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Effect of Postthrombotic Syndrome on Health-Related Quality of Life After Deep Venous Thrombosis
Susan R. Kahn, MD, MSc;
Andrew Hirsch, MD;
Ian Shrier, MD, PhD
Arch Intern Med. 2002;162:1144-1148.
ABSTRACT
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Background Postthrombotic syndrome (PTS) is a frequent chronic complication of
deep venous thrombosis, yet its impact on health-related quality of life has
not been well characterized. We compared generic and venous disease–specific
quality of life in patients with and without PTS, and assessed whether quality
of life correlated with severity of PTS.
Methods Subjects with previous deep venous thrombosis were participants in a
study of the effects of exercise after deep venous thrombosis. We ascertained
PTS and its severity using a validated clinical scale. Subjects completed
generic (the 36-Item Short-Form Health Survey) and disease-specific (Venous
Insufficiency Epidemiologic and Economic Study quality-of-life questionnaire
[VEINES-QOL] and its validated subscale of 10 items on venous symptoms [VEINES-Sym])
quality-of-life measures. Age- and sex-adjusted mean quality-of-life scores
were compared in patients with and without PTS, and by severity of PTS.
Results Of the 41 subjects (mean age, 51.2 years), 19 (46%) had PTS. Subjects
with PTS had significantly worse disease-specific quality-of-life scores than
those without PTS (mean ± SD VEINES-QOL score, 44.5 ± 11.6 vs
54.8 ± 5.4, respectively [P<.001]; mean
± SD VEINES-Sym score, 45.6 ± 11.4 vs 54.1 ± 6.7, respectively
[P = .003]), which worsened significantly with increasing
severity of PTS. We found no differences in generic quality-of-life scores
between subject groups.
Conclusions Postthrombotic syndrome has a significant impact on disease-specific
quality of life that may not be captured by generic quality-of-life measures.
Patient-based quality-of-life measures correlated well with physician-assessed
PTS. Further research is indicated to assess the value of including quality
of life as a routine measure of outcome in clinical studies of patients with
deep venous thrombosis and PTS.
INTRODUCTION
POSTTHROMBOTIC syndrome (PTS), a chronic condition consisting of leg
pain, edema, venous ectasia, and skin induration and ulceration, is estimated
to occur in 20% to 50% of patients after an episode of deep venous thrombosis
(DVT) and usually becomes established within the first 2 years after the acute
thrombotic episode.1-3
Deep venous thrombosis affects adults of all age groups, and the incidence
of associated PTS is high; hence, the population prevalence of PTS is considerable.
Little doubt remains among the clinicians caring for patients with DVT
and among the patients that PTS adversely affects several aspects of quality
of life, including limitations in daily activity, interference with work and
social activities, psychological distress, and change in health perceptions.4-5 However, despite its high prevalence
and associated morbidity, the impact of PTS on the quality of life of these
patients has not been adequately quantified.3
For chronic conditions such as PTS, assessment of quality of life may provide
important information on burden of illness that is not adequately captured
by traditional measures of morbidity and mortality.4, 6
In the course of performing the recently completed cohort study, the
Venous Insufficiency Epidemiologic and Economic Study (VEINES),7
the VEINES quality-of-life questionnaire (VEINES-QOL),8
a venous disease–specific measure of quality of life that is intended
for use in quantifying outcomes of interventions in patients with chronic
venous disease, was developed and validated. The objectives of the present
study were to compare generic and venous disease–specific quality of
life in patients with and without PTS after DVT, and to examine whether quality
of life correlates with severity of PTS.
SUBJECTS AND METHODS
SUBJECTS
Study subjects were recruited from the Thrombosis Clinic of the Sir
Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, where all patients
with a diagnosis of venous thromboembolism are seen and followed up (about
350 cases per year). Sequential patients with a first diagnosis of unilateral
DVT established by means of objective testing at least 1 year before were
approached for participation in a study on the impact of treadmill exercise
on the affected limb after DVT,9 for which
a sample size of 17 subjects with and 17 without PTS was required. Subjects
who participated in the exercise study served as the convenience sample for
the quality-of-life portion of the study, presented herein. Subjects were
excluded if they had bilateral or recurrent DVT, symptomatic pulmonary embolism
with the DVT episode, or a medical condition(s) that precluded treadmill exercise
(eg, cardiorespiratory disease and arthritis of the lower extremity), if they
were incapable of self-administering a questionnaire in French or English,
or if they were unable or refused to provide informed consent. Before its
initiation, the hospital's Research Ethics Committee approved the study.
STUDY PROCEDURES
Only those procedures that pertain to the quality-of-life portion of
the study are described herein.
One of 2 research assistants collected data from the subjects' hospital
records on age, sex, objective test used to diagnose DVT, and side and site
of DVT. The physician supervising the exercise experiment (one of the 3 coauthors),
who was unaware of data from the hospital record, ascertained the diagnosis
and the severity of PTS in the affected leg at baseline. We used the Villalta
Scale,10 a clinical PTS scale based on physician-assessed
symptoms and signs that assigns a general severity score (ie, with no time
frame specified) from 0 (not present or minimal) to 3 (severe) for 5 symptoms
(pain, cramps, heaviness, pruritus, and paresthesia) and 6 signs (edema, skin
induration, hyperpigmentation, venous ectasia, redness, and pain during calf
compression). The points are summed, and an overall score of 4 or less indicates
absence of PTS; 5 to 14, mild/moderate PTS; and 15 or more, or the presence
of a venous ulcer, severe PTS. The Villalta Scale has been shown to have high
interobserver agreement and high sensitivity and specificity for discriminating
mild/moderate vs severe PTS.9
Generic quality of life was measured using the 36-Item Short-Form Health
Survey (SF-36).11 Standard algorithms were
used to calculate scores for the Mental Component Scale, a summary score that
reflects scores on the vitality, social functioning, mental health, and emotional
role scales, and the Physical Component Scale, a summary score that reflects
scores on the physical functioning, physical role, bodily pain, and general
health perceptions scales.12
Venous disease–specific quality of life was measured using the
25-item VEINES-QOL questionnaire, which was previously shown to be acceptable,
valid, reliable, and responsive in 1531 patients with a wide spectrum of chronic
venous disorders,8 10% of whom had physician-reported
previous DVT. The VEINES-QOL contains 10 items on venous symptoms (9 items
on frequency of each of the following leg symptoms: heavy feeling, aching,
swelling, night cramps, heat or burning sensation, restless legs, throbbing,
itching, and tingling, and 1 item on intensity of leg pain during the past
4 weeks), 9 items on limitation in daily activities due to chronic venous
disease, 5 items on the psychological impact of the leg problem, and 1 item
on the change in the leg problem during the past year. We also assessed the
specific impact of symptoms on quality of life associated with PTS using a
validated subscale of the VEINES-QOL,8 which
contains only the 10 items on venous symptoms described in this paragraph
(VEINES-Sym). As for the SF-36 questionnaire, scores for individual items
on the VEINES-QOL and VEINES-Sym are combined to create a raw summary score,
which is then transformed to T scores based on a mean of 50 and an SD of 10
to give an easily understood range of scores.13
For all quality-of-life measures, lower scores indicate worse quality of life.
STATISTICAL ANALYSIS AND SAMPLE SIZE
We compared mean quality-of-life scores, adjusted for age and sex, in
subjects with and without PTS and by severity of PTS using analysis of covariance.
In subjects with PTS as defined by the Villalta Scale, we also calculated
mean PTS scores according to most proximal venous segment affected by the
index DVT, which are presented descriptively. Unless otherwise indicated,
results are reported as mean ± SD. We assessed the correlation between
quality-of-life scores and the Villalta Scale PTS score expressed as a continuous
variable using the Pearson coefficient of correlation. For all statistical
tests, a P value of .05 or less was considered significant.
The sample size achieved for the exercise study provided a power of 82% to
detect a 6-point difference and 67% power to detect a 5-point difference in
mean quality-of-life scores. Differences of as low as this order of magnitude
are considered to be clinically meaningful.11-12
RESULTS
STUDY POPULATION
Forty-three patients were recruited for the study during a 1-year period
(September 1, 1999, through November 30, 2000). Two patients were excluded
(one had a history of bilateral DVT and the other was not capable of following
the research assistant's instructions), leaving a study population of 41 subjects.
Postthrombotic syndrome was present in 19 subjects (46%), and was categorized
as mild/moderate in 17 and severe in 2. No differences were found in mean
age or number of years since DVT diagnosis in patients with PTS compared with
those without PTS (Table 1). Although
higher proportions of subjects with PTS were women and had proximal (vs distal)
DVT compared with those without PTS, these differences were not statistically
significant. Among subjects with proximal DVT (n = 29), the most proximal
venous segment affected was the iliac vein in 3 subjects, the common femoral
vein in 8, the superficial femoral vein in 4, and the popliteal vein in 14.
Fifteen subjects with proximal DVT (52%) had PTS (mild/moderate in 13 and
severe in 2) compared with 4 (33%) of the 12 subjects with distal DVT (mild/moderate
in all 4).
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Characteristics of Study Subjects*
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QUALITY-OF-LIFE SCORES
Missing Data
There were no missing data for any items on the quality-of-life questionnaires.
Generic Quality of Life
Mean Mental Component Scale score was 46.3 ± 14.5 in subjects
with PTS and 52.2 ± 6.5 in subjects without PTS (P = .10)
(Figure 1). For
the Physical Component Scale, mean scores in subjects with PTS were 51.7 ±
6.3 vs 50.8 ± 7.1 in subjects without PTS (P
= .69). The Mental Component Scale and Physical Component Scale scores were
similar whether PTS was absent, mild/moderate, or severe (data not shown).
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Figure 1. Generic and disease-specific quality-of-life
scores in subjects with and without postthrombotic syndrome (PTS). Analyses
are adjusted for age and sex. Error bars represent SDs. Comparisons are between
subjects with and without PTS. MCS indicates Mental Component Scale; PCS,
Physical Component Scale; VEINES-QOL, Venous Insufficiency Epidemiologic and
Economic Study quality-of-life measure; and VEINES-Sym, a validated subscale
of the VEINES-QOL that contains only the 10 items on venous symptoms.
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Disease-Specific Quality of Life
Subjects with PTS had significantly worse scores on the VEINES-QOL questionnaire
and VEINES-Sym subscale compared with subjects without PTS (Figure 1). Furthermore, the VEINES-QOL and VEINES-Sym scores worsened
significantly with increasing categories of severity of PTS (Figure 2) and were inversely correlated with the Villalta Scale
score expressed as a continuous measure (VEINES-QOL, r
= -0.63 [P<.001]; VEINES-Sym, r = -0.61 [P<.001]) (Figure 3). These r values represent moderate
to good correlation.14 The 2 clear outliers
on both figures were the same 2 subjects, one aged 39 years and the other,
29 years, both of whom had severe PTS (Villalta Scale score of 19 each). Exclusion
of these outliers did not appreciably change the above-noted correlations.
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Figure 2. Disease-specific quality of life
according to severity of postthrombotic syndrome (PTS). Analyses are adjusted
for age and sex. Error bars represent SDs. Comparisons are between subjects
with none, mild/moderate, and severe PTS. Abbreviations are described in the
legend to Figure 1. Ratings of severity of PTS are described in the "Study
Procedures" subsection of the "Subjects and Methods" section.
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Figure 3. Correlation between Villalta Scale
postthrombotic syndrome (PTS) score and VEINES-QOL (A) and VEINES-Sym (B)
scores. Outer curves represent 95% confidence limits. Higher Villalta Scale
scores indicate worse PTS; lower VEINES-QOL and VEINES-Sym scores, worse quality
of life. Abbreviations are described in the legend to Figure 1.
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COMMENT
In a population of relatively young and healthy patients with previous
DVT, we found that the presence of PTS, as defined by means of the Villalta
Scale, had a significant impact on disease-specific quality of life, as measured
by means of the VEINES-QOL questionnaire and its symptom subscale, the VEINES-Sym.
Furthermore, patients with severe PTS had significantly worse quality of life
than did those with mild to moderate PTS. To our knowledge, this is the first
study to show that PTS and its clinical severity result in a measurable, graded,
adverse effect on health-related quality of life in patients with DVT.
In contrast, we found no demonstrable effect of PTS on generic quality
of life in our study patients. Moreover, the overall mean scores for the Mental
Component Scale and Physical Component Scale in our study population were
similar to the population-based normative scores for a community-dwelling
Canadian population of similar age and sex distribution to our study subjects,15 suggesting that DVT at least 1 year before, on average,
does not affect generic quality of life. However, because of the limited power
afforded by our sample size, further study of the potential usefulness of
a generic quality-of-life tool in discriminating between DVT patients with
and without PTS is indicated.
For chronic conditions such as PTS, assessment of quality of life may
provide important information on burden of illness that is not adequately
captured by traditional clinical measures of morbidity and mortality.4 Comprehensive measurement of quality of life requires
generic and disease-specific measures.4, 6
Generic measures allow comparison of findings with those of patients with
different diseases, whereas disease-specific measures may be more responsive
to change in a particular condition because of their greater specificity and
relevance to a given patient group.6
Few published studies exist on quality of life after DVT. Beyth and
coworkers16 interviewed 52 surviving patients
from a cohort of 124 patients who had DVT 6 to 8 years earlier. They found
that patients who reported symptoms of PTS had poorer perceptions of their
health, lower levels of physical functioning, and more severe role limitations
due to physical health, as measured by the SF-36 generic quality-of-life instrument.
However, the mean age of their population was about 10 years older than ours;
many of their patients had severe comorbid conditions that could have independently
affected quality of life, not all of which were adjusted for; and PTS was
not assessed using a validated scale. Although quality of life was not measured
using a standardized instrument, an earlier study of the long-term effects
of iliofemoral DVT17 showed that among 21 patients
followed up for 10 years or longer, 11 of the 12 men were disabled and unable
to maintain a steady job because of their leg symptoms, and 7 of the 9 women
were unable to perform household duties and required a housekeeper.
An important limitation in the field of PTS research to date has been
the lack of comparability of studies due to differing definitions of PTS.
Also, overall, poor correlation exists between objective measures of deep
venous dysfunction such as reflux and venous hypertension and patient-based
measures such as symptoms and signs.3 Our finding
that the impact on quality of life as measured by means of the VEINES-QOL
and VEINES-Sym varied directly with clinically diagnosed PTS and its severity
suggests that these disease-specific quality-of-life instruments are useful
measures of the burden of PTS as perceived by the patient. Furthermore, there
may be a role for the use of these instruments as standardized, patient-based
measures of outcome in clinical studies of patients with deep venous thrombosis
and PTS.
Our study has several limitations. First, there is no single objective,
criterion standard test to diagnose PTS.3 However,
we used a validated clinical scale that has been used in prospective studies
of long-term outcome after DVT1-2
to diagnose and establish the severity of PTS. Nevertheless, it is possible
that misclassification of diagnosis or severity of PTS may have occurred for
some subjects. Second, our study population was a convenience sample of patients
attending our Thrombosis Clinic who volunteered to participate in an exercise
study; hence, we may have selected less severely affected patients, since
those with more severe symptoms at baseline or with symptoms that worsen with
exercise might have declined participation. However, this might have decreased
the likelihood of finding a measurable difference in quality of life between
groups. Third, subjects who had medical conditions that precluded exercise
testing (eg, cardiorespiratory illness and arthritis of the lower limbs) were
ineligible for the study. Although this exclusion likely helped to avoid confounding
by comorbid conditions that could independently affect quality of life, it
could limit the quantitative generalizability of our findings to patients
with PTS with a broader spectrum of severity than that of our subjects. However,
it is unlikely to affect the qualitative conclusions.
CONCLUSIONS
We have shown that patients with DVT in whom PTS develops have a worse
disease-specific quality of life than those without PTS, and that quality
of life worsens with severity of PTS. Further prospective studies on larger
and more diverse populations of patients with DVT are required to determine
the value of using disease-specific quality-of-life measures to assess outcome
in studies examining therapies to prevent or treat DVT and PTS. The use of
such patient-based outcome measures may allow the effectiveness of treatment
to be assessed in more relevant terms, for the patient, than those of traditional
clinical measures. Also, further evaluation of the impact of DVT and PTS on
generic quality of life would help to determine whether use of generic quality-of-life
tools provides additional information to that provided by disease-specific
quality-of-life measures in this patient population.
AUTHOR INFORMATION
Accepted for publication September 26, 2001.
Drs Kahn and Shrier are Chercheurs Boursier Clinicien (Clinical Research
Scholars) supported by the Fonds de Recherche en Santé du Québec,
Montreal. This study was supported by an unrestricted grant-in-aid from the
Beiersdorf-Jobst Research Program of the American College of Phlebology, Oakland,
Calif.
This study was presented in part as a poster at the 42nd Annual Meeting
of the American Society of Hematology, San Francisco, Calif, December 3, 2000.
We thank our research assistants, Laurent Azoulay and Michael Haber,
and our recruiting nurse, Carla Strulovitch, RN, for their help.
Corresponding author: Susan R. Kahn, MD, MSc, Center for Clinical
Epidemiology and Community Studies, Sir Mortimer B. Davis Jewish General Hospital,
3755 Cote Ste, Catherine Room A-114, Montreal, Quebec, Canada H3T 1E2 (e-mail: susan.kahn{at}mcgill.ca).
From the Department of Medicine (Drs Kahn and Hirsch) and the Center
for Clinical Epidemiology and Community Studies (Drs Kahn and Shrier), Sir
Mortimer B. Davis Jewish General Hospital, Montreal, Quebec.
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