PE and DVT
Pathogenesis of VT
Virchow’s triad:
– Damage to vessel wall
– Venous stasis
– Hypercoagulability
Source
Most PE’s originate from thrombi in the deep
venous system of the legs, although they may
also originate in the pelvic, renal or upper
extremity veins.
HOWEVER, less than 30% of pts will have
symptoms in their legs at the time of diagnosis of
PE
20% of calf vein thrombi propagate above the
popliteal fossa.
20% of lower extremity venous emboli begin in
the proximal veins without prior calf involvement.
Acquired Risk Factors
Age
Previous thrombosis
Immobilization
Major surgery – especially Ortho
Estrogen – OCP, HRT, SERMs
Antiphospholipid Ab syndrome
Malignancy
Nephrotic syndrome
Inflammatory bowel disease
Myeloproliferative d/o – esp p. vera and ET
PNH
Long distance air travel
HIT
Inherited Risk Factors
Factor V Leiden mutation
G20210A prothrombin gene mutation
Antithrombin deficiency
Protein C or S deficiency
Dysfibrinogenemia
Hyperhomocysteinemia
Presentation
Dyspnea
Pleuritic chest pain
Cough +/- hemoptysis
On exam may have
Tachypnea
Tachycardia
S4
Loud P2
May have fever – rarely >102
In massive PE can have hypotension and shock
Look at legs for swelling and Homan’s sign – but
only helpful if positive.
Homan’s Sign
Passive dorsiflexion of the foot with the
knee straight may give pain in the calf and
back of the knee when there is a deep
venous thrombosis.
Some concern that vigorous dorsiflexion of
the foot can expel clot from the veins and
so this test may have its dangers.
The sign is not specific for DVT
DDX swollen calf
DVT
Bakers Cyst
Cellulitis
Gout – if really bad it can sometimes look
like a cellulitis
If bilateral think about CHF, Nephrotic
syndrome, liver failure, venous
insufficiency, pregnancy or pelvic mass,
vasodilators esp nifedipine
ABG
Usually shows hypoxia, hypocapnia, respiratory alkalosis
A-a gradient:
Normal 7-14 depending on age
Increases with age, FiO2 and supine posture
Estimate of normal for age:
– Age/4 +4
A-a gradient = (FiO2 x713 – pCO2/0.8) – PaO2
If A-a gradient normal, PaO2 <80, Pa CO2 >45 then
hypoventilation accounts for hypoxia
Increased A-a gradient occurs in V/Q mismatch, shunting
and any kind of barrier to diffusion (e.g. pulmonary
edema)
BUT can be normal and still have PE!
Labs
Troponin, LDH, AST and BNP may all be
elevated
Check baseline CBC, PT/PTT/INR, Cr
D-dimer
Normal D-dimer excludes PE, but positive D-Dimer
is not helpful (as it can be positive in many
conditions including sepsis, immobility, post Sx and
CAP)
EKG
May have non specific ST and T wave changes
“Typical” SI, QIII, TIII - rare.
Sinus tachycardia
T wave inversions in right to mid chest leads
Poor R wave progression (acute RV dilation)
P pulmonale
RV conduction delays
Right axis shift
CXR
May have area of atelectasis
May have wedge shaped infarct
peripherally
Pleural effusion occurs in about 40%
DVT – D-Dimer
Fibrin degradation 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, lowmoderate Wells DVT
score and negative ddimer only 1 (NPV
99.6%) had DVT over
next 3 months
• Sensitive d-dimer testing can rule out DVT in lowmoderate risk patients
Bates SM, Kearon C, Crowther M, et al. Ann Intern Med.
2003;138:787-94
Doppler US of lower extremities
If high clinical suspicion should be
repeated 7-10 days after initial scan as
below knee DVT can propagate
Also remember that some pt develop
DVT’s elsewhere – so you may not find a
DVT in their legs if the source was their
arm!
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
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 surgery
Pitting edema greater
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
PE – Imaging Studies
PIOPED study quantified the value of V/Q scans
in diagnosing PE
– Normal/near-normal scans exclude PE in lowmoderate 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
Clinical Models to Assess PE Risk
PIOPED Criteria – Correlates well with incidence of PE
Based entirely of clinician impression, not clinical risk
factors
Pretest Clinical Gestalt
of PE Probability
Actual PE Rate on PA
Angiogram
Low (“<20%” should
have PE)
9%
Intermediate (“20-79%”
should have PE)
30%
High (“80-100%” should
have PE)
68%
PIOPED Investigators. JAMA 1990; 263: 2753-2759.
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
Roy’s SR
V/Q scanning
Look for evidence of ventilation perfusion
mismatch
Can only really be done if pt has normal CXR
Normal scan virtually excludes PE even if
pretest clinical probability was felt to be high.
If a patient with intermediate clinical probability
of PE has an intermediate scan then need
further testing
A 60-year-old man with asthma is evaluated in the emergency
department because of the acute onset of chest pain while lifting a
heavy object. The pain is sharp and accentuated by deep breathing
and by movement of the upper extremities. It is located over the left
precordium.
The physical examination and chest x-ray are normal. A ventilationperfusion lung scan shows matched areas of perfusion and
ventilation.
Which one of the following is the correct interpretation of the
ventilation-perfusion lung scan?
( A ) Normal
( B ) Low probability
( C ) Indeterminate
( D ) High probability
Correct Answer = A
The lung scan is normal, with matched perfusion and
ventilation. This lung scan rules out a pulmonary
embolism, and another source for the chest pain should
be sought. Often asthma does complicate the
interpretation of the lung scan, but the problem relates to
matched defects in which the airway obstruction
decreases the ventilation to an area of the lung. The
consequent hypoxia in that area leads to reduction in
blood flow in the same area. These areas are rarely
segmental.
Spiral CT/CT angiogram
Used if CXR not normal
Picks up large central emboli but is less
sensitive for the smaller peripheral emboli.
True pulmonary angiography rarely used
now, though can do direct thrombolysis in
massive PE.
Echo
More than 80% of pts with PE will have
abnormalities of RV size or function, or TR.
McConnells sign – regional wall motion
abnormalities that spare the R ventricular apex
are very suggestive of PE
BUT echo is only really used for Dx of massive
lifethreatening PE’s when rapid diagnosis is
needed to determine whether thrombolysis
should be given.
Treatment
Identify any contraindications to
anticoagulations – if yes then IVC filter
Inquire about h/o HIT
If yes, then use direct thrombin inhibitor
Assess need for hospitalization
Extensive iliofemoral DVT with circ compromise
Increased risk of bleeding
Limited cardioresp reserve
Poor compliance
CI to LMW heparin
Treatment
Administer LMW heparin or unfractionated
heparin
Goal 1.5-2.5 x PTT in first 24 hours
Check platelet count on day 3-5
Treat at least five days and until patient’s
INR is >2 on coumadin for two
consecutive days
Start coumadin on day 1
Treatment Duration
3-6 months in most patients
Indefinite treatment:
–
–
–
–
–
>1 spontaneous event
One spontaneous life threatening event
Antiphospholipid syndrome
Antithrombin deficiency
>1 genetic allelic abnormality
– Homozygote for Factor V Leiden or prothrombin gene mutation
– Heterozygote for both
– Protein C/S deficiency
– Continuing RF especially active advanced CA
Contraindications to
Anticoagulation
Absolute
– Active bleeding
– Severe bleeding diathesis
– Platelet count <20
– Neurosurgery, ocular surgery or intracranial
bleeding within the past 10 days
Contraindications to
Anticoagulation
Relative
– Mild/moderate bleeding diathesis or
thrombocytopenia
– Brain mets
– Major abdominal surgery within 2 days
– GI or GU bleeding within 14 days
– Endocarditis
– Severe HTN (SBP >200, DBP > 120)
Inferior Vena Cava Filter
Reduce risk of PE but carry increased risk
of DVT
Use in pts with DVT who cannot take
anticoagulation e.g. due to bleeding risk
Also used with or without anticoagulation
in patients with high risk of death should
further PE occur.
Hypercoagulation Workup
Test all patients for unprovoked VT for
antiphospholipid ab syndrome and
hyperhomocysteinemia
Hypercoagulation Workup
Test for Factor V Leiden, prothrombin gene
mutation and deficiencies of antithrombin,
protein C/S in the following patients:
Family h/o VT
VT before the age of 50
Recurrent VT
Thrombosis in an unusual site (mesenteric, renal, cerebral,
hepatic)
Heparin resistance (antithrombin deficiency)
Warfarin induced skin necrosis (protein C/S def)
Neonatal purpura fulminans
Hypercoagulation Workup
Wait to check for deficiency in
antithrombin, protein C or S until 2 weeks
after anticoagulation rx is completed
VTE – Prevention Underutilized
DVT-FREE
prospective
registry of
5,451 patients
at 183 US
hospitals
Only 32% of
medical
patients with
DVT received
DVT
prophylaxis
45
40
35
30
25
20
15
10
5
0
US 1991
US 2001
Canada
2002
UK 2005
VTE – Prophylaxis in Medical
Patients
Indications
– CHF or severe respiratory disease
– Bedrest with additional
risk factor
•Acute neurologic disease
Cancer
Prior VTE
•Inflammatory bowel disease
– Most ICU patients
Options
– Low dose unfractionated heparin or LMWH
– Sequential compression devices
– Graduated compression stockings