Factors Associated with Subjective Well-Being in Adults with Hemophilia

Objectives: To evaluate the positively and negatively factors associated with the subjective well-being of adults with hemophilia from two associations of patients. 
Methods: This study is a cross-sectional survey, carried out with convenience sampling in two patient associations. Data collection took place in November and December of 2015. The evaluation protocol consisted of the application of two instruments: Hemophilia Well-Being Index and a collection form of sociodemographic and clinical data. 
Results: Fifty-three adults with hemophilia, and male, participated in the study. Their age ranged from 21 to 54 years old. It was observed a higher prevalence of participants with single marital status and third education level. The age and marital status of the participants did not influence their well-being. 
Conclusion: The high level of education was positively associated with the well-being of the participants, related to the item “economic situation.”  
Keywords: Hemophilia A; Hemophilia B; Adult; Subjective Well-Being Scale.


Introduction
Hemophilia A and B are hereditary hemorrhagic coagulopathies linked to the X chromosome, characterized by the quantitative deficiency of coagulation factors VIII and IX, with prevalence in Brazil of 1: 10,000 and 1: 35,000 male births, respectively [1,2].Data from the "Profile of hereditary coagulopathies in Brazil: 2014" show that the country has 21,066 patients with hereditary coagulopathies, 9,616 (45.65%) of them corresponding to hemophilia A, 1,881 (8.93%) corresponding to hemophilia B and 9,569 (45.42%) corresponding to other coagulopathies and hemorrhagic disorders [2].
The disease can be categorized as severe (factor ˂1% of the normal amount), moderate (factor from 1 to 5% of the normal amount) and mild (factor between ˃5 to ˂40% of the normal amount).These three categories define the presence and intensity of hemorrhagic manifestations.However, the clinical phenotype is varied [4].
Bleeding in the joints (hemarthroses) and muscles represent characteristic manifestations in hemophilia, corresponding to 80% of clinical findings [5].The chronic joint disease from repetitive joint bleeds is a complication of the disease, called hemophilic arthropathy [6].It is an important cause of chronic pain and disability, with frequent surgical indication [7], impacting the patients´ physical and mental health.
Subjective well-being (SWB) is not only determined by patients´ health status and response to treatment, but also it implies to social and psychological dimensions [8].It is reflected in the way patients perceive and react to aspects of their health and other aspects of life, addressing satisfaction, overall health, and self-esteem [9].The mental health of hemophilia patients and the family environment are important as well as their beliefs and way of coping with the disease, allowing a positive influence on clinical improvement, response to treatment and quality of life [10].
Remor [11] developed a specific instrument for evaluating SWB in adults with hemophilia called Hemophilia Well-Being Index (HWBI), available in Spanish, Portuguese (Brazilian version), English and Russian.This instrument assesses how hemophilia affected relevant areas of the patient´s life such as family, health and well-being, work or school, friends and affective relationships, emotional life and couple relationship, economic situation, recreational or leisure activities, and social activity.The evaluation of these elements allows obtaining a welfare index for hemophilia.
This article aims to evaluate the positively and negatively factors associated with the subjective wellbeing of adults with hemophilia from two associations of Brazilian patients, through the application of the specific instrument Hemophilia Well-Being Index (HWBI).

Method
This study is a cross-sectional survey with a quantitative approach and a convenience sampling.The study was carried out with patients with clinical diagnosis of hemophilia linked to the Association of hemophiliacs and the Association of volunteers, researchers and patients with coagulopathies (AJU-DE-C) from Brazil.
Sixty-three participants with hemophilia, male, and older than 18 years old were included, with 14 of them belonging to Association of hemophiliacs and 49 belonging to AJUDE-C.The participants accepted to participate voluntarily and signed the Informed Consent Term (TCLE).Participants with cognitive impairment and indigenous race were excluded due to their vulnerability.
The data collection took place in both associations, where the researcher attended meetings and events at previously informed dates, in November and December of 2015.She made an individual invitation to the patients, briefly explaining the research, and then handed the TCLE to appreciation.
In the case of patient consent, the researcher carried out the application of the instruments, in an individual and reserved way.An evaluation protocol including the Hemophilia Well-Being Index (HWBI) instrument and a form for collecting sociodemographic and clinical data were applied.
The Hemophilia Well-Being Index (HWBI) instrument is a specific questionnaire to evaluate the subjective well-being of people with hemophilia.It has been translated into Portuguese (Brazilian version) and validated to use it in Brazil [11].Before the use of the instrument, the researcher (D. R. H.) formally requested the permission to use it directly with the author of the instrument.The instrument has eight items referring to the following areas: family; health and well-being; school and work; friends and affective relationships; sentimental life and couple relationship; economic situation; recreational or leisure activities; social activity.The response format is Likert-type with response options ranging from 0 (heavily affected) to 4 (not affected).The instrument investigates how the eight proposed items were adversely affected by hemophilia in the last month.The sum of the items allows identifying the well-being index where 0 indicates the worst level of well-being possible and 32 points, indicating the best level of well-being possible [11].
The sociodemographic and clinical data collection form developed by the research team included sociodemographic variables (age, race/color, education and marital status) and clinical variables (a type of hemophilia, clinical severity, development of inhibitors and viral infections -HIV/HCV).
The study was submitted to the Human Research Ethics Committee of the Federal University of Mato Grosso do Sul (UFMS) for approval, and it was approved under opinion nº 1,300,316.
The evaluation of the association between hemophilia type and the variables "hemophilia severity," "inhibitor development," "viral infection by treatment with contaminated blood products" and "what viral infection" evaluated in this study was performed by the chi -square test.
Spearman´s linear correlation test was used to correlate the age of hemophilia patients with the well-being index.
The comparison between unmarried and married hemophilia adults with the well-being index and their items as well as the comparison between hemophilia patients with different clinical severities of the disease with the well-being index and its items was performed through the Mann-Whitney test.
The comparison between hemophilia patients with different levels of education in the well-being index and their items was performed by the Kruskal-Wallis test and the Dunn post-test.
Statistical analysis was performed using the statistical software SPSS, version 22.0 (SSP, Inc., Chicago, IL., USA), considering a level of significance of 5%.

Results
A total of 63 adults with hemophilia and male participated in this study, 49 of them (77.8%) were associated with AJUDE-C and 14 (22.2%) were associated with Association of hemophiliacs.The age ranged from 21 to 54 years old (mean age and standard deviation 32.30±8.61).It was observed a higher prevalence of participants with brown ethnicity (52.4%), single marital status (58.7%) and third degree of complete or incomplete education level (55.5%) (Table 1  Regarding the clinical variables, there was a higher prevalence of hemophilia A (82.5%) than hemophilia B (17.5%), and the severe form of the disease was more prevalent 47 (74.6%).Regarding the comorbidities related to the disease, 3 participants (4.8%) developed inhibitors and 31 participants (49.2%) were infected with HIV (HCV, HCV and/or HCV) due to treatment with contaminated blood products (Table 1).
Table 2 shows the results regarding the type of hemophilia and other variables such as clinical severity, development of inhibitors and presence of viral infections by treatment with contaminated blood products.The p-values in the chi-square test do not have significant differences.Hemophilia A with severe clinical classification is the most prevalent disease in the sample (78.8%).All the three hemophiliacs who developed a coagulation factor inhibitor have to type A disease, and in the viral infections due to the use of contaminated blood products, 27 (87%) have hemophilia A, and 4 (13%) have hemophilia B.
There was no significant correlation between the age of hemophilia patients and the well-being index (HWBI) (Spearman´s linear correlation test, p=0.055, r=-0.243).
Table 3 shows the results regarding the comparison between single and married hemophilia adults in the well-being index (HWBI) and their items.
Table 4 shows the results regarding the comparison between hemophilia patients with different levels of education, about the HWBI and their items.There was a statistically significant difference in the item "economic situation," according to the p-value in the Kruskal-Wallis test followed by the Dunn post-test.
Table 5 shows the results regarding the comparison between the different clinical severities of he-   mophilia about the well-being index (HWBI) and its items.
The results are presented as the mean ± standard deviation of the mean.P-value in the Kruskal-Wallis test.Different letters in the row, in the dimension "Economic situation," indicate a significant difference between levels of instruction (Dunn post-test, p <0.05).
There was no significant linear correlation between the educational level of hemophilia patients and the well-being index (HWBI) (p=0.549,r=0.077).
Table 6 shows the results regarding the comparison between hemophilia patients who presented viral infection by treatment with contaminated blood products and those who did not present this complication, in the HWBI and its items.There were no significant statistical differences according to the p-values in the Mann-Whitney test.

Discussion
Most recent studies with adults with hemophilia have prioritized the assessment of health-related quality of life [12,13], with poor perception of wellbeing in this population [11].This article contributes to the literature in the evaluation of subjective wellbeing in the population with hemophilia, specifically in Brazil, bringing some interesting results that will be presented.However, it had limitations (sample selected for convenience and restricted to the central region of the country, with a cross-sectional design).
In this study, there were no elderly participants.Garbin et al. [14] conducted a study in adults with hemophilia, with a mean age of 34.36±11.9years old (between 18-66 years old) and a predominance of individuals aged 21-29 years old.They explain that the smallest proportion of the elderly in the sample was probably due to high mortality, especially due to HIV infection for the use of contaminated blood products, occurred in the 1980s.
In this study, most participants reported being brown (more than 50%), followed by whites and blacks.Zago, Falcão, and Pasquini [5] report that the prevalence of hemophilia A and B do not have racial differences, but there were rate cases in Chinese and Africans.Ethnicity in adults with hemophilia differs in studies, with a higher prevalence of white individuals: 83.3% [14] and 63.7% [15], agreeing The results are presented as the mean ± standard deviation of the mean.P-value in the Mann-Whitney test.
with the ethnic group most prevalent in the region where the research was conducted.
Regarding the marital status, the research showed a predominance of single participants (58.7%).These findings corroborated with those found by Garbin et al. [14], where 60% of adults with hemophilia lived alone (single or divorced), according to Nunes et al. [16] with 78.3% of the sample and in the study by Almeida et al. [15], with 69.7% of participants.
These results can be explained due to the difficulty of coping with the disease and its consequences, the presence of concomitant viral infections due to the use of contaminated blood products, physical limitations and, consequently, difficulties to work [14].Caio et al. [17] mentioned that the constitution of a family represents an important point of support for the adult with hemophilia.However, the lack of access to a satisfactory regular employment is the major factor of social inadequacy.Also, 65% of people with hemophilia prefer not to have children if they ran the hypothetical risk of generating a child with the disease.
In this study, when we compared single and married patients in the HWBI and their items, we observed higher scores in the single participants, and there were no significant differences between the items of the instrument.
Divergent results were presented by et al. [18].They conducted a study comparing a group of adults with hemophilia and a control group.The results showed a greater number of married individuals and fewer divorced individuals in the hemophilia group.They justified such results by mentioning that such participants sought protection or stability in the family environment, associating marriage with a beneficial effect on their personal well-being, since there was an increase in the quality of treatment, resulting in a decrease in mortality and morbidity as well as an increase in autonomy and life expectancy of patients.
Shapiro and Keyes [19] report that there is a positive relationship between marriage and physical and mental well-being.Married individuals have advantages regarding social well-being when compared to single individuals.Comparisons using measures to assess psychological well-being indicate important differences in the marital status in individual well-being.
Regarding the educational level of this sample, 55.5% of the participants reported having a complete (36.5%) or incomplete (19.0%) higher education.Caio et al. [17] reported that there were no significant differences between the levels of education among patients with hemophilia and their nonhemophilia siblings.The results of the research carried out by Ferreira et al. [20] demonstrated that 21 (53.8%)patients with hemophilia had the highest number of years of study (ranging from 9 to ≥12 years).Differing results were presented by Garbin et al. [14], where there was a predominance of hemophilia patients with complete secondary education (40%) followed by incomplete elementary school level (30%) and the research developed by Nunes et al. [16], where the predominant educational level was the incomplete elementary (45.5%).Caio et al. [17] reported that school absenteeism was frequent in people with hemophilia, related to the physical impairment that the disease gives the affected individual and 50% of the sample recorded interference of the disease in school life.
Regarding the results of the comparison between hemophilia patients with different levels of education in the score in each item of the HWBI instrument, there were significant differences in the item "economic situation", with higher scores in the participants with higher education, suggesting that the level of education is a protection factor associated with the better economic situation.Keyes, Shmotkin, and Ryff [21] agree with the findings and state that well-being is directly associated with increasing age and educational level.
This result may be related to the empowerment of the individual with a higher level of education reflected in the possibility of acquiring work/employment as well as in the relationship with co-workers, satisfaction from paid salary and promotion opportunity [22].Siqueira and Padovam [23] state that the self-assessment of well-being should be cognitive (global satisfactions with life, marriage, work), and should include a personal analysis of the frequency and positive and negative emotions are experienced.However, it should be noted that such evaluation should include positive components that do not necessarily involve elements of economic prosperity, among other things.[24].
Divergent results were presented by Botelho and Pereira [25] when studying QOL, optimism and coping in patients with colorectal cancer.Patients with low educational level used more social, emotional support and religion as strategies to cope with the disease, compared to patients with higher educational level.This latter presented better physical functioning and more intrafamilial stress.
The results of this study demonstrate the higher prevalence of hemophilia A in participants (82.5%) compared to hemophilia B (17.5%).Hemophilia A is considered more prevalent than B, with its prevalence rate between 1/20,000 to 1/10,000 individuals, while for hemophilia B it is 1/30,000 to 1/50,000 individuals [5].
The results of this study regarding the classification of clinical severity of hemophilia show a predominance of severe disease (74.6%), followed by moderate (19.0%) and mild (6.3%).Zago, Falcão, and Pasquini [5] describe that severe classification occurs in approximately 50% of patients with hemophilia, 10% are classified as moderate, and 40% are mild.Almeida et al. [15] corroborate these findings and describe that the clinical classification of its participants was 60.6% severe, 33.4% moderate and 6% mild.The fact that there is a greater number of patients with moderate clinical categorization in these studies to the detriment of those with mild categorization is due to the patient´s dependence on their place of treatment, greater knowledge about their disease and participation in the patients' association, besides living under constant threat of unexpected bleeding [17].Often, mild hemophilia is diagnosed only in adulthood, with bleeding after trauma or surgery [5].
In this study, comparing the participants with different clinical severities of the disease in the wellbeing index and its items, there were higher scores in the patients who had the disease with mild and moderate categorization in detriment of the severe disease, with no significant differences between the items of the instrument.
Triemstra et al. [26] reported that the effects of joint damage and concomitant disability, more common in patients with severe hemophilia, influence satisfaction with life, health and self-esteem.The anxiety and self-esteem were psychological characteristics with significant differences between the clinical categorization of hemophilia observed.Participants with severe hemophilia reported high anxiety and low self-esteem compared to those with the mildly categorized disease.
Differing results were presented by Carruyo-Vizcaíno et al. [10], where an instrument was applied to analyze the patient´s attitude toward hemophilia.They obtained positive results in the attitude of the participants, finding no significant differences between such attitude (confrontation) and clinical severity, as well as with the type of treatment and physical disability.
Concerning the complications, 3 (4.8%)participants developed an inhibitor of the clotting factor, being these with severe hemophilia A. Wisniewski and Kluthcovsky [27] performed a sociodemographic and clinical characterization study in 39 patients with coagulopathies, reporting that 5 (12.8%) participants developed a coagulation factor inhibitor.This important complication occurs in greater proportion in hemophilia A and patients with major genetic defects compared to cases of simple mutation [28].Fischer et al. [29] report that the development of inhibitors occurs in about 30% of patients with severe hemophilia, with the results below this index of this study.
This study shows that 31 (49.2%) of the participants had viral infections, predominantly hepatitis C (24 participants -38.09%).Similar results were reported by Garbin et al. [14], where 20 (66.6%) of the participants reported infectious comorbidities, and a predominance of hepatitis C infection (12 participants -40%).Carmo et al. [30] reported that hemophilia patients were at high risk for hepatitis C infection before viral inactivation treatments.They demonstrate that hepatitis C infection is a major problem in Brazilian hemophiliacs, being associated with age, co-infection with hepatitis B and development of coagulation factor inhibitor.
Regarding the results of the comparison between hemophilia patients who presented viral infection by treatment with contaminated blood products and those who did not, in the Well-being Index (HWBI) and their items, showed lower scores in all items of the tool as well as the general well-being index for the group that had a viral infection.However, there were no significant statistical differences.This result can be explained by the patient´s coping with his or her chronic illness.Binnema et al. [31] reported that severe hemophilia patients used adequate coping strategies to deal with their disease, focusing on the problem, and generating efforts to control the situation.The processes of adaptation or habituation in continuous conditions and coping are central components in modern theories of subjective well-being since it presupposes adjustment of the individual to situations [32].

Limitations
A limitation of this study refers to the population, since it investigated subjects from a single geographic region of Brazil.Another limitation concerns the lack of studies with the same objective of this study and with the same target population.

Conclusion
The high level of education was positively associated with the well-being of the participants.The participants with the highest educational level had a positive impact on their well-being related to the item "economic situation." The "married" marital status did not have a positive impact on the well-being of the participants, diverging from studies on the subject.Nor did participants with mild and moderate hemophilia achieve a better well-being index when compared to participants with severe hemophilia.

Table 1 .
Sociodemographic and clinical information on adults with hemophilia from two associations of patients in the Federal District and Goiás, 2016. ).

Table 2 .
Results related to the evaluation of the association between the type of hemophilia and other variables evaluated in this study, in two associations of patients from the Federal District and Goiás, 2016.
The results are presented in relative frequency (absolute frequency).P-value in the chi-square test.a: Human immunodeficiency virus.b : Hepatitis C virus.c : Coinfection with hepatitis C virus and human immunodeficiency virus.d : Coinfection with hepatitis C virus and hepatitis B virus

Table 3 .
Results regarding the comparison between single and married hemophilia adults, in the well-being index and their items, in two associations of patients, Federal District and Goiás, 2016.
P-value in the Mann-Whitney test.

Table 5 .
Results regarding the comparison between adult hemophilia patients with different clinical severities of the disease, in the HWBI index and their items, in two patient associations, Federal District and Goiás, Brazil, 2016.
The results are presented as the mean ± standard deviation of the mean.P-value in the Mann-Whitney test.

Table 4 .
Results regarding the comparison between adults with hemophilia with different levels of education in the Well-being Index (HWBI) and their items, in two associations of patients, Federal District and Goiás, 2016.The results are presented as the mean ± standard deviation of the mean.P-value in the Kruskal-Wallis test.Different letters in the row, in the dimension "Economic status," indicate a significant difference between levels of instruction (Dunn post-test, p <0.05).

Table 6 .
Results are referring to the comparison between adults with hemophilia who presented viral infection due to the use of contaminated blood products and those who did not, in the Well-being Index (HWBI and its items, in two associations of patients, Federal District and Goiás, 2016.