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Summary of 2016 CHEST Guidelines: Antithrombotic Therapy
for VTE Disease
Strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A),
moderate- (Grade B) and low- (Grade C) quality evidence
1. Non Cancer patients
i. Direct Oral Anticoagulants (DOAC) is recommended over vitamin
K antagonist (VKA) (Grade 2B)
ii. VKA is recommended over lower molecular weight heparin
(LMWH) (Grade 2C)
iii. LMWH (Grade 2C)
2. Cancer patients
i. LMWH (Grade 2C)
ii. VKA is equivalent to DOAC
3. Proximal DVT of leg, arm or PE
a. Duration of Therapy
i. 3 months for VTE secondary to
1. surgery (Grade 1B)
2. nonsurgical transient risk factor (estrogen therapy,
pregnancy, leg injury, flight.>8 hours) (Grade 1B)
3. unprovoked DVT (isolated distal or proximal) or PE (Grade
a. after 3 months weigh risk versus benefit of
extended therapy
b. patient sex and D-dimer measured 1 month after
stopping anticoagulant therapy can further stratify
the risk of recurrence
i. men have a ~75% (1.75 fold) risk of
recurrence compared to women
ii. positive D-dimer result have double the risk
of recurrence. D-dimer testing will often
influence a female’s decision but not a
male’s decision.
iii. predictive value of 2 risk factors additive
c. first or second unprovoked & high risk of bleeding
(>2 bleeding risk factors)
d. if patient declines extended anticoagulant therapy &
there are no contraindications to aspirin, suggest
indefinite ASA 100mg/day
i. not equivalent to other anticoagulants but
reduced recurrent VTEs in first unprovoked
patients by 1/3 (in patients who completed
3-18 months of anticoagulation)
ii. Lifelong (extended) duration for VTE in the following scenarios:
1. First unprovoked proximal DVT or PE with low (no bleeding
risk factors, see table 11) or moderate (1 risk factor) risk of
bleeding (Grade 2B)
2. Second unprovoked & low (Grade 1B) or moderate (Grade
2B) risk of bleeding
3. Cancer-associated thrombosis irrespective of bleeding risk
factor in patients with active cancer
4. Distal DVT
a. To treat or not to treat?
15% of untreated distal DVT expected to extend into the popliteal
vein & may cause PE
Risk factors for extension & hence favor anticoagulation in
patients with
1. Positive D-dimer
2. Extensive thrombosis
3. Thrombosis close to proximal veins
4. No reversible provoking factor for DVT
5. Active cancer
6. History of VTE
7. Inpatient status
8. Thrombosis that involves the axial (true deep, peroneal,
tibial) veins
9. Severe symptoms
10. High bleeding risk favors surveillance
iii. Without severe symptoms or risk factors, recommend serial
imaging of deep veins for 2 weeks over anticoagulation (Grade
1. Patients at high risk for bleeding are more likely to benefit
from serial imaging
2. Patients who place a high value on avoiding the
inconvenience of repeat imaging & a low value on
inconvenience of treatment & on the potential for bleeding
are likely to choose initial anticoagulation over serial
3. No anticoagulation if thrombus does not extend (Grade 1B)
iv. Anticoagulation if:
1. Severe symptoms or risk factors (Grade 2C)
2. Thrombus extends but remains confined to distal veins
(Grade 2C)
3. Thrombus extends to proximal veins (Grade 2C)
b. Prevention of complications
i. Do not use compression stockings to prevent post-thrombotic
syndrome (Grade 2B)
5. Catheter-Directed Thrombolysis for acute DVT of the leg
i. Proximal DVT
1. Anticoagulant therapy alone over catheter directed
thrombolysis (Grade 2C)
6. IVC in addition to anticoagulation for acute DVT or PE
i. Not recommended (Grade 1B)
7. Sub-segmental PE & no proximal DVT in the legs who have
i. If low risk for recurrent VTE, consider surveillance (serial LE u/s or
UE if central venous catheter) over anticoagulation (Grade 2C)
1. Patient should return for re-evaluation if symptoms persist
or worsen
ii. If high risk for recurrent VTE, consider anticoagulation (Grade 2C)
1. inpatient
2. low mobility
3. active cancer
4. no reversible risk factor
5. low cardiopulmonary reserve
8. Treatment of Acute PE out of hospital
i. Low risk PE, treatment at home or early discharge ok if:
1. Clinically stable with good cardiopulmonary reserve
2. No contraindications such as recent bleeding, severe renal
or liver disease or severe thrombocytopenia (<70K)
3. Expected to be compliant with treatment
4. Patient feels well enough to be treated at home
5. Absence of right ventricular dysfunction or increased
cardiac biomarker levels should discourage treatment out
of hospital
9. Systemic thrombolytic therapy is recommended for patients with
i. Acute PE associated with hypotension (SBP<90 mmHg for 15
minutes) & without high risk of bleeding (Grade 2C)
ii. Acute PE & cardiopulmonary deterioration after starting
anticoagulant therapy but have to yet develop hypotension & low
bleeding risk (Grade 2C)
iii. Use systemic thrombolytic therapy using a peripheral vein over
catheter directed thrombolysis (CDT)
10. Catheter directed thrombolysis is recommended for patients with
i. high risk of bleed
ii. failed systemic thrombolysis or shock that is likely to cause death
before systemic thrombolysis can take effect (eg within hours)
11. Catheter based mechanical disruption/removal may be considered at
centers that have expertise in these modalities (VM has expertise in
catheter directed therapy [thrombolysis and mechanical
disruption/removal]; activate the pulmonary embolism response teamPERT).
12. Anticoagulation alone is recommend over catheter directed
thrombolysis for proximal DVT of the leg
13. UEDVT that involves the axillary or more proximal veins
i. Anticoagulation over thrombolysis (Grade 2C)
14. Management of Recurrent VTE while on anticoagulation therapy
i. Risk factors:
1. Treatment factors
a. Higher risk during 1st week (or month) vs 2nd week
(or month) ie risk diminishes with time
b. Was LMWH used?
c. Patient compliant?
d. VKA sub therapeutic
e. Was anticoagulant therapy prescribed correctly?
f. DOAC Drug Interaction? (For interactions refer to
the anticoagulation manual in VNet)
g. Anticoagulant dose (other than VKA) reduced?
h. Taking other medications that increase risk of
thrombosis (estrogen, cancer chemo)
2. Patient’s Intrinsic Risk
a. Active cancer
b. Antiphospholipid syndrome (under dosing of VKA
due to spurious increases in INR results)
c. Taking other medications that can increase the risk
of thrombosis
ii. If on VKA or DOAC switch to LMWH (Grade 2C)
iii. If on LMWH, increase dose by 25 to 30% (influenced by LMWH
prefilled syringe dose options). Change from once a day to twice a
day dosing. (Grade 2C)
iv. If no reversible cause for recurrent VTE & anticoagulation intensity
cannot be increased because of risk of bleeding, consider vena
caval filter placement (last resort)
Table 1 Risk Factors for bleeding with anticoagulant therapy and estimated risk of
major bleeding in low, moderate and high risk categories
Risk Factors
Age >65 years
Age >75 years
Previous bleeding
Metastatic Cancer
Renal failure
Liver failure
Previous Stroke
Antiplatelet therapy
Poor anticoagulant control
Co-morbidity and reduced functional capacity
Recent surgery
Frequent falls
Alcohol abuse
Non-steroidal anti-inflammatory drug
Categorization of Risk of Bleeding
Estimated absolute risk of major bleeding
Low risk
Moderate risk
High risk
(0 risk factors)
(1 risk factor)
(> 2 risk factors)
Anticoagulation 0-3
Baseline risk (%)
Increased risk (%)
Total risk (%)
after firs 3 months
Baseline risk (%)
Increased risk (%)
Total risk (%)
Table 2- Recommended Duration of Secondary Prevention of VTE
Length of Therapy
ACCP 2016
3 Months
Provoked distal or proximal
DVT or PE (surgery,
estrogen therapy,
pregnancy, leg injury,
flight>8 hours)
First unprovoked proximal
or distal DVT or PE with
high risk of bleeding
At least 3 months
Extended Therapy
Second unprovoked VTE
and high risk of bleeding
First unprovoked DVT or
Evaluate for risk-benefit of
extended therapy at 3
First unprovoked proximal
DVT or PE and low or
moderate bleeding risk
Second unprovoked VTE
and low risk of bleeding
Second unprovoked VTE
and moderate risk of
DVT or PE and active
cancer and low and
moderate risk of bleeding
DVT or PE and active
cancer and high risk of
1. Kearon C, Akl E, et al. Antithrombotic Therapy for VTE Disease CHEST Guideline and Expert
Panel Report. CHEST 2016; 149(2): 315-352.