Introduction Venous thromboembolism (VTE) which includes deep
vein thrombosis (DVT) and pulmonary embolism (PE) has an annual
incidence of 0.1 -0.27% 5% of population affected by VTE Current
management decisions rest on a balance of risk and benefit of
treatment options
Slide 6
Introduction 3 phases of treatment to consider -acute (first
5-10days) -long-term first 3 months -extended beyond 3 months
3Etiology groups -provoked -unprovoked -malignancy
Slide 7
Introduction The diagnosis and treatment for acute and
long-term phases is the same for all cases of VTE not associated
with malignancy Etiology and specifically the unprovoked VTE
becomes important in the extended phase Differences in the
management of young patients with DVT also centre around the
extended phase will be discussed there
Slide 8
Diagnosis of DVT A certain diagnosis can only be established
with imaging It is good practice to rule out DVT using D-Dimer and
a standardised clinical probability assessment - reduces the
required number of imaging in a cost and staff constrained health
system Both tests should be used 40% of cases presenting as
possible DVT can be ruled out Very poor adherence to the guidelines
most patients have D-dimer test and imaging and clinical decision
rules are either not used or not acted on.
Slide 9
Diagnosis of DVT D-dimer The D-dimer can be positive in many
conditions other than VTE and is only useful to exclude DVT or PE
The higher the sensitivity of a specific D-dimer test, the lower
the risk of a false negative No D-dimer test has 100% sensitivity
us only in patients with a low clinical probability assessment
Clinical decision rule The best validated of the clinical decision
rules in DVT remains the Wells rule
Slide 10
Diagnosis of DVT
Slide 11
Imaging Contrast venography is not used any more Compression
ultrasonography (CUS) is the imaging of choice particularly for
proximal vein DVT Non- compressibility of the femoral or popliteal
vein by CUS is diagnostic of a first proximal DVT with a
sensitivity of 94% and specificity of 98% CT or MR venogram can be
used where the CUS cannot be used or is less reliable : casts,
morbid obesity or if DVT of the illiac veins or IVC is
suspected
Slide 12
Treatment of DVT acute and long-term phases If there is a high
probability of DVT and imaging is delayed start empiric therapy
Acute treatment prevents extension of the DVT as well as PE and
relieves symptoms
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Slide 14
Treatment of DVT acute and long-term phases Thrombolysis
Thrombolysis may restore the vein patency and prevent
postthrombotic syndrome (PTS) A meta-analysis of IV thrombolysis
suggested a decrease in PTS but with a risk of major bleeding and
no reduction in recurrence,PE or death
Slide 15
Treatment of DVT acute and long-term phases Thrombolysis
Catheter directed thrombolysis was compared to standard therapy for
illio-femoral DVT doubled vein patency at 6 months an decreased PTS
more bleeding same recurrence and mortality May be considered for
young well patients with symptoms less than 14 days and low
bleeding risk Should be used for threatened limbs
Slide 16
Treatment of DVT acute and long-term phases Vena Cava filters
Vena cava filters in the acute situation should be reserved for
patients with an absolute contraindication to anticoagulation eg
cerebral bleed Carry a risk of thrombosis of the filter Start
anticoagulation as soon as the contraindication resolves
Slide 17
Treatment of DVT acute and long-term phases Standard treatment
LMWH once daily is the treatment of choice with Enoxiparin given at
1.5mg/kg Unfractionated heparin only for very unstable patients
where rapid reversal may be needed or if creatinine clearance
Slide 18
Treatment of DVT acute and long-term phases Standard treatment
Warfarin is started after the LMWH in young well patients 10mg
daily x 2days is safe Pharmakogenetic testing definitely not
indicated in our setting Treatment continues for at least 3 months
INR 2-3 for all indications
Slide 19
Slide 20
Treatment of DVT acute and long-term phases New oral agents
Rivaroxiban direct factor X inhibitor can be used as monotherapy
for all phases of DVT treatment Non-inferior to LMWH/VKA interms of
bleeding and recurrence of VTE No need to monitor, few drug
interactions easier than warfarin
Slide 21
Treatment of DVT acute and long-term phases New oral agents
Pivotal trials did not include patients with creatinine
clearance
Slide 22
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Treatment of DVT acute and long-term phases Other management
issues Compressions stockings improve pain and edema as well as the
later symptoms of PTS, but no proof in RCT that it prevents PTS
Early mobilisation is recommended and a meta-analysis indicated
that it may reduce the severity of PTS Outpatient management of DVT
is safe and improves QOL with decreased cost Outpatient management
may not be possible in poor social circumstances and patients with
severe symptoms as well as severe renal impairment
Slide 24
Extended phase Management depends on the etiology Cancer
associated LMWH continued while active cancer Provoked with clear
secondary cause stop after 3 months Unprovoked evaluate risk of
recurrent thrombosis vs risk of bleeding
Slide 25
Unprovoked DVT DVT without any identifiable thrombotic risk
factor Recurrence rate of 10% after one year (12% for men and 8%
for women) and 30% at 5 years Extended if not lifelong
anticoagulation may be required Guidelines favour indefinite
anticoagulation over just extending to 6 months Indefinite
anticoagulation should be done in all cases with a second
unprovoked VTE
Slide 26
Unprovoked DVT The risk of VTE and it consequences must be
weighed up against the bleeding risk The case fatality rate of a
major bleed is 12% vs 4% for recurrent DVT and 8 % for PE The
recurrence risk must be high to justify extended or long term
anticoagulation Patient preference must also be considered
Slide 27
Unprovoked DVT Base line factors predicting risk of recurrent
VTE Inherited thrombophilia and family history -deficiency of
AT,protC,protS and patients with hyperhocysteienemia may have
higher recurrence when stopping VKA -not conclusive that family
history increases recurrence risk -? Do thrombiphilia screen in
young patient with unprovoked DVT if family history is strong or
thrombosis in unusual site
Slide 28
Unprovoked DVT Male gender -confirmed by meta-analysis of VTE
that male gender is associated with higher recurrence rate when
anticoagulation is stopped Age -associated with higher recurrence
than younger patients Obesity -higher risk of recurrence Fibrate
lipid lowering drugs -higher risk of recurrence
Slide 29
Unprovoked DVT Post- baseline factors predicting risk for
recurrent VTE Residual vein thrombosis -residual thrombosis on
ultrasound in a proximal DVT is a powerful independent risk for
recurrent thrombosis D-dimer - positive / negative D-dimer at time
of stopping anti-coagulation is a strong predictor of risk of
recurrence or not -can stop for a month and recheck then -can be
used to make decision to stop VKA or not Early development of PTS
-May predict for higher risk of recurrence Study now ongoing using
D-dimer and residual thrombosis to determine recurrence risk and
decide on indefinite anticoagulation
Slide 30
Patients with VTE who should be treated for 3 months and who
should be treated indefinitely. Kearon C, and Akl E A Blood
2014;123:1794-1801 2014 by American Society of Hematology
Slide 31
Unprovoked DVT New Scenarios for indefinite prevention of
recurrent VTE Low dose aspirin -shown in 2 recent studies to
decease the risk of recurrence of VTE by 30% vs 90% with
anticoagulation -bleeding risk significant New oral agents for
indefinite anticoagulation -recent studies using Rivaroxiban or
other oral agents compared to LMWH/VKA for VTE -during extended use
new oral agents were non-inferior in preventing VTE recurrence and
resulted in fewer major bleeds
Slide 32
Conclusion Unprovoked VTE is associated with as much as 50%
recurrence over years Ideally these patients should all have
indefinite anticoagulation Extending the anticoagulation from 3
-6months does not give significant benefit Risk of bleeding needs
to be weighed up against the thrombosis risk
Slide 33
Conclusion Gender,D-dimer test and CUS to determine of the vein
is occluded are the best predictors of risk of recurrence Consider
patients wishes New oral agents offer an effective,safe alternative
to warfarin COST Aspirin is less effective than warfarin and has a
significant bleeding risk