Prevention and Treatment of

Venous Thromboembolism
National Performance Measures And Recent
Guidelines

Dale W. Bratzler, DO, MPH

Professor and Associate Dean, College of Public Health
Professor of Medicine, College of Medicine
Chief Quality Officer – OU Physicians Group
University of Oklahoma Health Sciences Center
Dale W. Bratzler, DO, MPH
QIOSC Medical Director
August 3, 2012
 Outline
• The problem – VTE in US hospitals
• Need for national performance standards
• Update on National Guidelines for Prevention
of VTE
• Strategies for prevention of VTE

2
 Venous thromboembolism (VTE) = Deep vein
thrombosis (DVT) and Pulmonary embolism (PE)
 “The best estimates indicate
that 350,000 to 600,000
Americans each year suffer
from DVT and PE, and that at
least 100,000 deaths may be
directly or indirectly related to
these diseases. This is far too
many, since many of these
deaths can be avoided.
Because the disease
disproportionately affects
older Americans, we can
expect more suffering and
more deaths in the future as
our population ages–unless
we do something about it.”
Annual Incidence of VTE in Olmsted County,
MN: 1966-1995
By Age and Gender
1,200
Annual incidence/100,000

Men
1,000

800

600
Women
Women
400

200


Age
Age group
group (yr)
(yr) 5
 Prevention of Venous Thromboembolism
Introduction

• VTE Remains a major health problem

– In addition to the risk of sudden death
• 30% of survivors develop recurrent VTE within
10 years
• 28% of survivors develop venous stasis
syndrome within 20 years

Goldhaber SZ. N Engl J Med. 1998;339:93-104.

Silverstein MD, et al. Arch Intern Med. 1998;158:585-593.
Heit JA, et al. Thromb Haemost. 2001;86:452-463.
Heit JA. Clin Geriatr Med. 2001;17:71-92.
Heit JA, et al. Mayo Clin Proc. 2001;76:1102-1110. 6
 Risk of DVT in Hospitalized Patients
No prophylaxis + routine objective screening for DVT

Patient group DVT incidence

Medical patients 10 - 20 %
Major gyne/urol/gen surgery 15 - 40 %
Neurosurgery 15 - 40 %
Stroke 20 - 50 %
Hip/knee surgery 40 - 60 %
Major trauma 40 - 80 %
Spinal cord injury 60 - 80 %
Critical care patients 15 - 80 %
7
Associated Illnesses that are a Consequence
of VTE events
• Chronic thromboembolic pulmonary
hypertension
– Mean pulmonary artery pressure greater than 25
mm Hg that persists 6 months after PE
– 2-4% of patients after PE

• Post-thrombotic syndrome
– Calf swelling and skin pigmentation; venous
ulceration in severe cases
• Up to 43% of patients within 2 years – most mild
Goldhaber SZ, Bounameaux H. Lancet. 2012 May 12; 379:1835-46.
Prevention of Venous Thromboembolism
• The majority (93%) of estimated VTE-related
deaths in the US were due to sudden, fatal PE
(34%) or followed undiagnosed VTE (59%)

For many patients, the first symptom of VTE is

sudden death!

How many of those patients with sudden death in the

hospital or after discharge attributed to an acute coronary
event actually died of acute pulmonary embolism?

Heit JA, Cohen AT, Anderson FA on behalf of the VTE Impact Assessment Group.
9
[Abstract] American Society of Hematology Annual Meeting, 2005.
 National Body Position Statements
• Leapfrog1:
PE is “the most common preventable cause of hospital death in
the United States”
• Agency for Healthcare Research and Quality (AHRQ)2:
Thromboprophylaxis is the number 1 patient safety practice
• American Public Health Association (APHA)3:
“The disconnect between evidence and execution as it relates
to DVT prevention amounts to a public health crisis.”

The Leapfrog Group Hospital Quality and Safety Survey. Available at: www.leapfrog.medstat.com/pdf/Final/doc
Shojania KG, et al. Making Healthcare Safer: A Critical Analysis of Patient Safety Practices. AHRQ, 2001. Available
at: www.ahrq.gov/clinic/ptsafety/
White Paper. Deep-vein thrombosis: Advancing awareness to protect patient lives. 2003. Available at:
www.alpha.org/ppp/DVT_White_Paper.pdf 10
 Annual cost to treat VTE
• $11,000 per DVT episode per patient
• $17,000 per PE episode per patient
• Recurrence increases hospitalization costs by
20%
• Complications of anticoagulation
• Time lost from work
– Quality of life: venous stasis and pulmonary HTN

11
 Consequences of Surgical Complications

• Dimick and colleagues demonstrated increased costs

of care:
– infectious complications was $1,398
– cardiovascular complications $7,789
– respiratory complications $52,466
– thromboembolic complications $18,310

Dimick JB, et al. J Am Coll Surg 2004;199:531-7. 12

Do venous and arterial diseases have shared
risk factors?
“…..4 years after surviving a
PE, fewer than half will remain
free of MI, stroke, PAD, recurrent
VTE, cancer or chronic
thromboembolic pulmonary
hypertension.”

VTE and atherothrombosis have a

common pathophysiology that
includes inflammation,
hypercoagulability, and
endothelial injury.

Goldhaber SZ, Bounameaux H. Lancet. 2012 May 12; 379:1835-46.

 Inherited risk factors for DVT
Group 1 disorders Group 2 disorders
• Protein C deficiency (2.5-6%) • Factor V leiden (6%)
• Protein S deficiency (1.3-5%) • Prothrombin (G20210A) (5-
• Antithrombin deficiency (0.5- 10%)
7.5%) • Elevated VIII, IX, XI
• Hyperhomocysteinemia
• Arteriosclerosis

14
 Acquired Risk Factors
Risk Factor Attributable Risk
Hospitalization/Nursing home 61.2

Active malignant neoplasm 19.8

Trauma 12.5

CHF 11.8

CV catheter 10.5

Neurologic disease with paresis 8.2

Superficial vein thrombosis 4.3

Varicose veins/stripping 6

Many others….

Being in the hospital is the greatest risk factor for VTE!

15
 Risk Factors for DVT or PE
Nested Case-Control Study (n=625 case-control pairs)

Surgery
Trauma
Inpatient
Malignancy with chemotherapy
Malignancy without chemotherapy
Central venous catheter or pacemaker
Neurologic disease
Superficial vein thrombosis
Varicose veins/age 45 yr
Varicose veins/age 60 yr
Varicose veins/age 70 yr
CHF, VTE incidental on autopsy
CHF, antemortem VTE/causal for death
Liver disease

0 5 10 15 20 25 50
Odds ratio
16
 Independent Risk Factors for VTE after
Major Surgery*:
Olmsted County 1988-97 (n=163)
Risk Factor OR 95% CI P-value
Age (per 10 years) 1.26 1.07, 1.50 0.007
BMI (kg/m2, per 2-fold increase) 2.95 1.49, 5.82 0.002
ICU Length of Stay > 6 Days 3.97 1.46, 10.80 0.007
Central Venous Catheter 2.46 1.21, 5.03 0.013
Immobility Requiring Physical
2.18 1.17, 4.06 0.014
Therapy
Varicose Veins 1.87 1.08, 3.23 0.025
Any Infection 1.68 1.01, 2.82 0.046
Anticoagulation Prophylaxis 0.27 0.12, 0.59 0.001

*Controlled for Surgery Type, Active Cancer, and Event Year

Heit, et al. J Thromb Haemost 2005 17
 VTE is a Disease of Hospitalized and
Recently Hospitalized Patients

1000
Cases per 10,000 person-years

VTE 100X more common in

hospitalized patients!

100
Recently
hospitalized

10

1
Hospitalized patients Community residents
Heit JA. Mayo Clin Proc. 2001;76:1102 18
Cumulative Incidence of VTE After Primary Hip
or Knee Replacement

3.5
Primary hip
3.0
Primary knee
2.5
VTE
2.0
events
(%) 1.5

1.0

0.5

0.0
0 7 14 21 28 35 42 49 56 63 70 77 84 91

Days

White RH, et al. Arch Intern Med. 1998; 158: 1525-1531 19

Many events occur after hospital discharge.

• IMPROVE Registry
– 15,156 medical patients admitted to the hospital
• 184 patients had VTE events
– 45% developed VTE after discharge

• Other studies have shown that up to two-

thirds of VTE events occur in patients after
discharge

Spyropoulos AC, et al. Chest 2011; 140:706-14.

 VTE Facts
• Almost half of the
Days After Discharge
outpatients with VTE had
been recently hospitalized 0-29 30-59 60-90

70

Outpatients With VTE, %

• Less than half of the 60
recently hospitalized 50
patients had received VTE 40
prophylaxis during their 30
hospitalizations 20
10
• About half had a length 0
Medical Hospitalization
of stay (LOS) of < 4 days Hospitalization with Surgery
Only

Goldhaber S. Arch Intern Med. 2007;167:1451-2.

Spencer FA et al. Arch Intern Med. 2007;167(14):1471-5.
 Prevention of Venous Thromboembolism

• Despite the well known risk of VTE and the

publication of evidence-based guidelines for
prevention, multiple medical record audits
have demonstrated underuse of prophylaxis

Anderson FA Jr, et al. Ann Intern Med. 1991;115:591-595.

Anderson FA Jr, et al. J Thromb Thrombolysis. 1998; 5 (1 Suppl):7S-11S.
Bratzler DW, et al. Arch Intern Med. 1998;158:1909-1912.
Stratton MA, et al. Arch Intern Med. 2000;160:334-340. 22
 Published Audits of VTE Prophylaxis
General Surgery
Received Prophylaxis No Prophylaxis

280 97/250 (39%)

240

200

160
Cases

120
30/86 (35%) 33/83 (40%)
80

40

0
Moderate High Very High

Use of any form of prophylaxis based on level of risk for venous thromboembolism among 419 Medicare patients from
20 hospitals undergoing major abdominothoracic surgery. Measures were implemented for patients at moderate risk
(35%; 95% CI, 25-46%), at high risk (40%; 95% CI, 29-51%), and at very high risk (39%; 95% CI, 33-45%). Overall
utilization rate for prophylaxis was 38% (95% CI, 33-43%).
Bratzler DW, et al. Arch Intern Med. 1998;158:1909-1912.
 Thromboprophylaxis Use in Practice
1992-2002
Prophylaxis
Patient Group Studies Patients Use (any)
Orthopedic surgery 4 20,216 90 % (57-98)
General surgery 7 2,473 73 % (38-98)
Critical care 14 3,654 69 % (33-100)
Gynecology 1 456 66 %
Medical patients 5 1,010 23 % (14-62)
How many patients with COPD, CVA, heart failure, pneumonia, etc
do you have in your hospital that are not on DVT prophylaxis?

24
Prevention of VTE in Medical Patients

Amin A, Stemkowski S, Lin J, Yang G. J Thromb Haemost 2007; 5: 1610–6.

Prevention of VTE in Medical Patients

Amin A, Stemkowski S, Lin J, Yang G. J Thromb Haemost 2007; 5: 1610–6.

Diagnosis of VTE
• D-dimer (rule out
only)

• Compression
ultrasound

• CT angiography

Goldhaber SZ, Bounameaux H. Lancet. 2012 May 12; 379:1835-46.

Diagnosis of VTE

Goldhaber SZ, Bounameaux H. Lancet. 2012 May 12; 379:1835-46.

Prophylaxis and Treatment
 Prophylaxis Modalities
• Mechanical
– Graduated compression stockings (GCS) (e.g., “white
hose”)
– Sequential compression devices
• Venous foot pumps (currently recommended only for orthopedic
surgery in patients with bleeding risk)

In most studies, less effective than pharmacologic

prophylaxis and patient compliance rates are
generally low.
Rates of compliance with mechanical forms of prophylaxis in many studies is
less than 50% - has become a new target of malpractice litigation.

30
 Pharmacologic Prophylaxis
• Low-dose unfractionated heparin (LDUH)
• Low-molecular weight heparin (LMWH)*
• Fondaparinux*
• Direct inhibitors of activated factor X
– rivaroxaban
• Direct thrombin inhibitors
– dabigatran
• Warfarin
• Aspirin
*Cleared by the kidneys. 31
Approach to Treatment
 How long do you treat?
Evidence
Duration of Treatment Grade
First VTE event secondary to a 3 months 1A
reversible factor (“provoked”)
First idiopathic (“unprovoked) VTE At least 3 months 1A
At the end of initial 3-month period Assess for long-term Rx 1C
In the absence of contraindication Long-term Rx 1A
During long-term treatment Assess risk/benefit balance 1C
Recurrent VTE or strong thrombophilia Long-term Rx 1A
VTE secondary to cancer Long-term Rx, preferentially 1A
with LMWH during the first 3- 1C
6 months, then anticoagulate
as long as the cancer is
considered “active”

Kearon C, et al. Chest 2008; 133 (6 suppl):454S-545S.

Do we have to use warfarin long-term?

Multicenter, double-blind
study, patients with first-
ever unprovoked venous
thromboembolism who
had completed 6 to 18
months of oral
anticoagulant treatment
were randomly assigned
to aspirin, 100 mg daily,
or placebo for 2 years

Becattini C, et al. N Engl J Med 2012;366:1959-67.

Development of National Performance
Measures to Prevent and Treat VTE

35
Why the need for performance measures?
• Despite widespread publication and
dissemination of guidelines, practices have not
changed at an acceptable pace
– There are still far too many needless deaths from
VTE in the US

• Reasonably good evidence that using

performance measures for accountability can
accelerate the rate of change

36
37
 Venous Thromboembolism
Statement of Organization Policy

“Every healthcare facility shall have a written policy

appropriate for its scope, that is evidence-based and
that drives continuous quality improvement related to
VTE risk assessment, prophylaxis, diagnosis, and
treatment.”

38
 Venous Thromboembolism
Characteristics of Preferred Practices

General
• Protocol selection by multidisciplinary teams
• System for ongoing QI
• Provision for RA/stratification, prophylaxis,
diagnosis, treatment
• QI activity for all phases of care
• Provider education

39
 Venous Thromboembolism
Characteristics of Preferred Practices
(cont.)

Risk Assessment/Stratification
• RA on all patients using evidence-based policy
• Documentation in patient record that done

Prophylaxis
• Based on assessment & risk/benefit, efficacy/safety
• Based on formal RA, consistent with accepted,
evidence-based guidelines

40
 Venous Thromboembolism
Characteristics of Preferred Practices
(cont.)

Diagnosis
• Objective testing to justify continued initial therapy
Treatment and Monitoring
• Ensure safe anticoagulation, consider setting
• Incorporate Safe Practice 29
• Patient education; consider setting and reading levels
• Guideline-directed therapy
• Address care setting transitions in therapy

41
 Surgical Care Improvement Project
First Two VTE Measures Endorsed by NQF

• Prevention of venous thromboembolism

• Proportion who have recommended VTE
prophylaxis ordered

• Proportion who receive appropriate form of VTE

prophylaxis (based on ACCP Consensus
Recommendations) within 24 hours before or
after surgery

42
 Venous Thromboembolism
Technical Advisory Panel (TAP) charge

• Vet the 19 potential measures, agreed upon by the

Steering Committee, through TAP and The Joint
Commission survey processes
• Identify a subset of measures that help address the
identified gaps within the endorsed VTE domains
• Oversee final development and testing of measures for
Steering Committee and NQF endorsement
consideration

43
 6 Refined Measures That Were Endorsed

 Risk Assessment/Prophylaxis domain

 Prophylaxis w/in 24 hours of admission or surgery,
OR a documented risk assessment showing that the
patient does not need prophylaxis

 Prophylaxis/documentation w/in 24 hours after ICU

admission or surgery

44
6 Refined Measures That Were Endorsed

 Patients w/overlap of anticoagulation therapy

 At least five calendar days of overlap and discharge with INR
> 2.0, or discharge on overlap therapy

 Patient receiving UFH with dosage/platelet count

monitoring by protocol/nomogram
 Nomogram/protocol incorporates routine platelet count
monitoring

45
 6 Refined Measures Endorsed (cont.)

 Treatment/Monitoring Domain (cont.)

– Discharge instructions consistent with Joint Commission safety
goals (Follow-up Monitoring, Compliance Issues, Dietary
Restrictions, Potential for Adverse Drug Reactions/Interactions)

 Outcome
 Incidence of potentially-preventable VTE – proportion of
patients with hospital-acquired VTE who had NOT received VTE
prophylaxis prior to the event

46
New Guidelines and Controversies
New Guidelines

http://www.chestnet.org/accp/guidelines/accp-antithrombotic-guidelines-9th-ed-now-available
 ACCP Disclaimer
The ACCP recommends that performance measures for quality
improvement, performance-based reimbursement, and public
reporting purposes should be based on rigorously developed
guideline recommendations. However, not all recommendations
graded highly according to the ACCP grading system (1A, 1B)
are necessarily appropriate for development into such
performance measures, and each one should be analyzed
individually for importance, feasibility, usability, and scientific
acceptability (National Quality Forum criteria). Performance
measures developers should exercise caution in basing
measures on recommendations that are graded 1C, 2A, 2B, and
2C, according to the ACCP Grading System1 as these should
generally not be used in performance measures for quality
improvement, performance-based reimbursement, and public
reporting purposes.
 ACCP 9th Edition
General Overview

• For acutely ill hospitalized medical patients at

increased risk of thrombosis, we recommend
anticoagulant thromboprophylaxis with
LMWH, LDUH, or fondaparinux (Grade 1B)
– Mechanical prophylaxis (GCS or IPC) if bleeding or
high risk for bleeding
• Similar recommendation for critically ill
patients
 ACCP 9th Edition
General Overview

• For patients undergoing non-orthopedic

surgery
– Generally recommend the use of a risk assessment
tool (Rogers score or Caprini score) to determine
need for prophylaxis
• Low risk of VTE (Rogers score < 7.0, Caprini score 0) no
prophylaxis recommended other than early ambulation
Bahl V, et al. Ann Surg. 2010; 251:344-50.
Bahl V, et al. Ann Surg. 2010; 251:344-50.
Rogers SO, et al. J Am Coll Surg 2007;204:1211–1221.
Rogers SO, et al. J Am Coll Surg 2007;204:1211–1221.
 ACCP 9th Edition
General Overview

• Patients undergoing major orthopedic surgery

(THA, TKA, or HFS) recommend LMWH,
fondaparinux, apixaban, dabigatran,
rivaroxaban, LDUH, adjusted-dose warfarin,
aspirin (all Grade 1B), or an IPC device (Grade
1C).
– Subsequently recommend in THA, TKA, or HFS
LMWH the preferred agent (Grade 2B)
 ACCP Guidelines
• The technical expert panel is evaluating new
guidelines to consider revisions
– No revisions likely before January 2014
– Many of the recommendations in guidelines do
not have 1A and 1B grades and remain very
controversial
– Most hospitalized patients have additional risk
factors for VTE
Strategies for Improvement

59
 Strategies to Improve VTE Prophylaxis

• Hospital policy of risk assessment or routine

prophylaxis for all admitted patients
– Most will have risk factors for VTE and should
receive prophylaxis
– Preprinted protocols for surgical patients

60
 Electronic Alerts to Prevent VTE among
Hospitalized Patients
• Hospital computer system identified patient VTE risk factors
• RCT: no physician alert vs physician alert

Control Alert
group group P
No. 1,251 1,255
Any prophylaxis 15 % 34 % <0.001
VTE at 90 days 8.2 % * 4.9 % 0.001
Major bleeding 1.5 % 1.5 % NS

Kucher – N Engl J Med 2005;352:969 61

Electronic Alerts to Prevent VTE among
Hospitalized Patients
• Among hospitalized patients with risk
factors for VTE and not receiving
prophylaxis, use of a physician VTE risk
alert:
– Improved use of prophylaxis by 130%
– Reduced symptomatic VTE by 41%
– Did not increase bleeding

Kucher – N Engl J Med 2005;352:969 62

 Improving Compliance with Treatment
Protocols
• Use of standardized protocols, nomograms,
algorithms, or preprinted orders
– Address overlap (either 5 days in hospital or
discharge on overlap)
– When used, UFH should be managed by
nomogram/protocol, and the protocol should
ensure routine platelet count monitoring
 Essential Elements for Improvement

• Institutional support
• A multidisciplinary team or steering committee
• Reliable data collection and performance tracking
• Specific goals or aims
• A proven QI framework
• Protocols

SHM Resource Room. http://www.hospitalmedicine.org. Accessed September 2009.

 Risk Assessment Prophylaxis
Low Ambulatory patient without VTE risk Early ambulation
factors; observation patient with expected
LOS 2 days; same day surgery or minor
surgery

Moderate All other patients (not in low-risk or high- UFH 5000 units SC q 8
risk category); most medical/surgical hours; OR LMWH q day; OR
patients; respiratory insufficiency, heart UFH 5000 units SC q 12
failure, acute infectious, or inflammatory hours (if weight < 50 kg or
disease age > 75 years); AND
suggest adding IPC

High Lower extremity arthroplasty; hip, pelvic, LMWH (UFH if ESRD); OR

or severe lower extremity fractures; acute fondaparinux 2.5 mg SC
SCI with paresis; multiple major trauma; daily; OR warfarin, INR 2-3;
abdominal or pelvic surgery for cancer AND IPC (unless not
feasible)

Maynard GA, et al. J Hosp Med 2009 Sep 14. [Epub ahead of print]
Maynard GA, et al. J Hosp Med 2009 Sep 14. [Epub ahead of print]
 Conclusions
• VTE remains a substantial health problem in
the US

• VTE prophylaxis remains underutilized

• National performance measures may address

both prophylaxis and treatment of VTE across
broad hospital populations
67
dale-bratzler@ouhsc.edu