TRAINING and EDUCATION
Given the economic and
morbidity burden of post-
thrombotic syndrome, early
diagnosis and treatment is
essential to preserving patients’
health-related quality of life.
At this point, there are insufficient data available
about the protective ability of the various anticoagulants,
so possible better protection against PTS is not in itself
a valid reason to choose one available parenteral or oral
anticoagulant over another.
The following factors have little or no impact on the
risk of developing PTS: sex, whether DVT was provoked
or unprovoked, and inherited thrombophilia.
Risk factors apparent during follow-up after acute DVT
Ipsilateral DVT recurrence increases the risk of PTS by
four- to sixfold. Persistent venous symptoms and signs
one month after acute DVT also increase risk of subse-
quent PTS.
Inflammation markers associated with a higher PTS
risk include: C-reactive protein; interleukin (IL)-6, IL-8,
and IL-10; intercellular adhesion molecule (ICAM)-1;
and higher levels of matrix metalloproteinase (MMP)-1
and MMP-8, measured at varying time points after DVT
diagnosis. The predictive value of D-dimer levels has not
been established.
Preventing PTS
Patients with several risk factors at any point during DVT
diagnosis and follow-up should be closely monitored for
signs of PTS. For patients on VKA treatment, rigorous in-
ternational normalized ratio monitoring is recommended,
particularly during the first three months post-DVT.
Because recurrent ipsilateral DVT is an important
risk factor for PTS, preventing recurrent DVT by provid-
ing optimal, appropriate-duration anticoagulation for the
initial DVT is an important goal of management.
Elastic compression stockings (ECS) could plausibly
play a role in preventing PTS, but the data are conflicting.
In light of the available evidence and international con-
sensus guidelines, we do not routinely prescribe ECS to all
DVT patients, instead we prescribe a trial of 20 to 30 mm
Hg or 30 to 40 mm Hg below-knee ECS to patients who
have residual leg swelling or discomfort after proximal or
distal DVT. We monitor symptoms and continue ECS for
as long as the patient derives symptomatic benefit or is able
to tolerate them. To maximize benefit, patients should be
educated on how to apply and use ECS and on the impor-
tance of compliance.
Because inflammation may contribute to PTS devel-
opment, drugs with anti-inflammatory properties could
have a preventive effect on PTS, but this requires investi-
gation in randomized controlled trials.
In addition to optimal anticoagulation, early clot re-
moval, such as catheter-directed thrombolysis (CDT) or
pharmacomechanical CDT, can be considered for certain
patients, including those with severe DVT in which the
arterial circulation is compromised, because CDT is likely
to be associated with a lower risk of major bleeding than
systemic thrombolysis. CDT could also be considered
on a case-by-case basis in patients younger than 65 years
old with extensive acute proximal DVT who have a good
ASHClinicalNews.org
Fast Facts
✓ ✓ Post-thrombotic syndrome (PTS) is a form of chronic venous
insufficiency that develops in approximately 20 to 50 percent of people
who have experienced a deep vein thrombosis (DVT).
✓ ✓ The principal risk factors for PTS are anatomically extensive DVT,
recurrent ipsilateral DVT, obesity, and older age.
functional status and a
low risk of bleeding. ✓ ✓ Symptoms of PTS vary, and include heaviness, tiredness, swelling,
itching, cramps, paresthesia, and venous claudication. Symptoms
worsen with activity and improve with rest, but increase in intensity
over the course of a day.
Treating PTS ✓ ✓ Diagnosis of PTS should be deferred until 3 to 6 months after DVT, once
the initial pain and swelling has resolved.
Few treatment strate-
gies for established
PTS have been studied
in well-designed clini-
cal trials, so there is a
lack of evidence-based
management options.
✓ ✓ For patients with established PTS, treatment options include elastic
compression stockings (ECS), exercise, and lifestyle modifications;
however, the effectiveness of ECS is controversial. Patients with
refractory or severe forms of PTS may undergo surgical or endovascular
interventions.
Prolonged
anticoagulation
It is common clinical
practice to prolong
anticoagulation in
patients with PTS, but
there is no consensus
on the value of extending anticoagulation beyond the
duration recommended for the treatment of DVT in
patients with established PTS. It also is uncertain if hav-
ing PTS increases the risk of ipsilateral recurrent venous
thromboembolism after anticoagulation is stopped.
Exercise and lifestyle
Evidence from small studies suggest that exercise training
(focused on increasing leg strength, leg flexibility, and
overall cardiovascular fitness) lessened PTS severity and
improved quality of life.
Other lifestyle modifications include:
• promoting venous return by avoiding a sedentary
lifestyle
• elevating the legs when seated or in bed when lying
down
• avoiding prolonged exposure to heat
Medications
Venoactive drugs that have been considered for the
treatment of PTS include rutosides, defibrotide, and
hidrosmin. However, a meta-analysis evaluating the
effectiveness of these drugs for PTS found low-quality
evidence to support their use. Further, there is no
evidence that use of diuretics is effective for the treatment
of PTS-related edema.
Venous ulcer management
Patients who develop severe PTS and venous leg ulcers
should be managed by a multidisciplinary team including
an internist, dermatologist, vascular surgeon, and wound-
care nurse. PTS-related ulcers typically are treated with
compression therapy; leg elevation; topical dressings;
and pentoxifylline, a pharmacologic agent considered to
improve tissue blood flow and oxygen delivery. For recur-
rent ulcers or those that are refractory to therapy, surgery
or endovascular procedures should be considered.
Endovascular and surgical options
• maintaining a nonobese body weight
• using a moisturizing cream to avoid skin dryness
and subsequent skin breakdown
Compression therapy
As noted earlier, ECS are a cornerstone of PTS manage-
ment, although their use is based primarily on extrapola-
tion from experiences of patients with primary CVI. An
initial therapeutic trial of 20 to 30 mm Hg knee-length
ECS can be followed by stronger pressure (30-40 or 40-50
mm Hg) stockings if lower-pressure stockings are inef-
fective. For patients with severe symptoms unresponsive
to ECS, a trial of a venous-return assist device (such as
Venowave) is recommended. Intermittent pneumatic
compression is also an option for patients with moderate
to severe symptoms.
If conservative management fails to improve symptoms,
endovascular or surgical treatments (such as stent place-
ment for chronic iliac vein obstruction or venous bypass
surgery) can be considered for symptom relief in select
patients with severe PTS. However, the lack of good-
quality evidence prevents robust recommendations
regarding these procedures.
Research Needs
PTS is known to be a frequent complication of DVT,
yet there are several gaps in our understanding of the
prevention and management of PTS. An improved un-
derstanding of the pathophysiology of PTS, for example,
would help researchers identify future therapeutic targets.
Validated clinical prediction rules to predict PTS risk
would allow us to more accurately select patients for
preventive treatment. ●
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