How do patients and physicians perceive immune thrombocytopenia (ITP) as a disease? Results from Indian analysis of ITP World Impact Survey (I-WISh)

Abstract

Purpose
Immune thrombocytopenia (ITP) is primarily considered a bleeding disorder; its impact on patients’ health-related quality of life (HRQoL) is under-recognized. We aimed to assess how aligned patient and physician perceptions are regarding ITP-associated symptoms, HRQoL, and disease management in India.

Methods
Patients and physicians (hematologists/hemato-oncologists) from India who participated in the global ITP World Impact Survey (I-WISh) were included in this subgroup analysis (survey). Physicians were recruited via a local, third party recruiter in India. In addition to completing a survey themselves, physicians were asked to invite consulting patients on a consecutive basis to complete a survey. All surveys were completely independently by the respondents online in English. The respondents took 30 min to complete the questionnaire. Patients also completed the newly developed ITP Life Quality Index (ILQI) that included 10 questions on the impact of ITP on the following: work or studies, time taken off work or education, ability to concentrate, social life, sex life, energy levels, ability to undertake daily tasks, ability to provide support, hobbies, and capacity to exercise.

Results
A total of 65 patients and 21 physicians were included in this study. Average disease duration from diagnosis-to-survey-completion was 5.3 years. The most severe symptoms reported by patients at diagnosis were menorrhagia (15 of 19 patients [79%]), anxiety surrounding unstable platelet counts (17 of 28 patients [61%]), and fatigue (27 of 46 patients [59%]); these were also the key symptoms they wanted to be resolved. In contrast, physicians perceived petechiae (19 of 21 patients [90%]), bleeding-from-gums (8 of 21 patients [86%]), and purpura (16 of 21 patients [76%]) as the most common symptoms. While the important treatment goals for patients were healthy blood counts (42 of 65 patients [65%]), improved QoL (35 of 65 patients [54%]), and prevention of worsening of ITP (33 of 65 patients [51%]), physicians’ goals were reduction in spontaneous bleeding (17 of 21 physicians [81%]), better QoL (14 of 21 physicians [67%]), and symptom improvement (9 of 21 physicians [43%]). More than half the patients reported that ITP affected their work life/studies, social life, and energy levels, thereby negatively impacting their QoL. Patients were almost entirely dependent on family and friends for support.

Conclusions
This survey highlights the substantial discrepancy in patients’ and physicians’ perceptions regarding ITP-associated symptoms and treatment goals in India. Based on the identified gaps, educating physicians on aspects of ITP beyond bleeding, and highlighting patients’ under-recognized symptoms/needs through support-systems should be prioritized in the future.

Full text

Chakrabartietal.
Journal of Patient-Reported Outcomes (2022) 6:24
https://doi.org/10.1186/s41687-022-00429-y
RESEARCH
How dopatients andphysicians perceive
immune thrombocytopenia (ITP) asadisease?
Results fromIndian analysis ofITP World Impact
Survey (I-WISh)
Prantar Chakrabarti1, Biju George2, Chandrakala Shanmukhaiah3, Lalit Mohan Sharma4, Shashank Udupi5 and
Waleed Ghanima6*
Abstract
Purpose: Immune thrombocytopenia (ITP) is primarily considered a bleeding disorder; its impact on patients’ health-
related quality of life (HRQoL) is under-recognized. We aimed to assess how aligned patient and physician perceptions
are regarding ITP-associated symptoms, HRQoL, and disease management in India.
Methods: Patients and physicians (hematologists/hemato-oncologists) from India who participated in the global ITP
World Impact Survey (I-WISh) were included in this subgroup analysis (survey). Physicians were recruited via a local,
third party recruiter in India. In addition to completing a survey themselves, physicians were asked to invite consulting
patients on a consecutive basis to complete a survey. All surveys were completely independently by the respondents
online in English. The respondents took 30 min to complete the questionnaire. Patients also completed the newly
developed ITP Life Quality Index (ILQI) that included 10 questions on the impact of ITP on the following: work or stud-
ies, time taken off work or education, ability to concentrate, social life, sex life, energy levels, ability to undertake daily
tasks, ability to provide support, hobbies, and capacity to exercise.
Results: A total of 65 patients and 21 physicians were included in this study. Average disease duration from diagno-
sis-to-survey-completion was 5.3 years. The most severe symptoms reported by patients at diagnosis were menor-
rhagia (15 of 19 patients [79%]), anxiety surrounding unstable platelet counts (17 of 28 patients [61%]), and fatigue
(27 of 46 patients [59%]); these were also the key symptoms they wanted to be resolved. In contrast, physicians
perceived petechiae (19 of 21 patients [90%]), bleeding-from-gums (8 of 21 patients [86%]), and purpura (16 of 21
patients [76%]) as the most common symptoms. While the important treatment goals for patients were healthy blood
counts (42 of 65 patients [65%]), improved QoL (35 of 65 patients [54%]), and prevention of worsening of ITP (33 of 65
patients [51%]), physicians’ goals were reduction in spontaneous bleeding (17 of 21 physicians [81%]), better QoL (14
of 21 physicians [67%]), and symptom improvement (9 of 21 physicians [43%]). More than half the patients reported
that ITP affected their work life/studies, social life, and energy levels, thereby negatively impacting their QoL. Patients
were almost entirely dependent on family and friends for support.
Conclusions: This survey highlights the substantial discrepancy in patients’ and physicians’ perceptions regarding
ITP-associated symptoms and treatment goals in India. Based on the identified gaps, educating physicians on aspects
© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.
Open Access
Journal of Patient-
Reported Outcomes
*Correspondence: wghanima@gmail.com
6 Departments of Research and Hemato-Oncology, Østfold Hospital,
Østfold Hospital, PB 300, 1714 Grålum, Norway
Full list of author information is available at the end of the article

Page 2 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
Background
Immune thrombocytopenia (ITP) is an acquired autoan-
tibody-mediated bleeding disorder characterized by
both accelerated platelet destruction and impaired plate-
let production, which an estimated incidence in adults
between 1.6 and 3.9 per 100,000 person-years based
on the platelet count threshold used [1]. ITP requires
lifelong treatment in a substantial proportion of adult
patients, thereby negatively impacting the patient quality
of life (QoL) [1, 2]. Improvement in health-related QoL
(HRQoL) parameters has been identified as an important
treatment objective in the updated ITP guidelines (ASH,
ICR 2019) [3, 4]. However, in resource-limited countries,
such as India, where physicians have a higher patient
burden and can afford only limited in-clinic time [5–7],
assessment and treatment of HRQoL parameters is chal-
lenging. Physicians often tend to underestimate or ignore
HRQoL parameters in routine clinical practice, as the
major treatment goal for ITP is to treat or prevent bleed-
ing [2].
Recently, the ITP World Impact Survey (I-WISh) was
conducted to discern how ITP and associated treatments
affect patient lives and to evaluate how aligned patient
and physician perceptions are regarding symptoms,
HRQoL, and disease management [8, 9], and we have
conducted an analysis of data from the Indian patient
subgroup included in the I-WISh study. With ITP being
one of the most common non-infectious causes of throm-
bocytopenia in India [10, 11], the major objectives of this
study were to understand the challenges in the diagnostic
journey of patients with ITP in India; patient and physi-
cian perceptions of disease and symptoms; impact of ITP
on patient QoL, daily activities, and work; and existing
support systems for ITP and its management.
Methods
Survey participants andstudy conduct
e I-WISh India-specific analysis is based on data col-
lected as part of I-WISh 1.0, a cross-sectional survey of
adult patients (age ≥ 18years) with ITP and hematolo-
gists or hemato-oncologists who treat patients with ITP.
e global I-WISh study was conducted in 13 countries
(Canada, China, Colombia, Egypt, France, Germany,
India, Italy, Japan, Spain, Turkey, the United Kingdom,
and the United States).
Patient surveys were sent via mass email to patient sup-
port networks and physicians who were requested to dis-
seminate the surveys to patients. A steering committee
of disease experts and patient advocates led the design
of the survey materials and endorsed them prior to ini-
tiation of data collection. Physician surveys were emailed
by local fieldwork agencies. Physicians were recruited via
a local, third party recruiter in India. Physicians invited
patients to complete the survey following a routine con-
sultation for their ITP. In addition to completing a survey
themselves, physicians were asked to invite consulting
patients on a consecutive basis to complete a survey. All
surveys were completely independently by the respond-
ents online in English. As the surveys were online, it was
not possible for any respondent to omit to answer any
question. However, where deemed appropriate, respond-
ents were allowed to select ‘Not applicable’ or ‘Don’t
know’ for certain questions. In these cases, the ‘Don’t
know’ or ‘Not applicable’ responses were removed from
the individual analyses, but these patients were otherwise
eligible for inclusion in all other analyses. Overall, the
respondents took 30min to complete the questionnaire.
Fully deidentified respondent information was collated
and aggregated by local fieldwork partners such that the
surveys were unlinked and anonymized. Surveys and
details of the survey methods, including how patients
and physicians were identified, have been outlined in the
supplementary material and published previously [8, 9].
To understand the level of agreement that the respond-
ents had with a statement in the survey, a Likert scale of
1–7 was used; for assessment of symptoms, a score ≥ 5
on the Likert scale implied that the symptom in question
was considered to be “severe” by the patient. Patients also
completed the newly developed ITP Life Quality Index
(ILQI) that included 10 questions on the impact of ITP
on the following: work or studies, time taken off work
or education, ability to concentrate, social life, sex life,
energy levels, ability to undertake daily tasks, ability to
provide support, hobbies, and capacity to exercise [12];
additional details can be accessed from the global I-WISh
study [10].
All methods were carried out in compliance with
EphMRA guidelines and in full accordance with the US
HIPAA 1996. Separate protocols were submitted for
the patient and physician surveys (patient survey refer-
ence number: 02018/1056; physician survey reference
of ITP beyond bleeding, and highlighting patients’ under-recognized symptoms/needs through support-systems
should be prioritized in the future.
Keywords: Disease management, Health-related quality of life (HRQoL), Immune thrombocytopenia (ITP), India, ITP
World Impact Survey (I-WISh), ITP symptoms

Page 3 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
number: 02018/1049). Survey materials and protocol
were reviewed and approved by the Western Institutional
Review Board. Patients and physicians were given an
overview of the study and ethical approval details; those
who wished to participate had to provide consent via a
tick/check box before initiating.
Statistical analyses
It being a descriptive, exploratory study, it did not include
sample size calculations. e local recruiter conducted a
feasibility assessment prior to launching data collection
to confirm the achievable sample size for this study.
Patient and physician survey data were analyzed sepa-
rately using descriptive statistics. Analyses were descrip-
tive, and no formal hypothesis was tested. Missing data
were not imputed. Analyses were conducted using
STATA statistical software version 15.1 (StataCorp, Col-
lege Station, TX).
Results
Demographic characteristics andthediagnostic journey
ofpatients withITP
Overall, 21 physicians and 65 patients completed the
survey questionnaire from March 09, 2018 and May
02, 2018. Patients were recruited by either experienced
physicians treating ITP (64 of 65 patients [98%]) or
patient association groups (1 of 65 patients [2%]). Accu-
rate estimates on the number of individuals who were
approached for participation in the survey could not be
obtained. All respondents who participated in the survey
questionnaire provided their demographic information,
along with details of their diagnostic processes (Table1).
Patients
e mean (standard deviation [SD]) age of the patients
was 33 (12.62) years, with 39 of 65 patients (60%) being
male. e symptom burden was moderate to high in 24 of
57 patients (42.1%), of whom 17 patients (71%) reported
a poor health score (≤ 4 on the Likert scale). Patients met
an average of 5 healthcare professionals (HCPs; including
primary care physicians, nurses, emergency care doctors,
dentists, and others) before an accurate diagnosis of ITP,
which was confirmed by physicians specialized in the
management of ITP in 56 of 65 patients (86%). Overall,
21 of 65 patients (32%) expressed a delay in ITP diagno-
sis, thereby leading to severe anxiety (≥ 5 on the Likert
scale) in 8 of 21 patients (38%) (Table1).
Physicians
All physicians included in the survey were either hema-
tologists (n = 13) or hemato-oncologists (n = 8). More
than half of the physicians who participated in the sur-
vey (12 of 21 physicians [57%]) practiced in a private
setting. Of the average caseload, about 87 of 625 (13.9%)
were patients with ITP. ITP was rated as a “somewhat
less important” condition by 14 of 21 physicians (67%).
Nearly one-fourth (5 of 21 physicians [24%]) of the physi-
cians perceived that 26%-50% of patients were misdiag-
nosed (Table1).
Patient andphysician perception ofITP symptoms
andseverity
Patient perspective
e most commonly reported symptoms at diagno-
sis were heavy menstrual bleeding (19 of 26 patients
[73%]), fatigue (46 of 65 patients [71%]), petechiae (39 of
65 patients [60%]), hematoma (30 of 65 patients [46%]),
and anxiety surrounding unstable platelet counts (28 of
65 patients [43%]). e mean (SD) duration of the disease
from diagnosis to survey completion was 5.3 (6.77) years.
At survey completion, the most commonly reported
symptoms were fatigue (35 of 65 patients [54%]), heavy
menstrual bleeding (10 of 26 patients [38%]), anxiety
surrounding unstable platelet counts (23 of 65 patients
[35%]), petechiae (19 of 65 patients [29%]), and hema-
toma (11 of 65 patients [17%]) (Fig. 1A). Menorrhagia
(15 of 19 patients [79%]), anxiety surrounding unstable
platelet counts (17 of 28 patients [61%]), and fatigue (27
of 46 patients [59%]) were the most commonly reported
severe symptoms at diagnosis (considering symptoms
reported by at least 15 patients) (Fig.1A). e key symp-
toms that patients wanted to be resolved included fatigue
(27 of 65 patients [42%]), heavy menstrual bleeding (10
of 26 patients [38%]), and anxiety surrounding unstable
platelet counts (21 of 65 patients [32%]) (Additional file1:
Figure S1).
Physician perspective
e most common signs and symptoms reported by phy-
sicians, based on the inputs received from their patients,
were similar at diagnosis vs survey completion; these
included petechiae (19 of 21 physicians [90%] vs 19 of
21 physicians [90%]), bleeding from gums (18 of 21 phy-
sicians [86%] vs 18 of 21 physicians [86%]), purpura (16
of 21 physicians [76%] vs 18 of 21 physicians [86%]),
epistaxis (14 of 21 physicians [67%] vs 13 of 21 physicians
[62%]), and heavy menstrual bleed (11 of 21 physicians
[52%] vs 12 of 21 physicians [57%]) (Fig.1B). According
to physicians, hematuria, melena, or rectal bleed (17 of
21 physicians [81%]); profuse bleeding during surgery (16
of 21 physicians [76%]); menorrhagia (14 of 21 physicians
[67%]); anxiety surrounding unstable platelet counts (12
of 21 physicians [57%]); and hematoma (12 of 21 phy-
sicians [57%]) could have a major negative impact on
patient HRQoL (scored ≥ 5 on the Likert scale). Accord-
ing to physicians, about 37% patients experienced fatigue,

Page 4 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
Table 1 Patient/physician demographic characteristics and patient diagnostic pathways
Patients
N = 65
Mean age, years 33
Male, n (%) 39 (60%)
Female, n (%) 26 (40%)
Current health state (Score: 1, very poor health; 7, excellent health)
≤ 4 26 (40%)
Splenectomized, n (%) 6/64 (9.3%)
Diagnosis
Median (IQR) time from symptom presentation to diagnosis, months 1.5 (0.5–5.7)
Symptom presentation to first consultation, months 0.7 (0.1–3.0)
First consultation to diagnosis 0.5 (0.2–1.0)
Patients with a median time from initial presentation to ITP diagnosis > 6 months, n (%) 9/55 (16%)
Patients in whom diagnosis of ITP confirmed as a result of another health condition, n (%) 2 (3%)
Delay in diagnosis, n (%) 21 (32%)
Awaiting additional test results 8 (38%)
Specialist reference 7 (33%)
Patient support following diagnosis, n (%)
Family/friends 59 (91%)
Physicians 50 (77%)
Nurses 24 (37%)
Patients who needed more support during the diagnosis process, n (%) 27 (42%)
Physicians 20 (74%)
Family/friends 13 (48%)
Patient support groups 11 (41%)
Physicians
N = 21
Average total patient caseload 625
Number of ITP patients seen in the last 12 months 81
Practice setting
Private care 12 (57%)
Specialty cancer center 5 (24%)
University teaching hospital and community teaching hospital 4 (19%)
Year of qualification
Before 1981 1 (5%)
1981–1993 3 (14%)
1994–2003 5 (24%)
2004–2014 10 (48%)
After 2014 2 (10%)
Diagnosis
Median (IQR) time from symptom presentation to diagnosis, months 0.25 (0.25–0.62)
Primary ITP 70%
Secondary ITP 30%
Reasons for delay in diagnosis
Specialist reference 13 (62%)
Exclusion of other potential causes 12 (57%)
Causes of secondary ITP
Systemic lupus erythematosus 11 (52%)
Drug-induced thrombocytopenia 11 (52%)
Hepatitis C virus 10 (48%)

Page 5 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
and the severity was considered as low (≤ 4 on the Lik-
ert scale) in most patients (17 of 21 physicians [81%]).
Fatigue was considered to be very severe by 12 of 21
physicians (57%), 10 of 21 physicians (48%), and 8 of 21
physicians (38%) when platelet counts were <10 × 109/L,
10-29 × 109/L, and 30-39 × 109/L, respectively (Addi-
tional file2: Figure S2). Overall, fatigue was considered as
a major concern by only 7 of 21 physicians (33%).
Impact ofITP onQoL
Patient
Based on the ILQI scores, the parameters that signifi-
cantly had a negative impact on patient QoL very often
(more than half of the time) were work life/studies (19
of 50 patients [38%]), absence of work/education (16 of
48 patients [33%]), and energy levels (19 of 65 patients
[29%]) (Fig.2A).
e overall impact on emotional well-being was
scored ≥ 5 on the Likert scale by 25 of 65 patients (38%),
and the top 4 reported reasons with a severe impact were
anxiety surrounding unstable platelet counts (38 of 65
patients [58%]), importance of stable platelet counts (38
of 65 patients [58%]), fluctuation in platelet counts for no
apparent reason (34 of 65 patients [52%]), and frustra-
tion with ITP symptoms (31 of 64 patients [48%]) (Fig.3).
Overall, 60 of 65 patients (92%) did not receive any pro-
fessional support, of whom 20 patients (33%) expressed a
desire for additional support (data not shown).
ITP adversely affected the work and financial situation
of patients, with 10 of 38 patients (26%) reducing their
work hours and 9 of 36 patients (25%) seriously consid-
ering a reduction in their work hours. Patients reported
an average of 11.1h of missed work per week due to the
impact of ITP (Fig.4). e total monthly out-of-pocket
expense for a patient with ITP was $211 (~ 16,000 INR),
with medicines accounting for more than 60% of this
expense ($132 [~ 9600 INR]). Patients also spent an aver-
age of 6.1h/month traveling for their appointments.
Overall, 39 of 65 patients (60%) expressed the need
for support (either ‘rarely’, ‘sometimes’, or ‘often’) for an
average of 33.7h/week; homemaking (27 of 39 patients
[69%]), transportation (26 of 39 patients [67%]), health-
care (25 of 39 patients [64%]), and management of
finances (20 of 39 patients [51%]), were the primary rea-
sons for which support was requested. e key support
providers were parents (19 of 39 patients [49%]) and
spouses (9 of 39 patients [23%]) (data not shown).
Physician
Physicians felt that anxiety about platelet counts and
frustrations around having a long-term, rare disease had
a severe adverse impact on most of the patients (~ 90%).
Daily activities were severely impacted in 4 of 20 patients
(21%) and 5 of 20 physicians (25%) felt that ITP had nega-
tively impacted patients’ relationship with their spouses.
Overall, interference of ITP in the level of patients’ physi-
cal activity was reported as severe by 6 of 20 physicians
(30%), and 18 of 20 physicians (90%) felt that ITP greatly
impacted patients’ ability to play contact sports or sports
with a chance of bleeding injury. A negative impact of
ITP on patients’ sex lives (8 of 18 physicians [44%]) and
concerns around increased risk of bleeding impacting
travel plans (9 of 20 physicians [45%]) was reported by
45% physicians (data not shown).
Table 1 (continued)
Physicians
N = 21
Chronic lymphocytic leukemia 8 (38%)
Human immunodeficiency virus 7 (33%)
Investigation rates (asymptomatic vs high symptom burden)
Spleen evaluation 12 (57%) vs 16 (76%)
Coomb’s test 5 (24%) vs 13 (76%)
H. pylori 3 (14%) vs 8 (28%)
Computed tomography scan 1 (5%) vs 7 (33%)
Platelet specific assay 0% vs 4 (19%)
Misdiagnosis rates
Upto 25% patients are misdiagnosed 14 (67%)
26–50% patients are misdiagnosed 5 (24%)
Most commonly misdiagnosed conditions
Drug induced thrombocytopenia 12 (63%)
Leukemia 11 (58%)
Aplastic anemia 10 (53%)

Page 6 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
Fig. 1 Frequency and/or severity of symptoms of ITP at diagnosis and survey completion – Patient and physician perspective

Page 7 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
Almost all physicians (20 of 21 physicians [95%]) did
not use any QoL tool, but expressed their desire to use a
patient self-assessment questionnaire (12 of 20 physicians
[60%] would use it during every consultation, and 7 of
20 physicians [35%] would use it every 6months). Most
physicians (16 of 21 physicians [76%]) expressed that use
of a mobile-based app would help in recording patient
QoL, while 10 of 21 physicians (48%) expressed that com-
bining paper- and mobile app-based approach would be
the preferred method to use. No major differences were
Fig. 2 Impact of ITP on QoL – Patient and physician perspective

Page 8 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
Fig. 3 Impact of ITP on emotional well-being – Patient perspective
Fig. 4 Impact of ITP on work

Page 9 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
observed in the response assessments of physicians based
on their workload (data not shown).
Management ofgoals andtreatment options inITP
Patient
ITP diagnosis to treatment required an average of
0.9 months, with over half of the patients (34 of 65
patients [52%]) undergoing a period of “wait and watch.”
e important treatment goals for patients were healthy
blood counts (42 of 65 patients [65%]), improvement in
QoL (35 of 65 patients [54%]), prevention of episodes
on worsening of ITP (33 of 65 patients [51%]), reduction
in spontaneous bleeding (18 of 65 patients [28%]), and
an overall improvement in symptoms (17 of 65 patients
[26%]) (Fig.5A). A majority of patients (41 of 65 patients
[63%]) strongly agreed that their current treatment was
helping them reach their treatment goals.
A once-daily oral pill was preferred by 49 of 65 (75%)
patients. At the time of survey completion, the most fre-
quently administered treatments were corticosteroids (38
of 65 patients [58%]), androgens (9 of 65 patients [14%]),
anti-CD20 (9 of 65 patients [14%]), thrombopoietin
receptor agonists (TPO-RAs; 8 of 65 patients [12%]), and
other immunosuppressants (7 of 65 patients [11%]); the
average duration of these medications was 4.7months.
When the symptom burden was low, most patients
reported undergoing treatment with corticosteroids
(27 of 33 patients [82%]), and as the burden increased
to moderate and above, corticosteroid use decreased
slightly (17 of 24 patients [71%]). e use of androgens
(8 of 33 patients [24%] to 11 of 24 patients [46%]), anti-
CD20 (9 of 33 patients [27%] to 11 of 24 patients [46%]),
and TPO-RAs (3 of 33 patients [9%] to 7 of 24 patients
[29%]) increased with increasing symptom burden. Data
on treatment satisfaction were based on a low patient
number (data not presented here) (data not shown).
Physician
Approximately 39% of the newly diagnosed patients were
given a trial of observation only. Even among patients
who had been previously treated for > 12 months since
diagnosis, 30% were put on observation instead of being
treated. Splenectomy was considered in 23% of the
patients with chronic and recurrent course. Platelet count
Fig. 5 Treatment goals

Page 10 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
monitoring was done more routinely in newly diag-
nosed patients (every 15 days) compared with patients
with chronic ITP (every 1.7 months). e major treat-
ment goals for physicians were reduction in spontaneous
bleeding (17 of 21 physicians [81%]), better QoL (14 of 21
physicians [67%]), symptom improvement (9 of 21 phy-
sicians [43%]), healthy blood counts (6 of 21 physicians
[29%]), and reduction in fatigue symptom (5 of 21 phy-
sicians [24%]). Nearly 90% of physicians (18 of 21 physi-
cians [86%]) believed that they discussed and agreed on
treatment goals with their patients, and 14 of 21 physi-
cians (67%) aimed to limit the immunosuppressive effect
of the treatment (Fig.5B).
e most important attributes while making treatment
decisions for patients with ITP were offering cure or sus-
tained remission (83%), the ability to reduce bleeding risk
(80%), and keeping side effects to a minimum (79%). For
both newly diagnosed and chronic ITP, ~ 80% of physi-
cians preferred oral treatment options as the first line of
treatment. Corticosteroids (19 of 21 physicians [90%])
and intravenous immunoglobulins (IVIgs; 16 of 21 phy-
sicians [76%]) were the preferred treatments in newly
diagnosed patients with ITP. TPO-RAs (19 of 21 physi-
cians [90%]) and anti-CD20 (17 of 21 physicians [81%]),
followed by androgens (16 of 21 physicians [76%]), were
the preferred treatment options in patients with persis-
tent and chronic ITP (Fig.6; Additional file3: Figure S3).
For patients relapsing for the first time, corticoster-
oids (14 of 21 physicians [67%]), followed by androgens
(8 of 21 physicians [38%]) and IVIgs/anti-CD20 (7 of
21 physicians [33%] each), were preferred, while dur-
ing second relapse other immunosuppressants (9 of 21
physicians [43%]) followed by corticosteroids (8 of 21
physicians [38%]) were preferred; by the third relapse,
TPO-RAs (11 of 21 physicians [52%]), followed by anti-
CD20 therapy (8 of 21 physicians [38%]), were the pre-
ferred treatment option (data not shown).
Based on physician perspective, patients treated with
TPO-RAs had the least incidence of side effects. A total
of 13 of 21 physicians (62%) agreed that they were sat-
isfied with the current treatment options available. Lack
of efficacy (21 of 21 physicians [100%]), followed by side
effects (19 of 21 physicians [90%]), and cost/coverage (17
of 21 physicians [81%]), was the most important reason
for a change in therapy (data not shown).
Patient andphysician relationship
When compared with patients, a lower proportion of
physicians were completely satisfied with the various
aspects of ITP disease–related care and management
(data not shown). While responding to questions on
access to information on ITP for their patients, 9 of 21
physicians (43%) expressed that patients faced at least
some level of difficulty in accessing information. About
half of the physicians indicated that they provided dis-
ease management–related information in a leaflet format
explaining the contents of the leaflet (9 of 21 physicians
[43%]). From the patient perspective, 40 of 65 patients
(62%) had not received any information from their HCP.
For patients who recieved information from their HCP, it
Fig. 6 Management of ITP – Prescribed treatments

Page 11 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
was either through a leaflet (10 of 25 patients [40%]) or
through HCPs showing the website content during con-
sultation (8 of 25 patients [32%]) or by being directed to
the website for accessing information about the disease (7
of 25 patients [28%]). A large proportion of patients did
not have any contact with patient support groups (61 of
65 patients [94%]) (data not shown).
Among 64 of 65 patients (98%) who visited a specialist
doctor, an average of 6.5 visits were recorded in the last
12months, and of these patients, 49 (77%) perceived the
frequency of visits to be adequate. None of the patients
reported consultation with a psychologist (data not
shown).
Discussion
To the best of our knowledge, this questionnaire-based
survey is the first of its kind among patients with ITP
and treating physicians in the Indian subcontinent, and
provides an insight into the perceptions of both patients
and physicians regarding disease diagnosis, signs and
symptoms, impact of patient HRQoL, and the approach
toward disease management.
A marked difference was observed in the num-
ber of patients with ITP seen by physicians in the last
12months before survey completion between the Indian
and global survey data (India: 81, global: 43) [9]. In
India, the overall doctor-to-population ratio is 1:1800,
which is lower than that the ratio of 1:1000 suggested
by ‘High Level Expert Group (HLEG) for Universal
Health Coverage’ constituted by the Planning Commis-
sion, and endorsed by WHO [7, 13]. Moreover, in India,
the population-to-specialist ratio is high [7], which fur-
ther increases the patient burden of hematologists and
hemato-oncologists. It is now widely accepted that ITP
is a diagnosis of exclusion and an estimated 15% patients
with primary ITP are misdiagnosed (McMaster ITP Reg-
istry) [14]. It is also pertinent that the initial diagnosis of
ITP is accurate, while avoiding delays based on the chal-
lenges associated with patient navigation. Encouragingly,
in this survey, the time from symptom presentation to
first consultation, and first consultation to diagnosis were
both < 1 month based on patients’ response, although
from the physicians’ perspective the accuracy of the diag-
nosis was low, with ~ 25% of physicians estimating that up
to 50% patients were misdiagnosed. Even if an accurate
diagnosis is made, the high patient burden and the asso-
ciated low average primary care physician consultation
time of ~ 2 min in India [5], physicians tend to primar-
ily treat for bleeding episodes and often underestimate
the impact of ITP on QoL. It is therefore imperative that
auxiliary healthcare service providers, especially nurses,
are trained to assess HRQoL parameters, and along with
physicians, adopt app-based or other validated QoL tools
for better disease management.
Heavy menstrual bleeding, fatigue, and anxiety sur-
rounding unstable platelet counts were predominantly
reported as severe by patients at both diagnosis and
survey completion. Physician perspectives on the fre-
quency and/or severity of the most common symptoms
and their impact on QoL were not always similar to
those reported by patients. While fatigue was reported
as severe by ~ 60% of patients at diagnosis, about 33%
of physicians perceived it as a symptom that severely
affects patient QoL. is trend in underestimation of
fatigue by physicians was observed in both the Indian
and global data [9]. However, fatigue adversely impacts
patient work productivity and social life, and physicians
should consider patient-reported fatigue as an important
symptom that affects HRQoL [15]. A high frequency of
menorrhagia, iron-deficiency anemia, and other nutri-
tional anemias found among Indian patients could be an
important contributing factor for fatigue [16–18]. Similar
to fatigue events, menorrhagia also impacts a number of
HRQoL measures [19, 20] and was reported by a major-
ity of women (> 70%) in this analysis. e fear concerning
heavy menstruation could be a major cause of anxiety in
most women at the time of ITP diagnosis (based on low-
grade evidence) [21, 22]. Of note, anxiety was reported
by 43% patients at diagnosis and 35% patients at survey
completion. Given that anxiety could be associated with
repeated blood count testing, more healthcare visits than
required, and changing the consulting physician fre-
quently (doctor shopping), it could result in an overall
increase in healthcare cost. erefore, counselling and
participatory medicine is important to ensure a common
treatment goal for physicians and patients to address
anxiety in ITP. Interestingly, the proportion of patients
reporting anxiety as a severe symptom reduced from 61
to 16% from diagnosis to survey completion. is could
be partially attributed to the fact that the average disease
duration from the time of diagnosis to survey completion
was 5.3years, implying that most patients evaluated in
this analysis had chronic ITP. It is often speculated that
patients with newly diagnosed ITP have higher anxiety
levels due to the uncertainty associated with their disease
course [23].
e assessment and improvement of HRQoL param-
eters generally require a multidimensional approach
and should be tailored for the patient, while taking into
account the healthcare system, cultural, and economic
backgrounds of individual countries [24]. In this sub-
group analysis among patients from India, the ILQI
questionnaire scores showed that daily life was severely
impacted by ITP, with more than half the patients
reporting that their work life, education, concentration

Page 12 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
levels, social lives, and energy levels were negatively
affected. In general, the QoL parameters that were
highlighted as being a concern include anxiety about
platelet counts and frustrations around having a long-
term rare disease, high out-of-pocket expenses, inabil-
ity to perform intense physical exercise or play sports
with chances of bleeding injuries, and impact on travel
plans due to concerns about increased risk of bleed-
ing and taking medications abroad. e out-of-pocket
expenses account for nearly 63% of the total healthcare
expenditure in India—one of the highest in the world—
reiterating the importance of a country’s healthcare
infrastructure in supporting improvement of patients’
HRQoL [24–26]. Although a few public health insur-
ance programs in India cover nonmedical expenditure,
such as transportation, lodging, and food costs, for
patients and caregivers, there is no provision for incur-
ring the loss of pay suffered by patients or their spouses
[26], thereby increasing the socioeconomic burden
of the disease. e lack of patient support groups and
other professional support for patient counseling add
to the emotional burden of ITP in India, as patients
almost entirely depend on family, friends, and the treat-
ing doctor for support. Patient support groups could
not only provide a platform for patients to share their
disease experience and provide emotional and moral
support but also help educate patients/families, raise
public awareness, and aid in raising funds [27]. How-
ever, in India, engagement in patient support groups is
low. e major constraints in ensuring higher engage-
ment rates could be the lack of awareness, lack of time,
or anxiety around discussing the negative aspects of
the disease publicly [27]. ere is a need to consider a
holistic approach toward assessment of symptom bur-
den and impact of ITP on QoL in routine clinical prac-
tice in India.
Physician ability to effectively and compassionately
communicate the nature of disease and management
options is important to build trust in a patient–physi-
cian relationship, and shared decision-making is a key
element in improving patient–physician communica-
tion [28]. Although nearly 90% of physicians included
in this survey mentioned that they had included their
patients’ perspective during decision-making, the
implementation of a participatory decision-making
model in ITP, which has been in place for cancer man-
agement for a considerable period of time [29], may not
be feasible in the Indian context. is could be due to
the existing gaps in patient knowledge of the disease
and effectiveness of available treatment options [30].
Implementation of a shared-decision model in India
needs greater patient education, along with physician
awareness and willingness; patient support groups can
play a major role in bringing about this change.
A shared-decision model could also help in ensur-
ing that the treatment goals of patients and physicians
are completely aligned. Our survey results showed that
achievement of healthy blood counts was the most
important goal for patients, while for physicians, it
was reduction in spontaneous bleeds. Interestingly,
improvement in QoL was one of the most impor-
tant treatment goals for both patients and physicians,
underlining the importance of assessing HRQoL among
patients with ITP. is was consistent with the global
I-WISh data, wherein improvement in QoL was one of
the top 3 goals among 38% of patients and 64% of phy-
sicians [8, 9].
Overall, the survey data outcomes and driven conclu-
sions must be interpreted with caution, given the small
sample size of the respondents, specifically the patient
group. Also, this survey did not capture the number of
treatment lines received by patients or the remission sta-
tus. Recall bias and the use of a non-validated HRQoL
questionnaire (ILQI) are some of the other limitations of
the study. However, the study results need to be consid-
ered in the light of the fact that ITP is a rare disease, and
currently, in India, there is limited education/awareness
among patients regarding the disease.
Conclusion
Based on the overall respondent assessment, the study high-
lights the need for education/training of physicians and
other healthcare workers on all aspects of ITP disease man-
agement—especially fatigue, anxiety, and menorrhagia—and
general awareness among physicians and patients on disease
management, including treatment goals, and the impact of
ITP on QoL. Additionally, it also emphasizes some of the
neglected aspects of ITP and provides a good starting point
for large-scale future studies in this therapy area.
Abbreviations
HCP: Healthcare professional; HRQoL: Health-related quality of life; ILQI: ITP Life
Quality Index; IRB: Institutional Review Board; ITP: Immune thrombocytopenia;
IVIgs: Intravenous immunoglobulins; I-WISh: ITP World Impact Survey; QoL:
Quality of life; TPO-RAs: Thrombopoietin receptor agonists.
Supplementary Information
The online version contains supplementary material available at https:// doi.
org/ 10. 1186/ s41687- 022- 00429-y.
Additional le1. Figure S1: Symptoms that patients want to be resolved.
Additional le2. Figure S2: Physician perspective on fatigue.
Additional le3. Figure S3: Prescribed treatments based on platelet
counts.

Page 13 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
Acknowledgements
We extend enormous thanks to all the patients and physicians who took the
time to complete this survey. Funding was provided by Novartis to Adelphi
Real World for the survey design, data collection, and data analysis. Tom Bailey
coordinated data collection and statistical analysis. We thank Anupama Singh
of Novartis Healthcare Private Limited for providing medical writing assistance.
Authors’ contributions
All authors contributed in the interpretation of data, writing and critically
reviewing the manuscript, and approval of the final draft. All authors read and
approved the final manuscript.
Funding
This study was sponsored by Novartis Pharmaceuticals Corporation.
Availability of data and materials
Not applicable.
Declarations
Ethics approval and consent to participate
Survey materials and the study protocol were reviewed and approved by a
centralized Institutional Review Board (IRB). Patients and physicians were given
an overview of the study and the ethical approval details; those who wished
to participate were required to provide consent via a tick/check box before
initiation.
Consent for publication
Not applicable.
Competing interests
Dr. Shashank Udupi is a full-time employee of Novartis Healthcare Private
Limited. None of the other authors had any conflict of interest to declare.
Author details
1 Department of Hematology, Vivekananda Institute of Medical Sciences,
Machan, L 16 Panchasayar, Kolkata, West Bengal 700094, India. 2 Department
of Hematology, CMC Vellore, Vellore, Tamil Nadu 632004, India. 3 Department
of Clinical Hematology, KEM Hospital, 1902, 19th floor UG PG hostel, KEM
Hospital Campus, Parel, Mumbai, Maharashtra 400012, India. 4 Department
of Medical Oncology, MG Medical College, 67/166, Sector 6, Pratap Nagar,
Jaipur, Rajasthan, India. 5 Medical Affairs, Oncology (Hematology), Novartis
Healthcare Private Limited, Inspire BKC, Part of 601 & 701, 7th Floor, Bandra
Kurla Complex, Bandra (East), Mumbai, Maharashtra 400051, India. 6 Depart-
ments of Research and Hemato-Oncology, Østfold Hospital, Østfold Hospital,
PB 300, 1714 Grålum, Norway.
Received: 9 September 2021 Accepted: 28 February 2022
References
1. Michel M, Suzan F, Adoue D et al (2015) Management of immune throm-
bocytopenia in adults: a population-based analysis of the French hospital
discharge database from 2009 to 2012. Br J Haematol 170(2):218–222
2. Sestøl HG, Trangbæk SM, Bussel JB, Frederiksen H (2018) Health-related
quality of life in adult primary immune thrombocytopenia. Expert Rev
Hematol 11(12):975–985
3. Neunert C, Terrell DR, Arnold DM et al (2019) American Society of
Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv
3(23):3829–3866
4. Provan D, Arnold DM, Bussel JB et al (2019) Updated international con-
sensus report on the investigation and management of primary immune
thrombocytopenia. Blood Adv 3(22):3780–3817
5. Irving G, Neves AL, Dambha-Miller H et al (2017) International variations
in primary care physician consultation time: a systematic review of 67
countries. BMJ Open 7(10):e017902
6. Density of Physicians (Total Number per 1000 Population, Latest Available
Year), Global Health Observatory (GHO) Data. Situation and Trends. http://
www. who. int/ gho/ health_ workf orce/ physi cians_ densi ty/ en/. Accessed
15 Feb 2021.
7. Deo MG (2013) Doctor population ratio for India—the reality. Indian J
Med Res 137(4):632–635
8. Cooper N, Kruse A, Kruse C et al (2020) Immune thrombocytopenia (ITP)
World Impact Survey (iWISh): patient and physician perceptions of diag-
nosis, signs and symptoms, and treatment. Am J Hematol 96(2):188–198
9. Cooper N, Kruse A, Kruse C et al (2020) Immune thrombocytopenia (ITP)
World Impact Survey (I-WISh): impact of ITP on health-related quality of
life. Am J Hematol 96(2):199–207
10. Nampoothiri RV, Singh C, Lad D et al (2019) Immune thrombocytopenia
is still the commonest diagnosis on consultative hematology. Indian J
Hematol Blood Transfus 35(2):352–356
11. Mishra K, Pramanik S, Jandial A et al (2020) Real-world experience
of eltrombopag in immune thrombocytopenia. Am J Blood Res
10(5):240–251
12. Griffiths P, Grant L, Bonner N et al (2019) The psychometric proper-
ties of the ITP Life Quality Index assessed in a large multinational
“real-world” cohort of immune thrombocytopaenia patients. Blood.
134(Supplement_1):386–386
13. High Level Expert Group Report on Universal Health Coverage for India.
Planning Commission of India. New Delhi, November, 2011. http:// nhm.
gov. in/ images/ pdf/ publi cation/ Plann ing_ Commi ssion/ rep_ uhc08 12. pdf.
Accessed 19 Mar 2021.
14. Arnold DM, Nazy I, Clare R et al (2017) Misdiagnosis of primary immune
thrombocytopenia and frequency of bleeding: lessons from the McMas-
ter ITP Registry. Blood Adv 1(25):2414–2420
15. Hill QA, Newland AC (2015) Fatigue in immune thrombocytopenia. Br J
Haematol 170(2):141–149
16. Didzun O, De Neve JW, Awasthi A et al (2019) Anaemia among men
in India: a nationally representative cross-sectional study. Lancet Glob
Health 7(12):e1685–e1694
17. Kapil U, Bhadoria AS (2014) National Iron-plus initiative guidelines
for control of iron deficiency anaemia in India, 2013. Natl Med J India
27(1):27–29
18. Shankar B, Agrawal S, Beaudreault AR et al (2017) Dietary and nutritional
change in India: implications for strategies, policies, and interventions.
Ann N Y Acad Sci 1395(1):49–59
19. Shankar M, Chi C, Kadir RA (2008) Review of quality of life: menorrhagia
in women with or without inherited bleeding disorders. Haemophilia
14(1):15–20
20. Rajpurkar M, O’Brien SH, Haamid FW, Cooper DL, Gunawardena S, Chitlur
M (2016) Heavy menstrual bleeding as a common presenting symptom
of rare platelet disorders: illustrative case examples. J Pediatr Adolesc
Gynecol 29(6):537–541
21. Rodeghiero F, Marranconi E (2020) Management of immune thrombocy-
topenia in women: current standards and special considerations. Expert
Rev Hematol 13(2):175–185
22. Kruse C, Kruse A, Watson S et al (2018) Patients with immune thrombo-
cytopenia (ITP) frequently experience severe fatigue but is it under-rec-
ognized by physicians: results from the ITP World Impact Survey (I-WISh).
Blood 132(Supplement 1):2273–2273
23. Kruse A, Kruse C, Potthast N, Milligan K, Bussel JB (2019) Mental health
and treatment in patients with immune thrombocytopenia (ITP); Data
from the Platelet Disorder Support Association (PDSA) Patient Registry.
Blood 134(Supplement_1):2362–2362
24. Hurst JR, Agarwal G, van Boven JFM et al (2020) Critical review of
multimorbidity outcome measures suitable for low-income and middle-
income country settings: perspectives from the Global Alliance for
Chronic Diseases (GACD) researchers. BMJ Open 10(9):e037079–e037079
25. Sriram S, Khan MM (2020) Effect of health insurance program for the poor
on out-of-pocket inpatient care cost in India: evidence from a nationally
representative cross-sectional survey. BMC Health Serv Res 20(1):839
26. Patel V, Parikh R, Nandraj S et al (2015) Assuring health coverage for all in
India. Lancet 386(10011):2422–2435
27. Hu A (2017) Reflections: the value of patient support groups. Otolaryngol
Head Neck Surg 156(4):587–588
28. ACOG Committee Opinion No. 587 (2014) Effective patient-physician
communication. Obstet Gynecol 123(2 Pt 1):389–393

Page 14 of 14
Chakrabartietal. Journal of Patient-Reported Outcomes (2022) 6:24
29. Butow P, Harrison JD, Choy ET, Young JM, Spillane A, Evans A (2007)
Health professional and consumer views on involving breast cancer
patients in the multidisciplinary discussion of their disease and treatment
plan. Cancer 110(9):1937–1944
30. Wang KKW, Charles C, Heddle NM, Arnold E, Molnar L, Arnold DM (2014)
Understanding why patients with immune thrombocytopenia are deeply
divided on splenectomy. Health Expect 17(6):809–817
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in pub-
lished maps and institutional affiliations.