absence of inflammatory signs and absence of tamponade is predictive for chronic

idiopathic pericardial effusion, and tamponade without inflammatory signs for

neoplastic pericardial effusion. Epidemiologic considerations are very important,

as in developed countries acute idiopathic pericarditis and idiopathic pericardial

effusion are the most common etiologies, but in some underdeveloped geographic

areas tuberculous pericarditis is the leading cause of pericardial effusion. The

second point is the evaluation of the hemodynamic compromise caused by

pericardial fluid. Cardiac tamponade is not an “all or none” phenomenon, but a

syndrome with a continuum of severity ranging from an asymptomatic elevation

of intrapericardial pressure detectable only through hemodynamic methods to a

clinical tamponade recognized by the presence of dyspnea, tachycardia, jugular

venous distension, pulsus paradoxus and in the more severe cases arterial

hypotension and shock. In the middle, echocardiographic tamponade is recognized

by the presence of cardiac chamber collapses and characteristic alterations in

respiratory variations of mitral and tricuspid flow. Medical treatment of

pericardial effusion is mainly dictated by the presence of inflammatory signs and

by the underlying disease if present. Pericardial drainage is mandatory when

clinical tamponade is present. In the absence of clinical tamponade, examination

of the pericardial fluid is indicated when there is a clinical suspicion of purulent

pericarditis and in patients with underlying neoplasia. Patients with chronic

massive idiopathic pericardial effusion should also be submitted to pericardial

drainage because of the risk of developing unexpected tamponade. The selection

of the pericardial drainage procedure depends on the etiology of the effusion.

Simple pericardiocentesis is usually sufficient in patients with acute idiopathic or

viral pericarditis. Purulent pericarditis should be drained surgically, usually

through subxiphoid pericardiotomy. Neoplastic pericardial effusion constitutes a

more difficult challenge because reaccumulation of pericardial fluid is a concern.

The therapeutic possibilities include extended indwelling pericardial catheter,

percutaneous pericardiostomy and intrapericardial instillation of antineoplastic

and sclerosing agents. Massive chronic idiopathic pericardial effusions do not

respond to medical treatment and tend to recur after pericardiocentesis, so wide

anterior pericardiectomy is finally necessary in many cases. 5

CHAPTER II

LITERATURE REVIEW2.1. THALASSEMIA

2.1.1. DEFINITIONThalassemia syndromes are inherited genetic diseases caused by mutation

of alpha or beta globin genes, which result in abnormal hemoglobin synthesis. The patho-physiologic mechanisms can be divided into decreased production of par- ticular types of hemoglobin (Thalassemias) and production of abnormal structure of hemoglobin types (Hemoglobinopathies). These lead to not only abnormal morphologic of erythrocytes (red blood cells), but also shorten life span of erythrocytes due to increased in vivo fragility and extra-vascular red cell destruction (hemolysis) along with ineffective erythropoiesis (bizarre, dys- functional marrow production). Thalassemia gene is an autosomal inheritance, which implies that both parents of the affected child must have a silent carrier state, so called thalassemia trait or hetero- zygote, while they are both asymptomatic.

2.1.2. EPIDEMIOLOGYCertain types of thalassemia are more common in specific

parts of the world. β thalassemia is much more common in Mediterranean countries such as Greece, Italy, and Spain. Many Mediterranean islands, including Cyprus, Sardinia, and Malta, have a significantly high incidence of severe β thalassemia, constituting a major public health problem. For instance, in Cyprus, 1 in 7 individuals carries the gene, which translates into 1 in 49 marriages between carriers and 1 in 158 newborns expected to have b thalassemia major. As a result, preventive measures established and enforced by public health authorities have been very effective in decreasing the incidence among their populations. B thalassemia is also common in North Africa, the Middle East, India, and Eastern Europe.

Conversely, α thalassemia is more common in Southeast Asia, India, the Middle East, and Africa. Worldwide, 15 million people have clinically apparent thalassemic disorders. Reportedly, disorders worldwide, and people who carry thalassemia in India alone number approximately 30 million. These facts confirm that thalassemias are among the most common genetic disorders in humans; they are encountered among all ethnic groups and in almost every country around the world.2,4,5

Although β-thalassemia has >200 mutations, most are rare. Approximately 20 common alleles constitute 80% of the known thalassemias worldwide; 3% of the world's population

carries genes for β-thalassemia, and in Southeast Asia, 5– 10% of the population carries genes for α-thalassemia. In a particular area there are fewer common alleles. In the U.S., an estimated 2,000 individuals have β-thalassemia.1

2.1.3. ETIOLOGY

Thalassemia syndromes are characterized by varying degrees of ineffective hematopoiesis and increased hemolysis. Clinical syndromes are divided into α- and β-thalassemias, each with varying numbers of their respective globin genes mutated. There is a wide array of genetic defects and a corresponding diversity of clinical syndromes. Most β-thalassemias are due to point mutations in one or both of the two β-globin genes (chromosome 11), which can affect every step in the pathway of β-globin expression from initiation of transcription to messenger RNA synthesis to translation and post translation modification. Picture below shows the organization of the genes (i.e., ε and γ, which are active in embryonic and fetal life, respectively) and activation of the genes in the locus control region (LCR), which promote transcription of the β-globin gene. There are four genes for α-globin synthesis (two on each chromosome 16). Most α-thalassemia syndromes are due to deletion of one or more of the α-globin genes rather than to point mutations. Mutations of β-globin genes occur predominantly in children of Mediterranean, Southern, and Southeast Asian ancestry. Those of α-globin are most common in those of Southeast Asian and African ancestry.6

(source: Manual of Pediatric Hematology and Oncology)Major deletions in β thalassemia are unusual (in contrast to α thalassemia),

and most of the encountered mutations are single base changes, small deletions, or insertions of 1-2 bases at a critical site along the gene, as in the image below.

(source: Thalassemia, Emedicine Multimedia)

2.1.4. CLASSIFICATION

The thalassemias can be defined as a heterogeneous group of genetic disorders of hemoglobin synthesis, all of which result from a reduced rate of production of one or more of the globin chains of hemoglobin. This basic defect results in imbalanced globin chain synthesis, which is the hallmark of all forms of thalassemia. The thalassemias can be classified at different levels. Clinically, it is useful to divide them into three groups: the severe transfusion-dependent (major) varieties; the symptomless carrier states (minor) varieties; and a group of conditions of intermediate severity that fall under the loose heading thalassemia intermedia”. This classification is retained because it has implications for both diagnosis and management.4

β-THALASSEMIA2,8

The β-thalassemia syndromes are caused by abnormalities of the b-gene complex on chromosome 11. More than 150 different mutations have been described, and most of these are small nucleotide substitutions within the b gene

complex. Deletions and mutations that result in abnormal cleavage or splicing of β-globin RNA may also result in thalassemia characterized by absent (β0) or reduced (β+) production of β-globin chains.2,7

THALASSEMIA MINOR (THALASSEMIA TRAIT) Heterozygosity for a b-thalassemia gene results in a mild reduction of b-

chain synthesis and, therefore, a reduction in HbA and mild anemia. Hemoglobin levels are 10 to 20 g/L lower than that of normal persons of the same age and gender, but the anemia may worsen during pregnancy. This mild anemia usually produces no symptoms, and longevity is normal. Thalassemia trait is almost always accompanied by familial microcytosis and hypochromia of the red blood cells. Target cells, elliptocytes, and basophilic stippling are seen on the peripheral blood smear. Almost all individuals with b-thalassemia trait have MCVs less than 75 fL, and mean MCV is 68 fL. In thalassemia trait the MCV is disproportionately low for the degree of anemia because of a red blood cell count that is normal or increased. The RDW is normal in thalassemia trait. The ratio of MCV/RBC (Mentzer index) is <11 in thalassemia trait but >12 in iron deficiency. Iron studies are normal. In an individual with microcytic red blood cells, a diagnosis of b-thalassemia trait is confirmed by an elevated HbA2 (α2δ2) level. The normal level of HbA2 is 1.5 to 3.4%, and HbA2 >3.5% is diagnostic of the most common form of β-thalassemia trait. Levels of HbF (α2γ2) are normal (<2.0%) in about half of individuals with classical thalassemia trait and moderately elevated (2.0 to 7%) in the rest.

Less common forms of β-thalassemia trait include βδ-thalassemia trait, characterized by familial microcytosis, normal levels of HbA2, and elevated levels of HbF (5-15%), and Lepore hemoglobin trait, characterized by the presence of 5 to 10% HbLepore, a hemoglobin that migrates electrophoretically in the position of HbS. Lepore hemoglobin is a fusion product resulting from an unequal crossover between b and d genes and associated with decreased b-chain synthesis.

Occasionally a silent carrier is identified on the basis of being a parent of a child with severe thalassemia but slight or no microcytosis or elevations of HbA2

or HbF. The importance of establishing a diagnosis of β-thalassemia trait is to avoid

unnecessary treatment with medicinal iron and to provide genetic counseling. Two individuals with b-thalassemia trait face a 25% risk with each pregnancy of having a child with homozygous β-thalassemia. Populations with a high prevalence of thalassemia trait can be screened to provide genetic counseling. In at-risk pregnancies, prenatal diagnosis can be performed as early as 10 to 12 weeks of gestation using fetal DNA obtained by chorionic villus biopsy.

HOMOZYGOUS β-THALASSEMIA (THALASSEMIA MAJOR, COOLEY ANEMIA)

Homozygosity for β-thalassemia genes is usually associated with severe anemia because of a marked reduction of synthesis of the b-globin chains of HbA. However, reduction of HbA synthesis does not explain the hemolysis and ineffective erythropoiesis that are a consequence of unbalanced globin chain synthesis. In homozygous β-thalassemia, α-globin chains are produced in normal amounts and accumulate, denature, and precipitate in the RBC precursors in the bone marrow and circulating RBC. These precipitated α-globin chains damage the RBC membrane, resulting in destruction within the bone marrow (ineffective erythropoiesis) and in the peripheral blood.

The fetus and the newborn infant with homozygous β-thalassemia are clinically and hematologically normal. In vitro measurements demonstrate reduced or absent β-chain synthesis. Increasingly, homozygous β-thalassemia is being diagnosed in the United States by neonatal electrophoretic hemoglobin screening that shows only HbF and no HbA Symptoms of β-thalassemia major develop gradually in the first 6 to 12 months after birth, when the normal postnatal switchover from γ-chains to β-chains results in a decreased level of HbF). By the age of 6 to 12 months, most affected infants show pallor, irritability, growth retardation, jaundice, and hepatosplenomegaly as a result of extramedullary hematopoiesis. By 2 years of age, 90% of infants are symptomatic, and progressive changes in the facial and cranial bones develop. The hemoglobin level may be as low as 30 to 50 g/L at the time of diagnosis.

Other varian of β-thalassemia are:6

Silent carrier β thalassemia: Similar to patients who silently carry α thalassemia, these patients have no symptoms, except for possible low RBC indices. The mutation that causes the thalassemia is very mild and represents a β+ thalassemia.

Thalassemia intermedia: This condition is usually due to a compound heterozygous state, resulting in anemia of intermediate severity, which typically does not require regular blood transfusions.

β thalassemia associated with β chain structural variants: The most significant condition in this group of thalassemic syndromes is the Hb E/β thalassemia, which may vary in its clinical severity from as mild as thalassemia intermedia to as severe as β thalassemia major.

α-THALASSEMIA2,9 The a-thalassemia syndromes are prevalent in people from Southeast Asia

and usually result from deletion of one or more of the four α-globin genes on

chromosome 16. In general, the severity is proportional to the number of α-globin genes deleted which can be quantitated by DNA analysis.1,6

SILENT CARRIER (α2-THALASSEMIA TRAIT, - α/αα) Individuals with a single α-globin gene deletion are clinically and

hematologically normal, but they may be identified at birth by the presence of small amounts (1-3%) of the fast-migrating Barts hemoglobin (γ4) by neonatal hemoglobin electrophoresis. In later life, the diagnosis can be established only by determining the number of a-globin genes by DNA analysis.

α1-THALASSEMIA TRAIT (-α/-α OR --/αα) Individuals in whom two of four α-globin genes are deleted have mild

microcytic anemia. At birth, relative microcytosis with 5 to 8% of HbBarts is present. Barts hemoglobin disappears by 3 to 6 months of age, and the hemoglobin electrophoresis becomes normal. After the newborn period, a definitive diagnosis may be impractical in this mild disorder, and the diagnosis is usually suspected when other causes of microcytic anemia, such as β-thalassemia trait or iron deficiency, are ruled out.

α1-Thalassemia trait can occur in two ways: a cis-deletion in which the two deleted a genes are on the same chromosome 16, and a trans-deletion in which one a-gene is deleted from each of the 16 chromosomes. The cis-deletion is usual in Southeast Asian populations, whereas the trans-deletions are usual in people of African ethnicity. Thus, although α-thalassemia commonly occurs in African people, a maximum of only two genes can be deleted in any individual because of the trans-configuration. Consequently, the more severe α-thalassemia syndromes associated with three and four α-deletions are not seen.

HEMOGLOBIN H DISEASE (--/-α) Three α-globin gene deletions result in hemoglobin H disease, which is

associated with a marked imbalance between a- and β-globin chain synthesis. Excess free β chains accumulate and combine to form an abnormal hemoglobin, a tetramer of β chains (β4) called HbH. HbH is unstable and precipitates within red blood cells, leading to chronic microcytic, hemolytic anemia. Laboratory findings include a moderately severe microcytosic anemia (Hb 60-100 g/L with evidence of hemolysis). Precipitated HbH can be demonstrated in the red blood cells with supravital stains. On hemoglobin electrophoresis, HbH has a fast mobility and accounts for 10 to 15% of the total hemoglobin.

FETAL HYDROPS SYNDROME (--/--) Deletion of all four a-globin genes results in a syndrome of hydrops fetalis

with stillbirth or immediate postnatal death. In the absence of α-chain synthesis, such fetuses are incapable of synthesizing embryonic hemoglobins. At birth, hemoglobin electrophoresis shows predominantly Barts hemoglobin (γ4) and small amounts hemoglobin H (β4) as well as embryonic hemoglobins. The high oxygen affinity of Barts hemoglobin makes it oxygen transport ineffective, leading to the intrauterine manifestations of severe hypoxia, out of proportion to the degree of anemia. A number of infants with this syndrome who have been identified prenatally and treated with intrauterine and postnatal transfusions have survived. These infants are transfusion dependent, but some are developing normally. As in thalassemia major, the only curative therapy is bone marrow transplantation. Termination of the pregnancy is often recommended because of a high frequency of severe maternal toxemia associated with a hydropic fetus.

Thalassemias can also be classified at the genetic level into the α, β, δβ or εγδβ thalassemias, according to which globin chain is produced in reduced amounts. In some thalassemias, no globin chain is synthesized at all, and hence they are called α0 or β0 thalassemias, whereas in others some globin chain is produced but at a reduced rate; these are designated α+ or β+ thalassemias. The δβ thalassemias, in which there is defective δ and β chain synthesis, can be subdivided in the same way, i.e., into (δβ)+ and (δβ)0 varieties.4

(source: Pediatric Hematology)

2.1.5. PATHOGENESIS The basic defect in all types of thalassemia is imbalanced globin chain

synthesis. However, the consequences of accumulation of the excessive globin chains in the various types of thalassemia are different. In β thalassemia, excessive α chains, unable to form Hb tetramers, precipitate in the RBC precursors and, in one way or another, produce most of the manifestations encountered in all of the β thalassemia syndromes; this is not the situation in α thalassemia.

The excessive chains in α thalassemia are γ chains earlier in life and β chains later in life. Because such chains are relatively soluble, they are able to form homotetramers that, although relatively unstable, nevertheless remain viable and able to produce soluble Hb molecules such as Hb Bart (4 γ chains) and Hb H (4 β chains). These basic differences in the 2 main types of thalassemia are responsible for the major differences in their clinical manifestations and severity.

α chains that accumulate in the RBC precursors are insoluble, precipitate in the cell, interact with the membrane (causing significant damage), and interfere with cell division. This leads to excessive intramedullary destruction of the RBC

precursors. In addition, the surviving cells that arrive in the peripheral blood with intracellular inclusion bodies (excess chains) are subject to hemolysis; this means that both hemolysis and ineffective erythropoiesis cause anemia in the person with β thalassemia.

The ability of some RBCs to maintain the production of γ chains, which are capable of pairing with some of the excessive α chains to produce Hb F, is advantageous. Binding some of the excess a chains undoubtedly reduces the symptoms of the disease and provides additional Hb with oxygen-carrying ability.

Furthermore, increased production of Hb F, in response to severe anemia, adds another mechanism to protect the RBCs in persons with β thalassemia. The elevated Hb F level increases oxygen affinity, leading to hypoxia, which, together with the profound anemia, stimulates the production of erythropoietin. As a result, severe expansion of the ineffective erythroid mass leads to severe bone expansion and deformities. Both iron absorption and metabolic rate increase, adding more symptoms to the clinical and laboratory manifestations of the disease. The large numbers of abnormal RBCs processed by the spleen, together with its hematopoietic response to the anemia if untreated, results in massive splenomegaly, leading to manifestations of hypersplenism.

If the chronic anemia in these patients is corrected with regular blood transfusions, the severe expansion of the ineffective marrow is reversed. Adding a second source of iron would theoretically result in more harm to the patient. However, this is not the case because iron absorption is regulated by 2 major factors: ineffective erythropoiesis and iron status in the patient.

Ineffective erythropoiesis results in increased absorption of iron because of downregulation of the HAMP gene, which produces a liver hormone called hepcidin. Hepcidin regulates dietary iron absorption, plasma iron concentration, and tissue iron distribution and is the major regulator of iron. It acts by causing degradation of its receptor, the cellular iron exporter ferroportin. When ferroportin is degraded, it decreases iron flow into the plasma from the gut, from macrophages, and from hepatocytes, leading to a low plasma iron concentration. In severe hepcidin deficiency, iron absorption is increased and macrophages are usually iron depleted, such as is observed in patients with thalassemia intermedia.

Malfunctions of the hepcidin-ferroportin axis contribute to the etiology of different anemias, such as is seen in thalassemia, anemia of inflammation, and chronic renal diseases. Improvement and availability of hepcidin assays facilitates diagnosis of such conditions. The development of hepcidin agonists and antagonists may enhance the treatment of such anemias.

By administering blood transfusions, the ineffective erythropoiesis is reversed, and the hepcidin level is increased; thus, iron absorption is decreased and macrophages retain iron.

Iron status is another important factor that influences iron absorption. In patients with iron overload (eg, hemochromatosis), the iron absorption decreases because of an increased hepcidin level. However, this is not the case in patients with severe β thalassemia because a putative plasma factor overrides such mechanisms and prevents the production of hepcidin. Thus, iron absorption continues despite the iron overload status.

As mentioned above, the effect of hepcidin on iron recycling is carried through its receptor "ferroportin," which exports iron from enterocytes and macrophages to the plasma and exports iron from the placenta to the fetus. Ferroportin is upregulated by iron stores and downregulated by hepcidin. This relationship may also explain why patients with β thalassemia who have similar iron loads have different ferritin levels based on whether or not they receive regular blood transfusions.

For example, patients with β thalassemia intermedia who are not receiving blood transfusions have lower ferritin levels than those with β thalassemia major who are receiving regular transfusion regimens, despite a similar iron overload. In the latter group, hepcidin allows recycling of the iron from the macrophages, releasing high amounts of ferritin. In patients with β thalassemia intermedia, in whom the macrophages are depleted despite iron overload, lower amounts of ferritin are released, resulting in a lower ferritin level.

Most nonheme iron in healthy individuals is bound tightly to its carrier protein, transferrin. In iron overload conditions, such as severe thalassemia, the transferrin becomes saturated, and free iron is found in the plasma. This iron is harmful since it provides the material for the production of hydroxyl radicals and additionally accumulates in various organs, such as the heart, endocrine glands, and liver, resulting in significant damage to these organs.

2.1.6. CLINICAL MANIFESTATIONSHistory

Thalassemia minor usually presents as an asymptomatic mild microcytic anemia and is detected through routine blood tests. Thalassemia major is a severe anemia that presents during the first few months after birth. Thalassemia minor (beta thalassemia trait) usually is asymptomatic, and it typically is identified during routine blood count evaluation. Thalassemia major (homozygous beta thalassemia) is detected during the first few months of life, when the patient's level of fetal Hb decreases.

Physical ExaminationPatients with the beta thalassemia trait generally have no unusual physical

findings. The physical findings are related to severe anemia, ineffective

erythropoiesis, extramedullary hematopoiesis, and iron overload resulting from transfusion and increased iron absorption. Skin may show pallor from anemia and jaundice from hyperbilirubinemia. The skull and other bones may be deformed secondary to erythroid hyperplasia with intramedullary expansion and cortical bone thinning. Heart examination may reveal findings of cardiac failure and arrhythmia, related to either severe anemia or iron overload. Abdominal examination may reveal changes in the liver, gall bladder, and spleen.1,2,5

Hepatomegaly related to significant extramedullary hematopoiesis typically is observed. Patients who have received blood transfusions may have hepatomegaly or chronic hepatitis due to iron overload; transfusion-associated viral hepatitis resulting in cirrhosis or portal hypertension also may be seen. The gall bladder may contain bilirubin stones formed as a result of the patient's life-long hemolytic state. Splenomegaly typically is observed as part of the extramedullary hematopoiesis or as a hypertrophic response related to the extravascular hemolysis. Extremities may demonstrate skin ulceration. Iron overload also may cause endocrine dysfunction, especially affecting the pancreas, testes, and thyroid.11

2.1.8. DIAGNOSIS

1.History

The history in patients with thalassemia widely varies, 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 β

thalassemia trait are caused by a unique mutation, resulting in truncated or

elongated β chains, which combine abnormally with α 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 β 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 β thalassemia major usually demonstrate none of the initial

symptoms until the later part of the first year of life (when β chains are needed

to pair with α chains to form hemoglobin (Hb) A, after γ 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/β thalassemia may present with severe symptoms and a

clinical course identical to that of patients with β thalassemia major.

Alternatively, patients with Hb E/β 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

β thalassemia gene present (ie, β+ or β-0), the co-inheritance of an α thalassemia

gene, the high level of Hb F, or the presence of a modifying gene 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, as well as kidney stones, are

seen more frequently as patients with thalassemia major are living longer.

Chronic anemia and exposure to chelating agents were thought to be blamed for

this complication.

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.

o 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).

o 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.

o 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.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 widely vary, depending on how well the disease is controlled.

Findings include the following:

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 β

thalassemia major included the following:

o Severe anemia, with an Hb level of 3-7g/dL

o Massive hepatosplenomegaly

o Severe growth retardation

o 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.

2. Laboratory studies in thalassemia include the following:

The CBC count and peripheral blood film examination results are usually

sufficient to suspect the diagnosis. Hemoglobin (Hb) evaluation confirms the

diagnosis in β thalassemia, Hb H disease, and Hb E/β thalassemia.

o In the severe forms of thalassemia, the Hb level ranges from 2-8

g/dL.

o Mean corpuscular volume (MCV) and mean corpuscular Hb

(MCH) are significantly low, but, unlike thalassemia trait, thalassemia major is

associated with a markedly elevated RDW, reflecting the extreme anisocytosis.

o The WBC count is usually elevated in β thalassemia major; this is

due, in part, to miscounting the many nucleated RBCs as leukocytes.

Leukocytosis is usually present, even after excluding the nucleated RBCs. A

shift to the left is also encountered, reflecting the hemolytic process.

o Platelet count is usually normal, unless the spleen is markedly

enlarged.

o Peripheral blood film examination reveals marked hypochromasia

and microcytosis, hypochromic macrocytes that represent the

polychromatophilic cells, nucleated RBCs, basophilic stippling, and occasional

immature leukocytes, as shown below.

o

Peripheral blood film in Cooley anemia.

o Contrast this with the abnormalities associated with Hb H, an α

thalassemia, shownbelow.

Supra vital stain in hemoglobin H disease that reveals Heinz bodies (golf ball

appearance).

o Hb electrophoresis usually reveals an elevated Hb F fraction,

which is distributed heterogeneously in the RBCs of patients with β

thalassemia, Hb H in patients with Hb H disease, and Hb Bart in newborns

with α thalassemia trait. In β -0 thalassemia, no Hb A is usually present; only

Hb A2 and Hb F are found.

Iron studies are as follows:

o Serum iron level is elevated, with saturation reaching as high as

80%.

o The serum ferritin level, which is frequently used to monitor the

status of iron overload, is also elevated. However, an assessment using serum

ferritin levels may underestimate the iron concentration in the liver of a

transfusion-independent patient with thalassemia.

Complete RBC phenotype, hepatitis screen, folic acid level, and human

leukocyte antigen (HLA) typing are recommended before initiation of blood

transfusion therapy.9

3.Imaging Studies

Skeletal survey and other imaging studies reveal classic changes of the bones that

are usually encountered in patients who are not regularly transfused.

The striking expansion of the erythroid marrow widens the marrow spaces,

thinning the cortex and causing osteoporosis. These changes, which result from

the expanding marrow spaces, usually disappear when marrow activity is halted

by regular transfusions. Osteoporosis and osteopenia may cause fractures, even in

patients whose conditions are well-controlled.

In addition to the classic "hair on end" appearance of the skull, shown

below, which results from widening of the diploic spaces and observed on plain

radiographs, the maxilla may overgrow, which results in maxillary overbite,

prominence of the upper incisors, and separation of the orbit. These changes

contribute to the classic "chipmunk facies observed in patients with thalassemia

major

The classic "hair on end" appearance on plain skull radiographs of a patient with Cooley anemia.

Other bony structures, such as ribs, long bones, and flat bones, may also

be sites of major deformities. Plain radiographs of the long bones may reveal a

lacy trabecular pattern. Changes in the pelvis, skull, and spine become more

evident during the second decade of life, when the marrow in the peripheral bones

becomes inactive while more activity occurs in the central bones.

Compression fractures and paravertebral expansion of extramedullary

masses, which could behave clinically like tumors, more frequently occur during

the second decade of life. In a recent study from Thailand, investigating

unrecognized vertebral fractures in adolescents and young adults with thalassemia

syndrome, 13% of the patients studied were found to have fractures and 30% of

them had multiple vertebral fractures. Those who were thought to be older had

more severe disease, were splenectomized, and had been on chelation therapy for

a longer time.

MRI and CT scanning are usually used in diagnosing such complications.

Chest radiography is used to evaluate cardiac size and shape. MRI and CT

scanning can be used as noninvasive means to evaluate the amount of iron in the

liver in patients receiving chelation therapy.

A newer non invasive procedure involves measuring the cardiac T2* with

cardiac magnetic resonance (CMR). This procedure has shown decreased values

in cardiac T2* due to iron deposit in the heart. Unlike liver MRI, which usually

correlates very well with the iron concentration in the liver measured using

percutaneous liver biopsy samples and the serum ferritin level, CMR does not

correlate well with the ferritin level, the liver iron level, or echocardiography

findings. This suggests that cardiac iron overload cannot be estimated with these

surrogate measurements. This is also true in measuring the response to chelation

therapy in patients with iron overload. The liver is clear of iron loading much

earlier than the heart, which also suggests that deciding when to stop or reduce

treatment based on liver iron levels is misleading.

The relationship between hepatic and myocardial iron concentration was

assessed by T2-MRI in patients receiving chronic transfusion. A poor correlation

was noted, and approximately 14% of patients with cardiac iron overload were

identified who had no matched degree of hepatic hemosiderosis. Left ventricular

ejection fraction (LVEF) was insensitive for detecting high myocardial iron. For

this reason, cardiac evaluation should be addressed separately.

T2* MRI technique (T2* is the time needed for the organ to lose two

thirds of its signal, and it is measured in milliseconds (ms); when iron concentrate

increases, T2* shortens). R2* is the reciprocal of T2* and equals 1000/T2* and is

measured in a unit of inverse seconds. This technique has been recently validated

and is used for evaluation of cardiac and liver iron load. A shortening of

myocardial T2* to shorter than 20 ms is associated with an increased likelihood of

decreased LVEF, whereas patients with T2 value of longer than 20 ms have a very

low likelihood of decreased LVEF; values from 10-20 ms indicate a 10% chance

of decreased LVEF, 8-10 ms an 18% chance, 6 ms a 38% chance, and 4 ms a 70%

chance of decreased LVEF.[2]

This T2* MRI technique. is not readily available in many parts of the

world. For this reason, the need for simpler and more available procedure was

addressed in a study conducted recently in Italy, where serial echocardiographic

LVEF measurements were proved to be very accurate and reproducible. The study

suggested that a reduction in of LVEF greater than 7% , over time, as determined

by 2-dimensional echocardiography, may be considered a strong predictive tool

for the detection of thalassemia major patients with increased risk of cardiac

death.

Hepatic iron content (HIC) obtained by liver biopsy, cardiac function tests

obtained by echocardiography measurements, and multiple-gated acquisition scan

(MUGA) findings were compared with the results of iron measurements on R2-

MRI in the liver and heart.

Various iron overload patients were involved in the study, which revealed

that R2-MRI was strongly associated with HIC (weakly but significantly with

ferritin level) and represents an excellent noninvasive method to evaluate iron

overload in the liver and heart and to monitor response to chelation therapy. T2*

and R2* MRI are preferred by many, however, because they allow measurements

of both liver and cardiac iron at the same time.

HIC should be measured annually if possible in all patients on long-term

blood transfusion therapy. Normal HIC values are up to 1.8 mg Fe/g dry weight

levels, while a level of up to 7 mg/g/dry weight seen in carriers of

hemochromatosis was shown to be asymptomatic and without any adverse effects.

High levels of greater than 15 mg/g/dry weight is consistent with significant iron

deposition and is associated with progression to liver fibrosis. Nontransferrin-

bound iron (NTBI) is usually elevated in the plasma at this level.

4. The following tests may be indicated:

ECG and echocardiography are performed to monitor cardiac function.

HLA typing is performed for patients for whom bone marrow

transplantation is considered.

Eye examinations, hearing tests, renal function tests, and frequent blood

counts are required to monitor the effects of deferoxamine (DFO) therapy and

the administration of other chelating agents 

5.Procedures

Bone marrow aspiration is needed in certain patients at the time of the initial

diagnosis to exclude other conditions that may manifest as thalassemia major.

Liver biopsy is used to assess iron deposition and the degree of hemochromatosis.

However, using liver iron content as a surrogate for evaluation of cardiac iron is

misleading. Many studies have shown very poor correlation between the two;

hence, cardiac evaluation for the presence of iron overload needs to be addressed

separately.

Measurement of urinary excretion of iron after a challenge test of DFO is used to

evaluate the need to initiate chelation therapy and reflects the amount of iron

overload

6.Histologic Findings

All severe forms of thalassemia exhibit hyperactive marrow with erythroid

hyperplasia and increased iron stores in marrow, liver, and other organs. In the

untreated person with severe disease, extramedullary hematopoiesis in unusual

anatomic sites is one of the known complications.

Erythroid hyperplasia is observed in bone marrow specimens. Increased iron

deposition is usually present in marrow, as depicted in the image below, liver,

heart, and other tissues.

Excessive iron in a bone marrow preparation.

7.StagingSome use a relevant staging system based on the cumulative numbers of blood

transfusions given to the patient to grade cardiac-related symptoms and determine

when to start chelation therapy in patients with β thalassemia major or intermedia.

In this system, patients are divided into 3 groups.

The first group contains those who have received fewer than 100 units of packed

RBCs (PRBCs) and are considered to have stage I disease. These patients are

usually asymptomatic; their echocardiograms reveal only slight left ventricular

wall thickening, and both the radionuclide cineangiogram and the 24-hour ECG

findings are normal.

Patients in the second group (stage II patients) have received 100-400 units of

blood and may report slight fatigue. Their echocardiograms may demonstrate left

ventricular wall thickening and dilatation but normal ejection fraction. The

radionuclide cineangiogram findings are normal at rest but show no increase or

fall in ejection fraction during exercise. Atrial and ventricular beats are usually

noticed on the 24-hour ECG.

Finally, in stage III patients, symptoms range from palpitation to congestive heart

failure, decreased ejection fraction on echocardiogram, and normal cineangiogram

results or decreased ejection fraction at rest, which falls during exercise. The 24-

hour ECG reveals atrial and ventricular premature beats, often in pairs or in runs.

A second classification, introduced by Lucarelli, is used for patients with severe

disease who are candidates for hematopoietic stem cell transplantation

(HSCT).This classification is used to assess risk factors that predict outcome and

prognosis and addresses 3 elements: (1) degree of hepatomegaly, (2) presence of

portal fibrosis in liver biopsy sample, and (3) effectiveness of chelation therapy

prior to transplantation.

If one of these elements is unfavorable prior to HSCT, the chance of event-free

survival is significantly poorer than in patients who have neither hepatomegaly

nor fibrosis and whose condition responds well to chelation (class 1 patients). The

event-free survival rate after allogeneic HSCT for class 1 patients is 90%,

compared with 56% for those with hepatomegaly and fibrosis and whose

condition responds poorly to chelation (class 3).10

2.1.9. DIFFERENTIAL DIAGNOSIS

Iron-deficiency anaemia also produces a hypochromic, microcytic anaemia

but Fe and ferritin are low whilst iron-binding capacity is high.

Acute leukaemia may require bone marrow aspiration to differentiate.

Rhesus incompatibility is rare now and postmortem Hb electrophoresis

should differentiate in cases of hydrops fetalis.

Diamond-Blackfan syndrome is a rare congenital cause of erythroid

aplasia. It causes a severe normochromic, macrocytic anaemia usually in

infancy and is often associated with craniofacial or upper limb anomalies.11

2.1.10. TREATMENT

Person with thalassemia trait require no treatment or long term monitoring.

They usually do not have iron deficiency, so iron supplements will not improve

their anemia. Accordingly, iron therapy should only be administered if iron

deficiency occurs.

Blood transfusions

Person with beta thalassemia major require periodic and lifelong blood

transfusions to maintain a haemoglobin level higher than 9.5g per dl (95g per L)

and sustain normal growth. The need for blood transfusions may begin as early as

six months age. For persons with beta thalassemia intermedia, the decision to

transfuse is a more subjective clinical assessment. Transfusion requirements are

episodic and become necessary when the person’s haemoglobin is inadequate for

a normal life or when the anemia impairs growth and development.

Chelation

Transfusion- dependent patients develop iron overload because they have no

physiologic process to remove excess iron from multiple transfusions. Therefore

they require treatment with an iron chelator starting between five and eight years

of age. Deferoxamine, subcutaneously or intravenously, has been the treatment of

choice. Although this therapy is relatively nontoxic, it is cumbersome and

expensive. The U.S Food and Drug Administration recently approved oral

deferasirox(Exjade) as an alternative treatment. Adverse effects of deferasirox

were transient and gastrointestinal in nature,, and no cases of agranulocytosis were

reported.

Bone Marrow Transplant

Bone marrow transplantation in childhood is the only curative therapy for beta

thalassemia major. Hematopoietic stem cell transplantation generally results in an

excellent outcome in low-risk persons, defined as those with no hepatomegaly, no

portal fibrosis on liver biopsy, and regular chelation therapy, or at most, two of

these abnormalities.

Management of Specific Conditions

Hypersplenism

If hypersplenism causes a marked increase in transfusion requirements,

splenectomy may be needed. Surgery is usually delayed until at least four years of

age because of the spleen’s role in clearing bacteria and preventing sepsis. At least

one month before surgery, patient should receive the pneumococcal

polysaccharide vaccine. Children should also receive the pneumococcal conjugate

vaccine series. Antibiotic prophylaxis with penicillin, 250mg orally twice a day, is

recommended for all persons during the first two years after surgery and for

children younger than 16 years.

Cardiac

Serum ferritin has been used as a marker of iron storage to predict cardiac

complications. Ferritin levels less than 2500ng per ml are associated with

improved survival. However, ferritin levels are unrealiable when liver disease is

present.9

2.1.11. COMPLICATIONS

Iron overload is one of the major causes of morbidity in severe forms of

thalassaemia. Iron overload can occur even without transfusions as

absorption is increased by 2-5 g per year and this increases with regular

transfusions to an excess of over 10 g of iron per year. Excess iron is

deposited in body organs, especially the pancreas, liver, pituitary and heart,

causing fibrosis and eventual organ failure. Bleeding tendency and

susceptibility to infection are also related to iron overload. Endocrine

dysfunction secondary to iron overload is common in multiply transfused

patients, manifesting ashypogonadotrophic hypogonadism, short stature,

acquired hypothyroidism, hypoparathyroidism and diabetes mellitus.

Repeated transfusions increase the risk of blood-borne diseases,

including hepatitis Band C, although all blood is screened for known blood-

borne infections. Infection with rare opportunistic organisms may cause

pyrexia and enteritis in patients with iron overload. Yersinia

enterocolitica thrives with the abundant iron. Unexplained fever, especially

with diarrhoea, should be treated with gentamicin and co-trimoxazole, even

when cultures are negative.

Severe anaemia may cause high-output cardiac failure.

Osteoporosis is common and apparently multifactorial in aetiology but

alendronate or pamidronate is an effective treatment.

The long-term increased red-cell turnover causes hyperbilirubinaemia

and gallstones.

Hyperuricaemia may lead to gout.

With increasing length of survival, hepatocellular carcinoma is becoming

an increasing problem.

Desferrioxamine can cause toxicity:

Local reaction at the site of injection can be severe.

High-frequency hearing loss has been reported in 30-40% of patients.

Colour andnight blindness can occur. These complications may be reversible.

Eye and hearing examinations should be performed every 6-12 months in

patients on chelation therapy.12

2.1.12. PROGNOSIS

The prognosis depends on the severity of the disease and adherence to

treatment.

α thalassaemia:

The prognosis is excellent for asymptomatic carriers.

The overall survival for HbH disease is good overall but

variable. Many patients survive into adulthood, but some patients

have a more complicated course.

Hydrops fetalis is incompatible with life.

β thalassaemia:

Thalassaemia minor (thalassaemia trait) usually causes

mild, asymptomatic microcytic anaemia, with no effect on

mortality or significant morbidity.

Severe β thalassaemia major (also called Cooley's anaemia)

has traditionally had a poor prognosis with 80% dying from

complications of the disease in the first five years of life.

Until recently, patients who received transfusions only did

not survive beyond adolescence because of cardiac complications

caused by iron toxicity. The introduction of chelating agents to

remove excessive iron has increased life expectancy dramatically.

The overall survival following stem cell transplantation has

been shown to be 90% with a disease-free survival of 86% over a

mean follow-up period of 15 years.13

2.2. PERICARDIAL EFFUSION

2.2.1. DEFINITION

The normal pericardium is a fibro elastic sac surrounding the heart that

contains a thin layer of fluid. Pericardial effusion is the presence of an abnormal

amount of fluid and/or an abnormal character to fluid in the pericardial space. It

can be caused by a variety of local and systemic disorders, or it may be

idiopathic.6

2.2.2. AETIOLOGY

Inflammation of the pericardium (pericarditis) is a response to disease,

injury or an inflammatory disorder that affects the pericardium. Pericardial

effusion is often a sign of this inflammatory response.

Pericardial effusion may also occur when the flow of pericardial fluids is

blocked or when blood accumulates within the pericardium. It's not clear how

some diseases contribute to pericardial effusion, and sometimes the cause can't be

determined.

Specific causes of pericardial effusion may include:

Viral, bacterial, fungal or parasitic infections

Inflammation of the pericardium due to unknown cause (idiopathic

pericarditis)

Inflammation of the pericardium following heart surgery or a heart attack

(Dressler's syndrome)

Autoimmune disorders, such as rheumatoid arthritis or lupus

Waste products in the blood due to kidney failure (uremia)

Underactive thyroid (hypothyroidism))

Spread of cancer (metastasis), particularly lung cancer, breast cancer,

melanoma, leukemia, non-Hodgkin's lymphoma or Hodgkin's disease

Cancer of the pericardium or heart

Radiation therapy for cancer if the heart was within the field of radiation

Chemotherapy treatment for cancer, such as doxorubicin (Doxil) and

cyclophosphamide (Cytoxan)

Trauma or puncture wound near the heart

Certain prescription drugs, including hydralazine, a medication for high

blood pressure; isoniazid, a tuberculosis drug; and phenytoin (Dilantin,

Phenytek, others), a medication for epileptic seizures 7

2.2.3. CLINICAL MANIFESTATION

The 1st symptom of pericardial disease is often precordial pain. The major

complaint is a sharp, stabbing sensation over the precordium and often the left

shoulder and back; the pain may be exaggerated by lying supine and relieved by

sitting, especially leaning forward. Because of the absence of sensory innervation

of the pericardium, the pain is probably referred pain from diaphragmatic and

pleural irritation. Cough, dyspnea, abdominal pain, vomiting, and fever may also

occur. The presence of symptoms or signs associated with other organs depends

on the cause of the pericarditis.

Many of the findings on physical examination are related to the degree of

fluid accumulation in the pericardial sac. The presence of a friction rub is helpful

but is a variable sign in acute pericarditis; it usually becomes apparent when the

effusion is small. When the effusion is larger, muffled heart sounds may be the

only auscultatory finding. Narrow pulses, tachycardia, neck vein distention, and

increased pulsus paradoxus suggest significant fluid accumulation.

Pulsus paradoxus is caused by the normal slight decrease in systolic

arterial pressure during inspiration. With cardiac tamponade, this normal

phenomenon is exaggerated, probably because of decreased filling of the left side

of the heart with the inspiratory phase of respiration. The degree of pulsus

paradoxus is determined with a mercury manometer. The patient is told to breathe

normally without exaggeration. By allowing the manometer to fall slowly, the 1st

Korotkoff sound will initially be heard intermittently (varying with respirations).

This 1st point is noted, and the manometer is then allowed to fall until the 1st

Korotkoff sound is heard continuously. The difference between these two systolic

pressures is the pulsus paradoxus. A pulsus paradoxus greater than 20 mm Hg in a

child with pericarditis is an indicator of the presence of cardiac tamponade; a 10–

20 mm Hg change is equivocal. Increased pulsus paradoxus may also be seen in

patients with severe dyspnea of any cause, in patients with pulmonary disease

(emphysema or asthma), in obese individuals, or in patients being ventilated with

a positive pressure respirator. In these patients, the paradoxical pulse is due to a

marked increase in intrathoracic pressure. The cause of a paradoxical pulse in a

child maintained on a ventilator after heart surgery may therefore be difficult to

assess.8

2.2.4. PATHOPHYSIOLOGY

The pericardium consists of 2 layers, the visceral pericardium

(epicardium) and the parietal pericardium, which enclose a potential space (ie, the

pericardial cavity) between them. This cavity is normally lubricated by a very

small amount of serous fluid (< 30 mL in adults). Inflammation of the pericardium

or obstruction of lymphatic drainage from the pericardium of any etiology causes

an increase in fluid volume, referred to as a pericardial effusion.

Pericardial inflammation results in an accumulation of fluid in the

pericardial space. The fluid varies according to the cause of the pericarditis and

may be serous, fibrinous, purulent, or hemorrhagic. Cardiac tamponade occurs

when the amount of pericardial fluid reaches a level that compromises cardiac

function. In a healthy child, 10–15 mL of fluid is normally found in the pericardial

space, whereas in an adolescent with pericarditis, fluid in excess of 1,000 mL may

accumulate. For every small increment of fluid, pericardial pressure rises slowly;

once a critical level is reached, pressure rises rapidly and culminates in severe

cardiac compression. Inhibition of ventricular filling during diastole, elevated

systemic and pulmonary venous pressure, and if untreated, eventual compromised

cardiac output and shock occur.

Malignant involvement of the pericardium may be primary (less common)

or secondary (spreading from a nearby or distant focus of malignancy). Secondary

neoplasms can involve the pericardium by contiguous extension from a

mediastinal mass, nodular tumor deposits from hematogenous or lymphatic

spread, and diffuse pericardial thickening from tumor infiltration (with or without

effusion). In diffuse pericardial thickening, the heart may be encased by

an effusive-constrictive pericarditis.

Other rare mechanisms include chronic myelomonocytic leukemia and

intrapericardial extramedullary hematopoiesis with preleukemic conditions or

during blast crisis in chronic myeloid leukemia. Obstruction of lymphatic

drainage by mediastinal tumors, either benign or malignant, can also give rise to

pericardial effusion, which can be chylous. These mechanisms may act

independently or jointly in any particular child with malignancy. The underlying

myocardium is not involved in most patients.6

2.2.5. CLINICAL MANIFESTATION

History

A patient with pericardial effusion may report the following symptoms:

Cardiovascularo Chest pain, pressure, discomfort: Characteristically, pericardial

pain may be relieved by sitting up and leaning forward and is intensified by lying supine.

o Light-headedness, syncope

o Palpitations

Respiratory

o Cough

o Dyspnea

o Hoarseness

Gastrointestinal

o Hiccoughs

Neurologic

o Anxiety

o Confusion

Physical

Upon examination, a patient with pericardial effusion may have the following signs:

Cardiovascularo Classic Beck triad of pericardial tamponade (hypotension, muffled

heart sounds, jugular venous distension).

o Pulsus paradoxus: Exaggeration of physiologic respiratory variation in systemic blood pressure, defined as a decrease in systolic blood pressure of more than 10 mm Hg with inspiration, signaling falling cardiac output during inspiration.

o Pericardial friction rub: The most important physical sign of acute pericarditis may have up to 3 components per cardiac cycle and is high-pitched, scratching, and grating. It can sometimes be elicited only when firm pressure with the diaphragm of the stethoscope is applied to the chest wall at the left lower sternal border. The pericardial friction rub is heard most frequently during expiration with the patient upright and leaning forward.

o Tachycardia

o Hepatojugular reflux: This can be observed by applying pressure to the periumbilical region. A rise in the jugular venous pressure (JVP) of greater than 3 cm H2 O for more than 30 seconds suggests elevated central venous pressure. Transient elevation in JVP may be normal.

Respiratory

o Tachypnea

o Decreased breath sounds (secondary to pleural effusions)[4 ]

o Ewart sign - Dullness to percussion beneath the angle of left scapula from compression of the left lung by pericardial fluid

Gastrointestinal - Hepatosplenomegaly

Extremities

o Weakened peripheral pulses

o Edema

o Cyanosis

Causes

In up to 60% of cases, pericardial effusion is related to a known or suspected underlying process. Therefore, the diagnostic approach should give strong consideration to coexisting medical conditions.

Idiopathic: In many cases, the underlying cause is not identified. However, this often relates to the lack of extensive diagnostic evaluation.

Infectious

o HIV infection can lead to pericardial effusion through several mechanisms, including the following:

Secondary bacterial infection

Opportunistic infection

Malignancy (Kaposi sarcoma, lymphoma)

"Capillary leak" syndrome, which is associated with effusions in other body cavities

o Viral: The most common cause of infectious pericarditis and myocarditis is viral. Common etiologic organisms include coxsackievirus A and B, and hepatitis viruses.

o Pyogenic (pneumococci, streptococci, staphylococci, Neisseria, Legionella species)

o Tuberculous

o Fungal (histoplasmosis, coccidioidomycosis, Candida)

o Other infections (syphilitic, protozoal, parasitic)

Neoplasia

o Neoplastic disease can involve the pericardium through the following mechanisms:

Direct extension from mediastinal structures or the cardiac chamber

Retrograde extension from the lymphatic system

Hematologic seeding

As mentioned previously, the most common cases of malignant effusion are lung, breast, lymphoma, and leukemia. However, patients with malignant melanoma or mesothelioma have a high prevalence of associated pericardial effusions.

Postoperative/postprocedural

o Pericardial effusions are common after cardiac surgery. In 122 consecutive patients studied serially before and after cardiac surgery, effusions were present in 103 patients; most appeared by postoperative day 2, reached their maximum size by postoperative day 10, and usually resolved without sequelae within the first postoperative month. In a retrospective survey of more than 4,500 postoperative patients, only 48 were found to have moderate or large effusions by echocardiography; of those, 36 met diagnostic criteria for tamponade.[5 ]

o Use of preoperative anticoagulants, valve surgery, and female sex were all associated with a higher prevalence of tamponade. Symptoms and physical findings of significant postoperative pericardial effusions are frequently nonspecific, and echocardiographic detection and echo-guided pericardiocentesis, when necessary, are safe and effective; prolonged catheter drainage reduces the recurrence rate.[6 ]

o Pericardial effusions in cardiac transplant patients are associated with an increased prevalence of acute rejection.[7 ]

Other less common causes include the following:

o Uremia

o Myxedema

o Severe pulmonary hypertension

o Radiation therapy

o Acute myocardial infarction, including the complication of free wall rupture

o Aortic dissection, leading to hemorrhagic effusion in from leakage into pericardial sac

o Trauma

o Hyperlipidemia

o Chylopericardium

o Familial Mediterranean fever

o Whipple disease

o Hypersensitivity or autoimmune related

Systemic lupus erythematosus [8 ]

Rheumatoid arthritis

Ankylosing spondylitis

Rheumatic fever

Scleroderma

Wegener granulomatosis

o Drug-associated (eg, procainamide, hydralazine, isoniazid, minoxidil, phenytoin, anticoagulants, methysergide)

2.2.6. DIAGNOSIS AND LABORATORY STUDIES

The extent to which pericardial effusions should be evaluated with fluid analysis remains an area of some debate. Initially, in a patient with a new pericardial effusion, the likelihood of myocarditis or pericarditis should be assessed, and the initial diagnostic evaluation should be directed toward these conditions. In general, all patients with pericardial tamponade, suspected purulent effusion, or poor prognostic indicators in the setting of pericarditis should undergo diagnostic pericardiocentesis. Those with recurrent effusions or large effusions that do not resolve with treatment of the underlying condition may also warrant fluid analysis.

The following lab studies may be performed in patients with suspected pericardial effusion.

Electrolytes - Metabolic abnormalities (eg, renal failure) CBC count with differential - Leukocytosis for evidence of infection, as

well as cytopenias, as signs of underlying chronic disease (eg, cancer, HIV)

Cardiac enzymes: Troponin level is frequently minimally elevated in acute pericarditis, usually in the absence of an elevated total creatine kinase level. Presumably, this is due to some involvement of the epicardium by the inflammatory process. Although the elevated troponin may lead to the misdiagnosis of acute pericarditis as a myocardial infarction, most patients with an elevated troponin and acute pericarditis have normal coronary angiograms. An elevated troponin level in acute pericarditis typically

returns to normal within 1-2 weeks and is not associated with a worse prognosis.

Thyroid-stimulating hormone - Thyroid-stimulating hormone screen for hypothyroidism

Rickettsial antibodies - If high index of suspicion of tick-borne disease

Rheumatoid factor, immunoglobulin complexes, antinuclear antibody test (ANA), and complement levels (which would be diminished) - In suspected rheumatologic causes

PPD and controls

Pericardial fluid analysis - Routine tests (these should be considered part of the standard pericardial fluid analysis)

o Lactic (acid) dehydrogenase (LDH), total protein - The Light criteria (for exudative pleural effusion) found to be as reliable in distinguishing between exudative and transudative effusions

Total protein fluid-to-serum ratio >0.5

LDH fluid-to-serum ratio >0.6

LDH fluid level exceeds two thirds of upper-limit of normal serum level

o Other indicators suggestive of exudate - Specific gravity >1.015, total protein >3.0 mg/dL, LDH >300 U/dL, glucose fluid-to-serum ratio <1

o Cell count - Elevated leukocytes (ie, >10,000) with neutrophil predominance suggests bacterial or rheumatic cause, although unreliable

o Gram stain - Specific but insensitive indicator of bacterial infection

o Cultures - Signals and identifies infectious etiology

o Fluid hematocrit for bloody aspirates - Hemorrhagic fluid hematocrits usually significantly less than simultaneous peripheral blood hematocrits

Pericardial fluid - Special tests (these should be considered individually based on the pretest probability of the coexisting condition under concern)

o Viral cultures

o Adenosine deaminase; polymerase chain reaction (PCR); culture for tuberculosis; smear for acid-fast bacilli in suspected tuberculosis infection, especially in patients with HIV

o A definite diagnosis of tuberculous pericarditis is based on the demonstration of tubercle bacilli in pericardial fluid or on a histological section of the pericardium. Probable tuberculous pericarditis is based on the proof of tuberculosis elsewhere in a patient with otherwise unexplained pericarditis, a lymphocytic pericardial exudate with elevated adenosine deaminase levels, and/or appropriate response to a trial of antituberculosis chemotherapy.

Tumor markers: Elevated carcinoembryonic antigen (CEA) levels in pericardial fluid have a high specificity for malignant effusions.

Imaging Studies

Chest radiography

Findings include enlarged cardiac silhouette (so-called water-bottle heart) and pericardial fat stripe.

Image is from a patient with malignant pericardial effusion. Note the "water-bottle" appearance of the cardiac silhouette in the anteroposterior (AP) chest film.

A third of patients have a coexisting pleural effusion. Radiography is unreliable in establishing or refuting diagnosis of

pericardial effusion.

EchocardiographyEchocardiography is the imaging modality of choice for the diagnosis of

pericardial effusion, as the test can be performed rapidly and in unstable patients. Most importantly, the contribution of pericardial effusion to overall cardiac enlargement and the relative roles of tamponade and myocardial dysfunction to altered hemodynamics can be evaluated with echocardiography.[9 ]

Echocardiogram (parasternal, long axis) of a patient with a moderate pericardial effusion.

Subcostal view of an echocardiogram that shows a moderate-to-large amount of pericardial effusion.

This echocardiogram shows a large amount of pericardial effusion (identified by the white arrows).

2-D echocardiographyo Pericardial effusion appears as an echo-free space between the

visceral and parietal pericardium. Early effusions tend to accumulate posteriorly owing to expandable posterior/lateral pericardium. Large effusions are characterized by excessive motion within the pericardial sac. Small effusions have an echo-free space of less than 10 mm, and are generally seen posteriorly. Moderate-sized effusions range from 10-20 mm and are circumferential, and greater than 20 mm indicates a large effusion. Fluid adjacent to the right atrium is an early sign of pericardial effusion.[10 ]

o Severe cases may be accompanied by diastolic collapse of the right atrium and right ventricle (and in hypovolemic patients, the left atrium and left ventricle), signaling the onset of pericardial tamponade (see Cardiac Tamponade).

o

This image is from a patient with malignant pericardial effusion. The effusion is seen as an echo-free region to the right of the left ventricle (LV).

M-mode echocardiographyo M-mode is adjunctive to 2D imaging for the detection of

pericardial effusion. Effusions can be classified using M-mode according to a system proposed by Horowitz, et al.[11 ]

Type A: No effusion

Type B: Separation of epicardium and pericardium

Type C1: Systolic and diastolic separation of pericardium

Type C2: Systolic and diastolic separation of pericardium, attenuated pericardial motion

Type D: Pronounced separation of pericardium and epicardium with large echo-free space

o In the parasternal long-axis view, discordant changes in right and left ventricular cavity size can suggest pronounced interventricular dependence.

Doppler echocardiography

o Transmitral and transtricuspid inflow velocities should be interrogated to assess for respiratory variation. Decreases in flow during inspiration (transmitral) or expiration (transtricuspid) should raise the suspicion of clinically significant interventricular dependence and tamponade physiology.

o Pulmonic vein inflow may show a decrease in early diastolic flow with hemodynamically significant effusions. Hepatic vein diastolic flow reversal may also be seen.

False-positive echocardiograms can occur in pleural effusions, pericardial thickening, increased epicardial fat tissue, atelectasis, and mediastinal lesions.

Epicardial fat tissue is more prominent anteriorly but may appear circumferentially, thus mimicking effusion. Fat is slightly echogenic and tends to move in concert with the heart, 2 characteristics that help distinguish it from an effusion, which is generally echolucent and motionless.[9 ]

In addition to its mimicry, pericardial fat accumulation is a source of bioactive molecules, is significantly associated with obesity-related insulin resistance, and may be a coronary risk factor.[12,13 ]

In patients with pericardial effusion, imaging from low to midposterior thorax can provide additional diagnostic echocardiographic images and should be used in patients in whom conventional images are technically difficult or require additional information.

Transesophageal echocardiography (TEE) 

TEE maintains all of the advantages of transthoracic echocardiography and is useful in characterizing loculated effusions. However, this may be difficult to perform in patients with symptomatic effusions due to hemodynamic instability, making the required sedation more difficult.

Intracardiac echocardiography (ICE)

ICE is generally reserved for the assessment of pericardial effusion in the setting of percutaneous interventional or electrophysiology procedure. Phased array ICE systems can perform both 2-D and Doppler interrogations.

Computed tomography

CT can potentially determine composition of fluid and may detect as little as 50 mL of fluid.

CT can detect pericardial calcifications, which can be indicative of constrictive pericarditis.

CT results in fewer false-positive results than echocardiography.

CT can be problematic in patients who are unstable given the time required to transport to and from the scanner and perform the test.

Magnetic resonance imaging MRI can detect as little as 30 mL of pericardial fluid. May be able to distinguish hemorrhagic and no hemorrhagic fluids, as

hemorrhagic fluids have a high signal intensity on T-1 weighted images, whereas no hemorrhagic fluids have a low signal intensity.

Nodularity or irregularity of the pericardium seen on MRI may be indicative of a malignant effusion.

MRI is more difficult to perform than CT scan acutely, given the length of time the patient must remain in the scanner.

Both MRI and CT scan may be superior to echocardiography in detecting loculated pericardial effusions, especially when located anteriorly. Also, these modalities allow for greater visualization of the thoracic cavity and adjacent structures, and therefore may identify other abnormalities relating to the cause of the effusion.Other Tests

Electrocardiography 

Early in the course of acute pericarditis, the ECG typically displays diffuse ST elevation in association with PR depression. The ST elevation is usually present in all leads except for aVR, but postmyocardial infarction pericarditis, the changes may be more localized. Classically, the ECG changes of acute pericarditis evolve through 4 progressive stages:

o Stage I - Diffuse ST-segment elevation and PR-segment depression

o Stage II - Normalization of the ST and PR segments

o Stage III - Widespread T-wave inversions

o Stage IV - Normalization of the T waves

This electrocardiogram (ECG) is from a patient with malignant pericardial effusion. The ECG shows diffuse low voltage, with a suggestion of electrical alternans in the precordial leads.

Patients with uremic pericarditis frequently do not have the typical ECG abnormalities.

2.2.7. DIFFERENTIAL DIAGNOSIS

Cardiac Tamponade Pericarditis, Constrictive-Effusive Cardiomyopathy, Dilated Pericarditis, Uremic Myocardial Infarction Pulmonary Edema, Cardiogenic Pericarditis, Acute Pulmonary Embolism Pericarditis, Constrictive

2.2.8. TREATMENT

Medical Care

Initially, medical care of pericardial effusion is focused on determination of the underlying etiology.

Aspirin/nonsteroidal anti-inflammatory agents (NSAIDs)o Most acute idiopathic or viral pericarditis occurrences are self-

limited and respond to treatment with aspirin (650 mg q6h) or another NSAID.

o Aspirin may be the preferred nonsteroidal agent to treat pericarditis after myocardial infarction because other NSAIDs may interfere with myocardial healing.

o Indomethacin should be avoided in patients who may have coronary artery disease.

o Meurin et al performed a multicenter, randomized, double-blind trial on the effect of the NSAID diclofenac in reducing postoperative pericardial effusion volume. Diclofenac, 50 mg, or placebo twice daily for 14 days was given to 196 patients at high risk for tamponade because of pericardial effusion more than 7 days after cardiac surgery. The authors found that diclofenac was not effective at reducing the size of the effusion or preventing late cardiac tamponade.[15 ]

Colchicine: The routine use of colchicine is supported by results from the COlchicine for acute PEricarditis (COPE) trial. In this trial, 120 patients with a first episode of acute pericarditis (idiopathic, acute, postpericardiotomy syndrome, and connective tissue disease) entered a randomized, open-label trial comparing aspirin treatment alone with aspirin plus colchicine (1-2 mg for the first day followed by 0.5-1 mg/d for 3 mo). Colchicine reduced symptoms at 72 hours (11.7% vs 36.7%; P =0.03) and reduced recurrence at 18 months (10.7% vs 36.7%; P =0.004; 5 needed treatment). Colchicine was discontinued in 5 patients because of diarrhea. No other adverse events were noted. Importantly, none of the 120 patients developed cardiac tamponade or progressed to pericardial constriction.[16 ]

Steroids

o Steroid administration early in the course of acute pericarditis appears to be associated with an increased incidence of relapse after tapering the steroids.

o In the COPE trial, steroid use was an independent risk factor for recurrence (odds ratio=4.3). Also, an observational study strongly suggests that the use of steroids increases the probability of relapse in patients treated with colchicine.[16 ]

o Systemic steroids should be considered only in patients with recurrent pericarditis unresponsive to NSAIDs and colchicine or as needed for treatment of an underlying inflammatory disease. If steroids are to be used, an effective dose (1-1.5 mg/kg of prednisone) should be given, and it should be continued for at least 1 month before slow tapering.

o The intrapericardial administration of steroids has been reported to be effective in acute pericarditis without producing the frequent reoccurrence of pericarditis that complicates the use of systemic steroids, but the invasive nature of this procedure limits its use.

Hemodynamic support

o Patients who have effusions with actual or threatened tamponade should be considered to have a true or potential emergency. Most patients require pericardiocentesis to treat or prevent tamponade. However, treatment should be carefully individualized.

o Hemodynamic monitoring with a balloon flotation pulmonary artery catheter is useful, especially in those with threatened or mild tamponade in whom a decision is made to defer pericardiocentesis. Hemodynamic monitoring is also helpful after pericardiocentesis to assess both reaccumulation and the presence of underlying constrictive disease. However, insertion of a pulmonary artery catheter should not be allowed to delay definitive therapy in critically ill patients.

o Intravenous fluid resuscitation may be helpful in cases of hemodynamic compromise.

o In patients with tamponade who are critically ill, intravenous positive inotropes (dobutamine, dopamine) can be used but are of limited use and should not be allowed to substitute for or delay pericardiocentesis.

Antibiotics

o In patients with purulent pericarditis, urgent pericardial drainage combined with intravenous antibacterial therapy (eg, vancomycin 1 g bid, ceftriaxone 1-2 g bid, and ciprofloxacin 400 mg/d) is mandatory. Irrigation with urokinase or streptokinase, using large catheters, may liquify the purulent exudate, but open surgical drainage is preferable.

o The initial treatment of tuberculous pericarditis should include isoniazid 300 mg/day, rifampin 600 mg/day, pyrazinamide 15-30 mg/kg/day, and ethambutol 15-25 mg/kg/day. Prednisone 1-2 mg/kg/day is given for 5-7 days and progressively reduced to discontinuation in 6-8 weeks. Drug sensitivity testing is essential. Uncertainty remains whether adjunctive corticosteroids are effective in reducing mortality or progression to constriction. Surgical resection of the pericardium remains the appropriate treatment for constrictive pericarditis. The timing of surgical intervention is controversial, but many experts recommend a trial of medical therapy for noncalcific pericardial constriction and pericardiectomy in nonresponders after 4-8 weeks of antituberculosis chemotherapy.

Antineoplastic therapy (eg, systemic chemotherapy, radiation) in conjunction with pericardiocentesis has been shown to be effective in reducing recurrences of malignant effusions.

Corticosteroids and NSAIDs are helpful in patients with autoimmune conditions.

Surgical Care

Surgical care of pericardial effusion includes the following:

Subxiphoid pericardial window with pericardiostomy[17 ]

o This procedure is associated with low morbidity, mortality, and recurrence rates, and can be considered as a reasonable alternative diagnostic or treatment modality to pericardiocentesis in selected patients.

o It can be performed under local anesthesia. This is advantageous because general anesthesia often leads to decreased sympathetic tone, resulting in hemodynamic collapse in patients with pericardial tamponade and shock.

o It may be less effective when effusion is loculated.

o One study indicated it may be safer and more effective at reducing recurrence rates than pericardiocentesis. However, only patients who were hemodynamically unstable underwent pericardiocentesis, and no change in overall survival rate was observed.

Thoracotomy

o This should be reserved for patients in whom conservative approaches have failed.

o Thoracotomy allows for creation of a pleuropericardial window, which provides greater visualization of pericardium.

o Thoracotomy requires general anesthesia and thus has higher morbidity and mortality rates than the subxiphoid approach.

Video-assisted thoracic surgery[18 ]

o Video-assisted thoracic surgery (VATS) enables resection of a wider area of pericardium than the subxiphoid approach without the morbidity of thoracotomy.

o The surgeon is able to create a pleuropericardial window and address concomitant pleural pathology, which is especially common in patients with malignant effusions.

o One disadvantage of VATS is that it requires general anesthesia with single lung ventilation, which may be difficult in otherwise seriously ill patients.

Median sternotomy

o This procedure is reserved for patients with constrictive pericarditis.

o Operative mortality rate is high (5-15%).

Consultations

A cardiologist should be involved in the care of patients with pericardial effusion.

Cardiothoracic surgery may be required for recurrent or complicated cases (see Surgical Care).

2.2.9. COMPLICATIONS

Pericardial tamponadeo Can lead to severe hemodynamic compromise and death.

o Heralded by equalization of diastolic filling pressures.

o Treat with expansion of intravascular volume (small amounts of crystalloids or colloids may lead to improvement, especially in hypovolemic patients) and urgent pericardial drainage. Avoid positive-pressure ventilation if possible, as this decreases venous return and cardiac output. Vasopressor agents are of little clinical benefit.

Chronic pericardial effusion

o Effusions lasting longer than 6 months.

o Usually well tolerated.

2.2.11. PROGNOSIS

Most patients with acute pericarditis recover without sequelae. Predictors of a worse outcome include the following: fever greater than 38°C, symptoms developing over several weeks in association with immunosuppressed state, traumatic pericarditis, pericarditis in a patient receiving oral anticoagulants, a large pericardial effusion (>20 mm echo-free space or evidence of tamponade), or failure to respond to NSAIDs. In a series of 300 patients with acute pericarditis, 254 (85%) did not have any of the high-risk characteristics and had no serious complications. Of these low-risk patients, 221 (87%) were managed as outpatients and the other 13% were hospitalized when they did not respond to aspirin.

Patients with symptomatic pericardial effusions from HIV/AIDS or cancer have high short-term mortality rates.

CHAPTER III

CASE REPORT

Name : DA

Age : 10 years

Sex : Male

Date of Admission : July, 21th 2013

Main Complaint : Pallor

History : Pallor happen since one months ago, History of bleeding was not found. Sign of other spontaneous bleeding wasn’t found. Patient also complains of fever for about seven days. Fever was remittent and relieved by consumption of anti-pyretic drugs. Patient also complains of cough for about three days. sputum (-). Dyspnoe (-). Nausea (+). Vomitting (-). Patient also complaint loss of appetite since 2 months ago. Patient just eating 3-4 tablespoon per meal.Patient admitted of having a significant weight loss in the last two months. Diarrhea(-). Patient also complains of abdomen distention since two months ago. History of blood transfusion was not found.

Immunization : complete

History of Feeding: 0-6 months of breastfeeding, 6 months-1 years old of breast

feeding & soft rice. 1 years of soft rice.

History of previous illness: Patient was referral from Rumah Sakit Bandung and

diagnosed as anemia

History of previous medications: IVFD Ringer Lactate, Ceftriaxone Injection, Ranitidine Injection, Paracetamol

Physical Examination

Body weight : 12kg

Height : 108 cm

Presens status

Sens. Compos Mentis, Body temperature: 37.1 oC, Pulse: 92 bpm, Respiratory

Rate: 30 bpm.

Localized status

1. Head : Eye : Light reflexes(+/+), isochoric pupil, conjunctiva palpebra

inferior ane (+/+), icteric (-/-) , Ear : Normal appereance ,Mouth : Sianosis

(-), Nose: Normal appereance.

2. Neck : Lymph node enlargement (-)

3. Thorax : Symmetrical fusiformis. Epigastrial retraction (-). HR: 92 bpm,

reguler, murmur (+) systolic grade III-IV RR: 30 bpm, reguler. Crackles (-/-),

interposed rib clearly visible

4. Abdomen: distention (+), symmetrical, Decreased soepel, Peristaltic (+)

normal. Hepar: palpable 4cm BAC, blunt edge, flat surface, Pain(-)

5. Extremities : Pulse 90 bpm, regular, adequate pressure and

volume,warm acral, CRT< 3”. TD: 90/60mmhg, muscle hypotrophy, little

subcutaneous fat left. Beggy pants(+), pitting oedem(-).

Laboratory Result:

July,21th 2013

Darah Lengkap (CBC)

Hemoglobin (HGB) g% 1.30 12.0-14.4

Eritrosit (RBC) 106/ mm3 0.77 4.75-4.85

Leukosit (WBC) 103/ mm3 5.19 4.5- 13.5

Hematokrit % 4.80 36 – 42

Trombosit (PLT) 103/ mm3 129 150-450

MCV fL 62.30 75-87

MCH Pg 16.90 25-31

MCHC g% 27.10 33-35

RDW % 34.30 11.6 – 14.8

Hitung Jenis

Neutrofil % 59.10 37 – 80

Limfosit % 40.10 20 – 40

Monosit % 0.60 2 – 8

Eosinofil % 0.00 1 – 6

Basofil % 0.200 0 – 1

Neutrofil Absolut 103/µL 3.07 2.4 - 7.3

Limfosit Absolut 103/µL 2.08 1.7 - 5.1

Monosit Absolut 103/µL 0.03 0.2 - 0.6

Eosinofil Absolut 103/µL 0.00 0.10 - 0.30

Basofil Absolut 103/µL 0.01 0 - 0.1

Laboratory Result:

July, 21th 2013

Homeostasis Function unit value Normal value

Protombin

APTT

detik 1.97

Trombin 0.91

METABOLISME

KARBOHIDRAT

Glukosa ad random Mg/dl 250.50 <200

GINJAL

Ureum Mg/dl 18.60 <50

Kreatinin Mg/dl 0.26 0.50-0.90

ELEKTROLIT

Natrium (Na) mEq/L 129 135-155

Kalium (K) mEq/L 4.0 3.6-5.5

Klorida (Cl) mEq/L 109 96-106

Differential Diagnosis

Thalassemia+ Marasmus type malnutrition

Working Diagnosis

Thalassemia + Marasmus type malnutrition

Treatment

- O2 1-2 l/I nasal canule

- IVFD D5% NacL 0.45%

- Folic acid 1x5mg , 1x1 mg

- Inj.Ampicilin 250mg/6 hr/IV

- Multivitamin without Fe 1Xcth I

- Vitamin A 200.000 IU

- Diet F75 110cc/2 hr/oral

- Transfusion

- Consult to Respirology department

- Consult to nutritionand metabolic disease department

FOLLOW UP

July, 22 - 25th 2013

S: Pallor

O: Sens: CM, Temp: 36.8 oC

Head Eye : Light reflexes(+/+), isochoric pupil, pale conjunctiva palpebra inferior

(+/+), icteric (-/-) , Ear : Normal appereance ,Mouth : Sianosis (-), Nose:

Normal appereance.

Thorax Symmetrical fusiformis. Epigastrial retraction (-). HR: 92 bpm, reguler,

murmur (+) systolic grade III-IV RR: 30 bpm, reguler. Crackles (-/-),

interposed rib clearly visible

Abdomen distention (+), symmetrical, Decreased soepel, Peristaltic (+) normal. Hepar:

palpable 4cm BAC, blunt edge, flat surface, Pain(-)

Extremities Pulse 90 bpm, regular, adequate pressure and volume,warm acral, CRT<

3”. TD: 90/60mmhg, muscle hypotrophy, little subcutaneous fat left. Beggy

pants(+), pitting oedem(-).

A: Thalassemia + Marasmus Type Malnutrition+ Moderate – Severe Pericardial effusion

P: O2 1-2 l/I nasal canule

- IVFD D5% NacL 0.45%

- Folic acid 1x5mg , 1x1 mg

- Inj.Ampicilin 250mg/6 hr/IV

- Multivitamin without Fe 1Xcth I

- Vitamin A 200.000 IU

- Diet F75 110cc/2 hr/oral

- Inj.furosemid 15mg/12h

- Spironolacton 2x12.5mg

- Premed Furosemid 1mg before transfusion

Plan :

- Echocardiography

- Consult Nutrition and Metabolic disease

- Transfusion

Laboratory Result:

July, 22th 2013

Homeostasis Function unit value Normal value

Ferritin Hasil menyusul

(Fe/iron) mg/dl 173 51-157

TIBC µg/dl 165 112-346

Hepar

Total bilirubin mg/dl 1.20 <1

Direct bilirubin mg/dl 0.74 0-0.2

ALP mg/dl 37 <300

AST/SGOT U/L 20 <38

ALT/SGPT U/L 11 <41

Echocardiography Result (25th July 2013) : Moderate-Severe Pericardial Effusion

July, 26-29th 2013

S: Dyspnoe (+), Pallor(+)

O: Sens: CM, Temp: 36.8 oC,

Head Eye : Light reflexes(+/+), isochoric pupil, pale conjunctiva palpebra inferior

(+/+), icteric (-/-) , Ear : Normal appereance ,Mouth : Sianosis (-), Nose:

Normal appereance.

Thorax Symmetrical fusiformis. Epigastrial retraction (-). HR: 92 bpm, reguler,

murmur (-)RR: 30 bpm, reguler. Crackles (-/-), interposed rib clearly visible

Abdomen distention (+), symmetrical, soepel, Peristaltic (+) normal. Hepar: palpable

4cm BAC, blunt edge, flat surface, Pain(-).

Extremitie

s

Pulse 90 bpm, regular, adequate pressure and volume,warm acral, CRT<

3”. TD: 90/60mmhg, muscle hypotrophy, little subcutaneous fat left. Beggy

pants(+), pitting oedem(-).

A: Thalassemia + Marasmus Type Malnutrition+ Moderate – Severe Pericardial effusion

P: O2 1-2 l/I nasal canule

- IVFD D5% NacL 0.45%

- Folic acid 1x1mg

- Inj.Ampicilin 250mg/6 hr/IV

- Multivitamin without Fe 1Xcth I

- Diet F75 110cc/2 hr/oral

- Inj.furosemid 15mg/12h

- Spironolacton 2x12.5mg

- Premed Furosemid 1mg before transfusion

Plan: Transfusion

July, 30-31th 2013

S: Dyspnoe (+), Pallor(+)

O: Sens: CM, Temp: 36.8 oC,

Head Eye : Light reflexes(+/+), isochoric pupil, pale conjunctiva palpebra inferior

(+/+), icteric (-/-) , Ear : Normal appereance ,Mouth : Sianosis (-), Nose:

Normal appereance.

Thorax Symmetrical fusiformis. Epigastrial retraction (-). HR: 92 bpm, reguler,

murmur (-)RR: 30 bpm, reguler. Crackles (-/-), interposed rib clearly visible

Abdomen distention (+), symmetrical, soepel, Peristaltic (+) normal. Hepar: palpable

4cm BAC, blunt edge, flat surface, Pain(-).

Extremitie

s

Pulse 90 bpm, regular, adequate pressure and volume,warm acral, CRT<

3”. TD: 90/60mmhg, muscle hypotrophy, little subcutaneous fat left. Beggy

pants(+), pitting oedem(-).

A: Thalassemia + Marasmus Type Malnutrition+ Moderate – Severe Pericardial effusion

P: O2 1-2 l/I nasal canule

- IVFD D5% NacL 0.45%

- Folic acid 1x1mg

- Inj.Ampicilin 250mg/6 hr/IV

- Multivitamin without Fe 1Xcth I

- Diet F75 110cc/2 hr/oral

- Inj.furosemid 15mg/12h

- Spironolacton 2x12.5mg

- Premed Furosemid 1mg before transfusion

Plan: Transfusion

Laboratory Result:

July,31th 2013

Darah Lengkap (CBC)

Hemoglobin (HGB) g% 9.40 12.0-14.4

Eritrosit (RBC) 106/ mm3 2.43 4.75-4.85

Leukosit (WBC) 103/ mm3 4.32 4.5- 13.5

Hematokrit % 17.60 36 – 42

Trombosit (PLT) 103/ mm3 37 150-450

MCV fL 72.40 75-87

MCH Pg 25.10 25-31

MCHC g% 34.70 33-35

RDW % 21.70 11.6 – 14.8

Hitung Jenis

Neutrofil % 71.50 37 – 80

Limfosit % 24.80 20 – 40

Monosit % 2.30 2 – 8

Eosinofil % 1.40 1 – 6

Basofil % 0.000 0 – 1

Neutrofil Absolut 103/µL 3.09 2.4 - 7.3

Limfosit Absolut 103/µL 1.07 1.7 - 5.1

Monosit Absolut 103/µL 0.10 0.2 - 0.6

Eosinofil Absolut 103/µL 0.06 0.10 - 0.30

Basofil Absolut 103/µL 0.00 0 - 0.1

GINJAL

Ureum Mg/dl 27.70 <50

Kreatinin Mg/dl 0.35 0.50-0.90

Uric Acid Mg/dl 3.6 <7.0

Hepar

Total bilirubin mg/dl 1.88 <1

Direct bilirubin mg/dl 1.46 0-0.2

ALP mg/dl 61 <300

AST/SGOT U/L 86 <38

ALT/SGPT U/L 33 <41

August 1-3th 2013

S: Dyspnoe (+), Pallor(+)

O: Sens: CM, Temp: 37 oC,

Head Eye : Light reflexes(+/+), isochoric pupil, pale conjunctiva palpebra inferior

(+/+), icteric (-/-) , Ear : Normal appereance ,Mouth : Sianosis (-), Nose:

Normal appereance.

Thorax Symmetrical fusiformis. Epigastrial retraction (-). HR: 92 bpm, reguler,

murmur (-)RR: 30 bpm, reguler. Crackles (-/-), interposed rib clearly visible

Abdomen distention (+), symmetrical, soepel, Peristaltic (+) normal. Hepar: palpable

4cm BAC, blunt edge, flat surface, Pain(-).

Extremitie

s

Pulse 90 bpm, regular, adequate pressure and volume,warm acral, CRT<

3”. TD: 90/60mmhg, muscle hypotrophy, little subcutaneous fat left. Beggy

pants(+), pitting oedem(-).

A: Thalassemia + Marasmus Type Malnutrition+ Moderate – Severe Pericardial effusion

P: O2 1-2 l/I nasal canule

- IVFD D5% NacL 0.45%

- Folic acid 1x1mg

- Inj.Ampicilin 250mg/6 hr/IV

- Multivitamin without Fe 1Xcth I

- Diet F75 110cc/2 hr/oral

- Inj.furosemid 15mg/12h

- Spironolacton 2x12.5mg

- Premed Furosemid 1mg before transfusion

Plan: Transfusion

Laboratory Result: August 2, 2013

Darah Lengkap (CBC)

Hemoglobin (HGB) g% 7.00 12.0-14.4

Eritrosit (RBC) 106/ mm3 2.68 4.75-4.85

Leukosit (WBC) 103/ mm3 2.40 4.5- 13.5

Hematokrit % 20.00 36 – 42

Trombosit (PLT) 103/ mm3 20 150-450

MCV fL 74.60 75-87

MCH Pg 26.10 25-31

MCHC g% 35.00 33-35RDW % 21.10 11.6 – 14.8

Hitung Jenis

Neutrofil % 52.00 37 – 80

Limfosit % 41.70 20 – 40

Monosit % 4.20 2 – 8

Eosinofil % 1.30 1 – 6

Basofil % 0.800 0 – 1

Neutrofil Absolut 103/µL 1.25 2.4 - 7.3

Limfosit Absolut 103/µL 1.00 1.7 - 5.1

Monosit Absolut 103/µL 0.10 0.2 - 0.6

Eosinofil Absolut 103/µL 0.03 0.10 - 0.30

Basofil Absolut 103/µL 0.02 0 - 0.1

August 4-6th 2013

S: Seizure(+), Dyspnoe(-)

O: Sens:GCS 10( E4M4V2), Temp: 38.2 oC,

Head Eye : Light reflexes(+/+), isochoric pupil, pale conjunctiva palpebra inferior

(-/-), icteric (-/-) , Ear : Normal appereance ,Mouth : Sianosis (-), Nose:

Normal appereance. Neck:

Thorax Symmetrical fusiformis. Epigastrial retraction (+). HR: 160 bpm, reguler,

murmur (-)RR: 20 bpm, reguler. Crackles (-/-), interposed rib clearly visible

Abdomen distention (+), symmetrical, soepel, Peristaltic (+) normal. Hepar: palpable

4cm BAC, blunt edge, flat surface, Pain(-).

Extremitie

s

Pulse 90 bpm, regular, adequate pressure and volume,warm acral, CRT<

3”. TD: 90/60mmhg, muscle hypotrophy, little subcutaneous fat left. Beggy

pants(+), pitting oedem(-), reflex physiology(+) Normal, reflex pathology(-)

A:Thalassemia + Marasmus Type Malnutrition+ Moderate – Severe Pericardial effusion+Central

Nervous System Infection (dd: Meningitis,Encephalitis, Meningoencephalitis)

P: O2 1-2 l/I nasal canule

- IVFD D5% NacL 0.225%

- Folic acid 1x1mg

- Inj.Ampicilin 500mg/6 hr/IV

- Inj Ceftriaxone 500mg/12hr IV

- Multivitamin without Fe 1Xcth I

- Diet F75 110cc/2 hr/oral

- Inj.furosemid 15mg/12h

- Spironolacton 2x12.5mg

- Premed Furosemid 1mg before transfusion

- Potassium Correction :KCL 5meQ +20cc D5% finish in 2 hours.(4/8/2013)

- Acidosis Correction 42meQ(1/2 dose myelon in 200cc D5% finish in 1 hour/240gtt/mikro

(5/8/2013)

Plan: Transfusion

Check AGDA post correction I

Laboratory Result: August 4, 2013

Darah Lengkap (CBC)

Hemoglobin (HGB) g% 11.40 12.0-14.4

Eritrosit (RBC) 106/ mm3 4.13 4.75-4.85

Leukosit (WBC) 103/ mm3 9.03 4.5- 13.5

Hematokrit % 33.20 36 – 42

Trombosit (PLT) 103/ mm3 73 150-450

MCV fL 80.40 75-87

MCH Pg 27.60 25-31

MCHC g% 34.30 33-35

RDW % 21.30 11.6 – 14.8

Hitung Jenis

Neutrofil % 75.70 37 – 80

Limfosit % 16.40 20 – 40

Monosit % 7.00 2 – 8

Eosinofil % 0.00 1 – 6

Basofil % 0.900 0 – 1

Neutrofil Absolut 103/µL 6.84 2.4 - 7.3

Limfosit Absolut 103/µL 1.48 1.7 - 5.1

Monosit Absolut 103/µL 0.63 0.2 - 0.6

Eosinofil Absolut 103/µL 0.00 0.10 - 0.30

Basofil Absolut 103/µL 0.08 0 - 0.1

Laboratory Result:

August,4 2013

AGDA

Ph 7.174 7.35-7.45

pCO2 mmHg 60.8 38-42

pO2 mmHg 164.3 85-42

Bikarbonat (HCO3) mmol/L 21.9 22-26

Total CO2 mmol/L 23.7 19-25

Kelebihan Basa (BE) Mmol/L -6.6 (-2)-(+2)

Saturasi % 98.6 95-100

METABOLISME

KARBOHIDRAT

Glukosa ad random Mg/dl 362.00 <200

GINJAL

Ureum Mg/dl 15.00 <50

Kreatinin Mg/dl 0.34 0.50-0.90

ELEKTROLIT

Natrium (Na) mEq/L 135 135-155

Kalium (K) mEq/L 2.8 3.6-5.5

Klorida (Cl) mEq/L 106 96-106

Laboratory Result:

August,5 2013

AGDA

Ph 7.27 7.35-7.45

pCO2 mmHg 24 38-42

pO2 mmHg 83.5 85-42

Bikarbonat (HCO3) mmol/L 11.0 22-26

Total CO2 mmol/L 11.7 19-25

Kelebihan Basa (BE) Mmol/L 14.2 (-2)-(+2)

Saturasi % 93.6 95-100

METABOLISME

KARBOHIDRAT

Glukosa ad random Mg/dl 94.1 <200

ELEKTROLIT

Natrium (Na) mEq/L 145 135-155

Kalium (K) mEq/L 3.4 3.6-5.5

Klorida (Cl) mEq/L 164 96-106

Laboratory Result: August 6, 2013

Darah Lengkap (CBC)

Hemoglobin (HGB) g% 9.80 12.0-14.4

Eritrosit (RBC) 106/ mm3 3.62 4.75-4.85

Leukosit (WBC) 103/ mm3 4.26 4.5- 13.5

Hematokrit % 28.60 36 – 42

Trombosit (PLT) 103/ mm3 147 150-450

MCV fL 79.00 75-87

MCH Pg 27.10 25-31

MCHC g% 34.30 33-35

RDW % 20.60 11.6 – 14.8

Hitung Jenis

Neutrofil % 51.20 37 – 80

Limfosit % 37.60 20 – 40

Monosit % 10.10 2 – 8

Eosinofil % 0.70 1 – 6

Basofil % 0.200 0 – 1

Neutrofil Absolut 103/µL 2.18 2.4 - 7.3

Limfosit Absolut 103/µL 1.61 1.7 - 5.1

Monosit Absolut 103/µL 0.43 0.2 - 0.6

Eosinofil Absolut 103/µL 0.03 0.10 - 0.30

Basofil Absolut 103/µL 0.01 0 - 0.1

Laboratory Result:

August,6 2013

AGDA

Ph 7.543 7.35-7.45

pCO2 mmHg 37.5 38-42

pO2 mmHg 179.3 85-42

Bikarbonat (HCO3) mmol/L 31.6 22-26

Total CO2 mmol/L 32.8 19-25

Kelebihan Basa (BE) Mmol/L 8.5 (-2)-(+2)

Saturasi % 99.7 95-100

METABOLISME

KARBOHIDRAT

Glukosa ad random Mg/dl 138 <200

ELEKTROLIT

Natrium (Na) mEq/L 132 135-155

Kalium (K) mEq/L 2.4 3.6-5.5

Klorida (Cl) mEq/L 96 96-106

August 7-9th 2013

S: Seizure(-), Dyspnoe(-)

O: Sens: GCS 10( E4M4V2) , Temp: 37.2 oC,

Head Eye : Light reflexes(+/+), isochoric pupil, pale conjunctiva palpebra inferior

(-/-), icteric (-/-) , Ear : Normal appereance ,Mouth : Sianosis (-), Nose:

Normal appereance. Neck:

Thorax Symmetrical fusiformis. Epigastrial retraction (-). HR: 110 bpm, reguler,

murmur (-)RR: 20 bpm, reguler. Crackles (-/-), interposed rib clearly visible

Abdomen symmetrical, soepel, Peristaltic (+) normal. Hepar: palpable 4cm BAC, blunt

edge, flat surface, Pain(-).

Extremities Pulse 110 bpm, regular, adequate pressure and volume,warm acral, CRT<

3”. TD: 90/60mmhg, muscle hypotrophy, little subcutaneous fat left. Beggy

pants(+), pitting oedem(-), reflex physiology(+) Normal, reflex pathology(-)

A:Thalassemia + Marasmus Type Malnutrition+ Moderate – Severe Pericardial effusion+Central

Nervous System Infection (dd: Meningitis,Encephalitis, Meningoencephalitis)

P:

- O2 1 l/I nasal canule

- IVFD D5% NacL 0.45% + KCL 12mEq 45 gtt/I micro

- Inj.Ampicilin 500mg/6 hr/IV

- Inj Ceftriaxone 500mg/12hr IV

- Multivitamin without Fe 1Xcth I

- Diet pediasure 140cc/3 hours

- Inj.furosemid 3x12mg

- Spironolacton 2x12.5mg

- Inj. Phenytoin 24mg/12 hours/iv in 20cc NaCl 0.9% (7-8/8/2013)

- IVFD D5% NaCl 0.9% Correction : 487cc finish in 24 hour(20gtt/I mikro9

(9/8/2013 1930WIB)

METABOLISME

KARBOHIDRAT (8/8/2013)

ELEKTROLIT

Natrium (Na) mEq/L 127 135-155

Kalium (K) mEq/L 4.7 3.6-5.5

Klorida (Cl) mEq/L 96 96-106

August 10-12th 2013

S: Seizure(-), Dyspnoe(-)

O: Sens: GCS 10( E4M4V2) , Temp: 37.2 oC,

Head Eye : Light reflexes(+/+), isochoric pupil, pale conjunctiva palpebra inferior

(-/-), icteric (-/-) , Ear : Normal appereance ,Mouth : Sianosis (-), Nose:

Normal appereance. Neck:

Thorax Symmetrical fusiformis. Epigastrial retraction (-). HR: 96 bpm, reguler,

murmur (-)RR: 20 bpm, reguler. Crackles (-/-), interposed rib clearly visible

Abdomen symmetrical, soepel, Peristaltic (+) normal. Hepar: palpable 4cm BAC, blunt

edge, flat surface, Pain(-).

Extremities Pulse 96 bpm, regular, adequate pressure and volume,warm acral, CRT<

3”. TD: 90/60mmhg, muscle hypotrophy, little subcutaneous fat left. Beggy

pants(+), pitting oedem(-), reflex physiology(+) Normal, reflex pathology(-)

A:Thalassemia + Marasmus Type Malnutrition+ Moderate – Severe Pericardial effusion+ seizure

ec (dd -Central Nervous System Infection / electrolit imbalance)

P:

- O2 1 l/I nasal canule

- IVFD D5% NacL 0.45% + KCL 12mEq 45 gtt/I micro

- Inj.Ampicilin 500mg/6 hr/IV

- Inj Ceftriaxone 500mg/12hr IV

- Multivitamin without Fe 1Xcth I

- Diet pediasure 140cc/3 hours

- Inj.furosemid 3x12mg

- Spironolacton 2x12.5mg

- Inj. Phenytoin 24mg/12 hours/iv in 20cc NaCl 0.9%

- plan : check EEG + head CT scan (12/8/2013)

KIMIA KLINIK (9/8/2013)

ELEKTROLIT

Natrium (Na) mEq/L 129 135-155

Kalium (K) mEq/L 4.3 3.6-5.5

Klorida (Cl) mEq/L 102 96-106

KIMIA KLINIK (11/8/2013)

ELEKTROLIT

Natrium (Na) mEq/L 126 135-155

Kalium (K) mEq/L 4.3 3.6-5.5

Klorida (Cl) mEq/L 106 96-106

KIMIA KLINIK

(12/8/2013)

ELEKTROLIT

Kalsium (Ca) mEq/L 9.5 9.2-11.0

Natrium (Na) mEq/L 135 135-155

Kalium (K) mEq/L 4.6 3.6-5.5

Phospor mEq/L 4.0 3.4-6.2

Klorida (Cl) mEq/L 102 96-106

Magnesium (Mg) mEq/L 1.65 1.4-1.7

Laboratory Result: August 12, 2013

Darah Lengkap (CBC)

Hemoglobin (HGB) g% 10.30 12.0-14.4

Eritrosit (RBC) 106/ mm3 3.88 4.75-4.85

Leukosit (WBC) 103/ mm3 9.20 4.5- 13.5

Hematokrit % 30.60 36 – 42

Trombosit (PLT) 103/ mm3 328 150-450

MCV fL 78.90 75-87

MCH Pg 26.50 25-31

MCHC g% 33.70 33-35

RDW % 19.30 11.6 – 14.8

Hitung Jenis

Neutrofil % 67.80 37 – 80

Limfosit % 25.70 20 – 40

Monosit % 6.10 2 – 8

Eosinofil % 0.10 1 – 6

Basofil % 0.300 0 – 1

Neutrofil Absolut 103/µL 6.24 2.4 - 7.3

Limfosit Absolut 103/µL 0.54 1.7 - 5.1

Monosit Absolut 103/µL 0.43 0.2 - 0.6

Eosinofil Absolut 103/µL 0.01 0.10 - 0.30

Basofil Absolut 103/µL 0.03 0 - 0.1

August 13-15th 2013

S: Seizure(-), Dyspnoe(-)

O: Sens: GCS 10( E4M4V2) , Temp: 37.2 oC,

Head Eye : Light reflexes(+/+), isochoric pupil, pale conjunctiva palpebra inferior

(-/-), icteric (-/-) , Ear : Normal appereance ,Mouth : Sianosis (-), Nose:

Normal appereance. Neck:

Thorax Symmetrical fusiformis. Epigastrial retraction (-). HR: 92 bpm, reguler,

murmur (-)RR: 20 bpm, reguler. Crackles (-/-), interposed rib clearly visible

Abdomen symmetrical, soepel, Peristaltic (+) normal. Hepar: palpable 4cm BAC, blunt

edge, flat surface, Pain(-).

Extremities Pulse 92 bpm, regular, adequate pressure and volume,warm acral, CRT<

3”. TD: 90/60mmhg, muscle hypotrophy, little subcutaneous fat left. Beggy

pants(+), pitting oedem(-), reflex physiology(+) Normal, reflex pathology(-)

A:Thalassemia + Marasmus Type Malnutrition+ Moderate – Severe Pericardial effusion+ seizure

ec (dd -Central Nervous System Infection / electrolit imbalance)

P:

- O2 1 l/I nasal canule

- IVFD D5% NacL 0.45% + KCL 12mEq 45 gtt/I micro

- Inj.Ampicilin 500mg/6 hr/IV

- Inj Ceftriaxone 500mg/12hr IV

- Multivitamin without Fe 1Xcth I

- Diet F75 160cc/3 hours/NGT

- Bacefort syr 1xcth I

- Cotrimoxsazol syr 2xcth I

- Inj.furosemid 3x12mg

- Spironolacton 2x12.5mg

- Inj. Phenytoin 24mg/12 hours/iv in 20cc NaCl 0.9%

- Inj. Phenobarbital 20mg/12 hours/iv in NaCl 0.9%

Immunoserologi

(13/8/2013)

Tiroid

T3 total ng/mL 1.13 0.8-2

T4 total Ug/dL 7.70 5-14

TSH uIU/mL 9.450 0.27-4.2

Kimia Klinik

albumin g/dL 4.1 3.8-5.4

Laboratory Result: August 13, 2013

Darah Lengkap (CBC)

Hemoglobin (HGB) g% 9.70 12.0-14.4

Eritrosit (RBC) 106/ mm3 3.65 4.75-4.85

Leukosit (WBC) 103/ mm3 10.36 4.5- 13.5

Hematokrit % 28.70 36 – 42

Trombosit (PLT) 103/ mm3 306 150-450

MCV fL 78.60 75-87

MCH Pg 26.60 25-31

MCHC g% 33.80 33-35

RDW % 19.40 11.6 – 14.8

Hitung Jenis

Neutrofil % 71.60 37 – 80

Limfosit % 20.20 20 – 40

Monosit % 6.90 2 – 8

Eosinofil % 0.70 1 – 6

Basofil % 0.600 0 – 1

Neutrofil Absolut 103/µL 7.42 2.4 - 7.3

Limfosit Absolut 103/µL 2.09 1.7 - 5.1

Monosit Absolut 103/µL 0.72 0.2 - 0.6

Eosinofil Absolut 103/µL 0.07 0.10 - 0.30

Basofil Absolut 103/µL 0.06 0 - 0.1

KIMIA KLINIK

(14/8/2013)

ELEKTROLIT

Kalsium (Ca) mEq/L 9.5 9.2-11.0

Magnesium (Mg) mEq/L 5.5 1.4-1.7

Phospor mEq/L 2.00 3.4-6.2

Tiroid

T3 total

T4 total

TSH

ng/mL

ug/dL

uIU/mL

0.88

7.00

6.020

0.8-2

5-14

0.27-4.2

August 16-18th 2013

S: Seizure(-), Dyspnoe(-)

O: Sens: GCS 10( E4M4V2) , Temp: 37.1 oC,

Head Eye : Light reflexes(+/+), isochoric pupil, pale conjunctiva palpebra inferior

(-/-), icteric (-/-) , Ear : Normal appereance ,Mouth : Sianosis (-), Nose:

Normal appereance. Neck:

Thorax Symmetrical fusiformis. Epigastrial retraction (-). HR: 96 bpm, reguler,

murmur (-)RR: 20 bpm, reguler. Crackles (-/-), interposed rib clearly visible

Abdomen symmetrical, soepel, Peristaltic (+) normal. Hepar: palpable 4cm BAC, blunt

edge, flat surface, Pain(-).

Extremities Pulse 96 bpm, regular, adequate pressure and volume,warm acral, CRT<

3”. TD: 90/60mmhg, muscle hypotrophy, little subcutaneous fat left. Beggy

pants(+), pitting oedem(-), reflex physiology(+) Normal, reflex pathology(-)

A:Thalassemia + Marasmus Type Malnutrition+ Moderate – Severe Pericardial effusion+ seizure

ec (dd -Central Nervous System Infection / electrolit imbalance)

P:

- O2 1 l/I nasal canule

- IVFD D5% NacL 0.45% + KCL 12mEq 45 gtt/I micro

- Inj.Ampicilin 500mg/6 hr/IV

- Inj Ceftriaxone 500mg/12hr IV

- Multivitamin without Fe 1Xcth I

- Inj.furosemid 3x12mg

- Spironolacton 2x12.5mg

- Inj. Phenytoin 20mg/12 hours/iv in 20cc NaCl 0.9% finish in 20 minutes.

- Inj. Phenobarbital 20mg/12 hours/iv in NaCl 0.9%

- IVFD NaCl 3% 65cc/12 hours/iv finish in 2 hours (17-18/8/2013)

- Diet F100 160cc/3 hours/NGT

Laboratory Result: August 16, 2013

Darah Lengkap (CBC)

Hemoglobin (HGB) g% 9.40 12.0-14.4

Eritrosit (RBC) 106/ mm3 3.58 4.75-4.85

Leukosit (WBC) 103/ mm3 17.95 4.5- 13.5

Hematokrit % 28.10 36 – 42

Trombosit (PLT) 103/ mm3 577 150-450

MCV fL 78.50 75-87

MCH Pg 26.30 25-31

MCHC g% 18.70 33-35

RDW % 19.20 11.6 – 14.8

Hitung Jenis

Neutrofil % 90.80 37 – 80

Limfosit % 5.80 20 – 40

Monosit % 3.30 2 – 8

Eosinofil % 0.00 1 – 6

Basofil % 0.100 0 – 1

Neutrofil Absolut 103/µL 16.30 2.4 - 7.3

Limfosit Absolut 103/µL 1.04 1.7 - 5.1

Monosit Absolut 103/µL 0.59 0.2 - 0.6

Eosinofil Absolut 103/µL 0.00 0.10 - 0.30

Basofil Absolut 103/µL 0.02 0 - 0.1

KIMIA KLINIK

(16/8/2013)

ELEKTROLIT

Kalsium (Ca) mEq/L 9.9 9.2-11.0

Natrium (Na) mEq/L 134 135-155

Kalium (K) mEq/L 4.4 3.6-5.5

Phospor mEq/L 6.4 3.4-6.2

Klorida (Cl) mEq/L 106 96-106

Magnesium (Mg) mEq/L 2.16 1.4-1.7

CHAPTER IV

DISCUSSION AND SUMMARY