Southern Luzon State University Lucban, Quezon College of Allied Medicine

A Case study on

BETA THALASSEMIA

in Partial Fulfillment of the Course Bachelor of Science in Nursing

Prepared by: Adorcisco Zuiga Endaya

Presented to: Mrs. Jessica Sabas Mr. Medel Cabalsa Ms. Sheralaine Nombrefia

December 2010

OBJECTIVES:

After three days of thorough assessment and vivid rendering care for a client with Beta-thalassemia, the student nurse will be able to enhance knowledge, skills and attitude in dealing with the physical, emotional, spiritual, and holistic being with a client suffering Beta-thalassemia.

Furthermore, the student nurse will be able to:

1. Promote a good communication and build a good trusting relationship with client suffering Beta-thalassemia; 2. Make a total and thorough cephalocaudal assessment of a client with Betathalassemia; 3. Have a sufficient history taking of the sickness manifested by the client with beta-thalassemia; 4. Provide a good environment suitable and conducive for the health of the client; 5. Review related diagnostic processes and reveal its importance in terms of the sickness of the client; 6. Ensure provision of good health care for the betterment of client with Betathalassemia; 7. Bestow sufficient health education for clients health benefits; and 8. Create researches about the sickness and impart it to other health care team, specifically, other nursing students, for them to know also terms and care to be provided as they encounter same endeavor of client having Beta-thalassemia.

ANATOMY AND PHYSIOLOGY

HEMOGLOBIN

Hemoglobin (also spelled haemoglobin and abbreviated Hb or Hgb) is the iron-containing oxygen-transport metalloprotein in the red blood cells of

all vertebrates (except the fish family Channichthyidae) and the tissues of some invertebrates. Hemoglobin in the blood is what transports oxygen from the lungs or gills to the rest of the body (i.e. the tissues) where it releases the oxygen for cell use, and collects carbon dioxide to bring it back to the lungs. In mammals the protein makes up about 97% of the red blood cells' dry content, and around 35% of the total content (including water). Hemoglobin has an oxygen binding capacity of 1.34 ml O2 per gram of hemoglobin, which increases the total blood oxygen capacity seventyfold. Hemoglobin is involved in the transport of other gases: it carries some of the body's respiratory carbon dioxide (about 10% of the total)

ascarbaminohemoglobin, in which CO2 is bound to the globin protein. The molecule also carries the important regulatory molecule nitric oxide bound to a globin protein thiol group, releasing it at the same time as oxygen. Hemoglobin is also found outside red blood cells and their progenitor lines. Other cells that contain hemoglobin include the A9 dopaminergicneurons in the substantia nigra, macrophages, alveolar cells, and mesangial cells in the kidney. In these tissues, hemoglobin has a non-oxygen-carrying function as an antioxidant and a regulator of iron metabolism. Hemoglobin and hemoglobin-like molecules are also found in many invertebrates, fungi, and plants. In these organisms, hemoglobins may carry oxygen, or they may act to transport and regulate other things such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant of the molecule, called leghemoglobin, is used to scavenge as oxygen, to keep it from

poisoning anaerobic systems, ofleguminous plants. Research history

such

nitrogen-fixing

nodules

The oxygen-carrying protein hemoglobin was discovered by Hnefeld in 1840. In 1851, Otto Funke published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the

solvent from the resulting protein solution. Hemoglobin's reversible oxygenation was described a few years later by Felix Hoppe-Seyler. In 1959 Max Perutz determined the molecular structure of hemoglobin by X-ray crystallography. This work resulted in his sharing with John Kendrew the 1962 Nobel Prize in Chemistry. The role of hemoglobin in the blood was elucidated by physiologist Claude Bernard. The name hemoglobin is derived from the words hemeand globin, reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme (or haem) group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. The most common type of hemoglobin in mammalscontains four such subunits. Genetics Hemoglobin consists mostly of protein (the "globin" chains), and these proteins, in turn, are composed of sequences of amino acids. These sequences are linear, in the manner of letters in a written sentence or beads on a string. In all proteins, it is the variation in the type of amino acids in the protein sequence of amino acids, which determine the protein's chemical properties and function. This is true of hemoglobin, where the sequence of amino acids may affect crucial functions such as the protein's affinity for oxygen.There are questions like what does hemoglobin give off? There is more than one hemoglobin gene. The amino acid sequences of the globin proteins in hemoglobins usually differ between species, although the differences grow with the evolutionary distance between species. For example, the most common hemoglobin sequences in humans and chimpanzees are nearly identical, differing by only one amino acid in both the alpha and the beta globin protein chains. These differences grow larger between less closely related species. Even within a species, different variants of hemoglobin always exist, although one sequence is usually a "most common" one in each

species.Mutations in the genes for the hemoglobin protein in a species result in hemoglobin variants. Many of these mutant forms of hemoglobin cause no disease. Some of these mutant forms of hemoglobin, however, cause a group of hereditary diseases termed the hemoglobinopathies. The best known

hemoglobinopathy is sickle-cell disease, which was the first human disease whose mechanism was understood at the molecular level. A (mostly) separate set of diseases called thalassemias involves underproduction of normal and

sometimes abnormal hemoglobins, through problems and mutations in globin gene regulation. All these diseases produce anemia. Variations in hemoglobin amino acid sequences, as with other proteins, may be adaptive. For example, recent studies have suggested genetic variants in deer mice that help explain how deer mice that live in the mountains are able to survive in the thin air that accompanies high altitudes. A researcher from the University of Nebraska-Lincoln found mutations in four different genes that can account for differences between deer mice that live in lowland prairies versus the mountains. After examining wild mice captured from both highlands and lowlands, it was found that: the genes of the two breeds are virtually identical except for those that govern the oxygen-carrying capacity of their hemoglobin. The genetic difference enables highland mice to make more efficient use of their oxygen, since less is available at higher altitudes, such as those in the mountains. Mammothhemoglobin featured mutations that allowed for oxygen delivery at lower temperatures, thus enabling mammoths to migrate to higher latitudes during the Pleistocene. Synthesis Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the mitochondria and thecytosol of immature red blood cells, while the globin protein parts are synthesized by ribosomes in the cytosol. Production of Hb continues in the cell throughout its early development from the proerythroblast to the reticulocyte in the bone

marrow. At this point, the nucleus is lost in mammalian red blood cells, but not in birds and many other species. Even after the loss of the nucleus in mammals, residual ribosomal RNA allows further synthesis of Hb until the reticulocyte loses its RNA soon after entering the vasculature (this hemoglobin-synthetic RNA in fact gives the reticulocyte its reticulated appearance and name). Structure Hemoglobin exhibits characteristics of both the tertiary and quaternary structures of proteins. Most of the amino acids in hemoglobin form alpha helices, connected by short non-helical segments. Hydrogen bonds stabilize the helical sections inside this protein, causing attractions within the molecule, folding each polypeptide chain into a specific shape. Hemoglobin's quaternary structure comes from its four subunits in roughly a tetrahedral arrangement.

In most humans, the hemoglobin molecule is an assembly of four globular protein subunits. Each subunit is composed of a protein chain tightly associated with a non-protein heme group. Each protein chain arranges into a set of alphahelix structural segments connected together in a globin foldarrangement, so called because this arrangement is the same folding motif used in other heme/globin proteins such as myoglobin. This folding pattern contains a pocket that strongly binds the heme group. A heme group consists of an iron (Fe) ion (charged atom) held in a heterocyclic ring, known as a porphyrin. This porphyrin ring consists of four pyrrole molecules cyclically linked together (by methene bridges) with the iron ion bound in the center. The iron ion, which is the site of oxygen binding, coordinates with the four nitrogens in the center of the ring, which all lie in one plane. The iron is bound strongly (covalently) to the globular protein via the imidazole ring of the F8 histidine residue (also known as the proximal histidine) below the porphyrin ring. A sixth position can reversibly bind oxygen by a coordinate covalent bond,completing the octahedral group of six ligands. Oxygen binds in an "end-on bent" geometry where one oxygen atom binds Fe and the other protrudes at an angle. When oxygen is not bound, a very weakly bonded water molecule fills the site, forming a distorted octahedron. Even though carbon dioxide is carried by hemoglobin, it does not compete with oxygen for the iron-binding positions, but is actually bound to the protein chains of the structure. The iron ion may be either in the Fe2+ or in the Fe3+ state, but ferrihemoglobin (methemoglobin) (Fe3+) cannot bind oxygen. In binding, oxygen temporarily and reversibly oxidizes (Fe2+) to (Fe3+) while oxygen temporally turns into superoxide, thus iron must exist in the +2 oxidation state to bind oxygen. If superoxide ion associated to Fe3+ is protonated the hemoglobin iron will remain oxidized and incapable to bind oxygen. be able In to such cases, the

enzyme methemoglobin

reductase will

eventually

reactivate

methemoglobin by reducing the iron center. In adult humans, the most common hemoglobin type is a tetramer (which contains 4 subunit proteins) called hemoglobin A, consisting of two and two subunits non-covalently bound, each made of 141 and 146 amino acid residues, respectively. This is denoted as 22. The subunits are structurally similar and about the same size. Each subunit has a molecular weight of about 17,000 daltons, for a total molecular weight of the tetramer of about

68,000 daltons (64,458 g/mol). Thus, 1 g/dL = 0.01551 mmol/L. Hemoglobin A is the most intensively studied of the hemoglobin molecules.

In human infants, the hemoglobin molecule is made up of 2 chains and 2 gamma chains. The gamma chains are gradually replaced by chain s as the infant grows. The four polypeptide chains are bound to each other by salt

bridges, hydrogen bonds, and hydrophobic interactions. There are two kinds of contacts between the and chains: 11 and 12. In general, hemoglobin can be saturated with oxygen molecules (oxyhemoglobin), or desaturated with formed oxygen molecules

(deoxyhemoglobin).Oxyhemoglobin is

during physiological

respiration when oxygen binds to the heme component of the protein hemoglobin in red blood cells. This process occurs in the pulmonary capillaries adjacent to the alveoli of the lungs. The oxygen then travels through the blood stream to be dropped off at cells where it is utilized in aerobic glycolysis and in the production of ATP by the process of oxidative phosphorylation. It does not, however, help to counteract a decrease in blood pH. Ventilation, or breathing, may reverse this condition by removal of carbon dioxide, thus causing a shift up in pH. Hemoglobin exists in 2 forms, A Taut form (T) and a Relaxed form (R). Various factors such as low pH, high CO2 and high 2,3 DPG at the level of the tissues favours the taut form which has low oxygen affinity and releases oxygen in the tissues. The opposite of these aformentioned factors at the level of the lung capillaries favour the relaxed form which can better bind oxygen. Deoxyhemoglobin is the form of hemoglobin without the bound oxygen. The absorption spectra of oxyhemoglobin and deoxyhemoglobin differ. The oxyhemoglobin has significantly lower absorption of the 660 nm wavelength than deoxyhemoglobin, while at 940 nm its absorption is slightly higher. This difference is used for measurement of the amount of oxygen in patient's blood by an instrument called pulse oximeter. Iron's oxidation state in oxyhemoglobin Assigning oxygenated hemoglobin's oxidation state is difficult because oxyhemoglobin (Hb-O2), by experimental measurement, is diamagnetic (no net unpaired electrons), yet the low-energy electron configurations in both oxygen and iron are paramagnetic (suggesting at least one unpaired electron in the complex). The lowest-energy form of oxygen, and the lowest energy forms of the relevant oxidation states of iron, are these:

Triplet oxygen, the lowest energy molecular oxygen species, has two unpaired electrons in antibonding * molecular orbitals.

Iron(II) tends to exist in a high-spin configuration where unpaired electrons exist in Eg antibonding orbitals.

Iron(III) has an odd number of electrons, and thus must have one or more unpaired electrons, in any energy state. All of these structures are paramagnetic (have unpaired electrons), not

diamagnetic. Thus, a non-intuitive (e.g., a higher-energy for at least one species) distribution of electrons in the combination of iron and oxygen must exist, in order to explain the observed diamagnetism and no unpaired electrons. The three logical possibilities to produce diamagnetic (no net spin) Hb-O2 are: 1. Low-spin Fe2+ binds to singlet oxygen. Both low-spin iron and singlet oxygen are diamagnetic. However, the singlet form of oxygen is the higher-energy form of the molecule. 2. Low-spin Fe3+ binds to .O2- (the superoxide ion) and the two unpaired electrons couple antiferromagnetically, giving diamagnetic properties. 3. Low-spin Fe4+ binds to peroxide, O22-. Both are diamagnetic. Direct experimental data:

X-ray photoelectron spectroscopy suggests iron has an oxidation state of approximately 3.2

infrared stretching frequencies of the O-O bond suggests a bond length fitting with superoxide (a bond order of about 1.6, with superoxide being 1.5). Thus, the nearest formal oxidation state of iron in Hb-O2 is the +3 state,

with oxygen in the -1 state (as superoxide .O2-). The diamagnetism in this configuration arises from the single unpaired electron on superoxide aligning antiferromagnetically from the single unpaired electron on iron, to give no net spin to the entire configuration, in accordance with diamagnetic oxyhemoglobin from experiment. The second choice of the three logical possibilities above for diamagnetic oxyhemoglobin being found correct by experiment, is not surprising: singlet oxygen (possibility #1) and large separations of charge (possibility #3) are both unfavorably high-energy states. Iron's shift to a higher oxidation state in HbO2 decreases the atom's size, and allows it into the plane of the porphyrin ring, pulling on the coordinated histidine residue and initiating the allosteric changes seen in the globulins.

Early postulates by bio-inorganic chemists claimed that possibility #1 (above) was correct and that iron should exist in oxidation state II. This seemed particularly likely since the iron oxidation .O2state III as methemoglobin,

when not accompanied by superoxide

to "hold" the oxidation electron, was

known to render hemoglobin incapable of binding normal triplet O 2 as it occurs in the air. It was thus assumed that iron remained as Fe(II) when oxygen gas was bound in the lungs. The iron chemistry in this previous classical model was elegant, but the required presence of the required diamagnetic high-energy singlet oxygen was never explained. It was classically argued that the binding of an oxygen molecule placed high-spin iron(II) in an octahedral field of strong-field ligands; this change in field would increase the crystal field splitting energy, causing iron's electrons to pair into the low-spin configuration, which would be diamagnetic in Fe(II). This forced low-spin pairing is indeed thought to happen in iron when oxygen binds, but is not enough to explain iron's change in size. Extraction of an additional electron from iron by oxygen is required to explain both iron's smaller size and observed increased oxidation state, and oxygen's weaker bond. It should be noted that the assignment of a whole-number oxidation state is a formalism, as the covalent bonds are not required to have perfect bond orders involving whole electron-transfer. Thus, all three models for paramagnetic Hb-O2 may contribute to some small degree (by resonance) to the actual electronic configuration of Hb-O2. However, the model of iron in Hb-O2 being Fe(III) is more correct than the classical idea that it remains Fe(II). Binding for ligands other than oxygen Besides the oxygen ligand, hemoglobin which ligands binds also to hemoglobin in

a cooperative manner,

include competitive

inhibitors such ascarbon monoxide (CO) and allosteric ligands such as carbon dioxide (CO2) and nitric oxide. The carbon dioxide is bound to amino groups of the globin proteins as carbaminohemoglobin, and is thought to account for about 10% of carbon dioxide transport in mammals. Nitric oxide is bound to specific thiol groups in the globin protein to form an S-nitrosothiol which dissociates into free nitric oxide and thiol again, as the hemoglobin releases oxygen from its heme site. This nitric oxide transport to peripheral tissues is hypothesised to assist oxygen transport in tissues, by releasing vasodilatory nitric oxide to tissues in which oxygen levels are low.

Cooperative When oxygen binds to the iron complex, it causes the iron atom to move back toward the center of the plane of the porphyrin ring (see moving diagram). At the same time, the imidazole side-chain of the histidine residue interacting at the other pole of the iron is pulled toward the porphyrin ring. This interaction forces the plane of the ring sideways toward the outside of the tetramer, and also induces a strain in the protein helix containing the histidine as it moves nearer to the iron atom. This strain is transmitted to the remaining three monomers in the tetramer, where it induces a similar conformational change in the other heme sites such that binding of oxygen to these sites becomes easier. In the tetrameric form of normal adult hemoglobin, the binding of oxygen is, thus, a cooperative process. The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule, with the first oxygens bound influencing the shape of the binding sites for the next oxygens, in a way favorable for binding. This positive cooperative binding is achieved

through steric conformational changes of the hemoglobin protein complex as discussed above; i.e., when one subunit protein in hemoglobin becomes oxygenated, a conformational or structural change in the whole complex is initiated, causing the other subunits to gain an increased affinity for oxygen. As a consequence, the oxygen binding curve of hemoglobin issigmoidal, or S-shaped, as opposed to the normal hyperbolic curve associated with noncooperative binding. The dynamic mechanism of the cooperativity in hemoglobin and its relation with the low-frequency resonance has been discussed. Competitive Hemoglobin's oxygen-binding capacity is decreased in the presence of carbon monoxide because both gases compete for the same binding sites on hemoglobin, carbon monoxide binding preferentially in place of oxygen. The binding of oxygen is affected by molecules such as carbon monoxide (CO) (for example, from tobacco smoking, car exhaust, and incomplete combustion in furnaces). CO competes with oxygen at the heme binding site. Hemoglobin binding affinity for CO is 200 times greater than its affinity for oxygen, meaning that small amounts of CO dramatically reduce hemoglobin's ability to transport oxygen. When hemoglobin combines with CO, it forms a very bright red compound called carboxyhemoglobin, which may cause the skin of CO poisoning victims to appear pink in death, instead of white or blue. When inspired air

contains CO levels as low as 0.02%, headache and nausea occur; if the CO concentration is increased to 0.1%, unconsciousness will follow. In heavy smokers, up to 20% of the oxygen-active sites can be blocked by CO. In similar fashion, hemoglobin also has competitive binding affinity for cyanide (CN-), sulfur monoxide (SO), nitrogen dioxide (NO2), andsulfide(S2-), including hydrogen sulfide (H2S). All of these bind to iron in heme without changing its oxidation state, but they nevertheless inhibit oxygen-binding, causing grave toxicity. The iron atom in the heme group must initially be in the ferrous (Fe 2+) oxidation state to support oxygen and other gases' binding and transport (it temporarily switches to ferric during the time oxygen is bound, as explained above). Initial oxidation to the ferric (Fe3+) state without oxygen converts hemoglobin into "hemiglobin" or methemoglobin (pronounced "MET-

hemoglobin"), which cannot bind oxygen. Hemoglobin in normal red blood cells is protected by a reduction system to keep this from happening. Nitrogen dioxide and nitrous oxide are capable of converting a small fraction of hemoglobin to methemoglobin; however, this is not usually of medical importance (nitrogen dioxide is poisonous by other mechanisms, and nitrous oxide is routinely used in surgical anesthesia in most people without undue methemoglobin buildup). Allosteric Carbon dioxide occupies a different binding site on the hemoglobin. Carbon dioxide is more readily dissolved in deoxygenated blood, facilitating its removal from the body after the oxygen has been released to tissues undergoing metabolism. This increased affinity for carbon dioxide by the venous blood is known as the Haldane effect. Through the enzyme carbonic anhydrase, carbon dioxide reacts with water to give carbonic acid, which decomposes

into bicarbonate and protons: CO2 + H2O H2CO3 HCO3- + H+

Hence

blood

with

high

carbon

dioxide

levels

is

also

lower

in pH (more acidic). Hemoglobin can bind protons and carbon dioxide, which causes a conformational change in the protein and facilitates the release of oxygen. Protons bind at various places on the protein, while carbon dioxide binds at the -amino group. Carbon dioxide binds to hemoglobin and

forms carbaminohemoglobin. This decrease in hemoglobin's affinity for oxygen by the binding of carbon dioxide and acid is known as the Bohr effect (shifts the

O2-saturation curve to the right). Conversely, when the carbon dioxide levels in the blood decrease (i.e., in the lung capillaries), carbon dioxide and protons are released from hemoglobin, increasing the oxygen affinity of the protein. It is necessary for hemoglobin to release the oxygen that it binds; if not, there is no point in binding it. The sigmoidal curve of hemoglobin makes it efficient in binding (taking up O2 in lungs), and efficient in unloading (unloading O2 in tissues). In people acclimated to high altitudes, the concentration of 2,3Bisphosphoglycerate (2,3-BPG) in the blood is increased, which allows these individuals to deliver a larger amount of oxygen to tissues under conditions of lower oxygen tension. This phenomenon, where molecule Y affects the binding of molecule X to a transport molecule Z, is called a heterotropic allosteric effect. A variant hemoglobin, called fetal hemoglobin (HbF, 22), is found in the developing fetus, and binds oxygen with greater affinity than adult hemoglobin. This means that the oxygen binding curve for fetal hemoglobin is left-shifted (i.e., a higher percentage of hemoglobin has oxygen bound to it at lower oxygen tension), in comparison to that of adult hemoglobin. As a result, fetal blood in the placenta is able to take oxygen from maternal blood. Hemoglobin also carries nitric oxide in the globin part of the molecule. This improves oxygen delivery in the periphery and contributes to the control of respiration. NO binds reversibly to a specific cysteine residue in globin; the binding depends on the state (R or T) of the hemoglobin. The resulting Snitrosylated hemoglobin influences various NO-related activities such as the control of vascular resistance, blood pressure and respiration. NO is not released in the cytoplasm of erythrocytes but transported by an anion exchanger called AE1 out of them. A study was performed to examine the influence of the form of hemoglobin (Hb) on the partitioning of inhaled volatile organic compounds (VOCs) into [human and animal] blood. Benzene was the prototypic VOC used in the investigations for this research due to the similar properties it shares with many other VOCs. To be specific, this study analyses the influence of the water solubility of Hb on the partitioning coefficient (PC) of a VOC as compared to the influence of the species or form of Hb. The different forms of blood used include: human hemoglobin (HbA), rat Hb, and sickle-cell hemoglobin (HbS). Rat Hb contains little water and is in a quasi-crystalline form, found inside the red blood cells (RBC), meaning they are more hydrophobic than human Hb, which are water-soluble. Sickle-cell hemoglobin (HbS) is water-soluble, however it can become water-insoluble, forming hydrophobic polymers, when deoxygenated.

The findings state that the benzene PC for rat Hb was much higher than human that for Hb; however, the tests that measured the PCs of the oxygenated and deoxygenated forms of HbA and HbS did not differ, indicating that the affinity of benzene was not affected by the water solubility of Hb. Types in humans Hemoglobin variants are a part of the

normal embryonic and fetal development, but may also be pathologic mutant forms of hemoglobin in apopulation, caused by variations in genetics. Some wellknown hemoglobin variants such as sickle-cell anemia are responsible for diseases, and are considered hemoglobinopathies. Other variants cause no detectable pathology, and are thus considered non-pathological variants. In the embryo:

Gower 1 (22) Gower 2 (22) (PDB 1A9W) Hemoglobin Portland (22)

In the fetus:

Hemoglobin F (22) (PDB 1FDH)

In adults:

Hemoglobin A (22) (PDB 1BZ0) - The most common with a normal amount over 95%

Hemoglobin A2 (22) - chain synthesis begins late in the third trimester and in adults, it has a normal range of 1.5-3.5%

Hemoglobin F (22) - In adults Hemoglobin F is restricted to a limited population of red cells called F-cells. However, the level of Hb F can be elevated in persons with sickle-cell disease and beta-thalassemia.

Variant forms that cause disease:

Hemoglobin H (4) - A variant form of hemoglobin, formed by a tetramer of chains, which may be present in variants of thalassemia.

Hemoglobin Barts (4) - A variant form of hemoglobin, formed by a tetramer of chains, which may be present in variants of thalassemia.

Hemoglobin S (2S2) - A variant form of hemoglobin found in people with sickle cell disease. There is a variation in the -chain gene, causing a

change in the properties of hemoglobin, which results in sickling of red blood cells.

Hemoglobin C (2C2) - Another variant due to a variation in the -chain gene. This variant causes a mild chronic hemolytic anemia.

Hemoglobin E (2E2) - Another variant due to a variation in the -chain gene. This variant causes a mild chronic hemolytic anemia.

Hemoglobin AS - A heterozygous form causing Sickle cell trait with one adult gene and one sickle cell disease gene

Hemoglobin SC disease - Another heterozygous form with one sickle gene and another encoding Hemoglobin C.

Role in disease In sickle cell hemoglobin (HbS) glutamic acid in position 6 (in beta chain) is mutated to valine. This change allows the deoxygenated form of the hemoglobin to stick to each other. Hemoglobin deficiency can be caused either by decreased amount of hemoglobin molecules, as in anemia, or by decreased ability of each molecule to bind oxygen at the same partial pressure of

oxygen. Hemoglobinopathies (genetic defects resulting in abnormal structure of the hemoglobin molecule)[43] may cause both. In any case, hemoglobin deficiency decreases blood oxygen-carrying capacity. Hemoglobin deficiency is, in general, strictly distinguished from hypoxemia, defined as decreased partial pressure of oxygen in blood, although both are causes of hypoxia (insufficient oxygen supply to tissues). Other common causes of low hemoglobin include loss of blood, nutritional deficiency, bone marrow problems, chemotherapy, kidney failure, or abnormal hemoglobin (such as that of sickle-cell disease). High hemoglobin levels may be caused by exposure to high altitudes, smoking, dehydration, or tumors. The ability of each hemoglobin molecule to carry oxygen is normally modified by altered blood pH or CO2, causing an altered oxygen-hemoglobin dissociation curve. However, it can also be pathologically altered in, e.g., carbon monoxide poisoning. Decrease of hemoglobin, with or without an absolute decrease of red blood cells, leads to symptoms of anemia. Anemia has many different causes,

although iron deficiency and its resultant iron deficiency anemia are the most common causes in the Western world. As absence of iron decreases heme synthesis, red blood cells in iron deficiency anemia are hypochromic (lacking the red hemoglobin pigment) and microcytic (smaller than normal). Other anemias are rarer. In hemolysis (accelerated breakdown of red blood cells),

associated jaundice is caused by the hemoglobin metabolite bilirubin, and the circulating hemoglobin can cause renal failure. Some mutations in the globin chain are associated with

the hemoglobinopathies, such as sickle-cell disease and thalassemia. Other mutations, as discussed at the beginning of the article, are benign and are referred to merely as hemoglobin variants. There is a group of genetic disorders, known as the porphyrias that are characterized by errors in metabolic pathways of heme synthesis. King George III of the United Kingdom was probably the most famous porphyria sufferer. To a small extent, hemoglobin A slowly combines with glucose at the terminal valine (an alpha aminoacid) of each chain. The resulting molecule is often referred to as Hb A1c. As the concentration of glucose in the blood increases, the percentage of Hb A that turns into Hb A 1cincreases. In diabetics whose glucose usually runs high, the percent Hb A 1c also runs high. Because of the slow rate of Hb A combination with glucose, the Hb A1c percentage is representative of glucose level in the blood averaged over a longer time (the half-life of red blood cells, which is typically 5055 days). Glycosylated hemoglobin is the form of hemoglobin to which glucose is bound. The binding of glucose to amino acids in the hemoglobin takes place spontaneously (without the help of an enzyme) in many proteins, and is not known to serve a useful purpose. However, the binding to hemoglobin does serve as a record for average blood glucose levels over the life time of red cells, which is approximately 120 days. The levels of glycosylated hemoglobin are therefore measured in order to monitor the long-term control of the chronic disease of type 2 diabetes mellitus (T2DM). Poor control of T2DM results in high levels of glycosylated hemoglobin in the red blood cells. The normal reference range is approximately 45.9 %. Though difficult to obtain, values less than 7 % are recommended for people with T2DM. Levels greater than 9 % are associated with poor control of the glycosylated hemoglobin, and levels greater than 12 % are associated with very poor control. Diabetics who keep their glycosylated hemoglobin levels close to 7 % have a much better chance of avoiding the complications that may accompany diabetes (than those whose levels are 8 % or higher).

Elevated levels of hemoglobin are associated with increased numbers or sizes of red blood cells, called polycythemia. This elevation may be caused by congenital heart disease, cor pulmonale, pulmonary fibrosis, too

much erythropoietin, or polycythemia vera. Elevation in levels of hemoglobin were found in one study of the yogic practice of Yoga Nidra (yogic sleep) for half an hour daily. Diagnostic uses Hemoglobin concentration measurement is among the most commonly performed blood tests, usually as part of a complete blood count. For example it is typically tested before or after blood donation. Results are reported in g/L, g/dL or mol/L. 1 g/dL equals about 0.6206 mmol/L. Normal levels are:

Men: 13.8 to 18.0 g/dL (138 to 182 g/L, or 8.56 to 11.3 mmol/L) Women: 12.1 to 15.1 g/dL (121 to 151 g/L, or 7.51 to 9.37 mmol/L) Children: 11 to 16 g/dL (111 to 160 g/L, or 6.83 to 9.93 mmol/L) Pregnant women: 11 to 12 g/dL (110 to 120 g/L, or 6.83 to 7.45 mmol/L) Normal values of hemoglobin in the 1st and 3rd trimesters of pregnant

women must be at least 11 g/dL and at least 10.5 g/dL during the 2nd trimester. If the concentration is below normal, this is called anemia. Anemias are classified by the size of red blood cells, the cells that contain hemoglobin in vertebrates. The anemia is called "microcytic" if red cells are small, "macrocytic" if they are large, and "normocytic" otherwise. Hematocrit, the proportion of blood volume occupied by red blood cells, is typically about three times the hemoglobin level. For example, if the hemoglobin is measured at 17, that compares with a hematocrit of 51. Long-term control of blood sugar concentration can be measured by the concentration of Hb A1c. Measuring it directly would require many samples because blood sugar levels vary widely through the day. Hb A 1c is the product of the irreversible reaction of hemoglobin A with glucose. A higher glucose concentration results in more Hb A1c. Because the reaction is slow, the Hb A1c proportion represents glucose level in blood averaged over the half-life of red blood cells, is typically 5055 days. An Hb A1c proportion of 6.0% or less show good long-term glucose control, while values above 7.0% are elevated. This test is especially useful for diabetics.

OVERVIEW OF THE DISEASE

Beta Thalassemia

Background Beta thalassemia syndromes are a group of hereditary disorders characterized by a genetic deficiency in the synthesis of beta-globin chains. In the homozygous state, beta thalassemia (ie, thalassemia major) causes severe transfusion-dependent anemia. In the heterozygous state, the beta thalassemia trait (ie, thalassemia minor) causes mild-to-moderate microcytic anemia. In addition, hemoglobin (Hb) E, a common Hb variant found in Southeast Asia, is associated with a beta thalassemia phenotype, and this variant is included in the beta thalassemia category of diseases. Pathophysiology Mutations in globin genes cause thalassemias. Alpha thalassemia affects the alpha-globin gene(s). Beta thalassemia affects one or both of the beta-globin genes. These mutations result in the impaired synthesis of the beta globin protein portion, a component of Hb, thus causing anemia. In beta thalassemia minor (ie, beta thalassemia trait or heterozygous carrier-type), one of the beta-globin genes is defective. The defect can be a complete absence of the beta-globin protein (ie, beta-zero thalassemia) or a reduced synthesis of the beta-globin protein (ie, beta-plus thalassemia).

The genetic defect usually is a missense or nonsense mutation in the beta-globin gene, although occasional defects due to gene deletions of the betaglobin gene and surrounding regions also have been reported. In beta thalassemia major (ie, homozygous beta thalassemia), the production of beta-globin chains is severely impaired, because both beta-globin genes are mutated. The severe imbalance of globin chain synthesis (alpha >> beta) results in ineffective erythropoiesis and severe microcytic hypochromic anemia.

The excess unpaired alpha-globin chains aggregate to form precipitates

that damage red cell membranes, resulting in intravascular hemolysis. Premature destruction of erythroid precursors results in intramedullary death and ineffective erythropoiesis. The profound anemia typically is associated with erythroid hyperplasia and extramedullary hematopoiesis.

Frequency United States The frequency of disease varies widely, depending on the ethnic population. Beta thalassemia is reported most commonly in Mediterranean, African, and Southeast Asian populations. International The disease is found most commonly in the Mediterranean region, Africa, and Southeast Asia, presumably as an adaptive association to endemic malaria. The incidence may be as high as 10% in these areas. Mortality/Morbidity The major causes of morbidity and mortality are anemia and iron overload.

The severe anemia resulting from this disease, if untreated, can result in high-output cardiac failure; the intramedullary erythroid expansion may result in associated skeletal changes such as cortical bone thinning. The long-term increase in red-cell turnover causes hyperbilirubinemia and bilirubin-containing gallstones.

Increased iron deposition resulting from multiple life-long transfusions and enhanced iron absorption results in secondary iron overload. This overload causes clinical problems similar to those observed with primary hemochromatosis (eg, endocrine dysfunction, liver dysfunction, cardiac dysfunction).

Race Beta thalassemia genes are reported throughout the world, although more frequently in Mediterranean, African, and Southeast Asian populations.

Patients of Mediterranean extraction are more likely to be anemic with thalassemia trait than Africans because they have beta-zero thalassemia rather than beta-plus thalassemia.

The genetic defect in Mediterranean populations is caused most commonly by (1) a mutation creating an abnormal splicing site or (2) a mutation creating a premature translation termination codon.

Southeast Asian populations also have a significant prevalence of Hb E and alpha thalassemia.

African populations more commonly have genetic defects leading to alpha thalassemia.

Sex This genetic disorder is caused by abnormalities in the beta-globin gene, located on chromosome 11. It is not a sex-linked genetic trait. Age The manifestations of the disease may not be apparent until a complete switch from fetal to adult Hb synthesis occurs. This switch typically is completed by the sixth month after birth. Clinical History 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

Patients with the beta thalassemia trait generally have no unusual physical findings.

Beta thalassemia major

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.
o

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. 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.
o o

Extremities may demonstrate skin ulceration. Iron overload also may cause endocrine dysfunction, especially affecting the pancreas, testes, and thyroid.

Causes Beta thalassemia is caused by a genetic mutation in the beta-globin gene; however, many additional factors influence the clinical manifestations of disease. That is, the same mutations may have different clinical manifestations in different patients. The following factors are known to influence the clinical phenotype:

Intracellular fetal Hb concentrations

o

The level of expression of fetal Hb (ie, the expression level of the gamma-globin gene) determines, in part, the severity of the disease.

Patients with high fetal Hb have milder disease.

Co-inheritance of alpha thalassemia

o

Patients with co-inheritance of alpha thalassemia have a milder clinical course because they have a less severe alpha-beta chain imbalance.

The coexistence of sickle cell trait and beta thalassemia is a major and symptomatic hemoglobinopathy with most of the symptoms and complications of sickle cell disease. Unlike sickle cell trait, in which most Hb-on-Hb electrophoresis is Hb A (AS), S is the dominant Hb (SA) and usually constitutes about 60% of the circulating Hb.

Laboratory Studies

The diagnosis of beta thalassemia minor usually is suggested by the presence of an isolated, mild microcytic anemia, target cells on the peripheral blood smear, and a normal red blood cell count. An elevation of Hb A2 (2 alpha-globin chains complexed with 2 delta-globin chains) demonstrated by electrophoresis or column chromatography confirms the diagnosis of beta thalassemia trait. The Hb A2 level in these patients usually is approximately 4-6%. In rare cases of concurrent severe iron deficiency, the increased Hb A2 level may not be observed, although it becomes evident with iron repletion. The increased Hb A2 level also is not observed in patients with the rare delta-beta thalassemia trait.

An elevated Hb F level is not specific to patients with the beta thalassemia trait.

Free erythrocyte porphyrin (FEP) tests may be useful in situations in which the diagnosis of beta thalassemia minor is unclear. FEP level is normal in patients with the beta thalassemia trait, but it is elevated in patients with iron deficiency or lead poisoning.

Alpha thalassemia is characterized by genetic defects in the alpha-globin gene, and this variant has features similar to beta thalassemia. Patients with this disorder have normal Hb A2 levels. Establishing the diagnosis of the alpha thalassemia trait requires measuring either the alpha-beta chain synthesis ratio or performing genetic tests of the alpha-globin cluster (by Southern blot or polymerase chain reaction tests).

Iron studies (iron, transferrin, ferritin) are useful in excluding iron deficiency and the anemia of chronic disorders as the cause of the patient's anemia.

Patients may require a bone marrow examination to exclude certain other causes of microcytic anemia. Physicians must perform an iron stain (Prussian blue stain) to diagnose sideroblastic anemia (ringed

sideroblasts).

The Mentzer index is defined as mean corpuscular volume per red cell count. An index of less than 13 suggests that the patient has the thalassemia trait, and an index of more than 13 suggests that the patient has iron deficiency.

Prenatal diagnosis is possible.

Imaging Studies

The skeletal abnormalities observed in patients with thalassemia major include an expanded bone marrow space, resulting in the thinning of the bone cortex. These changes are particularly dramatic in the skull, which may show the characteristic hair-on-end appearance. Bone changes also can be observed in the long bones, vertebrae, and pelvis.

The liver and biliary tract of patients with thalassemia major may show evidence of extramedullary hematopoiesis and damage secondary to iron overload resulting from multiple transfusion therapy. Transfusion also may result in infection with the hepatitis virus, which leads to cirrhosis and portal hypertension. Gallbladder images may show the presence of bilirubin stones.

The heart is a major organ that is affected by iron overload and anemia. Cardiac dysfunction in patients with thalassemia major includes

conduction system defects, decreased myocardial function, and fibrosis. Some patients also develop pericarditis. Other Tests Molecular diagnostic tests can precisely determine whether a mutation is present any time after approximately 8 weeks of gestation. The physician can establish the diagnosis in utero using DNA obtained from amniocentesis or by chorionic villus sampling. In most laboratories, the DNA is amplified using the polymerase chain reaction technique and then is analyzed for the presence of

the thalassemia mutation using a panel of oligonucleotide probes corresponding to known thalassemia mutations. Procedures

Physicians often use splenectomy to decrease transfusion requirements. Because postsplenectomy sepsis is possible, defer this procedure until the patient is older than 6-7 years. In addition, to minimize the risk of postsplenectomy sepsis, vaccinate the patient

against Pneumococcusspecies, Meningococcus species, and Haemophilus influenzae. Also, administer penicillin prophylaxis to children after splenectomy.

Patients with thalassemia minor may have bilirubin stones in their gall bladder and, if symptomatic, may require treatment. Perform a cholecystectomy using a laparoscope or at the time of the splenectomy.

Histologic Findings The peripheral blood smear shows microcytic hypochromic red cells with target cells and anisopoikilocytosis. Medical Care Patients with thalassemia minor usually do not require any specific treatment. Treatment for patients with thalassemia major includes chronic transfusion therapy, iron chelation, splenectomy, and allogeneic hematopoietic transplantation.

Thalassemia minor
o o

Patients in the heterozygous state usually do not require treatment. Inform patients that their condition is hereditary and that physicians sometimes mistake the disorder for iron deficiency.

Some pregnant patients with the beta thalassemia trait may develop concurrent iron deficiency and severe anemia; they may require transfusional support if not responsive to iron repletion modalities.

Thalassemia major

The goal of long-term hypertransfusional support is to maintain the patient's Hb at 9-10 g/dL, thus improving the patient's sense of wellbeing while simultaneously suppressing enhanced erythropoiesis. This strategy not only treats the anemia, but also suppresses endogenous erythropoiesis so that extramedullary hematopoiesis and skeletal changes are suppressed.

Patients receiving transfusion therapy also require iron chelation with desferrioxamine.

Blood banking considerations for these patients include completely typing their erythrocytes prior to the first transfusion. This procedure helps future crossmatching processes.

Allogeneic hematopoietic transplantation may be curative in some patients with thalassemia major. An Italian group led by Lucarelli has the most experience with this procedure.1 This group's research documents a 90% long-term survival rate in patients with favorable characteristics (young age, HLA match, no organ dysfunction).

Surgical Care Patients with thalassemia minor rarely require splenectomy, although the development of bilirubin stones frequently leads to cholecystectomy. Diet

Drinking tea may help to reduce iron absorption through the intestinal tract.

Vitamin C may improve iron excretion in patients receiving iron chelation. Anecdotal reports suggest that large doses of vitamin C can cause fatal arrhythmias deferoxamine. when administered without concomitant infusion of

Activity Activity may be limited secondary to severe anemia. Medication Medical therapy for beta thalassemia primarily involves iron chelation. Deferoxamine is the intravenously administered chelation agent currently

approved for use in the United States. Deferiprone is an oral chelation agent, recently approved for use in Europe. While the results of studies on this oral agent are
2

encouraging,

complications

of

hepatic

fibrosis

may

develop. Deferiprone currently is not approved for use in the United States. Deferasirox is an orally administered chelation agent approved for use by the US FDA in 2005. The drug was undergoing review or investigation in other countries as of 2005. Additional treatments under development are experimental protocols to manipulate globin gene expression using gene therapy or using drugs that activate gamma-globin genes. Since fetal globin gene expression is associated with a milder phenotype, approaches to enhance intracellular Hb F levels (by activating gamma-globin gene expression) are under investigation. The 2 most widely studied drugs in this area are butyrates and hydroxyurea.

In a small study, Italia et al evaluated the clinical and hematologic response to hydroxyurea in 79 beta-thalassemia patients in western India with variable clinical severity and correlated the findings with genetic factors. 3 One group consisted of 38 beta-thalassemia intermedia patients, and a second group consisted of 41 beta-thalassemia major patients. Both groups were administered hydroxyurea therapy and followed up for 20-24 months. Findings consisted of the following :

Fifty-eight percent of the frequently transfused patients in the betathalassemia intermedia group became transfusion independent. Sixteen percent demonstrated a 50% reduction in post-therapy transfusions versus 32% in the beta-thalassemia major group, both correlating with a greater mean fold increase in HbF and gamma mRNA expression levels.

Forty-one percent of the beta-thalassemia intermedia group also had associated alpha-thalassemia, and 72.7% were XmnI (+/+).

Of beta-thalassemia intermedia patients who had a clinical and hematologic response to hydroxyurea therapy, 41% had a link to haplotype (- + + - + + - - +) as opposed to haplotype (+ - - - - - - - +), which was more common in patients without such a response. However, response was not associated with the beta-thalassemia mutations.

Both beta-thalassemia groups showed a significant decrease in serum ferritin.

Overall, the investigators found that clinical response to hydroxyurea in the beta-thalassemia intermedia group was better in patients with alphathalassemia, XmnI (+/+), and a higher mean fold increase in gamma mRNA expression. In those with beta-thalassemia major, one third showed a partial response. Gene-replacement therapy or gene therapy is being pursued by several research groups. Obstacles in gene therapy include inability to express high levels of the beta-globin gene in erythroid cells and inability to transduce hematopoietic pluripotent stem cells at high efficiency. In a recent report, one adult patient with severe transfusion-dependent -thalassemia became transfusion independent for 21months, 33 months after lentiviral -globin gene transfer, with peripheral blood hemoglobin being maintained between 9 and 10g/dL. Follow-up Inpatient & Outpatient Medications

Administer iron chelation daily as described under medication. Transfuse red blood cells to maintain the Hb concentration at 9-10 g/dL.

Deterrence/Prevention

Prenatal diagnosis is possible by analyzing DNA obtained via chorionic villi sampling at 8-10 weeks of gestation or by amniocentesis at 14-20 weeks of gestation. Since the genetic defects are quite variable, family genotyping usually must be completed for diagnostic linkage (segregation) analysis. With the anticipated availability of large-scale mutation screening by DNA chip technology, extensive pedigree analyses may be obviated. Physicians can perform fetal blood sampling for Hb chain synthesis at 1822 weeks of gestation, but this procedure is not as reliable as DNA analysis sampling methods.

Genetic therapy strategies are currently in the early stages of development.

Complications

Iron overload Extramedullary hematopoiesis Asplenia secondary to splenectomy

Medical complications from long-term transfusional therapy - Iron overload or transfusion-associated infections (eg, hepatitis)

Increased risk for infections resulting from asplenia (eg, encapsulated organisms such as pneumococcus) or from iron overload

(eg, Yersiniaspecies)

Cholelithiasis (eg, bilirubin stones)

Prognosis

Individuals with thalassemia minor (thalassemia trait) usually have asymptomatic mild anemia. This state does not result in mortality or significant morbidity.

The prognosis of patients with thalassemia major is highly dependent on the patient's adherence to long-term treatment programs, namely the hypertransfusion program and life-long iron chelation. Allogeneic bone marrow transplantation may be curative.

Patient Education

Educate patients with thalassemia minor about the genetic (hereditary) nature of their disease, and inform them that their immediate family members (ie, parents, siblings, children) may be affected. The presence of thalassemia major in both parents implies that children will likely have a form of the disease. (The presence of compound heterozygosity in the parents makes accurate phenotypic predictions for children incomplete).

Inform patients with thalassemia minor that they do not have iron deficiency and that iron supplementation will not improve their anemia.

CASE STUDY PROPER:

DEMOGRAPHIC DATA Name: Renz Natioco Pearada Age: 7mos old Birthday: September 1, 2010 Gender: Male Address: 83 Sandigan St.Tanza, Navotas Religion: Roman Catholic Name of Father: Name of Mother: Date Admitted: April 01, 2011 Time Admitted: 4:43am Admitting Doctor: Dr. Ronald G. Solo Admitting Diagnosis: Measles with pneumonia t/c Kochs pneumonia Final Diagnosis:

History of Present Illness:

Thirteen days prior to admission, the patient was admitted at a local hospital because of cough and diarrhea. Assessment of that time was Bronchopneumonia and Primary Kochs infection. He was discharged stable but with persistent of cough. Four days prior to admission, the patient was noted to have rashes on the faces. There were no associated symptoms at that time except for the cough. One day prior to admission, patient consulted a local health center. He was prescribed with salbutamol, disudrin, amoxicillin, and paracetamol. He

subsequently referred to San Lazaro Hospital.

Past Medical History:

The client was already diagnosed with the same disease since he was infant. He started to have blood transfusion since he was 8 months old. The disease was due to blood incompatibility of his parents, his mother with blood type of A - and his father with B+. Then, he received blood transfusion of Pack Red Blood Cells until now with 2 to 3 months intervals.

Family History:

Family history showed asthma.

Occupation and Environment:

Family history showed asthma.

Physical Assessment:

Vital Signs: 1ST DAY Temperature Respiratory Rate Pulse Rate Blood Pressure 36.7OC 28bpm 79bpm 100/70mmHg 2ND DAY 36.9OC 27bpm 82bpm 110/70mmHg

General:

- pale and weak in appearance - not in respiratory distress

Hair, Skin and Nails: - with short black hair - no dandruff and pediculosis noted - with moist smooth skin -with good skin complexion - with slightly poor skin turgor - with slightly pale nailbeds - capillary refill time of 2-3 seconds upon blanching

Head and Neck: - head is symmetrical without contusion or concussion - no headache noted -no edema noted - neck is symmetrical - no palpable nodules on neck noted

Eyes: - with whitish sclera - with pale conjunctivas - pupil equally rounded and reacting to light accommodation - no abnormal discharges noted

Ears:

- in line with the outer cantus of the eyes -pinna recoils after folded - no discharges noted -no cerumen noted

Nose: - symmetrical - same color as the face - with nasal discharges draining to whitish secretions; scanty in amount

Mouth: - with slightly pale and dry lips - with slightly pale oral mucosa - tongue at the center of the mouth - tonsils not inflamed

Thorax: - symmetrical chest expansion upon breathing - clear breath sounds heard on both lung fields upon auscultation - with productive cough draining to yellow-greenish secretions; scanty in amount

Abdomen: - with normoactive bowel movement - bowel sounds heard on right lower quadrant at 15 per minute upon auscultation - with soft non-tender abdomen upon palpation

Genitourinary: - voids freely to yellowish urine - bladder not distended

Extremities: - symmetrical - with full range of motion

COURSE IN THE WARD:

On November 29, 2010, the client visited Dr. Nadres and ordered him to be admitted in Tayabas Community Hospital, Inc. under his service. That he may had secured consent for the admission and management and to be at diet as tolerated. The physician also ordered him to have blood transfusion of 3u Pack RBC with his Blood typing and Cross-matching AB+ to be transfused within four to six hours. IVF of PNSS 1L run for 24 hours is also ordered. And a medication, dipenhydramine 50mg per capsule one capsule 30 minutes before blood transfusion. The client was officially admitted on December 01, 2010 at 8 o clock in the morning. Then on December 01, 2010 at 11:05 am, the following medications were prescribed by the physician: Cefrox 750mg IV every 8 hours, Klaz 500mg per capsule one capsule once a day, and Ventolin one tablet three times a day. At the same day, at exactly 4:00 pm, additional instruction from the physician was to infuse the blood with six hours interval. On the following day, December 02, 2010, three packs of RBC were totally consumed and the client seems to gain strength. Then the physician ordered him to go home and seek medical help on his clinic few weeks after being discharge.

LABORATORY RESULTS ANALYSIS:

December 01, 2010 Cross Matching and Blood Typing

Blood Type: AB Rh: positive (+)

- After the blood typing and cross matching done, the client has to receive blood transfusion of Pack RBC. The flowing are the serial numbers of the three packs of blood transfused to the client: 1. QMC 3279-10 (transfused on December 01, 2010 12:40pm to 5:25pm) 2. QMC 3282-10 (transfused on December 02, 2010; 12:50am to 4:30 am) 3. QMC 3281-10 (transfused on December 02, 2010; 12:15pm to 5:10pm)

- As a nurse handling a client with blood transfusion following interventions are done: a. b. c. d. Transfused the blood in slow rate for 10 to 15 minutes. Assessed for signs and symptoms of any blood reaction. Regulated the blood transfusion properly. Consumed blood transfusion for not less than 4 hours and not

more than 6 hours. e. Had at least 6 hours intervals for every transfusion.

PATHOPHYSIOLOGY:

Predisposing Factors: Rh Incompatibility of Parents upon Conception Family History of Anemia Family History of Beta-thalassemia

Mutation of beta globin genes

Poor synthesis of beta globin protein

Decreased production and malformation of hemoglobin

Anemia

Decreased oxygen supply to different body parts

body weakness

pale in appearance

pale conjunctiva

pale nailbeds

increased vulnerability to mild infections

cough and colds

NURSING CARE PLAN:

CUES AND CLUES O > pale in appearance > pale conjunctiva >slightly pale nailbeds > capillary refill time of 2-3 secs upon blanching NURSING DIAGNOSIS NURSING PLAN NURSING INTERVENTIONS > Assess general condition > Assess for contributing factors > Place in Semi-Fowlers position > Encourage to do deep breathing exercises > keep a clean, cool and well ventilated environment > Instruct to increase oral fluid intake > instruct to eat Vitamin C rich foods such as citrus fruits > Regulate blood transfusion properly > Instruct to have adequate sleep and rest periods RATIONALE EVALUATION

Altered Tissue Perfusion related to decreased oxygen carrying capacity of the blood secondary to disease condition

At the end of nursing interventions, the clients tissue perfusion will improve

- for baseline data

- to provide comfort - to help in having more O2 in the circulation - for better oxygenation

> seen sleeping comfortably on bed in a Semi Fowlers position >seen drinking ample amount of water > Blood transfusion done within 5 hours, no signs and symptoms of blood transfusion reaction noted

- for better Iron absorption - to avoid fluid overload in the body - for better circulation

CUES AND CLUES

NURSING DIAGNOSIS

NURSING PLAN

NURSING INTERVENTIONS > Assess general condition > Assess for contributing factors > Monitor Vital Signs especially RR > Place in Semi-Fowlers position > Encourage to do deep breathing exercises and proper coughing techniques > keep a clean, cool and well ventilated environment > Instruct to increase oral fluid intake up to 8 glasses per day > Instruct to have adequate sleep and rest periods

RATIONALE

EVALUATION

O > with nasal discharges draining to whitish secretions scanty in amount >with productive cough draining to yellowgreenish secretions scanty in amount >with clear breath sounds heard on both lung fields upon auscultation >RR = 31 bpm

Ineffective Airway Clearance related to presence of mucous secretions in the tracheobronchial tree

At the end of nursing interventions, the client will show improvement in airway clearance

- for baseline data

> seen sleeping comfortably on bed in a Semi Fowlers position >seen drinking ample amount of water > RR = 26bpm

- to provide comfort - to help in easier expectorating secretions - for better oxygenation - to loosen and liquefy secretions > for better circulation

CUES AND CLUES

NURSING DIAGNOSIS

NURSING PLAN

NURSING INTERVENTIONS > Assess general condition > Assess for contributing factors > Monitor Vital Signs especially RR > Place in Semi-Fowlers position > Encourage to do deep breathing exercises and proper coughing techniques > keep a clean, cool and well ventilated environment > Instruct to increase oral fluid intake up to 8 glasses per day > Instruct to have adequate sleep and rest periods

RATIONALE

EVALUATION

O > with nasal discharges draining to whitish secretions scanty in amount >with productive cough draining to yellowgreenish secretions scanty in amount >with clear breath sounds heard on both lung fields upon auscultation >RR = 31bpm

Ineffective Breathing Pattern related to presence of mucous secretions in the tracheo-bronchial tree

At the end of nursing interventions, the client will show improvement in breathing pattern

- for baseline data

> seen sleeping comfortably on bed in a Semi Fowlers position >seen drinking ample amount of water > RR = 26bpm

- to provide comfort - to help in easier expectorating secretions - for better oxygenation - to loosen and liquefy secretions > for better circulation

CUES AND CLUES O >T= 35.6 oC >with 3u of blood transfusion of PRBC >pale in appearance >exposed to cold environment

NURSING DIAGNOSIS

NURSING PLAN

NURSING INTERVENTIONS > Assess general condition > Assess for contributing factors > Monitor Vital Signs especially Temperature > Place in Semi-Fowlers position > keep a clean, cool and well ventilated environment > Instruct to increase oral fluid intake up to 8 glasses per day > Instruct to have adequate sleep and rest periods > Instruct to use thick clothing when cold >Instruct to wear socks and gloves

RATIONALE

EVALUATION

Risk for Imbalanced Body Temperature related to cooling effects of Blood transfusion

At the end of nursing interventions, the client will demonstrate ways to keep body temperature within normal range

- for baseline data

> seen sleeping comfortably on bed in a Semi Fowlers position >seen drinking ample amount of water > T =36.9 oC

- to provide comfort - to prevent heat loss by evaporation - for better circulation - to prevent heat loss by conduction

CUES AND CLUES O >weak and pale in appearance > with pale conjunctivas >T = 35.6oC

NURSING DIAGNOSIS

NURSING PLAN

NURSING INTERVENTIONS > Assess general condition > Assess for contributing factors > Monitor Vital Signs especially T > Place in Semi-Fowlers position >Emphasize the importance of personal hygiene >Instruct on proper and frequent hand washing > Encourage to do deep breathing exercises > keep a clean, cool and well ventilated environment > Instruct to increase oral fluid intake up to 8 glasses per day > Instruct to have adequate sleep and rest periods

RATIONALE

EVALUATION

Risk for Infection related to compromised host defense secondary to disease condition

At the end of nursing interventions, the client will prevent infection

- for baseline data

> seen sleeping comfortably on bed in a Semi Fowlers position >seen drinking ample amount of water > seen doing hand washing properly > T = 36.9 oC

- to provide comfort - to develop a good external defense -to prevent microorganism transfer

- to avoid environment acquired microbial infections

- for better circulation

>Instruct on proper waste management >Instruct on proper food handling and serving >instruct to avoid too much crowding

-to avoid microorganism build up -to prevent contamination -to prevent cross contamination

DRUGS STUDY:
Name Benadryl AH (Diphenhydramine Specific Action Antihistamine Mechanism of Action Inhibits histamine production Indication Contraindication Adverse Reactions Nursing Responsibilities

HCl)
1 capsule 30 minutes before Blood Transfusion

premature and Hay fever, urticaria, newborn; asthma vasomotor rhinitis, angioneurotic edema, drug sensitization, serum & penicillin reaction, contact dermatitis, atopic eczema, other allergic dermatoses, pruritus, food sensitivity, parkinsonism, motion sickness

CV andCNS effects; - Assess allergic blood disorders; GI reactions disturbances - Monitor Vital Signs - Increase fluid intake - give with meals - Instruct to avoid strenuous activities - instruct to avoid abrupt movements

EVALUATION:

After rendering care to the client for three days, the client was discharged and given health educations about precautions and maintenance of health. The blood being transfused shows negative reaction from the client. Even at the first pack, the client showed great improvement in terms of his appearance. As three packs were administered, the client was fresh as new, whereas he can do works with ease. He gained strength and in good condition as he went home.

From the scenario, the nursing student was been able to assess, take history and render care to the client having Beta-thalassemia. Its quite emphatic to the part of the student as he already know that this sickness is lifetime, whereas, as stated by the client, he already undergone previous blood transfusions as far as he was 8 months old that is consecutively with two to three months interval. Moreover, the student nurse now was equipped with enough knowledge, boosted skills, and stretched attitude in dealing with Beta-thalassemia.