CHEST-20121: High Points and Pearls2
Alan Brush, MD, FACP, Chief, Anticoagulation Management Service
Harvard Vanguard Medical Associates
Language: “suggestions” vs. “recommendations”: statements in CHEST-2012 set up as
suggestions and recommendations for and against; recommendations have stronger evidence
basis. There is general theme of weighing clotting risks of patient against bleeding risk of
treatment in all situations. Where there is a clash, the bleeding risk commonly takes precedence;
patient preference should be considered foremost when management is not clearly beneficial.
However, the patient or responsible caregiver must be part of this decision process.
Evidence-based Management of Anticoagulation
1. Loading dose initiation of warfarin: For healthy patients with DVT/PE or otherwise needing
LMWH, okay to start with loading dose of 10mg x 2 days; benefit: earlier rise of INR to
target range, but consider risks. Although suggested in CHEST-2012, we do not favor this
approach, and have already seen some unexpected early INR rises. However, AMS
managers will likely see patients discharged from the hospital on these doses.
2. Pharmacogenetic testing: not recommended.
3. Overlap with LMWH: Start warfarin on day 1 or 2 when LMWH used; no reason to wait
longer – just delays reaching therapeutic range without increasing safety.
4. Monitoring frequency: For stable patients, may extend INR follow-up date up to 12 weeks
per CHEST-2012; we permit up to 8 weeks in the AMS.
5. Management of single out of range result up to 0.5 above or below therapeutic range: if
patient previously stable, no change in dose required; brief hold or make-up dose(s) without
change in usual dosing often appropriate.
6. Bridging with LMWH for stable patients with single low INR: CHEST-2012 suggests against
bridging. Practically speaking this suggestion applies to most patients, with exceptions of
highest risk patients (e.g. recently cardioverted, prior event when INR low, and patients with
very low INR values and relatively recent event).
7. Use of vitamin K for stable patients with single high INR: CHEST-2012 suggests against
routine use of vitamin K unless INR >10) we recommend vitamin K when INR is lower but
patient is at high risk of bleeding. Intermediate risk patients may benefit from use of low
dose OTC vitamin K (200 mcg). Note current cost issues of prescribed vitamin K; however,
not many patients want to take 50 OTC tablets to reach 5 mg dosing!
1
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice
Guidelines; 2012
2
Presented February 28, 2013 to Harvard Vanguard Medical Associates anticoagulation managers and physician consultants as a review of
management suggestions and recommendations in CHEST-2012. The review includes some variations from the original documents related to
the specific needs of our program and practice population, and should not be considered applicable to other anticoagulation management
programs or individual clinician’s care.
8. Self-testing and self-management: considered reasonable standard of care when patients
demonstrate competence; we will support in a similar fashion to patients tested by VNA and
other external services. However, patients relying on self-management should not be part of
AMS.
9. Drug interactions to avoid: all NSAIDS and various antibiotics; use antiplatelet agents only
when benefit clearly is known or is highly likely to be greater than harm from bleeding, such
as patients with mechanical valves, patients with acute coronary syndrome, or patients with
recent coronary stents or bypass surgery. Note: all AMS patients taking aspirin require this
assessment by AMS clinician. When not clearly indicated, it should be brought to the
attention of the PCP and/or AMS consultant.
10. Optimal therapeutic INR ranges: should be 2.0-3.0 for most patients, 2.5-3.5 for certain highrisk patients. Patients awaiting cardioversion should be treated toward the high end of the
2.0-3.0 range. Note: patients wishing some long-term prevention of DVT/PE but unable to
test at usual intervals or having increased bleeding risks may in some cases use 1.5-2.0 goal
range (note: diverges from CHEST). Aspirin 81mg daily would be even less burdensome for
the patient although less effective than this low intensity anticoagulation
(http://www.nejm.org/doi/full/10.1056/NEJMoa1114238#Discussion). Note: all other ranges
require clinical justification beyond clinician personal preference, with rationale documented
in chart and approved by AMS physician consultant.
11. Dose Management of Subcutaneous (SC) UFH for DVT/PE: use weight-adjusted dosing (first
dose 333 units/kg, then 250 units/kg twice daily) without monitoring; may apply to
hemodialysis patients and rare situations when patients unable to afford enoxaparin.
12. Fondaparinux Dose Management by Weight: For patients with VTE and body weight over
100 kg, increase fondaparinux from the usual 7.5 mg to 10 mg daily.
13. VKA-associated major bleeding: when available, patient should receive four-factor
prothrombin complex concentrate rather than with plasma, in addition to vitamin 5-10 mg by
slow IV injection. Note: if oral vitamin K immediately available, no harm in having the
patient take 5 mg right away before going to the ERs, and in fact can only help the situation
given potential delays in treatment.
Prophylaxis for Higher Risk Patients in the Ambulatory Setting
1. Patients with Cancer but No Other Risk Factors for VTE: CHEST suggests against use of
LMWH and recommends against use of VKAs. This management applies regardless of the
presence of a central venous catheter.
2. Patients with Solid Tumors and Additional Risk Factors for VTE (e.g. previous venous
thrombosis, immobilization, hormonal therapy, and angiogenesis): LMWH or LDUH
suggested if bleeding risk low.
3. Chronically immobilized patients residing at home or NH; CHEST suggests against routine
use of thromboprophylaxis.
4. Persons Traveling Long-Distance: for long distance travelers at increased risk of VTE,
CHEST suggests frequent ambulation, calf muscle exercise, or sitting in an aisle seat when
feasible, and use of GCS at 15-30 mm Hg of pressure at the ankle. In the absence of risk
factors, CHEST suggests against use of GCS, and in general suggests against use of aspirin
and anticoagulants.
5. Persons With Asymptomatic Thrombophilia without previous history of VTE: CHEST
recommends against the long-term daily use of mechanical or pharmacologic
thromboprophylaxis to prevent VTE
Prevention of VTE in Orthopedic Surgery Patients
1. Patients Undergoing Major Orthopedic Surgery: Total Hip Arthroplasty (THA), Total Knee
Arthroplasty (TKA), and Hip Fracture Surgery (HFS): treat at least 10 to 14 days, ideally up
to 35 days.
a. TKA/THA: use either LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, lowdose unfractionated heparin (LDUH), adjusted-dose VKA, aspirin, or an intermittent
pneumatic compression device (IPCD); LMWH is preferred option. IPCD in addition to
an antithrombotic agent preferred during hospitalization.
b. HFS: same as above, except apixaban, dabigatran, and rivaroxaban not included.
c. When there is increased bleeding risk, IPCD suggested over pharmacologic treatment.
d. When injections and/or IPCD declined or infeasible, apixaban or dabigatran preferred
over VKA and rivaroxaban.
e. When all of above declined or contraindicated, no prophylaxis suggested over IVC filter.
2. Patients with Isolated Lower-Leg Injuries Distal to the Knee: Despite need for
immobilization, no thromboprophylaxis suggested. Obviously, previous history of the
patient should be considered.
Perioperative Management of Antithrombotic Therapy
1. Interruption of VKAs before Surgery: VKAs should be stopped 5 days before surgery (longer
if high-risk surgery and/or INR starting at higher therapeutic level. Make sure you know the
patient’s most recent up to date INR before making a recommendation.
2. Resumption of VKAs after Surgery: VKA should be resumed 12 to 24 hours after surgery
assuming adequate hemostasis.
3. Bridging Anticoagulation During Interruption of VKA Therapy:
a. Bridging suggested for high-risk patients, including patients with a mechanical heart
valve, high-risk atrial fibrillation, or VTE at high risk for thromboembolism. Note:
patients must buy in – those who place a higher value on avoiding bleeding than postoperative thromboembolism may decline bridging.
b. Bridging suggested against for patients with a mechanical heart valve, atrial fibrillation,
or VTE at low risk for thromboembolism.
c. Decision based on individual patient and surgery-related factors for patients at
intermediate risk for thromboembolism.
d. Note that all of these decisions carry a “suggestion” rather than “recommendation”.
Thus, there is room for specific clinical issues and patient preferences to sway the
decision.
4. Perioperative Management of VKA-Treated Patients Who Require Minor Procedures
a. For minor dental procedure, continuing VKAs with co-administration of an oral
prohemostatic agent or stopping VKAs 2 to 3 days before the procedure suggested
instead of alternative strategies.
b. For minor dermatologic procedures, continuing VKAs around the time of the procedure
and optimizing local hemostasis suggested.
c. For cataract surgery, continuing VKAs around the time of the surgery suggested. MEEI
ophthalmologists will perform uncomplicated cataract surgery with an INR below 3.0.
Note that complicated surgery, such as combination of glaucoma and cataract surgery,
does not fall into this category.
5. Patients taking Aspirin Undergoing a Minor Dental, Dermatologic, or Ophthalmologic
Procedure: continuing aspirin suggested for patients requiring secondary prevention of CV
disease or at moderate to high risk of CVD; stopping aspirin 7 to 10 days before the
procedure suggested for patients at low risk of CVD.
6. Patients Undergoing Coronary Artery Bypass Graft Surgery: continuing aspirin suggested;
in patients receiving dual antiplatelet therapy, stopping clopidogrel/prasugrel 5 days before
the procedure suggested.
7. Surgical Patients with Coronary Stents: deferring surgery for at least 6 weeks after
placement of a bare-metal stent and for at least 6 months after placement of a drug-eluting
stent suggested over undertaking surgery within these timeframes. If surgery cannot be
deferred for these durations, continuing dual anti-platelet therapy suggested. Patients may
decline to continue dual antiplatelet therapy based on potential increased risk of bleeding.
8. Perioperative Use of IV UFH: when used for bridging, IV UFH should be stopped 4 to 6
hours before surgery.
Antithrombotic Therapy for VTE Disease
1. Initial anticoagulation for patients with acute DVT of the leg
a. Treat immediately with LMWH when clinical suspicion is high or when expected delay
of diagnostic tests is >4 hours.
b. If clinical suspicion is low, wait for the results of diagnostic tests, assuming results are
expected within 24 hours
2. Anticoagulation in patients with isolated distal DVT
1. In patients with acute isolated distal DVT of the leg without severe symptoms or risk
factors for extension, serial imaging for 2 weeks suggested over initial anticoagulation.
2. In patients with acute isolated distal DVT of the leg and severe symptoms or risk factors
for extension, initial anticoagulation suggested over serial imaging.
3. Anticoagulation in patients with extensive superficial vein phlebitis: treatment with
prophylactic dose anticoagulation recommended over no treatment, and fondaparinux
suggested over LMWH.
4. Patients with acute DVT of the leg treated with LMWH: once daily administration suggested,
but only applies when the approved once-daily regimen uses the same daily dose as the
twice-daily regimen (i.e., the once-daily injection contains double the dose of each twicedaily injection). This recommendation has no practical application in AMS, since cannot be
done with most LMWH options. Unfortunately, this statement has been misunderstood in
several anticoagulation management programs. Tinzaparin (Innohep) is the only low
molecular weight heparin currently FDA approved for treatment for acute pulmonary
embolism that is dosed once daily. Note that fondaparinux (Arixtra), a non-heparin factor Xa
inhibitor, is approved for treatment of acute PE and can be dosed once daily.
5. Vena Cava Filters for the initial treatment of patients with DVT:
Clinical situation
Recommendation
DVT with no contraindication to
Use anticoagulation without the addition of a
anticoagulation or already on
filter
anticoagulation
DVT with contraindication to
Use filter
anticoagulation
DVT with contraindication to
Complete conventional course of
anticoagulation that has resolved (e.g.
anticoagulation
resolution of bleeding risk)
Note: Having a permanent IVC filter is not in itself an indication for extended course of
anticoagulation.
6. Early Ambulation of Patients with Acute DVT
a. In patients with acute DVT of the leg, early ambulation suggested over initial bed rest –
at last, the logic of avoiding bedrest, which tends to provoke venous thrombosis, has
prevailed over the age-old standard of DVT management!
b. If edema and pain are severe, ambulation may need to be deferred, and compression
therapy should be used.
7. Duration of Long-term Anticoagulant Therapy
Indication
Proximal DVT of the leg provoked by
surgery
Proximal DVT of the leg provoked by
a nonsurgical transient risk factor
Duration of anticoagulation
3 months recommended over shorter period,
longer period (6-12 months), or extended therapy
3 months recommended over shorter period,
longer period (6-12 months) or extended therapy
if high bleeding risk; suggested over other
options if low or moderate bleeding risk
Isolated distal DVT of the leg
provoked by surgery or by a nonsurgical transient risk factor
Unprovoked DVT of the leg (isolated
distal or proximal)
First VTE that is unprovoked proximal
DVT of the leg with low or moderate
bleeding risk
First VTE that is unprovoked proximal
DVT of the leg with high bleeding risk
First VTE that is unprovoked isolated
distal DVT of the leg with low or
moderate bleeding risk
First VTE that is unprovoked isolated
distal DVT of the leg with high
bleeding risk
Second unprovoked VTE with low
bleeding risk
Second unprovoked VTE with
moderate bleeding risk
Second unprovoked VTE with high
bleeding risk
DVT of the leg and active cancer with
low or moderate bleeding risk
DVT of the leg and active cancer with
high bleeding risk
3 months suggested over shorter period (if
decision to treat has occurred) and recommended
over longer period (6-12 months) or extended
therapy
At least 3 months recommended over shorter
duration. Evaluate risks/benefits of extended
therapy after 3 months
Extended therapy suggested over 3 months of
therapy
3 months of therapy recommended over extended
therapy
3 months suggested over extended therapy
3 months recommended over extended therapy
Extended therapy recommended over 3 months of
therapy
Extended therapy suggested over 3 months of
therapy
3 months suggested over extended therapy
Extended therapy recommended over 3 months of
therapy
Extended therapy suggested over 3 months of
therapy
Note: in all patients who receive extended anticoagulant therapy, the continuing use of
treatment should be reassessed at periodic intervals (e.g., annually).
8. Choice of anticoagulant regimen for long-term therapy without vs with cancer
Presence of cancer
No cancer present
Presence of cancer
Duration of anticoagulation
VKA therapy suggested over LMWH for longterm therapy; if not treated with VKA, LMWH
suggested over dabigatran or rivaroxaban for longterm therapy
LMWH suggested over VKA therapy; if not
treated with LMWH, VKA suggested over
dabigatran or rivaroxaban for long-term therapy
Other factors involved in the choice of treatment include the individual patient’s tolerance for
daily injections, need for laboratory monitoring, treatment costs, and presence or absence of
renal dysfunction.
9. Choice of anticoagulant regimen for extended therapy: Use of the same agent used in the
first three months suggested for extended therapy.
10. Treatment of patients with asymptomatic DVT of the leg: Treatment of asymptomatic
incidentally discovered DVT of the leg should follow same treatment principles as
symptomatic DVT.
11. Compression Stockings and IPCD to Prevent and Treat PTS:
a. Compression stockings suggested for symptomatic DVT of the leg to prevent PTS (postthrombotic or post-phlebitic syndrome). They should be worn for 2 years, longer if found
to be helpful. Note that patients favoring convenience and less concerned with PTS will
likely decline stockings.
b. In the presence of PTS, a trial of compression stockings suggested.
c. In the presence of PTS not responsive to compression stockings, a trial of an intermittent
compression device suggested. Pharmacologic treatment not recommended.
12. Parenteral Anticoagulation Prior to Receipt of the Results of Diagnostic Work-up for PE
Clinical Suspicion of Pulmonary
Embolism
High
Intermediate
Low
Suggested Action
Treatment with parenteral anticoagulants
suggested over no treatment while awaiting
the results of diagnostic tests
Treatment with parenteral anticoagulants
suggested over no treatment if the results of
diagnostic tests are expected to be delayed
for more than 4 hours
Awaiting the results of diagnostic tests,
assuming expected within 24 hours,
suggested over treatment while awaiting
results
13. Choice of Initial Parenteral Anticoagulant Regimen in Patients with PE
a. In patients with acute PE, LMWH or fondaparinux suggested over IV UFH and over SC
UFH.
b. In patients with acute PE treated with LMWH, once-daily injections suggested over
twice-daily injections, provided that the approved once-daily regimen uses the same daily
dose as the twice-daily regimen (i.e., the once-daily injection contains double the dose of
each twice-daily injection). Unfortunately, as above, this option does not apply to
enoxaparin, so we should NOT be using the once daily enoxaparin regimen for acute
treatment of PE.
Antithrombotic Therapy for Nonrheumatic (nonvalvular) Atrial Fibrillation
CHADS2
Score
Suggestion or Recommendation
0
1
≥2
No treatment recommended over anticoagulation or antiplatelet agent; if
treatment preferred by patient, aspirin suggested over VKA or
combination aspirin plus clopidogrel
Oral therapy recommended over no treatment, and anticoagulation
suggested over aspirin or combined aspirin plus clopidogrel
Oral anticoagulation recommended over no treatment, aspirin or combined
aspirin plus clopidogrel
Note: in CHEST-2012, dabigatran suggested over warfarin for all nonvalvular atrial
fibrillation situations where anticoagulation recommended! Newer agents were not
considered in CHEST-2012, as they had not been approved at the time of the conference.
Antithrombotic and Thrombolytic Therapy for Acute Ischemic Stroke
Condition
Acute stroke
Acute stroke and restricted
mobility
Noncardioembolic
ischemic stroke or TIA
History of stroke or TIA
and atrial fibrillation
Recommendation
For IV r-tPA if treatment can
be initiated within 3 h,
perhaps 4.5 h of symptom
onset. For early aspirin 160
to 325 mg
Suggestion
For use of intraarterial r-tPA
in patients ineligible for IV
tPA if treatment can be
initiated within 6 h; against
use of mechanical
thrombectomy
For prophylactic-dose heparin
or IPC devices; against use of
elastic compression stockings
For long-term aspirin (75-100 For use of clopidogrel or
mg once daily), clopidogrel
aspirin/extended-release
(75 mg once daily),
dipyridamole rather than
aspirin/extended release
aspirin or cilostazol
dipyridamole (25 mg/200 mg
bid), or cilostazol (100 mg
bid) rather than no
antiplatelet therapy, oral
anticoagulants, combined
clopidogrel plus aspirin, or
triflusal
For oral anticoagulation over
no antithrombotic therapy,
aspirin, or combined aspirin
and clopidogrel
VTE, Thrombophilia, Antithrombotic Therapy, and Pregnancy
Condition
Recommendation
Prevention and treatment of For use of LMWH, not UFH
VTE in pregnant women
Pregnant women with acute
VTE
Women with APLA
syndrome and three or
more pregnancy losses
For antepartum
administration of
prophylactic or intermediatedose UFA or prophylactic
LMWH in addition to lowdose aspirin (75-100 mg/d)
Suggestion
Continue anticoagulants at
least 6 weeks postpartum
(and at least total of 3
months)