Preventing Venous
Thromboembolism in Surgical
and Medical Patients
Susan Kahn MD MSc
Director, JGH Thrombosis Program
March 2011
Learning Objectives


To understand the importance of
thromboprophylaxis in hospitalized patients
To be aware of the most recent ACCP consensus
guidelines on venous thromboembolism (VTE)
prevention
2008
VTE: a very important and costly
complication of hospitalization

70% of all VTE in the community is attributable
to recent hospitalization!!
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2nd most common cause of excess length of stay
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3rd most common cause of excess mortality
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Doubles LOS and costs
Autopsy:
Fatal Pulmonary Embolism
Rationale for VTE prophylaxis
1.
2.
3.
High frequency in most hospitalized
patients
Adverse consequences of unprevented VTE
are numerous (PE death, PE, recVTE, PTS,
complications of AC)
Thromboprophylaxis is effective, safe and
cost-effective
Risk of DVT in Hospitalized Patients
(no thromboprophylaxis, and routine screening for DVT)
Patient group
DVT prevalence, %
Medical patients
10-20
General Surgery
15-40
Major gynecologic surgery
15-40
Major urologic surgery
15-40
Neurosurgery
15-40
Stroke
Hip, knee arthoplasty, hip
fracture
Major trauma
20-40
40-60
Spinal cord injury
60-80
40-80
Moderate
risk
High risk
Fig 1 Relative risk of venous thromboembolism by time since inpatient surgery and since
day case surgery
Sweetland, S. et al. BMJ 2009;339:b4583
Copyright ©2009 BMJ Publishing Group Ltd.
Thromboprophylaxis
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What is the evidence?…
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Hundreds of RCTs show that
thromboprophylaxis reduces:
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DVT
PE
Fatal PE
All-cause mortality
Costs
Thromboprophylaxis
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Ranked number 1 of >75 strategies to
improve patient safety in hospitalized
patients
More than 25 published evidence-based
guidelines since 1986 show clear evidence
of benefit and safety
ACCP Guidelines: Every hospital should
have a formal thromboppx protocol
11
Thromboembolism risk groups
addressed by ACCP guidelines
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General surgery
Vascular surgery
Gynecologic surgery
Urologic surgery
Thoracic surgery
Laparoscopic surgery
CABG
Knee arthoplasty
Hip arthoplasty
Knee arthoscopy
Hip fracture surgery
Spine surgery
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Lower extremity injuries
Neurosurgery
Major trauma
Spinal cord injuries
Burn patients
Medical patients
Cancer patients
CVCs
Critical care patients
Long distance travel
Geerts-Chest 2008;133:381S
Recommendation Grades
Grade 1 (strong recommendation)
Desirable effects clearly outweigh undesirable effects or vice versa
(secondary side effects, costs, patient inconvenience)
 Can apply to most patients in most to many circumstances

Grade 2 (weak recommendation: “suggestion”)
Desirable and undesirable effects closely balanced
 Best action may differ depending on patient circumstances or
society values

Guyatt GH et al. Grades of recommendation for antithrombotic agents. Chest 2008; 133:123S-131S
Quality of Evidence
QUALITY
METHODOLOGY
Strong (A)
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Moderate (B)
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Weak (C)
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One or more well-designed and wellexecuted RCT
 Well-done observational studies with very
large effects (RRR>=80%)
RCTs with important limitations
 Well-done observational studies with large
effects (RRR>=50%)

RCTS with very serious limitations
Observational studies yielding modest effects
Guyatt GH et al. Grades of recommendation for antithrombotic agents. Chest 2008; 133:123S-131S
Choose best thromboprophylaxis for:
• 80 yo F obese post hip # surgery
• 35 yo M appendectomy
• 72 yo F for ovarian cancer resection, recent
GI bleed
• 68 yo for colon cancer resection; MVR with
prior embolic TIA
PREVENTION OF VTE

GENERAL RECOMMENDATIONS (I)

Mechanical methods of thromboprophylaxis be used primarily in patients at
high risk of bleeding (Grade 1A), or possibly as an adjunct to
anticoagulant-based thromboprophylaxis (Grade 2A).
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Graduated compression stockings
Intermittent pneumatic compression
Venous foot pump
Increase venous outflow and/or
reduce venous stasis
Recommend against use of aspirin alone as thromboprophylaxis for any
patient group (Grade 1A)
Renal function should be considered when making decisions about the use
and/or dose of LMWH, fondaparinux, and other ACs cleared by the kidney,
especially in elderly patients, diabetics, or if high risk of bleeding. One of
the following is recommended (Grade 1B):
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Avoid use of AC that bioaccumulates with renal impairment, OR
Use lower dose OR
Monitor drug level or AC level
Geerts WH et al. Prevention of venous thromboembolism Chest 2008;133:381S-453S.
Mechanical prophylaxis
Advantages
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Can be used in high risk
bleeding patients
Efficacy demonstrated
in a number of patient
groups
May enhance
effectiveness of AC
thromboprophylaxis
May reduce leg swelling
Disadvantages
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Not as intensively studied as
pharmacologic strategies (fewer
studies and smaller)
No established standards
Many devices never tested in RCTs
Almost all RCTs unblinded
In high risk groups, less effective then
AC thromboprophylaxis
Greater effect on reducing calf DVT
than proximal DVT
Effect on PE or death unknown
Compliance by patients and staff often
poor
Cost associated with purchase,
storage, dispensing and cleaning,
ensuring optimal compliance
Anti-embolic (TED)
stocking
IPC: Sequential
Compression
Device (SCD)
IPC: Foot pump
VTE prophylaxis: Risk groups and
recommended thromboppx
Levels of Risk
Low risk
- Minor surgery in mobile patients
- Medical patients who are fully
mobile
Moderate risk
- Most general, open gynecologic or
urologic surgery patients
- Medical patients, bed rest or sick
- Moderate VTE risk plus high
bleeding risk
High risk
- Hip or knee arthroplasty, HFS
- Major trauma, SCI
- High VTE risk plus high bleeding risk
Approximate DVT Risk Without
Thromboprophylaxis
<10 %
10–40 %
Suggested Thromboprophylaxis
Options‡
No specific thromboprophylaxis and
“aggressive” ambulation
LMWH (at recommended doses),
LDUH bid or tid,
Fondaparinux
Mechanical thromboprophylaxis
40–80 %
LMWH (at recommended doses),
Fondaparinux,
Oral vitamin K antagonist (INR 2–3)
Mechanical thromboprophylaxis
Geerts WH et al. Prevention of venous thromboembolism Chest 2008;133:381S-453S.
UFH BID vs. TID
Patient-specific high risk
features for VTE
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Previous VTE
Increasing age
Obesity
Immobility, lower-extremity
paresis
Cancer (active or occult)
Cancer therapy (hormonal,
chemotherapy, angiogenesis
inhibitors, radiotherapy)
Venous compression (tumor,
hematoma, arterial abnormality)
Central venous catheterization
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Acute medical illness
Pregnancy and the postpartum period
Estrogen-containing oral
contraceptives or hormone
replacement therapy
Selective estrogen receptor modulators
Erythropoiesis-stimulating agents
Inflammatory bowel disease
Nephrotic syndrome
Myeloproliferative disorders
Paroxysmal nocturnal hemoglobinuria
Inherited or acquired thrombophilia
Trauma (major trauma or lowerextremity injury)
Geerts WH et al. Prevention of venous thromboembolism Chest 2008;133:381S-453S.
Low risk of VTE
Patient group:
•
•
Medical – fully mobile, brief admission
Surgical – procedure < 30 min, mobile,
and no additional VTE risk factors
•
•
Laparoscopic surgeries (gynecologic, gen Sx)
Transurethral procedures
Endoscopic procedures
Recommendations:


No specific prophylaxis
mobilization
Geerts-Chest 2008;133:381S
Moderate Risk: General Surgery
Recommendation/Suggestion
Major procedure for
benign disease
Major procedure for
cancer related
surgery
Major and multiple
RFs for VTE
High risk of bleeding
Grade
LMWH
LDUH bid
Fondaparinux
1A
LMWH
LDUH tid
Fondaparinux
1A
LMWH + mechanical method
LDUH tid + mechanical method
Fondaparinux + mechanical method
1C
Properly fitted GCS or IPC .
When risk of bleeding decreases,
AC be substituted or added
1A
1C
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For most patients, prophylaxis until discharge (and not mobilization) (grade 1A)
For selected high risk general surgery patients (cancer surgery, previous VTE),
consider LMWH for 28 days (grade 2A)
ACCP Antithrombotic and Thrombolytic therapy: CHEST 133, June2008
Moderate Risk: Gynecologic Surgery
Recommendation/Suggestion
Entirely laparoscopic
surgery in whom there
are additional VTE risk
factors
Major open procedure
for benign disease
Major open
procedure for cancer
or multiple RFs for
VTE
Grade
LMWH
LDUH bid
IPC
GCS
1C
LMWH
LDUH bid
IPC just before surgery and used
continuously while patient not ambulating
1A
1A
1C
LMWH
LDUH tid
IPC just before surgery and used
continuously while patient not ambulating
Any of above pharmacologic strategies
with GCS or IPC
1A
1A
1A
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1C
For most patients, prophylaxis until discharge (not mobilization) (grade 1A)
For selected high risk general surgery patients (cancer surgery, previous
VTE), consider LMWH for 28 days (grade 2C)
Moderate Risk: Urologic Surgery
Major open procedure
Major open procedure
at high risk of bleeding
Recommendation/Suggestion
Grade
LDUH bid or tid
IPC just before surgery and used
continuously while patient not ambulating
LMWH
Fondaparinux
Any of above pharmacologic methods
with optimal use of GCS or IPC
1B
1B

Properly fitted GCS or IPC .
When risk of bleeding decreases,
pharmacologic thromboprophylaxis be
substituted or added

1C
1C
1C
1A
1C
For most patients, prophylaxis until discharge (and not mobilization) (grade 1A)
For selected high risk general surgery patients (cancer surgery, previous VTE),
consider LMWH for 28 days (???)
Moderate Risk: Laparoscopic Surgery
Recommendation/Suggestion
Routine
Additional VTE risk
factors
Grade
No prophylaxis
Mobilization
1B
LMWH
LDUH bid
Fondaparinux
Mechanical methods
1C
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• Considerable uncertainty
•VTE rates appear to be low: 0%-5% screened DVT; 0.03%-0.06%
symptomatic VTE
•Pneumoperitoneum and reverse Trendelenburg may impact VTE risk
• Only 3 RCTs (LMWH vs placebo or mechanical) of thromboprophylaxis (very
small studies, heterogenous, venogram endpoints): no difference
•Society of American Gastrointestinal Endoscopic Surgeons recommends the
use of similar thromboprophylaxis options as for the equivalent open surgical
procedures.
Moderate Risk: Bariatric Surgery
Recommendation/Suggestion
Inpatient bariatric
surgery
LMWH
Higher doses
LDUH tid
than usual
Fondaparinux
Mechanical methods with any of the
above pharmacologic methods
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Grade
1C
•VTE rates vary widely (0.2%-2%); Fatal PE (0.2%)
•Optimal dose, timing and duration unknown
• Only 1 small RCT of thromboprophylaxis (nadroparin 5700 IU vs
9500 IU; no difference (no events at 3 and 6 months))
For most patients, prophylaxis until discharge (and not mobilization) (grade 1A)
For selected high risk general surgery patients (cancer surgery, previous VTE),
consider LMWH for 28 days (???)
Moderate Risk: Neurosurgery
Recommendation/Suggestion
Major neurosurgery
If high risk of
thrombosis (eg. cancer)
Grade
Optimal use of IPC
Post-operative LMWH
LDUH
1A
2A
2B
Mechanical method be combined with
LDUH or post-operative LMWH
2B
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• Intracranial (vs spinal), malignancy, prolonged procedures, leg weakness are
important RFs for VTE in neurosurgery
• Glioma patients carry a post-operative VTE risk of 15-25% at 3 months
• Mechanical thromboprophylaxis most studied in this population (RRR 68%
compared to no thromboprophylaxis)
• GCS alone not as effective as IPC
• GCS alone is not as effective as combination LDUH and GCS
• Concerns of bleeding with preoperative or early postoperative LMWH in
craniotomy patients (2-fold higher risk of bleeding at any site vs. mechanical
or no thromboprophylaxis)
High risk of VTE:
Elective hip replacement
Situation
Recommendation
Grade
LMWH

 High risk dose 12 h pre-op or 12-24 h
post-op
 Half dose 4-6 h post-op then high dose
following day
All THR patients
1A
Fondaparinux 2.5 mg 6-24 h post-op
VKA INR 2.5
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Use of:
ASA or Dextran or LDUH
• GCS or VFP
•
Do not use as sole method of
thromboprophylaxis
2A
VFP or IPC
If high risk of bleeding
When bleeding risk decreases

1A
Add or substitute pharmacological
prophylaxis
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1C
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Geerts-Chest 2008;133:381S
High risk of VTE:
Hip fracture surgery
Situation
Recommendation
Grade
HFS: routine prophylaxis
Fondaparinux
LMWH
Adjusted VKA INR 2.5
LDUH
Use of ASA
Against use of ASA alone
1A
If surgery delayed
LMWH or LDUH during time between
admission and surgery
1C
VFP (Venous foot pump) or IPC
1A
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If high risk of bleeding
When bleeding risk decreases
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Add or substitute pharmacological
prophylaxis
1A
1B
1B
1B
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1C
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Geerts-Chest 2008;133:381S
High risk of VTE:
Elective knee replacement
Situation
Recommendation
Grade
Routine prophylaxis
Fondaparinux
LMWH
Adjusted VKA INR 2.5
1A
1A
1A
Alternative option
Optimal use of IPC
1B
Use of:
Against use as only method of
thromboprophylaxis
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•
ASA or LDUH
If high risk of bleeding
When bleeding risk decreases

IPC
VFP
Add
or substitute pharmacological
prophylaxis
1A
1B
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1A
1B
1C
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Geerts-Chest 2008;133:381S
Duration of prophylaxis and
orthopaedics
Situation
THR, TKR, HFS
THR
Recommendation
At least 10 days
1A
Extend from 10 up to 35 days
1A
LMWH
• VKA
• Fondaparinux
1A
•1B
•1C
•
•
Extend from 10 to up to 35 days
TKR
LMWH
• VKA
• Fondaparinux
Fondaparinux
• LMWH
• VKA
•
1B
1C
•1C
•1C
•
•
Extend from 10 to up to 35 days
HFS
Grade
1A
1A
• 1C
• 1C
•
Geerts-Chest 2008;133:381S
Knee arthoscopy
Situation
Suggestion
Grade
No additional VTE risk
factors
No prophylaxis
Early mobilization
2B
Additional risk factors
LMWH
1B
Geerts-Chest 2008;133:381S
RECORD3: TKR patients, 10 days Rx
Rivaroxaban: oral direct Factor Xa inhibitor
20
Total VTE
RRR 49%
Enoxaparin
40 mg od
Rivaroxaban 10 mg od
Incidence (%)
15
10
Major VTE
5
Symptomatic VTE
RRR 62%
18.9%
0
9.6%
2.6%
1.0%
RRR 65%
2.0%
0.7%
Major bleeding
NS
0.5%
0.6%
RECORD1: THR patients, 35 days Rx
5
Rivaroxaban 10 mg once daily
Enoxaparin 40 mg once daily
Total VTE
Incidence (%)
4
RRR 70%
3
Major VTE
RRR 88%
2
Symptomatic VTE
Major bleeding
1
3.7%
0
1.1%
2.0%
0.2%
0.5%
0.3%
0.1%
0.3%
Patients with Renal impairment
 No dose adjustment required in patients with mild
(CrCl >50 mL/min) or moderate (CLCR: 30-49 mL/min)
renal impairment
 Subjects with CLCR <30ml/min excluded from clinical
trial program. Limited clinical data: rivaroxaban
levels sig increased in such patients
Moderate risk: Patients hospitalized for a medical condition
Recommendation/suggestion
1.
2.
3.
Congestive heart failure
Severe respiratory disease
Confined bed rest with one
or more of:
•
•
•
•
Active cancer
Previous VTE
Acute neurologic disease
Inflammatory bowel
disease
For some patients if
contraindication to
anticoagulation prophylaxis
LMWH
or
 LDUH bid
or
Fondaparinux
Grade
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Mechanical thromboprophylaxis with
GCS or IPC
1A
1A
50-70% of symptomatic VTE and 70-80% of fatal PE occur in hospitalized medical
patients
Geerts-Chest 2008;133:381S
Moderate risk: Patients hospitalized for a medical
condition
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Optimal duration remains unclear (EXCLAIM
study)
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4000 ill medical patients
Enoxaparin 6-14 days vs. 28 days
VTE at 1 month (enox 4.9% vs. extended enox 2.8%)
(p<0.05)
Major bleeding (1.1% extended enox vs. 0.3% enox)
(p<0.05)
No impact on all-cause mortality
Geerts-Chest 2008;133:381S
Moderate risk: Critical Care patients
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VTE risk varies considerably
Most ICU patients have multiple risk factors
Some acquired RFs include:
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pharmacologic paralysis, CVC lines, surgical procedures
sepsis, mechanical ventilation
vasopressor use, renal dialysis
Also, have risk factors for bleeding
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Trauma
Surgery
Low platelets
Liver disease
Geerts-Chest 2008;133:381S
Moderate risk: Critical Care patients
Recommendation/Suggestion
Grade
Any admitted patient
Assessment for VTE risk
Routine prophylaxis in most
1A
Moderate risk of VTE
(medically ill or
postoperative general
surgery)
LMWH or LDUH bid
1A
High risk of VTE (major
trauma or orthopedic
surgery)
LMWH (extrapolate from major trauma
and orthopedics population)
1A
GCS and / or IPC
1A
If high risk of bleeding
When bleeding risk
decreases

Add or substitute LMWH / LDUH
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1C
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Geerts-Chest 2008;133:381S
High risk: Hospitalized cancer patients
Recommendation/Suggestion
Surgery
Appropriate for the type of surgery
LWMH=LDUH tid

Grade
1A
Bedridden with an acute Thromboprophylaxis as for other high
risk medical patients
medical illness
1A
Chemotherapy or
hormonal therapy
1C
Indwelling CVCs
Ambulating, nonhospitalized
No role for prophylaxis

No role for prophylactic doses of LMWH
or mini-dose warfarin
1B
No role for prophylaxis to improve
survival
1B
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Geerts-Chest 2008;133:381S
Basic principles
•
•
•
•
•
•
•
•
Think about VTE prophylaxis in each and every patient
Assess risk of VTE
Determine if contraindications present
Assess if patient is in a higher than usual risk group that
might require more aggressive approach (stepped up dose,
dual modality, longer duration): e.g. previous VTE, cancer,
prolonged immobilization
REMEMBER to prescribe thromboprophylaxis
Assess ongoing need for thromboprophylaxis (or resolution
of contraindications) regularly
Low threshold to investigate if symptoms/signs VTE occur
Think HIT if VTE (MI, stroke) occurs in patient who received
heparin or LMWH
Choose best thromboprophylaxis for:
• 80 yo F obese post hip # surgery
• 35 yo M appendectomy
• 72 yo F for ovarian cancer resection,
recent GI bleed
• 68 yo for colon cancer resection; MVR
with prior embolic TIA
Gaps in knowledge
• Chronically immobilized nursing home or
rehab patients
• Value of extended thromboprophylaxis after
hospitalization for medical illness
• Post C section thromboprophylaxis
• Thromboprophylaxis after non- hip lower
extremity fracture (e.g. ankle, tibfib)