Sociological Dimension of Sickle Cell Disease

## **Chapter 6**

## Role of Sociodemographic and Economic Variables in Predisposition to Vaso-Occlusive Crisis and Mortality in Patients with SCD: Case Study of Sub-Saharan Africa

*Osaro Erhabor, Teddy Charles Adias, Tosan Erhabor, Osaro Mgbere, Sadiya Usman and Bibiana Nonye Egenti*

## **Abstract**

Sickle cell disease (SCD) is a major public health challenge. It is a common cause of acute and chronic illness and death, which results from a single amino acid substitution (glutamic acid to valine) at position 6 of the beta (β) chain of the hemoglobin molecule. The pathophysiology is based on the polymerization of deoxygenated hemoglobin S (HbS) and production of irreversibly sickled red cells and vaso-occlusive crisis (VOC). The disease is associated with recurrent episodes of acute pain and organ damage. This chapter highlights the role of SES on the predisposition to VOC and mortality among SCD patients. Findings from this review will enable the development and implementation of policies that can facilitate the effective management of SCD in the region. More awareness and education of parents of children and adults living with SCD are needed to identify factors that predispose patients to VOC and common-sense measures to prevent these triggers. SCD patients should be protected against malaria. The need for nutritional intervention, proper hydration, avoidance of dietary intake of sodium, strenuous physical activity, and extreme weather to reduce the incidence of VOC cannot be overemphasized. Protective immunization and access to effective prophylactic and therapeutic agents should be implemented.

**Keywords:** sociodemography, economy, vaso-occlusive crisis, mortality, SCD, sub-Saharan Africa

## **1. Introduction**

Sickle cell disease (SCD) is of major public health challenge globally, with majority of affected patients residing in sub-Saharan Africa [1]. It is a genetic disorder

resulting from the inheritance of abnormal gene (HbS) from both parents [2]. The difference between the abnormal hemoglobin S (HbS) and the normal adult hemoglobin A is a single amino acid substitution of valine for glutamic acid in the sixth position in the β-globin chain. In sub-Saharan Africa, about 300,000 infants are born with major hemoglobin disorders and about 2% of all children have SCD [3]. The frequency of the trait is between 15 and 30% in West Africa [4]. SCD disproportionately affects people in the African continent compared to other parts of the globe. The United Nations estimates that 12–15 million of the world's 25 million SCD patients live in the African continent [5], while an insignificant 10% live in highincome countries (HICs) [6]. The mortality rate from the disease in children under 5 years of age is estimated to exceed 50% in the African continent where healthcare infrastructure is suboptimal and the population are significantly impoverished [7]. Recurrent and random episodes of vaso-occlusive crisis (VOC) are the hallmark of sickle cell disease. The pathophysiology of vaso-occlusive crisis lies in the fact that upon deoxygenation, the mutant HbS molecule polymerizes and attains a characteristic sickle shape. The sickle-shaped red cells adhere to leukocytes immobilized to the endothelium, causing microvascular occlusion and vaso-occlusive crisis (VOC), tissue ischemia, and resultant pain. The actual causes of VOC are unknown. However, factors including exposure to cold (hypothermal), dehydration, infection, malaria infection, and stress may play a role [8]. Painful vaso-occlusive crisis (VOC) is the commonest cause of hospital admission in patients with SCD. Socioeconomic status (SES) and demographic variables seem to play a key role in the prevalence, development of complications, and mortality in several diseases including sickle cell disease (SCD) and particularly in low-income developing countries. The aim of this chapter is to review the several sociodemographic and socioeconomic variables that can predispose to vaso-occlusive crisis among sickle cell disease patients.

## **2. Effects of sociodemographic and economic factors in VOC in SCD**

Sociodemographic variables play a role in hospitalization of SCA children. The level of educational attainment of parents has a significant role in the incidence and presentation to hospital with VOC. A previous report in Sokoto, North Western Nigeria, indicated that majority of the parents of children presenting to the children emergency unit with vaso-occlusive crisis were either educated up to secondary school or had no formal education. Also, a SCD child's position in a family had a role in presentation in emergency unit with VOC. Majority of the subject presenting to hospital in VOC were ≥ 6th position [9]. Higher levels of education and income mitigate the deleterious effects of the psychosocial consequences (anxiety and depression) associated with SCD. Parents of SCD children with higher education or income are more likely to make better informed decision about nutritional requirements and use of insecticide-treated mosquito nets to protect their children from malaria. They are also able to afford the medication and the various treatment options required for the effective management of their SCD children [10]. There are several factors that play a role in an individual's socioeconomic status (education, profession, and income). SES of an individual can play a role in the development, complications, negative outcome, and increased mortality of patients with SCD [11]. The effects of these factors often begin in the prenatal stages before a child is born and tend to continue through life [12]. A study that investigated the influence of SES factors on

*Role of Sociodemographic and Economic Variables in Predisposition to Vaso-Occlusive Crisis… DOI: http://dx.doi.org/10.5772/intechopen.105685*

hematological and clinical parameters in children with SCD in Saudi Arabia [13] indicated that a significant number of children affected with the SCD were from the low socioeconomic class on <5000 SAR. The prevalence of VOC, adverse events, and more deranged hematological indices was more prevalent among patients in the lowest SES.

#### **2.1 Role of poverty on incidence of VOD in SCD patients**

Inability to pay for healthcare can have a significant effect on accessibility and promptness of assessing care for many indigent patients. Many SCD patients do not access care on time until complications have developed. This can potentially result in longer lengths of stay for the treatment of complications of their underlying disease [14]. A previous report in Sokoto, North Western Nigeria, indicated that majority of the parents of children in vaso-occlusive crisis had income of < N36,000 naira (equivalent of <\$75) monthly [9]. The management of SCD patients is not cheap. In the United States, the estimated total healthcare cost per year for children and adults with SCD stand at USD1.1 billion [15]. Children from low socioeconomic status (SES) with and without chronic disease have been reported to have worse health outcomes and higher utilization of health resources compared to those who are more advantaged [16]. They are more likely to be admitted to the hospital, have longer lengths of hospital stay, and generate more healthcare-associated costs particularly in the first 10 years of life compared to children from higher SES [17]. However, a previous report that examined the association between socioeconomic status and length of hospital stay for children with sickle cell disease observed that SES has no clinically important effect on the length of hospital stay [18]. Efforts are being made to better understand the pathophysiology, prevent and ameliorate the consequences, and ensure the effective management of VOC in sickle cell disease using novel targeted therapies [19]. The major challenge that may limit the access to these therapies in developing countries where this disease is more prevalent is cost [20]. Managing patients with SCD comes with a huge cost [21]. In 2004 alone, more than 80,000 hospitalizations were attributable to adult SCD patients in the United States, costing nearly \$500 million, with majority of the cost arising from inpatient hospitalization associated with VOC [8, 22]. Managing chronic illness like SCD in low- and middleincome countries (LMICs) can incur very high out-of-pocket (OOP) payments for healthcare. Many households do not have the necessary money. Some are left with no other option than to adopt one or more "coping strategies," such as borrowing money often times at outrageous interest rates, or selling assets like land, farm produce, and jewelleries [23]. Out-of-pocket expenditure can prevent a number of SCDs from accessing care promptly due to unaffordability, and this can affect the delivery of a prompt and efficient management of patients with sickle cell disease [24]. There is need for government across sub-Saharan Africa to provide universal access to quality care for patients with SCD as well as to improve the awareness among patients on the need to promptly access care to prevent complications. These implementations can potentially help improve health outcomes.

#### **2.2 Effect of malnutrition on the incidence of VOC in SCD**

There seems an interconnection between nutritional state, host defense, susceptibility, and disease outcomes. Previous report indicates that micronutrient deficiencies are associated with signs of poor growth, increased susceptibility to infection, and recurrent occurrences of VOC in patients with SCD and outcomes [25]. The important role nutrition plays in the health-related quality of life of patients cannot be overemphasized. A previous report indicated that the health-related quality of life of a cohort of SCD patients improved significantly after tailored micronutrient program was initiated among the patients [26, 27]. Qualitative malnutrition seen among SCD tends to be multifactorial and often results from suboptimal intake or uptake of macro- or micronutrients. SCD-related increased nutritional demands, presence of attendant chronic gastrointestinal diseases and infections, socioeconomic status, and lifestyle factors tend to predispose SCD patients to frequent hospitalizations primarily due to vaso-occlusive crises and other SCD-related complications [28]. Zinc and omega-3 fatty acid supplementation have been associated with limited reduction in vaso-occlusive crises [29]. The disparity in SES, migrations, food insecurity, fast-food habits, and social and cultural patterns seem to be the main causes of altered nutrition in individuals throughout the globe [30]. Suboptimal intake of macro- and micronutrients has been shown to be associated with predisposition and negative outcomes in SCD patients. Micronutrient deficiencies, including zinc, copper, folic acid, pyridoxine, vitamin E, B6, and B12, omega-3 fatty acids, vitamin D, and arginine have been shown to play a role [31–34]. Similarly, the use L-glutamine has been shown to be beneficial in decreasing the incidents of SCD-related vaso-occlusive (VOC) pain events without significant safety concerns [35]. Zinc supplementation has been associated with decreased incidence of infections, number of hospitalizations, and vaso-occlusive pain crisis among SCD patients [36]. The serum copper, selenium, RBC, HCT, HGB, MCV, MCH, and MCHC were significantly lower among sickle cell disease patients compared to controls. It is recommended that trace elements (copper and selenium) and hematological parameters are monitored routinely among sickle cell disease children to optimize the care offered to these individuals [9]. Vaso-occlusion is understood to be the root cause of sickle cell pain. Nitric oxide (NO) is a potent vasodilator [37] that plays a role in the vaso-occlusive complications of SCD [38]. Recent findings indicate that one of the pathophysiological pathways of sickle cell disease (SCD) lies on the role of red cell hemolysis and nitric oxide (NO) depletion on the occurrence of acute and chronic complications including VOC. Nitric oxide is produced in the endothelium from its obligate substrate L-arginine, which is converted to citrulline by a family of enzymes, the NO synthases (NOS). *P. falciparum* malaria is a common trigger of VOC in SCD patients. *P. falciparum* malaria is associated with hypoarginaemia among preschool children of African descent [39]. Arginine is a safe and inexpensive intervention with narcotic-sparing effects that may be a beneficial adjunct to standard therapy for sickle-cell-related pain in children [40–42]. SCD children have lower values of antioxidant enzymes compared to controls. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels in sickle cell disease patient in vaso-occlusive crisis are significantly lower compared to that of non-sickle cell controls [43]. There seems a justification to urgently develop dietary reference intakes (DRIs) and recommended dietary allowances (RDAs) for patients with SCD and integrate nutritional intervention as a vital adjunct in the prevention of VOC and the treatment of patients [44].

### **2.3 Socioeconomic disparity in access to health**

SES is defined as a complex combination of several factors including occupation, income, knowledge, education, and power in a society that affect an individual's well-being [45]. The quality of healthcare delivery is on a decline in many developing economies and limits access to health products particularly for those with low

### *Role of Sociodemographic and Economic Variables in Predisposition to Vaso-Occlusive Crisis… DOI: http://dx.doi.org/10.5772/intechopen.105685*

SES [46]. Abnormal growth, stunting, and a low BMI are commoner in children with SCD of lower socioeconomic class [47]. Data from the United Kingdom shows that SCD children from low SES constitutes the majority of those hospitalized. The hospital admissions were majorly due to episodes of VOC [18]. The need for government particularly in low-income settings to address the issue of inequalities in access to health products cannot be overemphasized. There is disparity in access to care in SCD in urban setting compared to those in rural settings. Reports from the island of Jamaica and the United States indicate that SCD patients with more severe genotypes tend to live in higher poverty-stricken rural settings and tend to travel longer distance to access healthcare services and advocate that government particularly in developing countries ensure that better access to healthcare services is provided for SCD patients residing in rural settings [48–50].

## **2.4 Lack of education and awareness on the management of patients at home to prevent the risk of VOC**

Painful crises are the causes of 50–60% of emergency visits and 60–80% of hospitalizations in children with SCD [51]. Triggers for VOC vary and can include inflammation, stress, increased viscosity, decreased flow, hemolysis, infection, exposure to cold, hypoxia, acidosis, dehydration, physically demanding activity, emotional stress, and malaria, or a combination of factors [19, 52]. A previous report from Nigeria indicates that malaria (76.7%) and bacterial infection (60%) were common trigger of VOC among SCD subjects [9]. A significant association has been observed between the parents' awareness of VOCs and a better disease outcome in their children, as they had fewer attacks and hospital admissions [53]. The need to provide information required to enable parents of children and adults with SCD effectively manage themselves at home to reduce the incidence VOC and need for hospitalization cannot be overemphasized. There are a number of commonsense measures that can be implemented to reduce the risk of VOC-related admissions. Parents of children and adult patients with SCD must take the issue of optimal hydration seriously. Poorly hydrated erythrocytes lead to increased viscosity and may contribute to the vaso-occlusive crisis in SCD [54]. It is crucial for SCD patients to promote proper hydration by frequent intake of water, avoidance of dietary intake of sodium, and avoidance of strenuous physical activity and extreme weather that result in excessive sweating [55, 56]. Majority of SCD patients live in *Plasmodium falciparum* endemic African countries [57]. SCD patients are highly vulnerable to malaria infection as a result of impaired splenic function which is a common feature in SCD patients [58]. Infection with *Plasmodium falciparum* in SCD patients can trigger painful vaso-occlusive crisis, increase the severity of anemia, and contribute to early childhood mortality [59]. Efforts must be made to keep SCD patients safe from malaria infection by providing them with antimalarial chemoprophylaxis and insecticides-treated mosquito nets, and the implementation of vector control measures [60, 61]. Evidence from the UK indicates that environmental factors including increased wind speed and low humidity have a significant effect on acute pain in SCD. Others indicates that low levels of carbon monoxide and nitric oxide were associated with increased numbers of VOC-related hospital admissions [62, 63]. Parents of children with SCD and adult patients have a duty of care to ensure that these preventive measures are implemented. Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive crisis (VOC). Patients with SCD tend to have impaired immunity due to splenic infarction which predisposes them to recurrent infections [64]. Other infection predisposing factors in SCD include abnormalities of

opsonization, suboptimal antibody production, impaired leukocyte functions, and cell-mediated immunity [65]. The clinical course of the disease is characterized by periodically painful vaso-occlusive crisis, which can be triggered by psychological, physical, and infective factors [66]. Hyposplenism predisposes SCD patients to severe infections with malaria and encapsulated organisms, including *Haemophilus influenza, Mycoplasma pneumoniae, Salmonella typhimurium, Staphylococcus aureus, Escherichia coli*, *and Streptococcus pneumoniae* [64, 67]. Respiratory tract infections are common in SCD and vary and range from mild upper tract infection to moderately severe uncomplicated pneumonia that can be managed with appropriate antibiotics. Respiratory tract infection if poorly managed can predispose patients to acute chest syndrome (ACS) which is a serious and potentially fatal complication. There is the need to reduce the burden of infection on SCD patients by ensuring that patients are administered the relevant protective immunization, have access to effective prophylactic and therapeutic use of antimicrobial, keep their environment, clean and are provided with barrier protection [68]. There is need for governments across the sub-Saharan Africa to take realistic steps to eradicate poverty and illiteracy as enshrined in the United Nations' millennium development goals for underdeveloped countries. This will go a long way in reducing the high incidence of infection among SCD patients in particular and improving the quality of life of patients.

## **2.5 Psychosocial realities of vaso-occlusive crisis in SCD**

A previous report indicated that sociodemographic characteristics and quality of life play a major role in SCD, and these have serious psychosocial consequences, especially anxiety and depression, on SCD patients [69]. Vaso-occlusive pain crises (VOC) is the most common cause of emergency department visits and hospitalizations in patients with sickle cell disease [70]. Sickle cell disease (SCD) patients with VOC may experience a broad range of mental health disorders. Pediatric patients with SCD and a history of a mental health diagnosis have longer length of stay (LOS) and higher admission rates for the management of VOC. Ultimately, these findings suggest that mental health pose a challenge to the management of VOC-related pain in patients with SCD [71]. Pediatric patients diagnosed with a psychiatric disorder, specifically mood or anxiety disorders, have longer LOS for VOC. These findings suggest that future interventions aimed at managing VOC may need to consider adjunctive psychiatric assessment and intervention [72]. Comorbid depression is significantly associated with longer LOS, more severity of illness, and higher hospital charges [73]. Healthcare providers caring for adults with SCD should consider screening and managing the mental health of SCD patients to improve the health-related quality of life. SCD patients with depression had a higher prevalence of acute vaso-occlusive pain and acute chest syndrome visits per year, developed more complications related to organ damage, and incurred significantly higher outpatient and inpatient total healthcare costs compared to controls [74]. VOC-related acute pain and fatigues resulting from anemia are major hallmarks of SCD. These factors predispose patients to psychological disorders, depression, anxiety, and a negative impact on their quality of life (QoL) [75]. Previous report indicates that the rates of depression in SCD patients (18–46%) are similar to those seen in other chronic diseases [76]. Depression seems prevalent in patients with SCD and may be correlated with demographic and social factors. A previous study investigated the prevalence of depression and anxiety among SCD patients from different sociodemographic groups in Jeddah, Saudi Arabia. *Role of Sociodemographic and Economic Variables in Predisposition to Vaso-Occlusive Crisis… DOI: http://dx.doi.org/10.5772/intechopen.105685*

Finding indicated that there was a significant association between depression rate and the two variables of patient employment status (49.3%; p = 0.047) and a family history of SCD (51%) [77]. A depression rate of 48.2% was reported among the SCD patients in Qitaf, Eastern Province of Saudi Arabia [78]. Depression among SCD patients in sub-Saharan African may even be higher for a number of reasons; apart from the fatigue and VOC-associated pain, many SCD patients have to grapple with paying for their healthcare cost which tends to be funded out of pocket, and patients also worry about the availability of safe blood transfusion (lack of effective screening for TTIs, risk of possible hemolytic transfusion reaction, and alloimmunization to foreign donor red cells antigens). Many blood transfusion laboratories in sub-Saharan African countries lack facilities for routine alloantibody screening and extended red cell phenotyping. There is also the risk of iron overload and the cost implication of iron chelation therapy [79]. There are a number of factors that may be responsible for the increased incidence of depression among patients with SCD particularly in low-income settings in sub-Saharan Africa; the higher the rate of healthcare utilization, there are higher costs of out-of-pocket medical care and the challenge associated with the effect of the VOC crisis-related pain [80, 81]. There is need to routinely examine the health-related quality of life and mental health status of SCD in relation to VOC-related pain during hospital admissions and target appropriate psychological interventions for the effective management of pain in these patients [82].

## **3. Conclusion**

This review indicates that socioeconomic and demographic factors play a key role in the prevalence of VOC, development of complications, and mortality in sickle cell disease (SCD) particularly in low-income developing countries.

## **4. Recommendations**


*Role of Sociodemographic and Economic Variables in Predisposition to Vaso-Occlusive Crisis… DOI: http://dx.doi.org/10.5772/intechopen.105685*

## **Author details**

Osaro Erhabor1 \*, Teddy Charles Adias2 , Tosan Erhabor3 , Osaro Mgbere4 , Sadiya Usman1 and Bibiana Nonye Egenti5

1 Department of Haematology, Usmanu Danfodiyo University Sokoto, Nigeria

2 Federal University Otuoke Bayelsa State, Nigeria

3 Medical Laboratory Science Council of Nigeria, Nigeria

4 Houston Health Department, Disease Prevention and Control Division, Houston, Texas, USA

5 Department of Community Medicine, College of Health Sciences, University of Abuja, Nigeria

\*Address all correspondence to: n\_osaro@yahoo.com; erhabor.osaro@udusok.edu.ng

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## **References**

[1] Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;**376**: 2018-2031. DOI: 10.1016/ S0140-6736(10)61029-X

[2] Oniyangi O, Omari AA. Malaria chemoprophylaxis in sickle cell disease. Cochrane Database of Systematic Reviews. 2006;**4**:CD003489

[3] WHO. Sickle-cell Anaemia. Geneva: Author; 2006

[4] Kyerewaa EA, Edwin F, Etwire V. Controlling sickle cell disease in Ghana ethics and options. The Pan African Medical Journal. 2011;**10**:14

[5] Aliyu ZY, Kato GJ, Taylor JT, Babadoko A, Mamman AI, Gordeuk VR, et al. Sickle cell disease and pulmonary hypertension in Africa: A global perspective and review of epidemiology, pathophysiology, and management. American Journal of Hematology. 2008;**83**:63-70. DOI: 10.1002/ajh.21057

[6] Aygun B, Odame IA. Global perspective on sickle cell disease. Pediatric Blood & Cancer. 2012;**59**:386-390. DOI: 10.1002/ pbc.24175

[7] Makani J, Cox SE, Soka D, Komba AN, Oruo J, Mwamtemi H, et al. Mortality in sickle cell anemia in Africa: A prospective cohort study in Tanzania. PLoS One. 2011;**6**:e14699. DOI: 10.1371/ journal.pone.0014699

[8] Jang T, Poplawska M, Cimpeanu E, et al. Vaso-occlusive crisis in sickle cell disease: A vicious cycle of secondary events. Journal of Translational Medicine. 2021;**19**:397. DOI: 10.1186/s12967-021-03074-z

[9] Erhabor O, Ogar K, Erhabor T, Dangana A. Some haematological parameters, copper and selenium level among children of African descent with sickle cell disease in Specialist Hospital Sokoto, Nigeria. Human Antibodies. 2019;**27**(3):143-154. DOI: 10.3233/ HAB-180360

[10] Ogunfowora OB, Durotoye MO, Gregory AS. A comparative study of academic achievement of children with sickle cell anemia and their healthy siblings. Nigerian Journal of Medicine. 2005;**97**:405-410

[11] Lubeck D, Agodoa I, Bhakta N, Danese M, Pappu K, Howard R, et al. Estimated life expectancy and income of patients with sickle cell disease compared with those without sickle cell disease. JAMA Network Open. 2019;**2**(11):e1915374. DOI: 10.1001/ jamanetworkopen.2019.15374

[12] National Research Council Panel on Race, E., Health in Later, L. The National Academies Collection: Reports funded by National Institutes of Health. In: Bulatao RA, Anderson NB, editors. Understanding Racial and Ethnic Differences in Health in Late Life: A Research Agenda. Washington, DC: National Academies Press (US), National Academies; 2004

[13] Khan SA, AlSiny F, Makki A, Ali A, AlAnsari I, Khan S. Socioeconomic status dependent medical complexities in children with sickle cell disease in Saudi Arabia. Saudi Journal of Biological Sciences. 2020;**27**(7):1781-1787. DOI: 10.1016/j.sjbs.2020.03.008

[14] Epstien AM, Stern RS, Weissman JS. Do the poor cost more? A multi-hospital study of patients' socioeconomic status and use of hospital resources. The New England Journal of Medicine. 1991;**322**(16):1122-1128

*Role of Sociodemographic and Economic Variables in Predisposition to Vaso-Occlusive Crisis… DOI: http://dx.doi.org/10.5772/intechopen.105685*

[15] Kauf TL, Coates TD, Huazhi L, Mody-Patel N, Hartzema AG. The cost of health care for children and adults with sickle cell disease. American Journal of Hematology. 2009;**84**(6):323-327

[16] O'Connor G, Quinton HB, Kneeland T, et al. Median household income and mortality rate in cystic fibrosis. Pediatrics. 2003;**11**(4):333-339

[17] Petrou S, Kupek E. Socioeconomic differences in childhood hospital inpatient service utilization and costs: Prospective cohort study. Journal of Epidemiology and Community Health. 2005;**59**:591-597

[18] Ellison AM, Bauchner H. Socioeconomic status and length of hospital stay in children with vasoocclusive crises of sickle cell disease. Journal of the National Medical Association. 2007;**99**(3):192-196

[19] Manwani D, Frenette PS. Vasoocclusion in sickle cell disease: Pathophysiology and novel targeted therapies. Blood. 2013;**122**(24):3892-3898. DOI: 10.1182/blood-2013-05-498311

[20] Telen MJ. Beyond hydroxyurea: New and old drugs in the pipeline for sickle cell disease. Blood. 2016;**127**(7):810-819. DOI: 10.1182/blood-2015-09-618553

[21] Steiner CA, Miller JL. Sickle Cell Disease Patients in U.S. Hospitals, 2004. Rockville, MD: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs; 2006

[22] Brousseau DC, Owens PL, Mosso AL, Panepinto JA, Steiner CA. Acute care utilization and rehospitalizations for sickle cell disease. JAMA. 2010;**303**:1288-1294

[23] Murphy A, McGowan C, McKee M, et al. Coping with healthcare costs for chronic illness in low-income and

middle-income countries: A systematic literature review. BMJ Globalization and Health. 2019;**4**:e001475

[24] Ogamba CF, Akinsete AM, Mbaso HS, Adesina OA. Health insurance and the financial implications of sickle cell disease among parents of affected children attending a tertiary facility in Lagos, south-west Nigeria. The Pan African Medical Journal. 2020;**36**:227

[25] Datta D, Namazzi R, Conroy AL, Cusick SE, Hume HA, Tagoola A, et al. Zinc for Infection Prevention in Sickle Cell Anemia (ZIPS): Study protocol for a randomized placebo-controlled trial in Ugandan children with sickle cell anemia. Trials. 2019;**20**(1):460. DOI: 10.1186/ s13063-019-3569-z, 20, 1

[26] Martyres DJ, Vijenthira A, Barrowman N, Harris-Janz S, Chretien C, Klaassen RJ. Nutrient insufficiencies/ deficiencies in children with sickle cell disease and its association with increased disease severity. Pediatric Blood & Cancer. 2016;**63**(6):1060-1064

[27] Mandese V, Marotti F, Bedetti L, Bigi E, Palazzi G, Iughetti L. Effects of nutritional intake on disease severity in children with sickle cell disease. Nutrition Journal. 2016;**15**(1):46

[28] Ruiz AJ, Buitrago G, Rodríguez N, Gómez G, Sulo S, Gómez C, et al. Clinical and economic outcomes associated with malnutrition in hospitalized patients. Clinical Nutrition. 2019;**38**(3):1310-1316

[29] Dekker LH, Fijnvandraat K, Brabin BJ, van Hensbroek MB. Micronutrients and sickle cell disease, effects on growth, infection and vaso-occlusive crisis: A systematic review. Pediatric Blood & Cancer. 2012;**59**(2):211-215

[30] Cannas G, Merazga S, Virot E. Sickle cell disease and infections in high- and

low-income countries. Mediterranean Journal of Hematology and Infectious Diseases. 2019;**11**(1). DOI: 10.4084/ mjhid.2019.042

[31] Hyacinth HI. Sickle-cell anaemia needs more food? Lancet Haematol. 2018;**5**(4):e130. DOI: 10.1016/ S2352-3026(18)30032-2

[32] Daak A, Rabinowicz A, Ghebremeskel K. Omega three fatty acids are a potential therapy for patients with sickle cell disease. Nature Reviews. Disease Primers. 2018;**4**:15. DOI: 10.1038/ s41572-018-0012-9

[33] Adegoke SA, Smith OS, Adekile AD, ueiredo MS. Relationship between serum 25-hydroxyvitamin D and inflammatory cytokines in paediatric sickle cell disease. Cytokine. 2017;**96**:87-93. DOI: 10.1016/j. cyto.2017.03.010

[34] Morris CR. Alterations of the arginine metabolome in sickle cell disease. A growing rationale for arginine therapy. Hematology/oncology Clinics of North America. 2014;**28**:301-321. DOI: 10.1016/j.hoc.2013.11.008

[35] Quinn CT. L-gutamine for sickle cell anemia: More questions than answers. Blood. 2018;**132**(7):689. DOI: 10.1182/ blood-2018-03-834440

[36] Prasad AS, Beck FW, Kaplan J, Chandrasekar PH, Ortega J, et al. Effect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD). American Journal of Hematology. 1999;**61**:194-202

[37] Moncada S, Higgs A. The L-arginine-nitric oxide pathway. The New England Journal of Medicine. 1993;**329**(27):2002-2012

[38] Kaul DK, Liu XD, Fabry ME, Nagel RL. Impaired nitric oxide-mediated

vasodilation in transgenic sickle mouse. American Journal of Physiology. Heart and Circulatory Physiology. 2000;**278**(6):H1799-H1806

[39] Kabiru M, Erhabor O, Isaac Z, Jiya NM, Knox VD, Abdulrahaman Y, et al. Hypoarginaemia among Pre-School Children of African Descent with Plasmodium Falciparum Malaria. Haematology International Journal. 2017;**1**(1):000102. DOI: 10.23880/ HIJ-16000102

[40] Morris CR, Kuypers FA, Lavrisha L, Ansari M, Sweeters N, Stewart M, et al. A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vasoocclusive pain episodes. Haematologica. 2013;**98**(9):1375-1382. DOI: 10.3324/ haematol.2013.086637

[41] Aslan M, Ryan T, Adler B, Townes T, Parks D, Thompson J, et al. Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proceedings of the National Academy of Sciences. 2001;**98**(26):15215-15220

[42] Matte A, Cappellini MD, Iolascon A, Enrica F, De Franceschi L. Emerging drugs in randomized controlled trials for sickle cell disease: Are we on the brink of a new era in research and treatment? Expert Opinion on Investigational Drugs. 2020;**29**(1):23-31

[43] Erhabor O, Jiya N, Abubakar M, Usman S. Some antioxidant enzymes among children with sickle cell disease attending Usmanu Danfodiyo University Teaching Hospital Sokoto, North Western Nigeria. Open Journal of Blood Diseases. 2019;**9**:60-76. DOI: 10.4236/ ojbd.2019.93007

[44] Umeakunne K, Hibbert JM. Nutrition in sickle cell disease: Recent *Role of Sociodemographic and Economic Variables in Predisposition to Vaso-Occlusive Crisis… DOI: http://dx.doi.org/10.5772/intechopen.105685*

insights. Nutrition and Dietary Supplements. 2019;**11**:9-17

[45] Burton DC, Flannery B, Bennett NM, Farley MM, Gershman K, Harrison LH, et al. Active Bacterial Core Surveillance/Emerging Infections Program N. Socioeconomic and racial/ ethnic disparities in the incidence of bacteremic pneumonia among US adults. American Journal of Public Health. 2010;**100**:1904-1911

[46] Link-Gelles R, Westreich D, Aiello AE, Shang N, Weber DJ, Holtzman C, et al. Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study. SSM Population Health. 2016;**2**:587-594

[47] Shah N, Bhor M, Xie L, Halloway R, Arcona S, Paulose J, et al. Treatment patterns and economic burden of sickle-cell disease patients prescribed hydroxyurea: A retrospective claimsbased study. Health and Quality of Life Outcomes. 2019;**17**(1):155

[48] Asnani MR, Knight Madden J, Reid M, Greene L-G, Lyew-Ayee P. Socio-environmental exposures and health outcomes among persons with sickle cell disease. PLoS One. 2017;**12**(4):e0175260. DOI: 10.1371/ journal.pone.0175260

[49] Haque A, Telfair J. Socioeconomic distress and health status: The urbanrural dichotomy of services utilization for people with sickle cell disorder in North Carolina. The Journal of Rural Health. 2000;**16**:43-55

### [50] Telfair J, Haque A,

Etienne M, Tang S, Strasser S. Rural/ urban differences in access to and utilization of services among people in Alabama with sickle cell disease. Public Health Reports. 2003;**118**:27-36

[51] Meier ER, Miller JL. Sickle cell disease in children. Drugs. 2012;**72**(7):895-906

[52] Yale SH, Guthrie T. Approach to the vaso-occlusive crisis in adults with sickle cell disease. American Family Physician. 2000;**61**(5):1349-1357

[53] Zolaly M, Al-Mohammadi G, Al-Saadi G, Qasim D. Vaso-occlusive crises in patients with sickle cell disease: Parents' perspectives and association with disease outcomes. Journal of Taibah University Medical Sciences. 2019;**14**(6):515-522

[54] Rinehart J, Gulcicek EE, Joiner CH, Lifton RP, Gallagher PG. Determinants of erythrocyte hydration: Current opinion in haematology. Current Opinion in Hematology. 2010;**17**(3):191-197. DOI: 10.1097/MOH.0b013e32833800d0

[55] Diaw M, Samb A, Diop S, et al. Effects of hydration and water deprivation on blood viscosity during a soccer game in sickle cell trait carriers. British Journal of Sports Medicine. 2014;**48**(4):326-331. DOI: 10.1136/ bjsports-2012-091038

[56] Williams-Hooker R, Hankins J, Ringwald-Smith K, et al. Evaluation of hydration status, sodium and fluid intake in children with sick cell anaemia. Journal of Blood Disorders Transfer. 2013;**4**(3):1-4. DOI: 10.4172/2155-9864.1000143

[57] Wiebe A, Longbottom J, Gleave K, Shearer FM, Sinka ME, Massey NC, et al. Geographical distributions of African malaria vector sibling species and evidence for insecticide resistance. Malaria Journal. 2017;**16**(1):85

[58] Makani J, Komba AN, Cox SE, Oruo J, Mwamtemi K, Kitundu J, et al. Malaria in patients with sickle

cell anemia: Burden, risk factors, and outcome at the outpatient clinic and during hospitalization. Blood. 2010;**115**:215-220

[59] McAuley CF, Webb C, Makani J, Macharia A, Uyoga S, Opi DH, et al. High mortality from *Plasmodium falciparum* malaria in children living with sickle cell anemia on the coast of Kenya. Blood. 2010;**116**:1663-1668

[60] Frimpong A, Thiam LG, Arko-Boham B, Owusu EDA, Adjei GO. Safety and effectiveness of antimalarial therapy in sickle cell disease: A systematic review and network meta-analysis. BMC Infectious Diseases. 2018;**18**(1):650

[61] Oniyangi O, Omari AA. Malaria chemoprophylaxis in sickle cell disease. Cochrane Database System Review. 2006;**2006**(4):CD003489

[62] Yallop D, Duncan ER, Norris E, Fuller GW, Thomas N, et al. The associations between air quality and the number of hospital admissions for acute pain and sickle-cell disease in an urban environment. British Journal of Haematology. 2007;**136**:844-848

[63] Mekontso Dessap A, Contou D, Dandine-Roulland C, Hemery F, Habibi A, et al. Environmental influences on daily emergency admissions in sickle-cell disease patients. Medicine (Baltimore). 2014;**93**:e280

[64] William BM, Corazza GR. Hyposplenism: A comprehensive review. Part I: Basic concepts and causes. Hema. 2007;**12**(1):1-13

[65] Salawu L, Orimolade EA, Durosinmi MA. Immuno-haematological characteristics of Nigerian sickle cell disease patients in asymptomatic steady state. European Journal of General Medicine. 2009;**6**:170-174

[66] Mousa SA, Al Momen A, Al Sayegh F, Al Jaouni S, Nasrullah Z, Al Saeed H, et al. Management of painful vaso-occlusive crisis of sickle-cell anemia: Consensus opinion. Clinical and Applied Thrombosis/Hemostasis. 2010;**16**(4):365-376

[67] Dieye TN, Ndiaye O, Ndiaye AB, Thiam D, Fall-Seck K, Diop S, et al. Complement and serum immunoglobulins in homozygous and heterozygous sickle cell anemia in Senegal. Dakar Médical. 1999;**44**(2):175-179

[68] Ahmed SG. The role of infection in the pathogenesis of vaso-occlusive crisis in patients with sickle cell disease. MJHID. 2011;**3**(1):e2011028. DOI: 10.4084/MJHID.2011.028

[69] Adzika VA, Glozah FN, Ayim-Aboagye D, Ahorlu CS. Sociodemographic characteristics and psychosocial consequences of sickle cell disease: The case of patients in a public hospital in Ghana. Journal of Health, Population, and Nutrition. 2017;**36**(1):4. DOI: 10.1186/s41043-017-0081-5

[70] Houston-Yu P, Rana SR, Beyer B, et al. Frequent and prolonged hospitalizations: A risk factor for early mortality in sickle cell disease patients. American Journal of Hematology. 2003;**72**(3):201-203

[71] Myrvik MP, Burks LM, Hoffman RG, Dasgupta M, Panepinto JA. Mental health disorders influence admission rates for pain in children with sickle cell disease. Pediatric Blood & Cancer. 2013;**60**(7):1211-1214. DOI: 10.1002/pbc.24394

[72] Myrvik MP, Campbell AD, Davis MM, Butcher JL. Impact of psychiatric diagnoses on hospital length of stay in children with sickle cell anemia. Pediatric Blood & Cancer. 2012;**58**(2):239-243. DOI: 10.1002/pbc.23117

*Role of Sociodemographic and Economic Variables in Predisposition to Vaso-Occlusive Crisis… DOI: http://dx.doi.org/10.5772/intechopen.105685*

[73] Onyeaka HK, Queeneth U, Rashid W, Ahmad N, Rajan SK, Jaladi PR, et al. Impact of depression in sickle cell disease hospitalization-related outcomes: An Analysis of the National Inpatient Sample (NIS). Medicina (Kaunas, Lithuania). 2019;**55**(7):385. DOI: 10.3390/ medicina55070385

[74] Jerrell JM, Tripathi A, McIntyre RS. Prevalence and treatment of depression in children and adolescents with sickle cell disease: A retrospective cohort study. ers. 2011;**13**(2)

[75] Al Zahrani OS, Mukhtar O, Al Subaie M, Al Howiti WE. Systematic psychiatric assessment of patients with sickle cell disease. Saudi Medical Journal. 2019;**40**(1):59-65

[76] Edwards CL, Green M, Wellington CC, Muhammad M, Wood M, Feliu M, et al. Depression, suicidal ideation, and attempts in black patients with sickle cell disease. Journal of the National Medical Association. 2009;**101**: 1090-1095

[77] Al-Marzouki AF, Alrefaie NI, Aljohani NA, Alandanusi RA, Alghamdi AA, Radhwi OO. The prevalence of depression and anxiety among sickle cell disease patients in King Abdulaziz University Hospital. Cureus. 2021;**13**(9):e18374. DOI: 10.7759/ cureus.18374

[78] Alhomoud MA, Gosadi IM, Wahbi HA. Depression among sickle cell anemia patients in the Eastern Province of Saudi Arabia. Saudi Journal of Medical Science. 2018;**6**(1):8-12

[79] Ademola Samson Adewoyin. Management of sickle cell disease: A review for physician education in Nigeria (Sub-Saharan Africa). Anaemia. 2015;**2015**:791498. DOI: 10.1155/2015/791498

[80] Jonassaint CR, Kang C, Prussien KV, Yarboi J, Sanger MS, Wilson JD, et al. Feasibility of implementing mobile technology-delivered mental health treatment in routine adult sickle cell disease care. Translational Behavioral Medicine. 2020;**10**(1):58-67

[81] Carroll PC, Haywood C Jr, Hoot MR, Lanzkron SA. preliminary study of psychiatric, familial, and medical characteristics of high-utilizing sickle cell disease patients. The Clinical Journal of Pain. 2013;**29**(4):317-323

[82] Anie KA, Grocott H, White L, et al. Patient self-assessment of hospital pain, mood and health-related quality of life in adults with sickle cell disease. BMJ Open. 2012;**2**:e001274. DOI: 10.1136/ bmjopen-2012-001274

## *Edited by Osaro Erhabor*

This book presents a comprehensive overview of sickle cell anemia, with chapters addressing diagnosis and clinical, psychosocial, and pharmacological management of patients with this disease. It is a vital resource for biomedical science and medical students, interns, pediatricians, general physicians, and other healthcare professionals involved in offering care and support to patients with sickle cell disease.

Published in London, UK © 2022 IntechOpen © Violka08 / iStock

Sickle Cell Disease

Sickle Cell Disease

*Edited by Osaro Erhabor*