|ORIGINAL RESEARCH REPORT
|Year : 2015 | Volume
| Issue : 1 | Page : 41-47
Avascular necrosis significantly impairs quality of life in sickle cell disease
Samuel Kolawole Mosaku1, Anthony Adebukola Oyekunle2, John Chinawaeze Aneke3, Ramoni Ayodele Bolarinwa2, Patrick Olanrewaju Osho4, Norah Olubunmi Akinola2
1 Department of Mental Health, Obafemi Awolowo University, Ile-Ife, Nigeria
2 Department of Hematology and Immunology, Obafemi Awolowo University, Ile-Ife; Department of Hematology and Blood Transfusion, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
3 Department of Hematology and Blood Transfusion, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife; Department of Hematology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria
4 Department of Hematology and Blood Transfusion, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
|Date of Web Publication||14-Jul-2015|
Dr. Anthony Adebukola Oyekunle
Department of Haematology and Immunology, Obafemi Awolowo University, Ile-Ife, Osun State
Source of Support: None, Conflict of Interest: None
Introduction: Quality of life (QoL) assessment has become an integral component of the assessment of the holistic care of patients with chronic diseases, including sickle cell disease (SCD). Objective: To evaluate the quality of life in patients with SCD managed in our centre. Patients and Methods: Eighty consecutive patients with confirmed hemoglobin SS or SC were recruited. Age and sex-matched volunteers served as controls. Ethical approval was obtained from the Institutional Review Board and all participants gave informed consent. Information on socio-demographic, quality of life and clinical variables, including the presence of complications were recorded in a modified version of the WHO Quality of Life Brief version (WHOQOL-BREF) questionnaire. Data was analyzed using Microsoft Excel and SPSS 17 computer softwares. Descriptive statistics were used to represent socio-demographic variables while the Student t-test was used to explore relationship between the variables and the quality of life domains. Results: Significantly fewer participants with SCD are married compared to their age- and sex-matched controls (P = 0.01). Similarly, participants with SCD scored significantly lower in the physical and psychological domains as well as in overall QoL and general health domains compared to controls (P = 0.001). Avascular necrosis of the femur significantly affected the overall QoL and general health of participants with SCD, respectively while the means of the QoL assessment domains were not significantly different in participants with SCD with and without complications, except in the general health domain (P < 0.001). Conclusion: Avascular necrosis of the femoral head significantly affects overall QoL in participants with SCD.
Keywords: Avascular necrosis, quality of life, sickle cell disease
|How to cite this article:|
Mosaku SK, Oyekunle AA, Aneke JC, Bolarinwa RA, Osho PO, Akinola NO. Avascular necrosis significantly impairs quality of life in sickle cell disease. J Clin Sci 2015;12:41-7
|How to cite this URL:|
Mosaku SK, Oyekunle AA, Aneke JC, Bolarinwa RA, Osho PO, Akinola NO. Avascular necrosis significantly impairs quality of life in sickle cell disease. J Clin Sci [serial online] 2015 [cited 2020 May 27];12:41-7. Available from: http://www.jcsjournal.org/text.asp?2015/12/1/41/160768
| Introduction|| |
Sickle cell disease (SCD) is the most common hemoglobinopathy in Nigeria, , arising from the co-inheritance of the qualitatively defective hemoglobin S (HbS) and another deleterious beta-globin variant. The hemoglobin S is the protein product of the point-mutated beta-globin gene, with valine replacing glutamine as the 6 th amino acid. On account of its markedly reduced solubility in the deoxygenated state, the HbS polymerizes to form tactoids which eventually result in the sickle shape of the sickled erythrocytes. The clinical severity of sickle cell disease however varies widely, depending on several factors, including the HbS variant or haplotype (based on the co-inherited genes).  Generally, individuals with the homozygous S gene (HbSS) tend to have a more severe disease compared to those with HbSC disease.  Inheriting a single HbS gene (i.e. HbAS) results in a relatively healthy carrier state that has some protection against severe forms of malaria and malaria-associated deaths; leading to a survival advantage for such individuals and the continued transmission of the HbS gene. Therefore, the incidence of SCD at birth in a population is believed to be a better gauge of the true prevalence of the HbS gene, as well as the healthy carriers, which has been reported to be as high as 15-30% in West Africa. ,,,, SCD is of significant public health concern in Africa. It has been reported that up to 5% of under-five deaths in Africa and 16% in West Africa, are directly attributable to the disease.  Nigeria, with an estimated population of 174 million and birth rate of 38.8 births/1,000 population,  has been reported to have a prevalence rate of about 2% for sickle cell anemia (SCA) and an estimated carrier rate of 24%.  This translates to an annual incidence of about 135,000 births with SCA. Sickle cell disease is therefore a major cause of morbidity and mortality in Nigeria. However, with increasing awareness and better management approaches, many sufferers are surviving to old age. Indeed Akinyanju et al., reported a reduction in mortality rate from 20.6% in 1988 to 0.6% in 1995 and the situation continues to improve with the introduction of a holistic approach to the care of people living with SCD. The result is that more people with HbSS disease now face the reality of living with a chronic illness with its attending physical and psychological challenges. It is recognized that this condition is often accompanied by pain, apprehension, difficulty with fulfilling personal and family obligations, stigma and the fear of the unknown, all of which can affect the patient's quality of life.  Since a good number of the participants with SCD survive into adulthood, complications such as organ system damage including stroke, pulmonary hypertension and failure, renal failure, congestive heart failure, leg ulcers and osteonecrosis of the femoral or humeral heads are increasingly encountered in routine practice. 
Quality of life has many meanings, including the ability to perform ordinary tasks of life such as going to school, work or raising a family, all of which can be affected by this condition. The World Health Organization defines quality of life as "an individual's perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns". , Studies on persons with SCD have shown that they experience a lower quality of life compared to adults in the general population.  An important factor that has been associated with reduced quality of life among persons with SCD is pain, a major complication of this disease ,,, which has been reported to be associated with deterioration in the physical and social domains of the patient's quality of life. ,
However, there continues to be a dearth of literature on the quality of life of Nigerian patients living with SCD; thus a study of this nature has become necessary. The aim of this study therefore was to compare the quality of life of participants with SCD with normal controls with a view to identifying variables that could affect the quality of life in this condition.
| Patients and Methods|| |
This study was conducted at the Sickle Cell clinic of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. The hospital serves as a tertiary referral center for Osun, Ondo, Ekiti and Ogun states. Ethical clearance for the study was obtained from the Ethics and Research Committee of the hospital. Written consent was obtained from all participants who agreed to take part in the study after the purpose and the risks of the study had been explained to them.
An extended World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire was used to collect information from all participants, on socio-demographic, quality of life and clinical parameters. Socio-demographic data such as age, sex, educational and occupational status of the patients were collected. Clinical information such as the number of pain crisis episode in the past year, liver and spleen size, number of blood transfusions in the past year, presence of leg ulcers and a diagnosis of avascular necrosis were also recorded; in the extended part of the questionnaire.
The body of the WHOQOL-BREF instrument comprises 26 items, which measure broad domains of quality of life; physical health, psychological health, social relationships, and environment. It assesses the individual's subjective perceptions of their quality of life in the context of their culture, value systems, personal goals, standards and concerns. It has four domains; (i) physical health which incorporates activities of daily living, energy and fatigue, pain and discomfort and work capacity among others, (ii) psychological health which incorporates, bodily appearance, negative and positive feelings, self-esteem, spirituality etc., (iii) social relationships, including personal relationships, social support and sexual activities, and (iv) environment, which incorporates financial resources, health and social care, home environment etc., Each domain has several individual questions which are rated on a scale of 1-5. Raw scores are however converted to standard transformed scores between 0-100 or 4-20.  For this study the raw scores were transformed to 4-20.
Consecutive patients attending the clinic with confirmed hemoglobin genotype (HbSS or HbSC) were invited to participate in the study; each patient who agreed to participate in the study was given a written consent form to sign before inclusion in the study. An assistant then completed the socio-demographic questionnaire. Controls were age- and sex-matched with study subjects and were equally administered the WHOQOL-BREF questionnaire; this took about 10 minutes, after which the questionnaires were then collected, checked for completion before the subjects were allowed to go. Out of the 100 patients approached, 80 patients consented to participate in the study.
Raw data from the questionnaires were transferred to MS Excel spreadsheets, and the scores were grouped according to the domains they tested, and converted to scores on the 4-20 scale. The transformed scores in various domains for patients were then tested against those of controls, using the Student T-test, to ascertain statistical differences. The outcomes of these tests were noted, and P values < 0.05 were considered statistically significant.
| Results|| |
An analysis of the socio-demographic variables revealed that 28 of the 80 (35%) age- and sex-matched controls were married compared to only 15 (19%) in the SCD arm. This difference was statistically significant (χ2 = 9.26, P = 0.01). The other variables did not show any significant difference between controls and participants with SCD [Table 1].
Among participants with SCD, 65 (81%) reported at least one major bone pain crisis in one year while 15 (19%) did not have any; 22 (28%) had at least one unit of blood transfusion in one year while 56 (71%) did not have any. Similarly, 20 (44%) of the female participants with SCD had bone pains associated with menstruation in the last one year while 26 (56%) did not. Among the male patients, 10 (32%) experienced priapism in the last one year while 21 (68%) did not [Table 2]. Yellow eyes, leg ulcer and avascular necrosis were present in 44%, 12% and 13% of all patients, respectively [Table 2].
Patients who have developed avascular necrosis (of the femoral head) had significantly worse overall QoL (P = 0.001, [Table 3]) compared to those who have not. Similarly and expectedly, patients who have had recent health challenges, as assessed by the questionnaire parameter "current illness", also reported significantly worse overall general health when compared to the other participants with SCD who have not (P = 0.003, [Table 3]). There were no significant associations between other socio-demographic and clinical variables and the overall QoL or general health of patients [Table 3].
|Table 3: Effect of Socio-demographic and clinical variables on overall quality of life and general health |
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On the domains of quality of life studied, the controls scored significantly higher in the physical and psychological domains (P = 0.0001), than participants with SCD; while the differences were not statistically significant in the social and environmental domains. Expectedly, the difference in the overall quality of life (t = 3.92, P < 0.0001) and the general health assessment (t = 3.59, P < 0.0001) were statistically significant [Table 4].
[Table 5] shows a comparison of participants with SCD who reported having suffered a complication related to SCD in the last one year and those who did not. There was a statistically significant difference between the mean scores of the two groups of patients in the general health domain (t = 4.99, P < 0.001), but not in the other domains. Overall, 38 (48%) has had at least one SCD-related complication in the past one year.
|Table 5: Comparison of means of quality of life (QOL) domains and SCD-related complications |
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| Discussion|| |
The controls in this study were matched for age and gender, as evidenced by the lack of statistical differences in the age and gender distribution of the study patients compared to controls [Table 1]. We observed that a higher proportion of participants with SCD had tertiary education (68%) compared to controls (53%). This difference approached statistical significance (P = 0.06, [Table 1]); and it may indicate that the course of the disease does not adversely affect the educational pursuit and performance of persons with SCD. Similar observations have been made in studies by Ezenwosu  and Ogunfowora,  who reported that academic performance was not significantly affected in persons with SCD in Enugu (South East Nigeria) and Sagamu (South West Nigeria), respectively.
In this study, we observed that significantly more controls were married, compared to participants with SCD (35% vs. 19%, P = 0.01, [Table 1]). This observation supports the finding of Noll et al.,  who reported that among persons with SCD in the US, the disease hindered the development of normal social relationships, this may lead to some difficulty in finding a spouse. In our environment, this effect may even be worse because of the pervasively low level of health literacy.
Socio-demographic variables such as gender, marital status and level of education have been variously reported as important determinants of quality of life in patients with chronic conditions such as cancer,  HIV infection,  and even SCD.  The impact of these variables on the QoL in these conditions were partly attributed to better knowledge of disease, coupled with better health-seeking behavior that comes with higher education as well as the positive support received from spouses, which may contribute to a positive perception of health and improved self-esteem.  The above observations were however at variance with our findings in which gender, marital status and level of education did not significantly affect the overall QoL or general health in our cohort of participants with SCD [Table 3].
Chronic leg ulcers are often associated with a more severe clinical course in SCD,  depending on the haemoglobin type and study population. It has been reported in as much as 25-75% of adolescents and adults.  We observed that 12% of our patients had chronic leg ulcers at the time of this study [Table 2], and it did not significantly affect the overall QoL or general health [Table 3]. In the comprehensive sickle cell centers clinical trial consortium report, Dampier et al. reported that 12% of persons with SCD had leg ulcer, and similarly no significant effect on the QoL scales was observed.
Avascular necrosis (AVN), in a recent study has been identified as one of the frequent and more debilitating complications of SCD.  It affects predominantly weight bearing joints (particularly the hip) and is thought to be due to the occlusion of femoral vessels by sickled cells,  coupled with the reduced levels of natural inhibitors of coagulation.  In this study, 13% of participants with SCD had AVN of the femoral head, [Table 2] and their overall QoL was significantly worse when compared to the other patients (P = 0.01, [Table 3]). Dampier et al. reported AVN in 29% of persons with SCD and equally noted that it significantly decreased QoL scores (particularly the physical functioning scale).  Similarly, a study by Akakpo-Numado et al. in Lome, Togo, associated AVN with multiple hospital admissions. The debilitating nature of this complication, coupled with the attendant impairment of physical functioning and recurrent hospitalizations may well explain the significant effect it had on the overall QoL.
Pain has long been recognized as an important factor affecting quality of life, especially with respect to social and recreational functioning, especially in adults.  In this study, 65 participants with SCD (81%) had at least one episode of bone pain in the preceding year, while 18 of them had more than 3 episodes [Table 2]. Some studies had attributed the poor quality of life reported by persons with SCD to complications associated with the disorder especially pain. , Indeed, Asnani et al. reported that persons with SCD who experienced more than 3 episodes of bone pains in a year had significantly reduced QoL in the domains including physical and mental health and role imitation, but not in the psychological domain.  This agrees with the current recommendation that persons with SCD with 3 or more major bone pain episodes in one year should be classified as having severe disease and as such should be considered for hydroxycarbamide therapy.  Interestingly, bone pain did not significantly affect overall QoL or general health of our patients in this study [Table 3].
We noted that 23 (28%) participants with SCD had at least one unit of blood transfusion in one year, while 2 of them had five or more transfusions [Table 2]. Judicious use of red blood cell transfusion can be life-saving in SCD, indeed regular transfusion programme is an established treatment modality for a number of complications in SCD, including stroke.  There was no significant association between the number of units transfused and overall QoL or general health of patients in this study [Table 3]. In contrast, Hasan et al. reported that multiply-transfused SCD patients may have poor psychosocial adjustment and are more likely to be depressed, with poorer outcome. 
Historically, priapism is thought to be present in about 5-10% of patients with sickle cell anaemia  and is often poorly reported due to a number of variables, ranging from cultural factors, shame and lack of perception of it being abnormal.  We observed that as much as 10 (32%) of our SCD cohort had at least one episode of priapism in the preceding year, while 3 of them had more than 10 episodes [Table 2]. Dampier et al. reported priapism in 16% of persons with SCD and did not identify any significant effect on QoL scales.  Similarly, we did not find any significant effect of priapism on overall QoL or general health of our patients [Table 3].
SCD patients reported significantly poorer quality of life scores in most domains of the WHOQOL measure in this study (except in the social and environmental domains), compared to controls (P = 0.001, [Table 4]). This is in agreement with earlier reports from the UK and the USA, which noted decreased QoL in persons with SCD compared with the general population. , Similarly, McClish et al. compared quality of life in persons with SCD and in patients with other chronic medical conditions such as cystic fibrosis, asthma and end-stage renal failure and reported that quality of life was poorer in persons with SCD, except in the area of mental health. 
In our cohort, there were no significant differences in the QoL assessment domains between participants with SCD experiencing complications such as avascular necrosis, bone pains, and organ enlargement and those who do not, except in the general health domain (P < 0.001, [Table 5]). This is at variance with previous reports which had shown significant association between the presence of complications such as pain and the QoL in SCD (particularly the physical domain). Barakat et al. reported a significant association between pain and the physical aspects of health-related quality of life, and concluded that pain is an important factor for a reduction in physical functioning among adolescents with SCD.  Similarly, Ballas et al. emphasized the influence of pain on the physical as well as overall quality of life of persons with SCD and equally advocates its early and effective management. 
The need to optimize the QoL in most chronic disease states (including SCD) has also been elucidated in previous studies. , The limitation of activity and the need for assistance with daily living which these patients may experience have been noted to be a significant contributor to the development of depression as well as increased incidence of early death. ,
| Conclusion|| |
In conclusion, this study has shown that the physical and psychological domains as well as the overall QoL and general health scores are significantly lower in participants with SCD, compared with controls. More so, the presence of SCD-related complications, particularly, avascular necrosis of the femoral head, significantly affects the overall quality of life of participants with SCD. It is therefore important that persons with SCD are regularly and holistically evaluated with a view to detecting and managing disease-related complications (particularly AVN) early, to mitigate its adverse effect on overall QoL and health.
Source of funding
No financial support exists.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]