CASE REPORT

Hb E / β - THALASSEMIA MAJOR IN AN ADOLESCENT BOY

Authors :

- Dessy Indri Astuti 090100120

- Sherwin 100100114

Supervisor:

dr. Olga RasiyantiSiregar,M.Ked (Ped), Sp.A

CHILD HEALTH DEPARTMENT

H.ADAM MALIK CENTRAL GENERAL HOSPITAL

FACULTY OF MEDICINE

UNIVERSITY OF SUMATERA UTARA

MEDAN

2014

i

PREFACE

Praise and gratitude the presence of Almighty God, who has given his blessing

and grace so that we can finish writing up this paper with the heading"Hb E / β -

Thalassemia Major".

Writing of this paper is one of the requirements to complete the senior clinical

work of Department of Pediatric of the Medical Education Program, Faculty of

Medicine, University of Sumatera Utara. On this occasion, the authors want to

give the best gratitude and the highest appreciation to dr. Olga

RasiyantiSiregar,M.Ked (Ped), Sp.A as the supervisor who has been guiding and

advising in finishing writing this paper so we can finish it on time.

The authors fully aware that the writing of this paper is far from being perfect,

both of the content and language structure, to the authors welcome any

suggestions and criticisms from readers who can establish the perfection of this

paper. Hopefully this paper will be useful. Thank you very much.

Medan, March23th 2014

Authors

ii

LIST OF CONTENTS

Preface ................................................................................................................. i

List of Contents.................................................................................................... ii

Chapter 1 Introduction....................................................................................... 1

1.1. Background............................................................................................. 11.2. Objective ................................................................................................ 1

Chapter 2 Literature Review.............................................................................. 3

2.1. Definition................................................................................................. 2

2.2. Epidemiology.......................................................................................... 2

2.3. Pathophysiology...................................................................................... 2

2.4. Classification........................................................................................... 3

2.5. Clinical manifestation.............................................................................. 4

2.6. Laboratory finding................................................................................... 8

2.7. Treatment................................................................................................. 9

2.8. Complication………………………………………………………….. 13

Chapter 3 Case Report........................................................................................ 14

Chapter 4 Discussion and Summary.................................................................. 21

References............................................................................................................ 24

1

Chapter 1

INTRODUCTION

1.1. Background

The thalassemias are the most common genetic disorder on a worldwide basis.

The selective pressures that have made the thalassemias so common are not

known, but are assumed to relate to the geographic distribution of malaria.

Children with thalassemias have a shorter red cell life, fetal hemoglobin in their

red cells until an older age than normal, and red cells that are more sensitive to

oxidative stress. The thalassemias are inherited disorders of hemoglobin synthesis.

Their clinical severity widely varies, ranging from asymptomatic forms to severe

or even fatal entities.1

Three percent of the world’s population carry genes for β-thalassemia, and

in Southeast Asia 5%-10% of the population carry genes for α-thalassemia. In a

particular are there are fewer common alleles. Worldwide, 15 million people have

clinically apparent thalassemic disorders. β-thalassemia is common in southern

Europe, the Middle East, India, and Africa. α-thalassemia is more common in

Southern Asia. Both sexes are equally affected with thalassemia.2

1.2. Objective

The aim of this paper is to complete the assignment in following the doctor’s

professional education program in the department of pediatrics. In addition,

providing knowledge to the author and readers about thalassemia.

2

Chapter 2

LITERATURE REVIEW

THALASSEMIA

2.1. Definition

The thalassemias are a heterogeneous group of disorders of hereditary anemia due

to diminished or absent normal globin chain production. Normally, four alpha-

globin genes and two beta-globin genes are expressed to make the tetrameric

globin protein, which then combines with a heme moiety to make the predominant

hemoglobin that is found in red cells, HbA (subunits α2 β2). Depending on the

number of genes that are deleted, the production of polypeptide chains is

diminished. In patients with alpha-thalassemia, alpha-globin production is

lowered; in patients with beta-thalassemia, beta-globin production is lowered.

When one class of polypeptide chains is diminished, this leads to a relative excess

of the other chain. The result is ineffective erythropoiesis, precipitation of

unstable hemoglobins, and hemolysis as a result of intramedullary RBC

destruction.3

2.2. Epidemiology

Thalassemia is among the most common genetic disorders worldwide; 4.83

percent of the world's population carry globin variants, including 1.67 percent of

the population who are heterozygous for α-thalassemia and β-thalassemia. In

addition, 1.92 percent carry sickle hemoglobin, 0.95 percent carry hemoglobin E,

and 0.29 percent carry hemoglobin C. Thus, the worldwide birth rate of people

who are homozygous or compound heterozygous for symptomatic globin

disorders, including α-thalassemia and β-thalassemia, is no less than 2.4 per 1000

births, of which 1.96 have sickle cell disease and 0.44 have thalassemias.5

3

2.3 Pathophysiology

Mutations in β-thalassemia involve globin gene deletions, promoter region

mutations, termination mutations, splices site mutations, and other rare mutations.

There are relatively few α-thalassemia mutations; most are deletions. The key

feature is the fact that there is a globin chain imbalance. In the bone marrow the

thalassemic mutations disrupt the maturation of the red cell, resulting in

ineffective erythropoiesis; the marrow is hyperactive, but there are relatively few

reticulocytes and severe anemia. In β-thalassemias there is an excess of α-globin

chains relative to β and γ globin chains; α-globin tetramers (α4) are formed, and

these inclusions interact with the red cell membrane and shorten red cell survival,

leading to anemia and increased erythroid production. The γ-globin chains are

produced in normal amounts, leading to an elevated Hb F (α2γ2). The δ-globin

chains are also produced in normal amounts leading to an elevated Hb A2 (α2δ2)

in β-thalassemia. In α-thalassemia there are relatively fewer α-globin chains and

an excess of β and γ globin chains. These excess chains form Bart’s hemoglobin

(γ4) in fetal life and Hb H (β4) after birth. These abnormal tetramers are not lethal

but lead to extravascular hemolysis.1

2.4. Classification

Most thalassemias are inherited as recessive traits. Beta-thalassemias can be

classified into:

- Beta-thalassemia:

• Thalassemia major

•Thalassemia intermedia

•Thalassemia minor

- Beta-thalassemia with associated Hb anomalies:

• HbC/Beta-thalassemia

• HbE/Beta-thalassemia

• HbS/Beta-thalassemia (clinical condition more similar to sickle cell disease than

to thalassemia major or intermedia)

- Hereditary persistence of fetal Hb and beta-thalassemia

4

- Autosomal dominant forms

- Beta-thalassemia associated with other manifestations

• Beta-thalassemia-tricothiodystrophy

• X-linked thrombocytopenia with thalassemia.6

2.5. Clinical Manifestation

The phenotypes of homozygous or genetic heterozygous compound beta-

thalassemias include thalassemia major and thalassemia intermedia. Individuals

with thalassemia major usually come to medical attention within the first two

years of life and require regular RBC transfusions to survive. Thalassemia

intermedia includes patients who present later and do not require regular

transfusion. Except in the rare dominant forms, heterozygous beta-thalassemia

results in the clinically silent carrier state. HbE/beta-thalassemia and HbC/beta-

thalassemia exhibit a great range in terms of diversity of phenotypes and spectrum

of severity.

Beta-thalassemia major

Clinical presentation of thalassemia major occurs between 6 and 24 months.

Affected infants fail to thrive and become progressively pale. Feeding problems,

diarrhea, irritability, recurrent bouts of fever, and progressive enlargement of the

abdomen caused by spleen and liver enlargement may occur. In some developing

countries, where due to the lack of resources patients are untreated or poorly

transfused, the clinical picture of thalassemia major is characterized by growth

retardation, pallor, jaundice, poor musculature, genu valgum,

hepatosplenomegaly, leg ulcers, development of masses from extramedullary

hematopoiesis, and skeletal changes resulting from expansion of the bone marrow.

Skeletal changes include deformities in the long bones of the legs and typical

craniofacial changes (bossing of the skull, prominent malar eminence, depression

of the bridge of the nose, tendency to a mongoloid slant of the eye, and

hypertrophy of the maxillae, which tends to expose the upper teeth).

5

If a regular transfusion program that maintains a minimum Hb concentration of

9.5 to 10.5 g/dL is initiated, growth and development tends to be normal up to 10

to 12 years. Transfused patients may develop complications related to iron

overload. Complications of iron overload in children include growth retardation

and failure or delay of sexual maturation. Later iron overload-related

complications include involvement of the heart (dilated myocardiopathy or rarely

arrythmias), liver (fibrosis and cirrhosis), and endocrine glands (diabetes mellitus,

hypogonadism and insufficiency of the parathyroid, thyroid, pituitary, and, less

commonly, adrenal glands). Other complications are hypersplenism, chronic

hepatitis (resulting from infection with viruses that cause hepatitis B and/or C),

HIV infection, venous thrombosis, and osteoporosis. The risk for hepatocellular

carcinoma is increased in patients with liver viral infection and iron overload.

Compliance with iron chelation therapy (see later) mainly influences frequency

and severity of the iron overload-related complications. Individuals who have not

been regularly transfused usually die before the second-third decade. Survival of

individuals who have been regularly transfused and treated with appropriate

chelation extends beyond age of 40 years. Cardiac disease caused by myocardial

siderosis is the most important life-limiting complication of iron overload in beta-

thalassemia. In fact, cardiac complications are the cause of the deaths in 71% of

the patients with beta-thalassemia major.

Beta-thalassemia intermedia

Individuals with thalassemia intermedia present later than thalassemia major, have

milder anemia and by definition do not require or only occasionally require

transfusion. At the severe end of the clinical spectrum, patients present between

the ages of 2 and 6 years and although they are capable of surviving without

regular blood transfusion, growth and development are retarded. At the other end

of the spectrum are patients who are completely asymptomatic until adult life with

only mild anemia. Hypertrophy of erythroid marrow with the possibility of

extramedullary erythropoiesis, a compensatory mechanism of bone marrow to

overcome chronic anemia, is common. Its consequences are characteristic

6

deformities of the bone and face, osteoporosis with pathologic fractures of long

bones and formation of erythropoietic masses that primarily affect the spleen,

liver, lymph nodes, chest and spine. Enlargement of the spleen is also a

consequence of its major role in clearing damaged red cells from the bloodstream.

Extramedullary erythropoiesis may cause neurological problems such as spinal

cord compression with paraplegia and intrathoracic masses. As a result of

ineffective erythropoiesis and peripheral hemolysis, thalassemia intermedia

patients may develop gallstones, which occur more commonly than in thalassemia

major. Patients with thalassemia intermedia frequently develop leg ulcers and

have an increased predisposition to thrombosis as compared to thalassemia major,

especially if splenectomised. Such events include deep vein thrombosis, portal

vein thrombosis, stroke and pulmonary embolism.

Although individuals with thalassemia intermedia are at risk of iron

overload secondary to increased intestinal iron absorption, hypogonadism,

hypothyroidism and diabetes are not common. Women may have successful

spontaneous pregnancies. However, if blood transfusions are necessary during

pregnancy, those never or minimally transfused are at risk of developing

hemolytic alloantibodies and erythrocyte autoantibodies. Intrauterine growth

retardation, despite a regular transfusion regimen, has been reported. Cardiac

involvement in thalassemia intermedia results mainly from a high-output state and

pulmonary hypertension, while systolic left ventricle function is usually

preserved. Pseudoxantomaelasticum, a diffuse connective tissue disorder with

vascular manifestation caused by degeration of the elastic lamina of the arterial

wall and calcium deposition, has been described in such patients.

Beta-thalassemia minor

Carriers of thalassemia minor are usually clinically asymptomatic but sometimes

have a mild anemia. When both parents are carriers there is a 25% risk at each

pregnancy of having children with homozygous thalassemia.

7

Dominant beta-thalassemia

In contrast with the classical recessive forms of beta-thalassemia, which lead to a

reduced production of normal beta globin chains, some rare mutations result in the

synthesis of extremely unstable beta globin variants which precipitate in erythroid

precursors causing ineffective erythropoiesis. These mutations are associated with

a clinically detectable thalassemia phenotype in the heterozygote and are therefore

referred to as dominant beta-thalassemias. The presence of hyper-unstable Hb

should be suspected in any individual with thalassemia intermedia when both

parents are hematologically normal, or in families with a pattern of autosomal

dominant transmission of the thalassemia intermedia phenotype. Beta globin gene

sequencing establishes the diagnosis.

Beta-thalassemia associated with other Hb anomalies

The interaction of HbE and beta-thalassemia results in thalassemia phenotypes

ranging from a condition indistinguishable from thalassemia major to a mild form

of thalassemia intermedia. Depending on the severity of symptoms three

categories may be identified:

- Mild HbE/beta-thalassemia: It is observed in about 15% of all cases in Southeast

Asia. This group of patients maintains Hb levels between 9 and 12 g/dl and

usually does not develop clinically significant problems. No treatment is required.

- Moderately severe HbE/beta-thalassemia: The majority of HbE/beta-thalassemia

cases fall into this category. The Hb levels remain at 6-7 g/dl and the clinical

symptoms are similar to thalassemia intermedia. Transfusions are not required

unless infections precipitate further anemia. Iron overload may occur.

- Severe HbE/beta-thalassemia: The Hb level can be as low as 4-5 g/dl. Patients in

this group manifest symptoms similar to thalassemia major and are treated as

thalassemia major patients.

Patients with HbC/beta-thalassemia may live free of symptoms and be diagnosed

during routine tests. When present, clinical manifestations are anemia and

enlargement of the spleen. Blood transfusions are seldom required.

8

Microcytosisand hypochromia are found in every case. The blood film shows

distinctive Hb C crystals with straight parallel edges, target cells, and irregularly

contracted cells with features of thalassemia such as microcytosis.

The association of hereditary persistence of fetal Hb (HPFH) with beta-

thalassemia mitigates the clinical manifestations which vary from normal to

thalassemia intermedia.

Individuals with HbS/beta-thalassemia have a clinical course similar to that of Hb

SS.

Beta-thalassemia associated with other features

In rare instances the beta-thalassemia defect does not lie in the beta globin gene

cluster. In cases in which the beta-thalassemia trait is associated with other

features, the molecular lesion has been found either in the gene encoding the

transcription factor TFIIH (beta-thalassemia trait associated with

tricothiodystrophy) or in the X-linked transcription factor GATA-1 (X-linked

thrombocytopenia with thalassemia).6

2.6. Laboratory Finding

Children with β-thalassemia minor have normal neonatal screening result but

subsequently develop a decreased MCV with or without mild anemia. The

peripheral blood smear typically shows hypochromia, target cells, and sometimes

basophilic stippling. Hemoglobin electrophoresis performed after 6-12 months of

age is usually diagnostic when level of hemoglobin A2, hemoglobin F, or both are

elevated. Beta thalassemia major is often initially suspected when HbA is absent

on neonatal screening. Such infants are hematologically normal at births but

develop severe anemia after the first few months of life. The peripheral blood

smear typically shows a severe hypochromic, microcytic anemia with marked

anisocytosis and poikilocytosis. Target cells are prominent, and nucleated red

blood cells often exceed the number of circulating white blood cells. The

hemoglobin level usually falls to 5-6 g/dL or less, and the reticulocyte count is

9

elevated significantly. Platelet and white blood cell counts may be increased, and

the serum bilirubin level is elevated. the bone marrow shows marked erythroid

hyperplasia but is rarely needed for diagnosis. Hemoglobin electrophoresis shows

only fetal hemoglobin and hemoglobin A2 in children with homozygous β0-

thalassemia. Those with β+ thalassemia genes make some hemoglobin A but have

a marked increase in fetal hemoglobin and hemoglobin A2 levels. The diagnosis

of homozygous β-thalassemia may also be suggested by the finding of β-

thalassemia minor in both parents.4

2.7. Treatment

The goals of transfusion therapy are correction of anemia, suppression of

erythropoiesis and inhibition of gastrointestinal iron absorption, which occurs in

non-transfused patients as a consequence of increased, although ineffective,

erythropoiesis. The decision to start transfusion in patients with confirmed

diagnosis of thalassemia should be based on the presence of severe anemia (Hb< 7

g/dl for more than two weeks, excluding other contributory causes such as

infections). However, also in patients with Hb> 7 g/dl, other factors should be

considered, including facial changes, poor growth, evidence of bony expansion

and increasing splenomegaly. When possible, the decision to start regular

transfusions should not be delayed until after the second- third year, due to the

risk of developing multiple red cell antibodies and subsequent difficulty in finding

suitable blood donors. Several different transfusional regimens have been

proposed over the years, but the most widely accepted aims at a pre-

transfusionalHb level of 9 to 10 g/dl and a post-transfusion level of 13 to 14 g/dl.

This prevents growth impairrment, organ damage and bone deformities, allowing

normal activity and quality of life. The frequency of transfusion is usually every

two to four weeks. Shorter intervals might further reduce the overall blood

requirement, but are incompatible with an acceptable quality of life. The amount

of blood to be transfused depends on several factors including weight of the

patient, target increase in Hb level and hematocrit of blood unit. In general, the

amount of transfused RBC should not exceed 15 to 20 ml/kg/day, infused at a

10

maximum rate of 5 ml/kg/hour, to avoid a fast increase in blood volume. To

monitor the effectiveness of transfusion therapy, some indices should be recorded

at each transfusion, such as pre- and post-transfusion Hb, amount and hematocrit

of the blood unit, daily Hb fall and transfusional interval. These measurements

enable two important parameters to be calculated: red cell requirement and iron

intake. Dedicated computerized programs (Webthal) are available to monitor

transfused thalassemia patients accurately. Although red cell transfusions are

lifesavers for patients with thalassemia, they are responsible for a series of

complications and expose the patients to a variety of risks. Iron overload is the

most relevant complication associated with transfusion therapy.6

Iron Overload Management

Iron overload causes most of the mortality and morbidity associated with

thalassemia. Iron deposition occurs in visceral organs (mainly in the heart, liver,

and endocrine glands), causing tissue damage and ultimately organ dysfunction

and failure. Cardiac events due to iron overload are still the primary cause of

death. Both transfusional iron overload and excess gastrointestinal absorption are

contributory. Paradoxically, excess gastrointestinal iron absorption persists

despite massive increases in total body iron load.5

Hepcidin is a small peptide that inhibits iron absorption in the small

bowel. Hepcidin levels normally increase when iron stores are elevated. Hepcidin

levels were found to be inappropriately low in patients with thalassemia

intermedia and thalassemia major. Furthermore, serum from patients with

thalassemia inhibited hepcidin messenger RNA expression in the HepG2 cell line,

which suggests the presence of a humoral factor that down-regulates

hepcidin. These observations suggest that the administration of hepcidin or agents

that increase hepcidin expression may be therapeutically useful for the inhibition

of inappropriate iron absorption.5

Accurate, preferably noninvasive measurement of iron stores is crucial for

the evaluation and management of chelation therapy. Serum ferritin is most

commonly measured as an indicator of iron stores. Ferritin levels below 2500 mg

11

per milliliter are associated with improved survival, free of cardiac

disease. However, serum ferritin levels are highly unreliable, particularly when

liver disease is present.Liver biopsy has often been used but is invasive. Direct

noninvasive measurement of hepatic iron stores is possible with the technique of

magnetic susceptometry (with the use of a superconducting quantum-interference

device) and is either equivalent to or more accurate than the measurement of

hepatic iron by liver biopsy. However, only four centers worldwide currently have

this capacity.5

It is noteworthy that hepatic iron may not accurately represent iron

deposition in other vital organs (such as the heart). Indeed, severe cardiac damage

has been observed in a few patients with presumably adequate chelation, and

myocardial iron and left ventricular function apparently cannot be predicted from

liver iron concentration, ferritin levels, or both. Therefore, noninvasive techniques

for the measurement of cardiac iron levels are being developed. Magnetic

resonance imaging (MRI) for the measurement of cardiac iron is technically

problematic. However, the application of T2gradient-echo sequencing is more

sensitive to hemosiderin deposition and appears to be useful for the measurement

of myocardial iron in thalassemia, but this approach requires further validation

and long-term studies to determine its usefulness in assessing the effectiveness of

chelation therapy.5

Elevated tissue iron stores are only one component of the damaging effects

of iron overload. A highly toxic form of iron, non–transferrin-bound iron, is

formed when the iron-binding capacity of transferrin has been exceeded. Non–

transferrin-bound iron is highly toxic because it can catalyze the formation of

reactive oxygen species through the Fenton reaction. A fraction of non–

transferrin-bound iron, the labile plasma iron, can be measured directly and may

serve as a clinically useful test for monitoring iron-chelation therapy.5

Iron-chelation therapy is largely responsible for doubling the life

expectancy of patients with thalassemia major. Deferoxamine continues to be the

most common iron-chelating agent in use, but it has several limitations: the need

12

for parenteral administration (which is painful and reduces compliance), side

effects, and cost (which is prohibitive in underdeveloped countries).

Much effort has been invested in the development of new orally active chelators.

Deferiprone, an orally administered chelator, was initially thought to be an

inadequate chelator that might worsen hepatic fibrosis. However, cumulative

worldwide experience indicates that the drug is safe and effective. Long-term

administration of deferiprone does not appear to be associated with liver

damage. Adverse effects of deferiprone include arthralgia, nausea and other

gastrointestinal symptoms, fluctuating liver enzyme levels, leukopenia, and rarely

agranulocytosis and zinc deficiency. Most of these effects can be monitored and

controlled.5

Deferiprone has a number of advantages over deferoxamine. It can

penetrate the cell membrane and chelate toxic intracellular iron species. In a

preliminary study, hemoglobin levels increased and transfusion requirements

decreased in a few patients with hemoglobin E thalassemia who were treated with

deferiprone for an average of 50 weeks.Most important, recent evidence suggests

that deferiprone may be more effective than deferoxamine in the removal of

myocardial iron.5

An encouraging new approach to chelation therapy is the sequential

combined administration of deferiprone and deferoxamine. Experimental evidence

suggests that intracellular iron chelated by deferiprone is transferred in the plasma

to the more powerful chelator, deferoxamine (the so-called “shuttle

hypothesis”). As a consequence, more iron is excreted with the use of combined

therapy than with the separate administration of each drug. Furthermore, the

compliance of patients was improved with the use of combined therapy because

fewer painful injections of deferoxamine were required.5

A number of new oral iron chelators are under development. Deferasirox

(ICL670) is particularly promising for its efficacy, which may be similar to that of

deferoxamine. Deferasirox is administered once daily and appears to have an

acceptable side-effect profile. Toxic effects that have been observed have been

related mainly to iron deprivation and transient gastrointestinal symptoms. No

13

cases of agranulocytosis have been reported in several phase 2 trials involving

several hundred patients.In summary, a growing body of evidence suggests that

deferiprone is an acceptable alternative for patients who are unable to receive

deferoxamine. The combination of deferiprone and deferoxamine appears very

promising but requires further verification. The preliminary data on deferasirox

are encouraging, and long-term clinical trials are still required. Finally, improved

noninvasive technologies (including imaging and blood tests) for quantitation of

iron overload will provide reliable information for the assessment of the efficacy

of present and future therapies.5

2.8.Complication

The life of patients with thalassemia has improved both in duration and in quality

in industrialized countries. Complications are still common and include heart

disease (heart failure and arrhythmias), chronic liver hepatitis, which can evolve

in cirrhosis and, rarely, in hepatocellular carcinoma, endocrine problems

(hypogonadism, hypothyroidism, diabetes, hypoparathyroidism), stunted growth,

osteoporosis, thrombophilia and pseudoxanthomaelasticum. The incidence of

complications is decreasing in younger cohorts of patients who have been

transfused with blood that has been screened for viruses and thanks to the

introduction of new oral iron chelators and imaging methods. The accurate

measurement of iron deposits allows better management of iron overload. In

addition, therapy for several complications is available.7

14

Chapter 3

CASE REPORT

IDENTITY

Name : N

Age : 7 years

Sex : Male

RM : 00.63.82.74

Address : Dusun IX Purwosari

Date of Admission : April,5 2015.

Main Complaint : Fever

It has happened for 10 days before admit to hospital. It is high Fever and responds

with Anti-Pyretic drug. He also had dyspnea since 10 days before His Parents

admit him to hospital and this dyspnea not related with His Activities,Weather.

Cyantoic Appereance is Rejected. Cough is found for 1 week. Mucous was’nt

found. Edema (+) in all of his Body happen for 10 days. Edema started from

palpebra and eyelid continue to hand and foot. Edema could not seen when

patient admit to hospital.

History of Gross Hematuria (+) happened at for one week. Dysuria (-).

History of Vomitting (+) happened for 3 days. Frequency 3-4 times for one day.

He vomitted what he ate and drunk with volume ± 62,5 cc.

He was referred from R.S Insana Stabat with Nefrotik Syndroma,

Glomerunephritis Post Streptococci Infection and Congestive Heart Failure.

He was Given Lasix Injection, Ranitidine injection, and Ondansentron Injection.

History of Previous Illness

The patient previously went to RS Insani Stabat with same complaints.

History of birth

15

Patient was born spontaneously and immediately cried. The birth was helped by

midwife. Birth weight 3600 grams.

Family History

The age of patient’s father is 33 years old whereas the age of her mother is 30

years old. Patient was the first child in his family.

Feeding History

The patient got exclusive breast milk until 4 months, continue with MP-ASI

(Promina) from 6 until 8 Months. From 8 Months-2 Years, He Got Poured Rice.

History of Immunization

The patient immunization was completed

Physical Examination

Generalized status

Body weight : 17 kg

Body length : 122 cm

Body weight in 50th percentile according to age : 24 kg

Body length in 50th percentile according to age : 123cm

Body weight in 50th percentile according to body length : 24 kg

BW/Age : 17/24 = 70%

TB/Age : 122/123 = 99%

BB/TB : 17/24 = 70 %

Presence StatusSensorium: Compos Mentis, HR = 120 bpm, RR= 40 x/min, temperature: 38,5oC.

Anemic (+), dyspnea (+), cyanotic (-), edema (-), icteric (-). Body weight (BW):

16

17 kg. Body length (BL): 122 cm. CDC: BW/Age = 70 %%, BL/Age = 99%,

BW/BL = 70%

Localized StatusHead : Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva

palpebra (+/+). Ear/ Nose/ Mouth: within normal limit/ O2 nasal

canule / within normal limit.

Neck : Lymph NodeEnlrgement (-)

Thorax :Symmetric fusiform, retraction (+) Epigastric Retraction, HR: 120

bpm, regular, murmur (+),gallop,RR: 40 x/minute, regular, ronchi

(-/-)

Abdomen : Ascites (+), Smily Umbilical (-), peristaltic (+) normal.

Liver : not palpable

Spleen : not palpable

Extremities : Pulse 120 bpm, regular, adequate pressure/volume, Warm Extremity,

CRT < 3, TD : 110/80 mmHg

Genitalia: Male, within normal limit.

Laboratory Result (General Hospital Insani Stabat)

April 5th, 2015

Hb/Ht/Leukosit/Trom : 10,7/37,8/10.390/171.000

Peripheral Blood Gas, Ph/PCO2/PO2/PHCO3/TCO2/BE/SaO2 :

7,417/25.7/128,7/16,2/16,9/-7,3/98,9 %

Albumin : 2,9 mg/dl

Blood Glucose : 145 mg/dl

Ureum/Creatine : 58,6/0,91

GFR :73,7

Ca/Na/K/Cl : 7,9/134/3,3/105

PCT : 133,47 mg/ml

17

Differential Diagnosis

- Acute Glomerunephritis

- Congestive Heart Failue e.c Acyanotic CHD

- Nephrotic Syndrome

Working Diagnosis

- Acute Glomerunephritis + CHF e.c Acyanotic CHD

Therapi

- O2 Nasal Canule ½-1 l/min

- IVFD D5% NaCl 0,45 % 15 gtt/min, Macro

- Cefoperazone inj 800 mg/12 Hours/ IV

- Furosemide oral 3 x 20 mg

- Spirinolactone 2 x 12,5 mg

- Fluid Balance / 6 Hours

- Diet MB RD 1350 kkal with 17 gr Protein

Plan : Urinalisa, Echocardiography

Follow UpApril 6th, 2015S Fever (+), Dyspnea (+)O Sensorium : Compos Mentis

Temperature : 37,8 CHead : Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (+/+). Ear/ Nose/ Mouth: within normal limit/ O2 nasal canule / within normal limit.Thorax :Symmetric fusiform, retraction (-), HR: 112 bpm, regular, murmur (+),gallop,RR: 36 x/minute, regular, ronchi (-/-)Abdomen : Soepel, peristaltic (+) normal.

Liver : not palpable Spleen : not palpable

Extremities : Pulse 112 bpm, regular, adequate pressure/volume, Warm Extremity, CRT < 3, TD : 80/50 mmHg

A Acute Kidney Injury e.c Acute Glomerunephritis, Nephrotic SyndromeP - O2 Nasal Canule ½-1 l/min

- IVFD D5% NaCl 0,45 % 15 gtt/min, Macro

18

- Cefoperazone inj 800 mg/12 Hours/ IV

- Furosemide oral 3 x 20 mg

- Spirinolactone 2 x 12,5 mg

- Fluid Balance / 6 Hours

- Diet MB RD 1350 kkal with 17 gr Protein

Laboratory ResultApril 6 Th, 2015Urinalisis Hasil RujukanWarna Kuning Keruh KuningGlukosa Negatif NegatifBilirubin Negatif NegatifKeton Negatif NegatifBerat Jenis 1.010 1.005-1.030Ph 5 5-8Protein Negatif NegatifUrobilinogen NegatifNitrit Negatif NegatifLeukosit NegatifDarah Positif NegatifEritrosit 30-40 <3Leukosit 0-1 <6Epitel 0-1Casts Negatif NegatifKristal Negatif

Kimia Klinik Hasil RujukanKolestrol Total 159 mg/dl <200Trigliserida 379 40-200HDL 23 >65LDL 61 <150

Asto : 200CRP Kualitatif : positifPCT : Menyusul

Follow UpApril 7th, 2015S Fever (-), Dyspnea (+)O Sensorium : Compos Mentis

Temperature : 36,8 C

19

Head : Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (+/+). Ear/ Nose/ Mouth: within normal limit/ O2 nasal canule / within normal limit.Thorax :Symmetric fusiform, retraction (-), HR: 108 bpm, regular, murmur (+),gallop,RR: 32 x/minute, regular, ronchi (-/-)Abdomen : Soepel, peristaltic (+) normal.

Liver : palpable 3 cm under arcus costaeSpleen : not palpable

Extremities : Pulse 108 bpm, regular, adequate pressure/volume, Warm Extremity, CRT < 3, TD : 90/60 mmHg

A Acute Kidney Injury stad Risk E.c GNAPS + CHF NYHA IIP - O2 Nasal Canule ½-1 l/min

- IVFD D5% NaCl 0,45 % 15 gtt/min, Macro

- Cefoperazone inj 800 mg/12 Hours/ IV on 3rd days stopped and

change in to Cefriazxon inj 800 mg/12 Hours/IV

- Furosemide oral 3 x 20 mg

- Spirinolactone 2 x 12,5 mg

- Fluid Balance / 6 Hours

- Diet MB RD 1350 kkal with 17 gr Protein

Laboratory Result

April 7th, 2015

Jenis Pemeriksaan Hasil Rujukan KeteranganANA test 4,13 <20 Moderate – 20-

60Strong : >60

Anti ds DNA 16,6 0-200 Moderate : 301-801Strong : >= 801

Follow UpApril 8 th,2015

20

S Fever (-), Dyspnea (+)O Sensorium : Compos Mentis

Temperature : 36,7 CHead : Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (+/+). Ear/ Nose/ Mouth: within normal limit/ within normal / within normal limit.Thorax :Symmetric fusiform, retraction (-), HR: 108 bpm, regular, murmur (+),gallop (-),RR: 32 x/minute, regular, ronchi (-/-)Abdomen : Soepel, peristaltic (+) normal.

Liver : palpable 3 cm under arcus costaeSpleen : not palpable

Extremities : Pulse 108 bpm, regular, adequate pressure/volume, Warm Extremity, CRT < 3, TD : 100/50 mmHg, MAP : 65 mmHg

A Acute Kidney Injury stad Risk E.c GNAPS + CHF NYHA IIP - Bed Rest

- O2 Nasal Canule ½-1 l/min

- IVFD D5% NaCl 0,45 % 15 gtt/min, Macro

- Cefoperazone inj 800 mg/12 Hours/ IV on 3rd days stopped and

change in to Cefriazxon inj 800 mg/12 Hours/IV

- Furosemide oral 3 x 20 mg

- Spirinolactone 2 x 12,5 mg

- Fluid Balance / 6 Hours

- Diet MB RD 1350 kkal with 17 gr Protein

21

Chapter 4

DISCUSSION AND SUMMARY

4.1. Discussion

The thalassemias are a group of heritable hypochromic anemias varying in

severity, caused by a defect in hemoglobin polypeptide synthesis. In β-thalassemia

mayor, the most common of the homozygous thalassemia syndromes, the affected

child produces little or no hemoglobin A and is usually transfusion-dependent

from early childhood. The clinical manifestations of β-thalassemia include anemia

(may be severe), jaundice, failure to thrive, hepatosplenomegaly, abnormal facies,

fractures due to marrow expansion and abnormal bone structure, generalized

osteoporosis, growth retardation, delayed puberty, primary amenorrhea in female,

and other endocrine disturbance secondary to anemia and iron overload.4,8,9In

this patient, there was no history of family illness that similar to

the patient. He showed the same clinical manifestation such as

paleness due to severe anemia, jaundice, and

hepatosplenomegaly.

Children with β-thalassemia major develop a decreased MCV with

anemia. The peripheral blood smear shows hypochromic, target cells, tear drop

cells. Hemoglobin electrophoresis is usually diagnostic when level of hemoglobin

A2, hemoglobin F, or both are elevated. Β-thalassemia is often suspected when

HbA is absent. The hemoglobin level usually falls to 5-6 g/dL or less, and the

reticulocyte count is elevated significantly.4In this patient, all above laboratory

finding in the theories are occurred. HbE was found in hemoglobin

electrophoresis and this patient was diagnosed with HbE/β-thalassemia major.

For patients with β-thalassemia major, two approaches to treatment are

now available: chronic transfusion with iron chelation or stem cell transplantation.

Programs of blood transfusion are generally targeted to maintain a hemoglobin

level of 9-10 g/dL. This approach gives increased vigor and well-being, improved

22

growth, and fewer overall complications. However, maintenance of good health

currently requires iron chelation. Small doses of supplemental ascorbic acid may

enhance the efficacy of iron chelation.4 In this patient, packed red cell transfusion

has been given to achieved a hemoglobin level of 9-10 g/dL. Iron chelation

therapy was not yet given because of his iron profile still in normal level range.

Because patients with thalassemia major and severe anemia invariably

have a lifelong dependence on red cell transfusions, the use of non-cross-matched

blood should be scrupulously avoided at the time of presentation to prevent

sensitization to foreign red cell antigens. Before initiating chronic transfusions,

the diagnosis of β-thalassemia should be confirmed and the parents counseled

concerning this life-long therapy. Beginning transfusion and chelation therapy are

difficult challenge for parents to face early in their child’s life. Before beginning

transfusion therapy, a red cell phenotype is obtained; blood products that are

leucoreduced and phenotypically matched for the Rh and Kellantigents are

required for transfusion. Surgical method such as spleenoctomy and bone marrow

transplantation may be indicated.1,9,10

Complications are still common and include heart disease (heart failure and

arrhythmias), chronic liver hepatitis, which can evolve in cirrhosis and, rarely, in

hepatocellular carcinoma, endocrine problems, stunted growth, osteoporosis,

thrombophilia and pseudoxanthomaelasticum. The other complication is the iron

overload due to routine blood transfusion. To overcome the iron overload, patient

with β-thalassemia should take iron chelation therapy. The accurate measurement

of iron deposits allows better management of iron overload.7

4.2. Summary

It has been reported, an adolescent boy with the main complaint of pale and was

diagnosed withHbE/β-thalassemia major. The diagnose was established based on

history taking, clinical manifestations, laboratory finding, and hemoglobin

electrophoresis. The patient got PRC transfusion and still need to be followed up.

23

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3.McKenzie SE. Hematology. In Polin RA, Ditmar MF. Pediatric Secrets. 4th

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