Venous Thromboembolism:

Deep Venous Thrombosis

and Pulmonary Embolism
2006 Capital Conference
Andrews Air Force Base
CDR Kenneth S. Yew MC, USN
Uniformed Services University
Edited by Paul Saleeb
 Objectives

Recognize common presentations of deep

venous thrombosis (DVT) and pulmonary
embolus (PE)
Understand evidence-based diagnostic and
therapeutic strategies for DVT/PE
Understand the role of prevention for
DVT/PE and use of prevention strategies
 Case 1
37 yo moderately obese female on OCP
presents to your office with a two day
history of painless R leg swelling. Shes
been elevating her leg several days after
a severe ankle sprain during a mother-
daughter soccer game.
No prior medical history, recent surgery
or weight loss. She is a non-smoker
and drinks rarely.
Exam is notable for R ankle splint and
pitting edema in R calf, which is 1.5 cm
 DVT Epidemiology and Etiology
Annual incidence of venous
thromboembolism (VTE) is 1/1000
DVT accounts for one half of VTE
Carefully evaluated, up to 80% of patients
with VTE have one or more risk factors
Majority of lower extremity DVT arise from
calf veins but ~20% begin in proximal veins
About 20% of calf-limited DVTs will
propagate proximally
 DVT VTE Risk Factors
Malignancy Presence of venous
Surgery catheter
Trauma Congestive failure

Pregnancy Antiphospholipid

Oralcontraceptives or antibody syndrome

hormonal therapy Hyperviscosity

Immobilization Nephrotic syndrome

Inherited Inflammatory bowel

thrombophillia disease
 DVT Clinical Presentation
Classically = calf pain, tenderness,
swelling, redness and Homans sign
Overall sens/spec = 3-91%
Unreliable for diagnostic decisions
Wells developed and tested a clinical
prediction model for DVT

Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest

probability of deep-vein thrombosis in clinical management. Lancet 1997;350
(9094):1795-8.
 DVT Wells Score
The following were assigned a point value of 1 if present:
Cancer Entire
leg swollen
Paralysis or plaster Calf > 3cm larger than
immobilization unaffected leg
Bedrest > 3d or Pitting edema greater
surgery in past 4 wks than unaffected leg
Localized tenderness Collateral superficial
veins
Alternative diagnosis more likely than DVT = - 2 points
Probability High ( 3), Moderate (1-2) or Low (0 or less)
DVT risk: High 75%, Moderate 17%, Low 3%
Wells PS, Andersen DR, Bormanis J et al. Lancet. 1997;350:1795-8
 DVT Case 1
Our patient has 2-3 risk factors (OCP, +/-
immobilization and trauma
Her Wells score gives her a moderate
pretest probability for DVT
A d-dimer test is performed
 DVT D-Dimer
Fibrindegradation product elevated in active
thrombosis
Negative test can help exclude VTE
Preferred test
Quantitative Rapid ELISA sensitivity 96/95%
for DVT/PE
Other methods include latex agglutination and
RBC agglutination (SimpliRED)
Stein PD, Hull RD, Patel KC, et al. D-dimer for the exclusion of acute venous thrombosis
and pulmonary embolism: a systematic review. Ann Int Med. 2004;140(8):589-602
 DVT D-Dimer
In 283 patients
with suspected
DVT, low-moderate
Wells DVT score
and negative d-
dimer only 1 (NPV
99.6%) had DVT
Sensitive d-dimer testing can rule out DVT in low-
over next
moderate 3 months
risk patients
Bates SM, Kearon C, Crowther M, et al. Ann Intern Med.
2003;138:787-94
 DVT Case 1

Our patient
has a
positive
quantitative
ELISA
Unfortunatel
y a positive
d-dimer is
not helpful
diagnostically
An imaging
 DVT Imaging

Available imaging and ancillary

tests:
Compression US first
line test, high sens/spec
Venography gold
standard
MRI Lower quality
evidence only at present
Impedance
plesmythography not
in US
 DVT Case 1
Compression US negative
Options include:
Venography or MRI
Serial compression US single US done at 5-7
days reliably excludes calf-limited DVT
Follow clinically for resolution of symptoms
riskier, no data supporting safety of this option

American Thoracic Society guidelines: The approach to acute venous

thromboembolism. Am J Respir Crit Care Med. 1999;160:1043. Fraser JD, Anderson DR.
Radiology. 1999;211(1):9-24
Diagnostic algorithm using D-dimer testing and ultrasound imaging in patients with suspected DVT

* Imaging done from proximal veins to calf trifurcation.

Reproduced with permission from Scarvelis, D, Wells, P. Diagnosis and treatment of deep-vein thrombosis. CMAJ 2006; 175:1087. Copyright 2006 Canadian Medical
Association.
 Case 2
The patient in Case 1 elected to be followed
clinically. She returned to clinic 3 days later
with persistent swelling, but no new
symptoms
She was to return the following week, but
instead you are called to the ER 10 days
later after she presents with acute onset of
dyspnea and pleuritic chest pain
 PE Epidemiology and Etiology
100-200,000 deaths per year due to PE
Most PE arise from lower extremity DVT
In patients with DVT, 40-60% will have a PE
on V/Q scanning

Pulmonary embolus is not a disease. It is a

complication of DVT. Ken Moser MD
 PE Clinical Presentation

Dyspnea, pleuritic pain and cough most

common symptoms
Tachypnea, rales and tachycardia most
common signs
ABG limited value for diagnosis
EKG and CXR often abnormal, but usually
lacking specificity to aid diagnosis
PIOPED Study. JAMA. 1990;263(20):2753-59. Stein PD, Goldhaber SZ, Henry JW.
Chest 1995;107:139-43
S1Q3T3
 CXR FINDINGS
Hamptons Hump:
-wedge-shaped configuration at lung
periphery due to infarcted lung

Westermark sign:
-pulmonary oligemia
 PE Case 2

Findings in the ER
Alert white female, mildly anxious
T 101, HR 105, RR 18
R LE edema and redness
Lungs clear to auscultation
ABG mild respiratory alkalosis; aA gradient =
17
CXR showing mild atelectasis
D-dimer positive as before, troponin normal
 PE Assigning Pretest Probability
Single most important step in the diagnosis
of pulmonary embolism
May be done based on clinical judgment or
aided by a clinical scoring system
Modified Wells Criteria is the most widely
used and studied
Reliably stratifies patients by likelihood of PE
to allow selection of safe (<2% VTE risk if
no anticoagulation) management strategy
PE Assigning Pretest Probability
 PE Use of D-Dimer
Not helpful when positive, but sensitive
assay can exclude PE in low risk patient
In patients with moderate pretest
probability only rapid quantitative ELISA can
adequately exclude PE
Patients judged to be high risk for PE would
still have a posttest PE probability of 5-20%
even after negative ELISA and require
further testing
Roy PM, Colombet I, Durieux R, et al. Systematic review and meta-analysis of strategies
for the diagnosis of suspected pulmonary embolism. BMJ. 2005;331(7511):259
 PE Case 2

High risk for PE by Modified Wells Criteria

(Wells score = 9)
Positive D-dimer, but negative test would
not have safely excluded PE
Options include:
CT angiogram
V/Q scan
Lower extremity compression US
 PE Imaging Studies
PIOPED study quantified the value of V/Q
scans in diagnosing PE
Normal/near-normal scans exclude PE in low-
moderate risk patients
High probability scans confirm PE in moderate-
high risk patients
Drawbacks: more difficult test and 73% patients
had indeterminate scans
LE compression US showing DVT helps
diagnostically, but a negative study
insufficient to exclude VTE
PIOPED Study. JAMA. 1990;263(20):2753-59
 PE Helical CT (CTA)
Eng performed a systematic review (SR) of all studies &
SRs on CTA prior to 2003
Only 1/6 SRs and 3/8 primary studies found CTA >90% sensitive
for PE
In a similar SR in 2005 Roy concluded
Negative CTA could safely exclude PE in low risk patients
Negative LE US plus negative CTA could exclude PE in moderate
risk patients
At the time of those SRs no studies of faster multidetector
CTA (MDCT) were available

Eng J, Krishnan JA, Segal JB, et al. AJR 2004;183(6):1819-27. Roy PM, Colombet I,
Durieux P, et al. BMJ 2005;331(7511):259.
 PE PIOPED II
Published June 2006 in NEJM
1090 consecutive patients with suspected PE
All given Modified Wells Score
MDCT - mostly 4 slice
Gold standard composite - V/Q, angiogram & LE US
Findings
MDCT: sens 83% & spec 96% for PE
Positive predictive value >90% in moderate/high risk
Negative predictive value 96% in low risk patients but
only 89% in moderate risk patients
Findings generally consistent with Roys SR

Stein PD, Fowler SE, Goodman LR, et al. Multidetector Computed Tomography for Acute
Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327.
 PE Case 2
MDCT segmental
embolus
Therapy
Enoxaparin 1mg/kg sq
every 12 hours for 5 days
Warfarin started day 1 at
5 mg a day
CBC on day 3-5 and INR
every day if inpatient
May stop enoxaparin
after 5 days if INR > 2.0
 VTE Other Therapy Issues

Anticoagulation same for DVT & PE

Thrombolysis - risk/benefit uncertain;
clinical outcomes generally not improved
Vena cava filters
Contraindication to anticoagulation
Rarely survivors of massive PE
Rare patients with recurrent VTE on adequate
anticoagulation
Prophylaxis in certain high risk patients
 VTE Prevention Underutilized

DVT-FREE prospective
45

40
registry of 5,451 35
patients at 183 US 30
hospitals 25

Only 32% of medical 20

patients with DVT 15

received DVT 10

prophylaxis 5

Goldhaber S & Tapson V. Am J Cardiol 2004. 0

Slide adapted from Dr. Michael Streiff. US 1991 US 2001 Canada UK 2005
2002

Anderson & Wheeler. Arch Surg 1992. Rahim, et al. Thromb

Res 2003. Tapson, et al. Blood 2004
VTE Prophylaxis in Medical Patients

Indications
CHF or severe respiratory disease
Bedrest with additional risk factor
Cancer
PriorVTE
Acute neurologic disease
Inflammatory bowel disease

Most ICU patients

Options
Low dose unfractionated heparin or LMWH
 Take Home Points
DVT and PE are the same disease
Assigning pretest probability for VTE is an essential step in
diagnosis
DVT & PE can diagnosed or excluded in many but not all
patients using noninvasive means
VTE for can be safely managed with heparin for at least 5
days and simultaneous warfarin without a loading dose
Always consider VTE prophylaxis in inpatients