Health-related quality of life, developmental milestones, and self-esteem in young adults with bleeding disorders
Health-related quality of life, developmental milestones, and self- esteem in young adults with bleeding disorders
P. F. Limperg 0 1 2 3 4 5 6 7
L. Haverman 0 1 2 3 4 5 6 7
H. Maurice-Stam 0 1 2 3 4 5 6 7
M. Coppens 0 1 2 3 4 5 6 7
C. Valk 0 1 2 3 4 5 6 7
M. J. H. A. Kruip 0 1 2 3 4 5 6 7
J. Eikenboom 0 1 2 3 4 5 6 7
M. Peters 0 1 2 3 4 5 6 7
M. A. Grootenhuis 0 1 2 3 4 5 6 7
Abbreviations HRQOL YA PedsQL_YA 0 1 2 3 4 5 6 7
0 Amsterdam Public Health Research Institute , Amsterdam , The Netherlands
1 Psychosocial Department, Emma Children's Hospital , AMC, Postbox 22660, 1100 DD Amsterdam , The Netherlands
2 & M. A. Grootenhuis
3 Health-Related Quality of Life Young adults Pediatric Quality of Life Inventory Young Adult Version Course of Life Questionnaire Rosenberg Self-Esteem Scale Dutch Hemophilia Patient Society Young Adult committee
4 Department of Pediatric-Hematology, Emma Children's Hospital and Hemophilia Comprehensive Care Treatment Center, AMC , Amsterdam , The Netherlands
5 Department of Thrombosis and Hemostasis, Leiden University Medical Center , Leiden , The Netherlands
6 Department of Hematology, Hemophilia Comprehensive Care Treatment Center, Erasmus University Medical Center , Rotterdam , The Netherlands
7 Department of Vascular Medicine, Hemophilia Comprehensive Care Treatment Center, AMC , Amsterdam , The Netherlands
Background The treatment of bleeding disorders improved in the last decades. However, the effect of growing up with bleeding disorders on developmental, emotional, and social aspects is understudied. Therefore, this study assesses HRQOL, developmental milestones, and self-esteem in Dutch young adults (YA) with bleeding disorders compared to peers. Methods Ninety-five YA (18-30 years) with bleeding disorders (78 men; mean 24.7 years, SD 3.5) and 17 women (mean 25.1 years, SD 3.8) participated and completed the Pediatric Quality of Life Inventory Young Adult version, the Course of Life Questionnaire, and the Rosenberg Self-Esteem Scale. Differences between patients with bleeding disorders and their peers, and between hemophilia severity groups, were tested using Mann-Whitney U tests.
Hemophilia; Young adults; Health-related quality of life; Developmental milestones; Self-esteem
The term bleeding disorder refers to a deficiency of the
blood clotting system, in which bleeding is prolonged and
excessive. Hemophilia A and B and von Willebrand
(VWD) are the most common bleeding disorders identified
]. Hemophilia is X-linked; women are carriers and men
are affected. Symptoms of hemophilia are spontaneous and
posttraumatic bleeds [
]. Other inherited bleeding
disorders, such as VWD, affect men and women. For those,
mildly affected patients may suffer from frequent
nosebleeds and bruises, while patients with a more severe type
may have symptoms similar to those of hemophilia [
women with bleeding disorders, heavy menstruation and
postpartum bleeding are common [
Mid previous century people with bleeding disorders
could only be treated with whole blood or fresh plasma
obtained from donors [
]. Most people affected by severe
hemophilia died in childhood or in early adulthood [
Since the 1980s, as a result of the hepatitis and human
immunodeficiency virus (HIV) crises that occurred in
Western Europe and the US due to contaminated blood
products, safe plasma concentrates of coagulation factors
have been produced, and genetically engineered factors led
to the industrial production of factor products [
2, 4, 6
Prophylactic treatment was used in order to prevent
bleeding and joint damage, ultimately allowing patients to
maintain a near normal lifestyle .
Despite the available adequate treatment, patients with
bleeding disorders still endure difficulties and impairments
in daily life, such as hospital visits, frequent injections, and
limited participation in (sport) activities [
]. A vulnerable
group of patients with bleeding disorders are adolescents
and young adults (YA). Transition into adulthood is a
critical phase for all children, but growing up with a
bleeding disorder brings additional challenges compared
with healthy children; acceptance of the limitations of the
bleeding disorder, the shift from parental care to self-care,
the move from a pediatric to an adult treatment facility, the
search for employment that provides adequate medical
insurance, or starting a family [
]. Adolescents with
bleeding disorders usually start with learning self-infusion
around the age of eleven, a procedure which involves
complex self-management skills [
]. Despite the
advantages of being able to provide care at home (e.g., less
hospital visits, more independence), the large responsibility
for management of the bleeding disorder is burdensome,
especially for patients with hemophilia [
During childhood, psychosocial care in the Netherlands
is extensive for children with bleeding disorders [
prepare them for the transition period. Patients are
expected to be independent and fully responsible for their own
treatment when they are 18 years making the transition to
adult healthcare challenging. Research in YA with
hemophilia in Canada showed that YA have more joint disease
and slightly worse HRQOL with regard to physical
functioning and pain than their younger counterparts and
healthy peers [
]. On top of that, research has
demonstrated that the mean age of YA for complete
self-management and responsibility is not reached until they are
22 years [
To identify what elements are relevant and impact daily
life of YA (ages 18–30 years) with bleeding disorders, we
conducted a foregoing qualitative study. Focus groups
revealed that, despite growing up in this era and in a
developed country with adequate treatment available, YA
still do experience obstacles and issues in daily life with
regard to their treatment and condition [
]. For example,
being autonomous (in relation to parents, travel, sports,
professionally), as well as development of self-esteem
(illness perception, acceptance, and being able to pursue
ambitions as much as healthy peers), were identified as
major issues [
These qualitative results have led us to conceive the
current study, in which we aim to quantify our findings in a
larger group of YA with bleeding disorders. By
administering validated questionnaires we can capture the themes
retrieved from the focus groups, in a larger sample of YA
with bleeding disorders. By comparing them to the peers
from the general population, we hope to gain insight into
the HRQOL, psychosocial development, and self-esteem of
YA with bleeding disorders. Furthermore, in this study, we
will examine the influence of severity of hemophilia on
these outcomes in YA men with hemophilia, as this is the
Eligible patients were YA aged 18–30 years with
hemophilia A/B [clotting factor \1% (severe) or 1–40%
(nonsevere)], VWD, or other congenital bleeding disorders.
Patients were treated in one of the three participating
treatment centers in the Netherlands (Academic Medical
Center Amsterdam, Erasmus University Medical Center
Rotterdam and Leiden University Medical Center) or a
member of the Dutch Hemophilia Patient Society Young
Adult committee (DHPSYA; which includes patients with
different congenital bleeding disorders meeting the
After approval by the Medical Ethics Committees of the
Academic Medical Centre, invitational letters, including
login codes for online questionnaires, were sent out
between May and October 2015 to the eligible patients of
the medical centers and to members of the DHPSYA. To
recruit additional respondents, the DHPSYA emailed their
members, and posted an online call for participation on
their website and Facebook page. Informed consent was
obtained from all participants.
Sociodemographics and medical characteristics
Sociodemographics of the participants were assessed with
questions from the Course of Life Questionnaire (CoLQ)
], regarding age, gender, ethnicity, education,
employment, and marital status. Education was divided
into three categories according to the classification of
Statistics Netherlands; low (primary education, lower
vocational education, lower and middle general secondary
education), middle (middle vocational education, higher
secondary education, pre-university education), high
(higher vocational education, university). In addition, the
respondents were asked medical questions regarding the
type of disease, severity [severe hemophilia: \1% clotting
factor present in blood, non-severe hemophilia (1–40%
clotting factor)], treatment, and number of bleedings that
occurred over the past 6 months that required treatment.
Pediatric Quality of Life Inventory (PedsQL 4.0) generic core scales young adult version
The Dutch version of the Pediatric Quality of Life
Inventory generic core scales young adult version (PedsQL_YA)
was used [
]. The PedsQL_YA is a generic self-report
HRQOL instrument developed for YA aged 18–30 years
and contains 23 items in four scales; physical health (eight
items), emotional functioning (five items), social
functioning (five items), and work/school functioning (five
items). A psychosocial health scale score and a total scale
score can be computed. Answers are divided over a 5-point
Likert scale, consisting of the options ‘never’ (0) to ‘almost
always’ (4). Each answer is reversed scored and rescaled to
a 0–100 scale. Higher scores on the PedsQL_YA indicate
better reported HRQOL. The validity and reliability of the
PedsQL scales are good . The internal consistencies
(Cronbach’s alpha) in our sample ranged from .72 (social
functioning) to .90 (total scale). A norm group of 649 YA
peers from the Dutch population (18–30 years), healthy
and with chronic illnesses, was available [
Course of life questionnaire (CoLQ)
The Course of life questionnaire (CoLQ) was used to assess
the psychosocial developmental trajectory retrospectively
(course of life; CoL) [
]. The CoLQ has 74 items in
five scales, concerning behaviors that are characteristic of
certain age stages, developmental tasks, and the limitations
patients might encounter when growing up with a chronic
illness. We used three scales of the CoLQ that covered
psychosocial development: development of autonomy (six
items, score 6–12), social development (12 items, score
12–24), and psychosexual development (four items, score
6–12). A higher score on the scales indicates the
accomplishment of more developmental milestones and therefore
a more favorable course of life . The validity and the
test–retest reliability of the CoLQ scales are good [
The internal consistencies (Cronbach’s alpha) in our
sample ranged from 0.48 (development of autonomy) to 0.77
(psychosexual development). A recently updated norm
group of 655 YA peers from the general Dutch population
(18–30 years) was available.
Rosenberg self-esteem scale (RSES)
The Rosenberg self-esteem scale (RSES) was used to
assess self-esteem [
]. The RSES measures the
self-acceptance aspect of self-esteem or the overall sense of being
capable, worthwhile, and competent. The RSES is a
selfadministered questionnaire with 10-items on a 4-point
scale, ranging from one (strongly agree) to four (strongly
disagree), with possible scores ranging from 10 to 40 [
A higher score indicates a higher self-esteem. The internal
consistency (Cronbach’s alpha) in our sample was 0.80. A
norm group of 1002 YA peers (18–30 years) was available
The Statistical Package for Social Sciences (SPSS) version
23.0 was used for all statistical analyses [
preparatory analyses were performed: calculation of
internal consistencies (Cronbach’s alpha), computing of scale
scores, and the distributions of scale scores were
Next, descriptive analyses were performed to describe
the sample. Demographic characteristics of our sample and
the norm groups or peers were compared (age, gender,
ethnicity, education, employment, and marital status) using
v2-tests for categorical data and t tests for continuous data.
Differences on the PedsQL scale scores, CoLQ scales,
and RSES between the patients with bleeding disorders and
their peers were analyzed with Mann–Whitney U tests.
Differences on the scale items of the CoLQ, which
represent the achievement of the individual milestones,
were analyzed with v2-tests. To adjust for multiple testing,
we used a Bonferroni correction for the PedsQL YA (0.05/
6 = 0.008) and CoLQ scale scores (0.05/3 = 0.017) and as
well as for the individual milestones (autonomy: 0.05/
6 = 0.008, social development: 0.05/12 = 0.004, and
psychosexual development: 0.05/4 = 0.013).
Since hemophilia affects primarily men, the sample of
YA with bleeding disorders had a significantly higher
percentage (p \ 0.01, 82%) of men than the peer groups
(49%). In addition, bleeding disorders have a different
impact on men and women, and therefore we analyzed the
outcomes for gender separately. Since bleeding disorders
other than hemophilia have a less clear distinction in
severity, differences between YA men with severe and
non-severe hemophilia were analyzed only, using Mann–
Whitney U tests.
For the results of the Mann–Whitney U tests, effect sizes
(r) were calculated by dividing the Z-scores by the square
root of the sample size. Effect sizes up to 0.1, 0.3, and 0.5
were considered to be small, moderate, and large,
Sociodemographic and medical characteristics
In total, 95 YA completed the online questionnaires. From
the Academic Medical Center Amsterdam 34 YA
participated (46% response rate), from the Erasmus University
Medical Center Rotterdam 37 YA participated (46%
response rate), from Leiden University Medical Center 10
YA participated (33% response rate), from the DHPSYA
10 YA participated (83% response rate), and the online call
yielded another 3 YA (response rate unknown). The mean
age of the 78 men (82.1%) was 24.7 years (SD 3.5) and of
the 17 women (17.9%) 25.1 years (SD 3.8). Table 1
represents the sociodemographic and medical characteristics
of the study population. The YA men in our sample were
more often not employed in a paid job (p \ 0.05) than
peers in the PedsQL and CoLQ norm populations. Age,
educational level, ethnicity, and marital status did not differ
from these norm populations. Age did not differ from the
RSES norm population.
YA men with bleeding disorders reported significantly
lower HRQOL on the total scale, physical health scale, and
school/work functioning scale in comparison to healthy
men on the PedsQL_YA, with small effect sizes (see
Table 2). There were no differences found between
HRQOL of YA with bleeding disorders and HRQOL of
peers with chronic illnesses. YA men with severe
hemophilia (median 81.25, mean 78.86, SD 19.39) reported
lower physical functioning than men with non-severe
hemophilia (median 93.75, mean 93.06, SD 7.21, p \ 0.01,
r = 0.45) on the PedsQL_YA. HRQOL scores did not
differ on the other PedsQL_YA scales between severity
groups (data not shown).
The HRQOL of YA women with bleeding disorders did
not differ significantly from their healthy or chronically ill
Regarding YA men with bleeding disorders, no differences
were found compared with peers on autonomy
development scale level. When looking at the single items
(milestones) in the scale, the sample of YA men with bleeding
disorders showed a higher score in ‘paid chores,
elementary school,’ but a delay in ‘paid jobs, during middle and/or
high school.’ On the social development scale, no
differences were found on a scale level between YA men with
bleeding disorders and their peers, nor on item level. YA
men with bleeding disorders scored significantly higher
than their peers on the psychosexual development scale,
indicating that they achieved more milestones (see
Table 3). When looking at the single items (milestones) in
the scale, the sample of YA men with bleeding disorders
reported a higher score on ‘first time sexual intercourse
\18 years’ than their peers (see Table 5 in Appendix).
With regard to severity of hemophilia in men, no
differences were found in the achievement of developmental
milestones on the scales or at item level (data not shown).
Regarding YA women with bleeding disorders, no
differences were found compared with peers on autonomy
development scale level. However, when looking at the
single items (milestones) in the scale, the sample of YA
women with bleeding disorders showed a delay in ‘paid
jobs, during middle and/or high school.’ No differences
were found between YA women with bleeding disorders
and their peers on the social development and
psychosexual development scales, nor at item level, of the CoLQ (see
Table 3 and Appendix Table 6).
YA men with bleeding disorders reported significantly
lower self-esteem than their peers (Table 4), with a small
effect size. No differences were found between hemophilia
severity groups (data not shown). Self-esteem of YA
women with bleeding disorders did not differ significantly
from their peers.
N number, M mean, SD standard deviation
Highest level completed: Low: primary education, lower vocational education, lower and middle general
secondary education; Middle: middle vocational education, higher secondary education, pre-university
education; High: higher vocational education, university
This study demonstrates that YA men with bleeding
disorders show slight impairments in total HRQOL, physical
functioning, school/work functioning (PedsQL_YA), and
self-esteem (RSES), in comparison to their (healthy,
sexmatched) peers. No differences were found on the CoLQ
scales (autonomy and social development), except for
The YA (aged 18–30 years) in our patient population
have been born just after the hepatitis and HIV crises [
The current generation of YA with bleeding disorder is
therefore expected to grow up with less problems than
previous generations. However, our results show that
growing up with a bleeding disorder these days still can
have a negative impact on daily life of YA, which is in line
with research on YA growing up with a chronic illness
]. Despite adequate treatment, YA men with bleeding
disorders still experience moderately impaired physical
functioning compared to their healthy peers, especially
those with severe hemophilia. Although bleeds occur less
frequent than in previous generations, joint bleeds cause
cumulative and irreversible damage to joints, with
arthropathy and limited physical functioning as a result
when boys grow up to be YA.
The finding that YA men with bleeding disorders are
still facing difficulties in daily life underlines the findings
from the focus groups [
]. This study covers three of the
important themes from the focus groups. In line with the
qualitative results, we found difficulties with school/work
functioning and self-esteem. However, not all results based
on the outcomes of the questionnaires are in concordance
with the findings from the focus groups. For example,
during the focus groups, autonomy development (e.g.,
gaining independence from parents) was mentioned as
challenging, which was not confirmed in this study.
The current findings regarding school/work functioning
is not only in line with our former focus group study, but
also with other studies. For example, previous research in
2001 in the Netherlands demonstrated that men with severe
hemophilia participated less in full-time work compared
with the general population [
]. In addition, on the
sociodemographic characteristics of our sample, we found a
significantly lower rate of paid jobs in YA men with bleeding
disorders compared to peers, which has also been found in
studies in the US [
]. Of the YA men in our sample, 50%
indicated they were still in college, while their peers were
already working. An explanation could be that YA men with
bleeding disorders are more likely to apply for ‘white collar’
jobs, which are often more suitable jobs for hemophilia
patients, since the risk of bleeding due to physical activities
in this type of work is lower . In this case, patients with
bleeding disorders are more likely to follow full-time
education over a longer period of time.
The problems related to school or professional
functioning are also interesting in relation to the finding that
young adult men with bleeding disorders report a somewhat
lower self-esteem than their peers. One can imagine that
when a YA feels less successful in a professional sense, or
when a YA is not able to pursue professional goals due to
physical limitations, this could lead to a decreased
self-esteem. Work experience during adolescence, which has
shown to be less frequent in adolescents with bleeding
disorders, is not only an excellent way to discover skills and
interests, but also to experience negative feelings related to
limitations of physical capacities [
]. Finding an education
or job that fits with some of the physical restrictions that YA
with bleeding disorders encounter is important, and
guidance and support is desirable, for example, by a social
worker or professional coach and strengthen work-related
psychosocial skills [
]. As an example, Emma at Work,
a job mediation agency for YA with chronic diseases at the
Academic Medical Center in Amsterdam, can be a useful
YA men reported to have achieved slightly more
psychosexual developmental milestones than their peers (‘first
time intercourse \18 years’). Although this result is in
contradiction to our expectations, this finding suggests that
YA men growing up with bleeding disorders do not feel
limited by their condition, with regard to discovering
psychosexual relations during adolescence. However, the CoLQ
used in this study measures retrospectively. This does not
imply that sexual functioning at present is not hindered by
their bleeding disorder or physical impairments, which may
have decreased over the years due to bleeds. For example,
(fear of) pain, or fear of bleeding during intercourse, may
affect sexual functioning. Furthermore, arthropathy in joints
may place limitations on sexual functioning, while women
with bleeding disorders may experience impaired sexuality
due to long lasting heavy menstruation [
]. It would be
interesting to explore current sexual functioning more for
this population, especially since patients seem to be keen to
talk about this subject with their healthcare providers .
Psychosexual development and functioning of YA receives
very little attention in clinical practice and in literature, and it
is important to study this aspect more in depth in the future
YA women with bleeding disorders do not show any
impairments in HRQOL, psychosocial development on scale
level, and self-esteem in comparison to their peers. Only on the
autonomy scale of the CoLQ, women with bleeding disorders
scored lower on the item ‘paid jobs, middle and/or high school.’
We assume that because women experience less joint bleeds
and consequences from their condition compared to men, this
results in less impaired functioning in daily life. Research has
shown that women with bleeding disorders are impacted
majorly by menstrual disorders compared with their peers,
especially during teenage years [
]. Unfortunately, the
questionnaires used in this study do not cover questions regarding
menorrhagia, which would be interesting to include in the
future when studying women with bleeding disorders. Still, we
wanted to include this group of young adult women, albeit so
small, because research on women with bleeding disorders is
scarce. The small sample size causes warranty however in
generalization of results.
Some limitations of this study should be taken into
account. First, the internal consistency of the autonomy
scale was low. However, we looked at individual items on
the CoLQ scales to overcome this issue. In addition, these
internal consistencies are not exceptional and are in
concordance with other studies using the CoLQ [
Secondly, we did not have all sociodemographic and
medical information of non-respondents. Thirdly, the exact
response rate of our study is unknown, due to the fact that
we recruited additional participants through on online call.
We decided to add this call, because recruitment was quite
difficult, possibly due to the time consuming nature of
completing the questionnaires. Therefore, we do not know
whether the results are representative for YA with bleeding
disorders and we could be dealing with an under- or
overestimation of the problems of this group YA. Also,
effect sizes found in our study are quite small. This should
be kept in mind when interpreting and generalizing the
results. In addition, it would be interesting to collect
longitudinal data during the transitional phase to identify
factors that may influence HRQOL and psychosocial
adaptation in YA with bleeding disorders, especially
because the problems seem to increase from childhood to
adulthood . Adding a disease-specific HRQOL
questionnaire, which is usually more sensitive for changes over
time (e.g., Hemophilia Well-Being Index [
]), can be valuable in collecting longitudinal
HRQOL data [
In conclusion, this study demonstrates that YA men with
bleeding disorders show some impairments in physical
functioning, school/work functioning, and self-esteem.
Although these YA are functioning quite well, systematic
monitoring of HRQOL and psychosocial functioning over
time in YA with bleeding disorders in daily clinical
practice is important since possible influencing psychosocial
factors can change over time. This way, problems can be
identified early, especially with regard to their physical and
professional/school functioning, in order to optimize their
well-being and adaptation to society in the process of
transition to adulthood.
Acknowledgements We would like to thank all participating young
adults in this study. Also, we are grateful to the Dutch Hemophilia
Patient Society for assisting the patient recruitment. We would like to
thank Pfizer Pharmaceuticals BV for providing an unrestricted
research grant to execute this study.
Funding This study was funded by an unrestricted research grant
from Pfizer Pharmaceuticals.
Author’s contribution PL carried out the literature study, organized
data collection, led data analysis, and drafted the manuscript. LH
supervised data collection and data analysis, and critically revised the
manuscript. HMS supervised data collection and data analysis, and
critically revised the manuscript. MC, CV, MK, and JE contributed in
organizing data collection and critically revised the manuscript for
intellectual content. MP conceived the study, supervised data analysis,
and critically revised the manuscript. MG conceived the study,
supervised data collection, and critically revised the manuscript for
intellectual content. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest All authors declare that he/she has no conflict of
Ethical approval All procedures performed in studies involving
human participants were in accordance with the ethical standards of
the institutional and/or national research committee and with the 1964
Helsinki Declaration and its later amendments or comparable ethical
Informed consent Informed consent was obtained from all
individual participants included in the study.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://creative
commons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give appropriate
credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
See Tables 5 and 6.
* p \ 0.008 based on v2 adjusted for multiple testing (autonomy development)
** p \ 0.004 based on v2 adjusted for multiple testing (social development)
*** p \ 0.013 based on v2 adjusted for multiple testing (psychosexual development)
Regular chores/tasks in your family, elementary school
Paid chores, elementary school
Regular chores/tasks in your family, middle and/or high school
Paid jobs, middle and/or high school
At the age of 18 or younger 9
At the age of 19 or older/never 8
For the first time vacation without adults
At the age of 17 or younger 7
At the age of 18 or older/never 10
* p \ 0.008 based on v2 adjusted for multiple testing (autonomy development)
** p \ 0.004 based on v2 adjusted for multiple testing (social development)
*** p \ 0.013 based on v2 adjusted for multiple testing (psychosexual development)
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