How I Treat In Brief
Recently, Anat Rabinovich, MD, of Soroka University Medical Center at the Ben-Gurion University of the Negev in Israel and
Susan R. Kahn, MD, MSc, of the Center for Clinical Epidemiology and the department of medicine at McGill University in
Montreal, discussed how to manage post-thrombotic syndrome, a chronic complication of deep vein thrombosis. Below, we
summarize their approach.
This material was repurposed from “How I treat post-thrombotic syndrome,” published in the May 17, 2018 issue of Blood.
Managing Post-Thrombotic Syndrome
Post-thrombotic syndrome (PTS) is a form of chronic
venous insufficiency (CVI) with varying clinical mani-
festations ranging from minimal discomfort to chronic
pain. PTS is increasingly being recognized as a frequent
consequence of deep vein thrombosis (DVT), affecting
between 20 to 50 percent of patients.
PTS presents a substantial economic and morbidity
burden. Total PTS-associated treatment costs (includ-
ing imaging studies, laboratory and pathology testing,
pharmacy claims, and hospital admissions – which are the
main cost driver) are much higher among patients with
DVT who develop PTS, compared with those who do
not. Surveys also have shown that patients’ self-reported,
health-related quality of life was on par with people living
with severe chronic diabetes or congestive heart failure.
Given this burden, early diagnosis and treatment of
PTS is essential to preserving patients’ health-related
quality of life.
What Causes PTS?
PTS is thought to develop after DVT because of the
onset of ambulatory venous hypertension, which leads
to reduced calf muscle perfusion and increased tissue
permeability, causing chronic edema, tissue hypoxia,
progressive calf pump dysfunction, subcutaneous fibrosis,
and, ultimately, skin ulceration.
DVT leads to chronic venous hypertension via two
principal mechanisms: valvular reflux and residual
venous obstruction. DVT also triggers inflammation-
induced valvular damage in involved segments.
Signs and Symptoms of PTS
The signs, symptoms, and severity of PTS vary from
patient to patient, ranging from minimal discomfort to
severe chronic pain, intractable edema, and leg ulcer-
ation ( TABLE 1 ). They tend to worsen with activity and
improve with rest. The intensity of symptoms generally
increases over the course of the day and can wax and
wane over time.
Symptoms of PTS include leg heaviness, tiredness,
swelling, itching, cramps, paresthesia, and venous clau-
dication (limping and/or pain due to inadequate venous
drainage from the legs). Signs of PTS include dermato-
logic manifestations, like redness, hyperpigmentation,
and skin thickening.
Diagnosing PTS
There is no objective diagnostic test for PTS, which is
primarily diagnosed on clinical grounds in a patient with
manifestations of CVI and a previous episode of DVT in
the preceding three months. However, the International
Society on Thrombosis and Haemostasis recommends
performing two consecutive assessments using the
Villalta scale, a clinical scale developed specifically for
PTS: The first is sufficient to make a diagnosis, and the
second assessment three months later measures grade
and severity ( TABLE 2 ).
There also is no specific recommended time limit
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following DVT to diagnose PTS.
Because it can take a few months
for the initial pain and swelling
associated with acute DVT to
resolve, a diagnosis of PTS should
be deferred at least until after the
acute phase (about 3 to 6 months)
following the DVT.
Predicting PTS
The risk factors for PTS are not
completely understood, making it
difficult to predict which pa-
tients will develop PTS. However,
recent studies have improved our
understanding of the epidemiol-
ogy, risk factors, and prevention of
PTS, and we have identified several
clinical and biologic factors that
influence the risk.
Risk factors apparent at the time of
DVT diagnosis
The risk of PTS is two- to threefold
higher in patients who develop
proximal DVT (especially with
involvement of the iliac or com-
mon femoral vein), compared
with those who develop distal
DVT. Pre-existing primary venous
insufficiency also increases the risk
of PTS up to twofold. Other risk
factors include a body mass index
(BMI) of more than 30 kg/m 2 and
older age.
In our clinic, we use a clinical
prediction rule for PTS in patients
with a first proximal DVT that
includes the following high-risk
factors at the time of DVT diagno-
sis: index DVT in iliac vein, BMI
≥35 kg/m 2 , and severe acute DVT
symptoms and signs.
Risk factors related to the treatment
of DVT
Insufficient or subtherapeutic
anticoagulation with vitamin K
agonists (VKAs) in the first three
months after DVT has been associ-
ated with an increased risk of PTS.
Low-molecular-weight heparins
may be more effective than VKAs
for PTS prevention, and it is still
unclear whether DVT treatment
with newer, direct oral anticoagu-
lants is more effective than VKAs
for PTS prevention.
TABLE 1.
Symptoms and Signs of PTS
Symptoms
•
•
•
•
•
•
•
•
Leg heaviness or fatigue
Swelling
Itching
Cramps
Paresthesia
Bursting pain
Venous claudication
Symptom pattern: worse with
activity, standing, walking; better
with rest, lying down, maximum
at end of day
TABLE 2.
Edema
Venous ectasia
Redness
Hyperpigmentation
Dependent cyanosis
Skin thickening
Eczema
Atrophie blanche (white scar tissue)
Lipodermatosclerosis (fibrosis of
subcutaneous tissues)
• Ulcer(s)
•
•
•
•
•
•
•
•
•
The Villalta Scale for PTS Severity
Symptoms
•
•
•
•
•
Signs
Pain
Cramps
Heaviness
Paresthesia
Pruritis
Signs
•
•
•
•
•
•
•
Pretibial edema
Skin induration
Hyperpigmentation
Redness
Venous ectasia
Pain on calf compression
Venous ulcer
Each symptom is self-rated by the patient, and each clinical sign is rated by the clinician as 0 (absent),
1 (mild), 2 (moderate), or 3 (severe), except ulcer, which is marked as present or absent.
A total score of 0 to 4 indicates the absence of PTS, and a score of >4 indicates PTS: mild = 5-9; moder-
ate = 10-14; severe >14 or the presence of an ulcer.
December 2018