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Sickle Cell Disease: A Genetic Disorder of Beta-Globin

Submitted: October 18th, 2017 Reviewed: February 2nd, 2018 Published: July 11th, 2018

DOI: ten.5772/intechopen.74778

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Abstract

Sickle cell illness (SCD) is a structural and monogenetic genetic disorder due to a mutation that occurs in the globin β-chain, resulting in the formation of hemoglobin S (Hb S), a protein composed of two normal, and two β-type mutant chains. Estimates indicate that the prevalence among live births is iv.4% in the earth. The difficulty in circulating the sickle cell, its interaction with endothelial cells, leukocytes, platelets, endothelial dysfunction, and the abnormal expression of adhesion molecules permeate the beginning of the blood vessel occlusion process as well every bit pathophysiological aspects of SCD. Amidst the secondary complications are the stroke, pulmonary hypertension, leg ulcer, renal disorders, and all complications associated with vascular dysfunction. Clinical and biochemical markers of disease severity can be used to predict risk, prevent complications, and increment the expectation and quality of life of the SCD population. The entire scenario generated past Hb Due south has implications for the wellness and social inclusion of patients, and then the treatment of the person with SCD needs an approach focused on the prevention of these complications in an individualized way.

Keywords

  • sickle cell disease (SCD)
  • hemoglobin
  • genetic disturber
  • nucleation
  • molecular interaction

1. Introduction

According to global estimates, approximately five% of the population has some type of hemoglobin variant, and more than 300,000 babies are built-in each year with hemoglobinopathies, with sickle cell disease (SCD) beingness the most prevalent type [1, 2]. Information technology is estimated that the prevalence of live births with the disease is four.4% in the world, where rates remain high on the main continents of Africa, Southeast Asia, and the Americas [two].

In 2013, perform a first show analysis focusing on sickle hemoglobin using a 2010 dataset combined with demographic data and modern geostatistical modeling techniques that explain spatial heterogeneities and precision measurements of global statistics most sickle jail cell disease neonates (Figure one) [3]. In 2010, the births of infants with sickle cell anemia (SCA-Hb SS) deemed for 2.4% of the world'due south most severe cases of the disease [3]. Withal, worrying estimates indicate that the number of newborns with SCA will increment from approximately 305,000 in 2010 to 404,000 in 2050 [4, five].

Effigy 1.

Distributions HbS information points. Ruddy points indicate surveys showing the presence of HbS and blue points signal surveys showing an absence of HbS. Source: Adaptation of Piels et al. [three].

The African continent, which has 3.vi 1000000 new cases of sickle cell trait (HbAS) and 238,000 SCA, remains the largest cradle of SCD genetic inheritance [iii]. Nigeria, and the Democratic Republic of Congo would urgently need to program policies for prevention and management of SCA, so that implementations carried out in 2015 could salvage many lives by 2050 (Effigy 2) [four, 5].

Effigy 2.

Numbers of Newborns with Sickle Cell Anemia (SCA) in 2015. Source: Adaptation of Piels et al., 2017.

In Southeast Asia where a hemoglobin variant Hb E is more prevalent, a heterozygosity with Hb S has increased mainly due to immigration and interracial relationships [half-dozen, vii, 8]. Nevertheless, according to data between the years 1990 and 2013, an almanac mortality rate SCD HbSE per 100,000 inhabitants decreased by 63.9%, keeping them in the media of two.8% per year [9]. It is estimated that the prevalence of live births with the SCD is 1.i% in the American continent [ii]. In the United states, it is estimated that 113,000 hospitalizations are in the occurrence of the disease and the cost of hospitalization for SCD reaches 488 million dollars per twelvemonth [ten].

In Brazil, the estimated incidence of SCD is ane case per 2700 alive births: Bahia, Rio de Janeiro, and Minas Gerais being the chief states with the highest prevalence [11, 12, xiii]. According to data from the Ministry of Health of Brazil, child and perinatal intendance lethality rates can reach 80% and between twenty% and 50%, respectively, of uncared children who cannot attain 5 years of life [fourteen]. Among the adults followed in the loftier prevalence states, such as Bahia and Rio de Janeiro, the median age of decease due to SCD is however low, 26.5 years and 31.5 years, respectively [15]. Yet, in the last 13 years, the Brazilian government implemented several public health policies focused on the detection of new cases by neonatal screening and on improving the quality of treatment provided to these patients, implying an increase in life expectancy, with individuals reaching the fourth, fifth, and up to the 6th decade of life [sixteen, 17, 18, 19].

The pathological presentment of SCD begins with the process of formation of Hb S polymers triggers dehydration and increased cell stiffness, giving rise to the vaso-occlusion event [xx, 21]. This miracle leads to the appearance of several pathophysiological events such equally tissue ischemia, anemia, inflammation, and hemolysis [twenty, 21, 22, 23, 24].

Hemolysis consists of the early destruction of the erythrocytes by membrane rupture, being a common issue in the pathophysiological process of SCD [25, 26, 27]. During hemolysis, vasodilation, transcriptional activation of endothelin and vascular adhesion molecule are reduced, whereas nitric oxide is exposed directly to free Hb S, causing its degradation [28, 29]. Chronic hemolysis in SCD causes vascular imbalance, reflecting directly on hemoglobin concentration, reticulocyte count, bilirubin levels, lactic dehydrogenase (LDH), and nitric oxide bioavailability [28, 30, 31]. The reduction of the supply of oxygen to the tissues and organs causes the appearance of several complications secondary to disease [five].

Nevertheless, genetic, age, gender, hematological, and environmental factors afford to interfere on the characteristics of SCD and also bear on on the quality and life expectancy of patients, mainly reducing their social insertion [32, 33, 34, 35].

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2. The hemoglobin: origins and part

Hemoglobin is one of the most arable proteins in animals, performing important functions such as oxygen transport, started when hemoglobin binds to oxygen that arrives from the airways in the lungs and is taken to organs and tissues that need it to maintain life through red blood cells [36, 37, 38]. The genomic construction of genes encoding hemoglobin subunits, characterized past three exons and two introns, are highly similar among vertebrate animal strains [39].

Despite this, the function of some proteins belonging to the contemporary hemoglobin family in vertebrates is to store oxygen in tissues such as myoglobin, a protein formed by a globin chain, gives the red colour to the muscular tissues and has structural and genomes similar to globins that grade hemoglobin [37, 40, 41, 42, 43].

Composed of 4 polypeptide subunits, 2 alpha chains and two beta chains (α1β1; α2β2), respectively, each of the 4 globin groups has a porphyrin band (Heme group) containing the iron element in its constitution (Figure 3) [38, 44].

Effigy iii.

Structure quaternary of hemoglobin. Source: Antranik website: Bachelor inhttp://antranik.org/blood-components-hemoglobin-typerh-factor-agglutination.

Hemoglobin is considered an allosteric molecule considering it regulates its functionality very well, especially in situations of change in the environment where it is present, in the increase or subtract of the concentration of a certain ligand [45, 46]. A classic example of this can be highlighted in how oxygen binds cooperatively in the heme cluster [47, 48].

Previously, researchers admitted that the base of hemoglobin allosterism was based on the Monod Wyman-Changeux (MWC) ii-state allosteric model, which corresponded to oxyhemoglobin (spring) and deoxyhemoglobin (unlinked) forms [44, 46, 49]. It is currently believed that hemoglobin can prefer several allosteric conformations in dynamic equilibrium, as well implying dissimilar functionalities (Figure 4) [44, 48].

Effigy iv.

Presentation and comparing of ix quaternary structures of hemoglobin. In (a) diagram showing the orientation of α2β2 dimers relative to αoneβone. In (b) the presentation of the β2 subunit with the same nine conformations represented in nine colors and at different angles. Source: Adapted from Shibayama et al. [44].

Over fourth dimension hemoglobin has been consistently an object of scientific enquiry given its relevance to biology [50, 51, 52]. One of the most important aspects is related to the study of its origin and its relation with oxygen, a very reactive metal, simply necessary for mammalian metabolism [53, 54, 55].

From the evolutionary betoken of view, almost iv billion years ago, the gaseous layer that enveloped the Globe was equanimous only of nitrogen, marsh gas, h2o effluvia, and ammonia [37]. Probably many organisms that emerged in the early days used these gases for their own subsistence [56]. It is believed that atomic number 26 and magnesium were involved in many of these actions in the metabolism of these extremely primitive organisms [57, 58].

In order to increment the efficiency of life-generating energy systems, somehow still not so enlightened and despite being toxic, oxygen has been incorporated by organisms [37, 50]. It is believed that initially this big poly peptide complex that now bears oxygen-dependent organisms, organs, and tissues was very archaic, probably composed only of a metal that was able to bind and carry oxygen [37].

In the process of development, at i point, it was necessary that this structure is wrapped within a porphyrin ring and then embedded in enovelled protein [52]. During development, this ring-shaped structure has accompanied generations of organisms of animal origin (Heme group) and plant (Clorofila group) [37, 59].

The Heme group not only binds to globin molecules to form hemoglobin simply tin can bind other molecules with a certain function to give rise to oxygenases proteins, cytochromes, and even fungal ligninases [37]. Chlorophyll, the green-coloured substance in plants, is basically an organic molecule characterized by a porphyrin ring that contains magnesium, and its function is to absorb electromagnetic energy through sunlight, which will be used in photosynthesis [58, lx, 61].

Studies to identify the origin of hemoglobin compare their respective coding genes with several parent organisms in guild to detect the changes that take been made throughout evolutionary history and time [37]. But the modify identified in hemoglobins was more than in the form of how they are genetically regulated than in their structural basis from which they were strongly conserved [58]. In full general, studies point that hemoglobin appeared about 500 1000000 years ago (Figure 5), prior to the time that eukaryotic cells diverged from eubacterial cells [37].

Figure 5.

Phylogenetic tree model of globin genes in vertebrate animals. Source: Adapted from Hardison [58].

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3. Pathophysiology of Hb S: a mutation, an amino acid, a illness

Multipotent hematopoietic stem cells have the potential to be targeted to a number of special differentiation pathways that originate several blood cell lines in mammals [62, 63, 64]. I of the pathways, erythropoiesis, is responsible for the production of ruddy claret cells, discoid and anucleated cells that carry oxygen (O2) and carbon dioxide (CO2) through an intracellular metalloprotein called hemoglobin throughout the body [39, 65].

Every bit seen previously, hemoglobin is a heterotetramer equanimous of two α-globin and β-globin subunits linked past a non-covalent bond [2, 39]. Each globin subunit has a heme group containing the bivalent fe ion [64, 66].

Dissimilar globin genes are activated or deactivated both in embryonic, fetal and adult life in social club to meet different oxygen demands and facilitate the placental transfer of oxygen from the mother to the embryo (Figures six and seven) [64, 66, 67].

Effigy six.

Representation of the red jail cell maturation process, molecular regulation of hemoglobin (embryonic, fetal, and developed) with focus on β globin and globin synthesis. Source: For more details, look upwards the Sankaran article reference of the year 2011 [68].

In humans, throughout embryonic life to machismo, various types of hemoglobin can be expressed and this process is regulated in a complex fashion, involving several molecular mediators in order to stimulate hemoglobin production (Figure vi) [2, 66, 68 ]. The globin genes α and β, arranged on chromosomes xvi and 11, respectively, control the production of globins through the expression of the subunits from the α globin locus: ζ (embryonic) and α-globin (adult) genes; and locus β globin: ε (embryonic), γG and γA (fetal), and δ and β-globin (developed) (Figure 7) [64, 66].

Figure vii.

Variation of hemoglobin types in the embryonic, fetal, and adult period. Source: Adapted from Weatherall and Clegg [113].

However, due to spontaneous mutations, variant hemoglobins may arise and be structurally unlike [68, 69]. These mutations can, for case, trigger a change in the amino acid sequence, leading to the decrease or suppression of the production of a globin chain, as observed in β Thalassemia [70, 71]. Such genetic changes frequently pb to the onset of diseases, which are called hemoglobinopathies [2, 8, 72].

A mutation in the gene of the sixth codon of exon one in the DNA of chromosome 11, which synthesizes the β globin, leads to the replaced adenine nitrogen base of operations (from the GAG codon) past thymine (GTG), resulting in the substitution of glutamic acid for valine in position 6 of the N-terminal finish in the Beta (β) concatenation of globin [73, 74, 75, 76] .The pathophysiology of sickle cell affliction (SCD), a monogenetic disorder that gives rising to the formation of hemoglobin Southward (Hb S), a protein equanimous of two normal α-chains and two mutant chains of the β-type (α2A β2S) (Figure 8).

Figure viii.

Crystalline structure of deoxy hemoglobin S (deoxy-Hb S). Source: For more information, see details in the report past Harrington et al., 2017.

Three levels straight the scientific knowledge related to the pathophysiological changes present in SCD: molecular and cellular, tissue and organism [77, 78, 79, lxxx]. At the molecular level, the exchange of amino acids with different isoelectric points, glutamic acid (IP = 5.97) per valine (IP = 2.77), causes an imbalance because of the loss of negative charges of Hb Due south in relation to Hb A (Figure nine) [81, 82]. These changes in the physical structure of hemoglobin volition imply impairments in its functionality, mainly related to oxygen loading [83, 84, 85].

Figure 9.

Representation of the mutated amino acid structures present in HbS. Glutamic acid has an acted construction and with more than negative charges. Valine is an amino acrid with hydrophobic characteristics that tend to take the most neutral charge. Source: Wishart et al., 2013.

In certain periods or situations where hypoxia occurs (absence or decrease of oxygen tension in the body), oxygenated mutant hemoglobin (oxy-HbS) loses oxygen, adopting deoxygenated conformation (deoxy-Hb S) [81, 86, 87].

In its ain structure, the formation of hydrogen bonds between the amino acids valine of position n1 of the globin beta S (normal position) and the mutant valine of the same globin begins [82, 83, 84]. Hydrogen bridges promote intermolecular approximations and contacts between the amino acids of hemoglobins (GLU121→ GLY16, ASP73→ THR4, etc.) that favor the formation of Hb S polymers [84, 85]. Nonetheless, it is through the hydrophobic interactions betwixt valine (βVAL6) and the hydrophobic concavity formed mainly by leucine (βLEU88) and phenylalanine (βFEN85) that the germination of Hb South polymers occurs [81, 83, 88].

Polymerization in SCD is a process triggered past a phenomenon known as nucleation in which a number of molecules come together within an embryo of the new phase that resembles a first transition stage like to a gas-solid transformation [88, 89]. The nucleation progressively progresses through the initial fiber growth and its branching, due to the secondary nucleation of new fibers on acme of the existing ones, as if it were a double nucleation [77, 88, 90, 91].

Polymerization of HbS is a primary result in the pathophysiology of SCD, generally favored by several factors such equally insufficient oxygen saturation, loss of potassium and h2o, reductions in blood pH, increased the concentration of 2, 3-diphosphoglycerate [81, 82, 86]. In the formation of HbS fibers, they are capable of generating 14 members of T-shaped conformation fibers when hemoglobin is in the deoxygenated land [87, 88]. Among these aligned fibers hydrophobic contacts occur, which are initiated between the valine of the HbS molecule and alanine, phenylalanine and leucine of adjacent Hb Due south molecules [88]. In the case of a high degree of polymerization, the deoxy-HbS presents a behavior characteristic of a polymer gel [88, ninety].

Subsequently polymerization progresses through enveloped fibers, which will modify the structure of the red jail cell, mainly through the formation of more elongated fibers and mechanisms of atmospheric precipitation in the cell wall with the formation of Heinz bodies, triggering the appearance of sickle-shaped red blood cells, rather than discoid and malleable (Effigy ten) [81, 82, 87].

Figure ten.

Summary of the pathophysiology of SCD. (A) Representation of the structural differences in the conformation of HbS when it is in oxygenated and deoxygenated form. (B) HbS polymerization procedure with details of the chief amino acids involved in the mechanism. (C) Formation of the deoxy-HbS fibers through the phenomenon of homogeneous and heterogeneous nucleation. (D) Microscopic findings of sickle prison cell. Left cells of the blood with the formation of Heinz bodies (fluorescence method). In the eye, smear blade containing scythe-shaped cells. On the right is a lysed sickle cell showing several deoxy-HbS fibers. Source: See details at Howard Hughes Medical Plant, 2018; Galkin et al. [88]; Rooter, 2005; Liu et al., 1996.

The analogousness of oxygen for hemoglobin, Hb S concentration, dehydration, the minimum concentration of gelation, acidosis and elevated temperature are determinant events, which directly influence the falcization process [92].

Sickle cells have a rigid, adherent and fragile structure, which compromises their circulation in the bloodstream [86, 87]. Cell harm and deformation of erythrocytes occur every bit a result of polymerization of deoxy-HbS and high concentrations of unpolymerized oxy-HbS, every bit well as influenced by cellular levels of HbF, water content, pH, temperature and mechanical stresses that will result in membrane injury [84].

The difficulty of circulating the sickle cell, its interaction with endothelial cells, leukocytes, platelets, endothelial dysfunction and the abnormal expression of adhesion molecules permeate the beginning of the process of apoplexy of the blood vessels, generating tissue hypoxia, hemolysis, increased oxidative stress and other pro-inflammatory phenomena [80, 87, 91, 93].

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4. Clinical consequences of the presence of Hb S

SCD is a chronic hemolytic anemia characterized by clinical events involving recurrent vaso-apoplexy, and its principal clinical manifestations are anemia, hurting, and multiple organ failures [18, fourscore, 87]. To empathize the clinical aspects of SCD, we must get a bit further into the pathophysiological and molecular aspects of this genetic disorder.

As we saw earlier, the presence of a genetic alteration in the nitrogen base in the cistron that encodes the β globin production triggers the formation of HbS, modifies the construction of the erythrocytes (Figure xi), and implies a series of pathophysiological complications for individuals with SCD. Many of the following events do non occur in isolation and are directly involved in the pathogenesis of SCD.

Figure xi.

Microscopic finding showing structural differences observed in normal form (oxy-HbS) and sickle cell (Deoxy-HbS), responsible for the pathological aspects in individuals with SCD. Source: Site of Howard Hughes Medical Institute, 2018.

The sickle jail cell has many difficulties in permeating the blood vessels. Due to the speed of the bloodstream, many end up clinging to each other thus harming the passage. Sickle jail cell occlusion mechanism is started. Spleen cells are pounded, violently pushed, lysed, and intravascular hemolysis causes the red blood cells to release a series of biocomponents, mainly hemoglobin and arginase that will collaborate with nitric oxide (NO) produced in the endothelium, reducing its bioavailability and arginine and its primary precursor [84, 94, 95].

The vessel occlusion plus constant hemolysis initiates tissue hypoxia. At the same fourth dimension, early on oxidation of NO increases oxidative stress implying endothelial dysfunction, with imbalances in the mechanisms of vessel dilatation and constriction [84, 85].

At a fourth dimension when local occlusion ends, and blood perfusion returns, more than free radicals are produced, and they further increment lesions to the endothelium, which becomes more adherent, specially to red blood cells and leukocytes, making the vascular wall over again exposed to a new occlusion [84, 95, 96].

Among the main adhesion pathways that progress the sickle prison cell and endothelial cell interactions are the soluble adhesion proteins (thrombospondin, fibrinogen, fibronectin, and von Willebrand gene), integrins (α4β1, αVβ3) and their membrane-jump receptors and sulfated glycolipids), immunoglobulins VCAM-one and ICAM-iv, endothelial selectin, as well as leukocyte activation by epinephrine through β-AR stimulation [85, 96].

Recurrent hemolysis eventually becomes chronic, and the inflammatory country is established. Thus, the organism needs to increase the production of red claret cells past the bone marrow, resulting in high cardiovascular piece of work, with increased cardiac output in society to facilitate the rapid delivery of blood with a college content of oxygen to the organs, avoiding hypoxia and tissue death [97]. More precisely, a compensatory mechanism is established that increases eye rate, leading to increased myocardial energy demand with the event between myocardial energy requirements and full trunk [98, 99, 100].

The hypermetabolism nowadays in these patients has an impact on body limerick and has been related to increased energy expenditure, increased poly peptide turnover, increased oxidative stress, higher reticulocyte levels, and reduced torso mass [97, 99, 101, 102].

Progressive degeneration of the organs results from infarctions in the affected areas, leading to several secondary complications that directly compromise patients' lives and survival [18, 80, 103].

Patients with SCD are more likely to have episodes of vascular accident, pulmonary hypertension, proteinuria and chronic kidney illness, all complications associated with vascular dysfunction caused by the disease [78, 94, 104, 105].

Vasodilation is reduced in patients with SCD and may have other consequences, such equally the advent of leg ulcers [94, 106, 107]. These lower limb ulcer lesions represent eight to ten% of the cases and take a higher incidence in people with SCA males and in the age grouping between 10 and 50 years [99, 107, 108, 109].

Ulcerations may appear afterwards trauma, insect bites, excessive dryness of the skin or spontaneously generally in the talocrural joint or malleolar region (middle or lateral portion), where there are less subcutaneous tissue and blood flow as a consequence of tissue hypoxia, endothelial dysfunction, and vaso-occlusion [107, 108, 110].

Infections in these patients are as well a major cause of business organisation both in childhood and in adulthood [76, 78, 111, 112]. In general, this and other complications (Effigy 12) bring many misfortunes to individuals with SCD and basically compromise the quality of life of these patients. Despite all the consequences of HbS formation, the degree of severity of the disease depends on numerous factors, and the first i is the genotype.

Figure 12.

Major complications secondary to SCD. Source: The analogy has been adapted from the Toda Matéria website. For more details, refer to the articles Ballas et al. [78]; Saraf et al. [104]; Saraf et al., [105]; Gordbach et al., 2012; Piels et al., 2017; Di nuzzo & Fonseca [76]; Machado, 2007; Gumiero et al., 2007; Brunetta et al., 2010; Paladino, 2007; Hyacinth et al. [99]; Marques et al., 2012; Cançado, 2007; Lobo et al., 2010; Borsato et al., 2000; Saad eTraina, 2007, Marques et al., 2012; Caridade et al., 2007.

SCD can be subdivided into distinct genotypes, six of which are more frequent in the world, SCA (Hb SS), heterozygotes (Hb SC, Hb SE, Hb SD), sickle thalassemia (Hb Sβ+ and Hb Sβ0), and sickle prison cell trait (Hb Equally) [8, 84, 104, 113, 114]. Individuals with Hb SS genotypes, heterozygoses and associations with thalassemia are by and large symptomatic, and at each gestation, at that place is a 25% chance that the child will be born with SCD from parents carrying some S gene or other variant hemoglobin (Figure 13) [84, 104, 115]. In general, the HbAS genotype is considered to be asymptomatic in that it hardly develops any clinical picture, but it represents a type of hemoglobinopathy, since the recessive cistron is probable to exist inherited for the adjacent generation [115, 116, 117, 118].

Figure 13.

Genograms showing the most prevalent SCD genotypes in the world and the likelihood of homozygous or heterozygosis independent of sexual activity when the parents have some type of hemoglobin variant that can generate SCD. The GENOPRO® software version 2016 was used to brand the genograms.

Other indicators of affliction severity are bilirubin, PCV, erythropoiesis charge per unit, leukocytes, LDH, fetal hemoglobin, creatinine, proteinuria, reticulocytes, HSV, phenotypes, days of hospitalization per year, severe vaso-occlusive crisis per year, number of transfusions per twelvemonth, hip disease, leg ulcer, hepatobiliary complications, neurological events, renal disorders and torso mass alphabetize [84, 119, 120, 121, 122, 123].

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5. Treatment of SCD: general aspects

Treatment, in general, is differentiated by pathophysiological changes during life and will besides depend on the type of genotype, which is accompanied by a hematologist. The employ of folic acid supplements is included in order to contain hemolysis and to accelerate the product of blood-red blood cells.

Likewise used are: (A) antibiotics, especially in children nether v years, since generalized infections tin lead to death inside a few hours due to splenic sequestration; (B) analgesics, codeine, morphine, and anti-inflammatories in the presence of acute or chronic pain crises; venous hydration in the vessel occlusion; (C) transfusion or claret exchange; (D) periodic and special immunizations; and (E) treatment of the sequelae or chronic consequences acquired past the disease [eighteen, 124, 125].

The use of hydroxyurea medication over the years as a handling that greatly increased the quality of life of patients. All the same, not all individuals are eligible or adjusted to their use [77, 126]. Alternative treatments, transplantation, and factor therapy are welcome measures for clinical treatment; however, some of these are still under discussion and crave technical and scientific clarification for their implementation.

Clinical and biochemical markers of disease severity should be used to predict adventure, prevent complications, and increase the expectation and quality of life of the population with SCD [77, 87, 127]. Often patients with SCD written report the development of vaso-occlusive symptoms afterward emotional/psychological stress, temperature changes, and concrete exertion [95]. Therefore, patients undergoing treatment and their caregivers are encouraged to do self-intendance, with measures that tin prevent acute events, improve prognosis, and permit a better quality of life [128].

In general, people with SCD due to chronic hemolysis and inflammatory land have college energy expenditure to develop daily activities and tendency to anorexia [109, 129, 130]. Pain crises generate a subtract in food consumption, which has a straight touch on on caloric and nutrient intake. Probably, the pain crises associated with the constant hospitalizations contribute to the lower food consumption that consequently compromises the nutritional status [127, 129, 130]. Thus, this population calls for nutritional monitoring for the intervention of the issues related to food and nutrition. In general, it is important the presence of a multi-professional squad, centered in the assistance and matrix support to the hematologist physician and the patients assisted with SCD.

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6. Conclusion

Scientific research and technical work around the globe have been done to better sympathise the pathophysiological and clinical aspects of SCD. It is a astringent hemolytic disease that causes great morbidity and mortality, especially in underdeveloped countries. The entire scenario generated by HbS has implications for the wellness and social inclusion of patients, so the handling of the person with SCD needs an approach focused on the prevention of these complications in an individualized style.

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Acknowledgments

The author cheers the invitation to write the affiliate and to Kristina Kardum for the noble assistance.

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Conflict of interest

The writer does non present conflicts of interest.

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Submitted: October 18th, 2017 Reviewed: Feb 2nd, 2018 Published: July 11th, 2018

© 2018 The Author(south). Licensee IntechOpen. This chapter is distributed nether the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted utilise, distribution, and reproduction in any medium, provided the original piece of work is properly cited.

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