Acute Pulmonary Embolism

Peter DeLong MD
Pulmonary and Critical Care Medicine
DHMC

December 15, 2008
What we will cover
Definition
Epidemiology
Risk factors
Diagnosis
Presentation
tests
algorithm
Treatment
Risk stratification
Duration of therapy

Monday mornings can be hard
for everyone.
This will be fast I will try to keep you awake
Definition
Blood clot, usually from the deep veins
of the leg, also air, fat, tumor, that
occludes pulmonary vasculature
Epidemiology


PE is a major cause of death in the United
States, with as many as 650,000 cases/yr
50,000 to 200,000 fatalities annually.

>400,000 diagnoses of PE are missed in the
United States annually.

Most deaths from PE are due to failure to
diagnose rather than failure to treat adequately.

Two thirds of patients die within 1 hour of
symptom onset; this is the golden hour.
Epidemiology
Mortality is 15% within 3 months after
occurrence

In 25% of PE, the initial manifestation is
death
Risk Factors
Virchows triad
1. Stasis
2. Venous injury/endothelial damage
3. Hypercoagulability

Most patients have several of these

Risk Factors
Inherited
Factor V leiden
Prothrombin gene mutation
Low protein C, protein S, antithrombin III
Family history of VTE

Acquired
Age
Smoking
Obesity
immobility
Malignancy
APL Ab syndrome [venous and arterial]
Hyperhomocysteinemia (can be acquired) [venous and arterial]
OCPs or hormone replacement
Atherosclerosis
Trauma, surgery, hospitalization
Infection
Long haul air travel
Electronic leads, indwelling catheters
Who gets Evaluated For
Thrombophilia?
Patients in whom there is a high clinical suspicion for
underlying disorder
PE not associated with acquired risk factor
Can be after first event!
Family history

Initial evaluation directed towards most common

Most common
Factor V Leiden
Prothrombin gene mutation
APL Ab syndrome
Hyperhomocysteinemia

Less common
Protein C&S deficiency, ATIII deficiency
Diagnosis

pathophysiology is complex and
results in variable clinical
presentation

Acute PE: Pathophysiology
Gas exchange abnormalities
Right to left shunt
Leads to
Hypoxemia
Increased a-A gradient
V/Q MM
Increased dead space
Respiratory alkalosis from hyperventilation
Often a sign of increased dead space and
impaired minute ventilation
may suggest massive PE
Acute PE: Pathophysiology
Hemodynamic abnormalities
Depends on size of embolus
Increased vascular resistance/RV afterload
May cause RV dilation, hypokinesis,
tricuspid regurgitation, FAILURE
Interventricular flattening, impaired LV filling
Increased wall stress and ischemia

Diagnosis
Symptoms and Signs
Symptoms
Dyspnea
Chest pain (pleuritic)
Apprehension
Cough
Hemoptysis
Syncope
Palpitations
Wheezing
Leg pain
Leg swelling

Signs
Tachycardia
Tachypnea
hypoxemia
Accentuated S2
Fever
Diaphoresis
Signs of DVT
Cardiac murmur
Jugular venous distention
Cyanosis
Hypotension


Diagnosis
Laboratory Evaluation
D-dimer
Non specific measure of fibrinolysis
Measured by ELISA
High sensitivity (positive in presence of dz)
High negative predictive value (dz is absent when
test is negative) in the outpatient setting

Useful in outpatient setting/emergency room,
not an inpatient test for ruling out PE
Diagnosis
Chest XR
CXR
Most often normal
May show collapse, consolidation, small
pleural effusion, elevated diaphragm.

Uncommon findings include
Westermarks sign
Dilation of vessels proximal to embolism
Hamptons hump
Pleural based opacities with convex medial margins

Diagnosis
ECG
ECG may show
Complete or incomplete RBB
T wave inversions anteriorly, S1Q3T3
The latter is very overrated..
Diagnosis
VQ Scan
Perfusion
Ventilation
Mismatch
Diagnosis
V/Q scans
Old standard

Currently reserved for
Renal impairment
IV contrast allergies
Pregnancy
Chronic PE (controversial)
Diagnosis
CT scan New Standard
Data suggests CT is as accurate as
invasive angiography (gold standard)

Negative predictive value of 99%
Quiroz et al, JAMA 2005
Diagnosis
Spiral CT/ Multislice
Ascending Aorta
Lt Pulmonary Artery
Main Pulmonary Artery
Rt Pulmonary Artery
Descending Aorta
Thrombus
Pulmonary Angiogram
Diagnosis
MRI MR Angiogram
Very good to visualize the blood flow.
Almost similar to invasive angiogram
A word about test
Interpretation
Bayes theorem
Interpretation is based on an assessment
of the likelihood of a given outcome

Therefore pretest probability impacts
interpretation of test results

The level of clinical suspicion is
primary in diagnosis of PE!!
Even in the age of CT scans..
Another word about test
Interpretation
As with the discrepancy between NYHA
class and EF:
there is poor correlation between
radiographic clot burden and
symptoms in PE

So you must evaluate and manage the
patient clinically
Diagnostic algorithm
Outpatient/ED Inpatient
D-dimer
normal Elevated
No PE
Chest CT
3
rd
gen scanner Ist gen scanner
No PE PE No PE PE
Ultrasound of leg veins
DVT No DVT
PAgram if continued clinical suspicion
You have diagnosed a PE
What now?

(heparin, then.)

Risk stratification

Essentially based on hemodynamic stability
Elevated biomarkers troponins, BNP should
prompt ECHO
Some argue for routine ECHO

ECHO for Risk Stratification
Insensitive for diagnosis but can risk stratify
in patients with known PE

In normotensive patients RV dysfunction is
an independent risk factor for early death

Regional RV dysfunction with free wall apical
sparing is thought to be specific for PE
(McConnells sign)
Risk stratification algorithm
Hemodynamically stable/no shock
Unstable/shock
Fibrinolysis, embolectomy
BNP BNP (RV on CT)
Troponin troponin
(RV on CT)
ECHO
No RV dysfunction RV dysfunction
anticoagulation
Treatment
Anticoagulation
Mainstay of therapy
Unfractionated heparin for PTT 60-80 secs
Preferred in pts undergoing further therapy as it can be
reversed
Weight based nomograms are effective for
initiating therapy
LMWH
More predictable response
No dose adjustments
Renally cleared. Some some pts need adjustments
Kidney dz, pregnancy, massive obesity may need anti
factor Xa monitoring
Usefulness questioned as correlation with
antithrombotic effect not clear
Treatment
Warfarin
Vitamin K antagonist

Dose response variation may be in part
attributable to the vitamin K epoxide
reductase complex 1 (VKORC1)
Testing not usually performed

Treatment
Newer agents
Fondaparinux
Synthetic pentasaccharide with anti- Xa
activity

Once daily

No adjustments

No risk of HIT
Treatment Complications
HIT
Both UFH and LMWH can cause HIT
LMWH much less so
HIT from IgG against heparin platelet
factor IV complex
Screen when platelets drop by >50%
if suspected, stop all heparin
Start direct thrombin inhibitor like
lepirudin or argatroban
Treatment
Thrombolytics
T-PA (alteplase) FDA approved for PE
100 mg infused over 2 hrs

no difference in mortality or recurrent PE
at 90 days compared to UFH
Treatment
Surgical embolectomy requires a
specialized center
Can be safe
Can be effective
Small published numbers

Catheter directed embolectomy
Emerging as effective therapy when
fibrinolysis cannot be used
Can be performed up to 5 days after event
Treatment
Duration algorithm
PE
Risk stratify
Not high risk High risk
Anticoagulation fibronlysis/embolectomy
Heparin or heparin
LMWH
fondaparinux
Warfarin, 6 mos
Stop if due to trauma/surgery
No signs of DVT
If idiopathic, continue lifetime
If thrombophilic, continue lifetime
If sxs DVT, doppler until clot resolved
Recommendations
From the evidence-based
recommendations of the Seventh
American College of Chest
Physicians (ACCP) Consensus
Conference on Antithrombotic
Therapy
Buller, HR, Agnelli, G, Hull, RD, et al. Antithrombotic therapy for venous
thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and
Thrombolytic Therapy. Chest 2004; 126:401s
Recommendations
Therapy of acute deep vein thrombosis
or pulmonary embolism should be
initiated with IV heparin
Recommendations
Heparin therapy should be continued for at least five
days.

Oral anticoagulation should be overlapped with
heparin therapy for four to five days.

Heparin and warfarin therapy can be initiated
simultaneously, with heparin therapy discontinued
on day five or six if the INR has been therapeutic for
two consecutive days.

Longer periods of initial heparin therapy may be
considered in the case of massive pulmonary
embolism or iliofemoral thrombosis.
Recommendations
LMW heparin may be used in place of
unfractionated heparin.

Dosing requirements are individualized
for each product.

Recommendations
Duration of therapy
First thromboembolic event in the context of a
reversible risk factor
-- treated for three to six months

Idiopathic first thromboembolic event
-- AT LEAST full six months of treatment
-- further therapy at discretion of clinician

Recurrent venous thrombosis or a continuing risk
factor -- treated indefinitely.

Recommendations
IVC filter placement is recommended when
-- anticoagulation is contraindicated

-- recurrent thromboembolism despite adequate
anticoagulation

-- chronic recurrent embolism with pulmonary
hypertension

-- high-risk of recurrent embolization

-- conjunction with the performance of pulmonary
embolectomy or endarterectomy
Treatment
IVC filter
With filter 5% risk of
recurrent pulmonary
embolus, especially after 6
mos.

complication of leg swelling
can occur.

anticoagulation is continued
if possible.

Summary

Heparanize (or anticoagulate somehow)

Think about pre-test probability

Think about risk stratification beyond
immediate hemodynamic stability

Questions?
Outpatient/ED Inpatient
D-dimer
normal Elevated
No PE
Chest CT
3
rd
gen scanner Ist gen scanner
No PE PE No PE PE
Ultrasound of leg veins
DVT No DVT
PAgram if continued clinical suspicion
Hemodynamically stable/no shock
Unstable/shock
Fibrinolysis, embolectomy
BNP BNP (RV on CT)
Troponin
(RV on CT)
ECHO
No RV dysfunction RV dysfunction
anticoagulation
PE
Risk stratify
Not high risk High risk
Anticoagulation fibronlysis/embolectomy
Heparin or heparin
LMWH
fondaparinux
Warfarin, 6 mos
Stop if due to trauma/surgery
No signs of DVT
If idiopathic, continue lifetime
If thrombophilic, continue lifetime
If sxs DVT, doppler until clot resolved
Diagnosis
integrated clinical decision rule
Wells rule
Chest XR
Initial CxR always
NORMAL.

May show Collapse,
consolidation, small
pleural effusion,
elevated diaphragm.

Westermark sign
Dilatation of pulmonary
vessels proximal to
embolism along with
collapse of distal
vessels, often with a
sharp cut off.

Chest XR
Initial CxR always
NORMAL.

May show Collapse,
consolidation, small
pleural effusion,
elevated diaphragm.

Pleural based opacities
with convex medial
margins are also known
as a Hampton's Hump
Chest XR
Signs of Infarction
Consolidation
Cavitation
Pleural effusion (bloody
in 65%)
SSA
No air bronchograms
Melting sign of
healing
Heals with linear scar
Diagnosis
V/Q Scan
Pulmonary Angiogram
Westermark sign
Dilatation of
pulmonary vessels
proximal to embolism
along with collapse of
distal vessels, often
with a sharp cut off.
Prevention
Only

low-molecular-weight heparin
graded compression stockings

have been shown to reduce the incidence of
pulmonary embolism in hospitalized patients.