Pulmonary Embolism
Raed Abu Sham’a, M.D
PULMONARY EMBOLISM
Sudden lodgment of a blood clot in a
pulmonary artery with subsequent
obstruction of blood supply to the
lung parenchyma
PULMONARY EMBOLISM • The most common type of pulmonary embolus
is a thrombus
• Other types of pulmonary embolus:
• Fat emboli
• Amniotic fluid emboli
• Air and gas emboli
• Tissue emboli
• They obstruct primarily the pulmonary microcirculation rather than arteries
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
• Virchow’s triad
1.Stasis
2.Venous injury/endothelial damage
3.Hypercoagulability
• Most patients have several of these…
Risk factors for PE Nurses’ Health Study
1) Obesity (RR = 3.0, with BMI >29)
2) Cigarette smoking (RR = 2.1, with > 35 cigs/d)
3) Hypertension (RR = 1.5)
JAMA 1997; 277:642
Hypercoagulability work-up
High yield (> 20%)
1) Factor V Leiden – Genetic mutation that causes
resistance to activated protein C
2) Plasma homocysteine level – Rx with folate, B6, B12
3) Lupus anticoagulant screen – Requires intensive anticoagulation;
Possible steroid/ASA responsiveness
Factor V Leiden/recurrent VTE
after discontinuing warfarin
• RR = 4.7 (p = 0.047)
(PHS: Circulation 1995; 92:2800)
• RR = 2.4 (p < 0.01)
(Padua: NEJM 1997; 336:399)
• No increased risk
(Rintelen: Thromb Haemostas 1996; 75:229)
Anti Cardio Lipin Antibody [ACLA]
and VTE in 412 Swedish patients 14% ACLA in men
17% ACLA in women
29% recurrence in ACLA positive
vs 14% recurrence in ACLA negative
15% vs 6% 4-year mortality
Am J Med 998; 104:332
Prothrombin gene mutation
1) risk DVT/PE
(Ann Intern Med 1998; 129:89)
2) risk cerebral vein thrombosis
(NEJM 1998; 338:1793)
Hypercoagulability work-up
Low yield
1) antithrombin III deficiency
(spurious value on heparin)
2) protein C deficiency
(spurious value on warfarin, BCP or when pregnant)
3) protein S deficiency
(spurious value on warfarin, BCP or when pregnant)
Pathophysiology
• 65 to 90% of PE arise from thrombi originating in the deep
venous system of the lower extremities
• They may also originate in the pelvic, renal, or upper extremity
veins and in the right heart
• Iliofemoral thrombi is the source of most clinically recognized PE
PATHOPHYSIOLOGY • The majority of thrombi that arise in the calf vein resolve
spontaneously
• Approximately 20% of calf vein thrombi propagate up
• An additional 20% of lower extremity venous thrombi begin in
the proximal veins
PATHOPHYSIOLOGY
• Large thrombi may lodge at the bifurcation of the
main pulmonary artery or the lobar branches and
cause hemodynamic compromise
• Smaller thrombi continue traveling distally and are
more likely to produce pleuritic chest pain
• Cardiogenic shock occurs in persons
without preexisting cardiopulmonary
disease only after massive PE involving at
least 50% and usually 75% or more of the
pulmonary vascular bed
PATHOPHYSIOLOGY
• Only about 10% of emboli cause pulmonary
infarction
• Most pulmonary emboli are multiple
• The lower lobes being involved in the majority of cases
• Pulmonary infarction is hemorrhagic consolidation of lung
parenchyma
• Collateral circulation from the bronchial artery probably
keeps the lung tissue viable despite pulmonary artery
blockage
• PI is sometimes due to thrombosis of the pulmonary arteries
in situ
Causes of Pulmonary Infarction
• Stasis
• Hypercoagulable state
• Thrombus
• Deep vein thrombosis
• Atrial myxoma
• Polycythemia rubra vera
• Sickle cell anemia
• Pancreatic carcinoma
• Burn
• Surgery
• Oral contraceptives
• Trauma
• Hip fracture
• Immobilization
• CHF
• SBE
• The apex of the wedge is at the point
where the pulmonary artery has been
blocked by an embolus
• Wedge-shaped area of haemorrhagic
infarcted lung tissue in the lower lobe
PATHOPHYSIOLOGY
• Impairment of gas exchange cannot be explained
solely by mechanical obstruction
• It is probably more closely related to the release of
inflammatory mediators
Inflammatory mediators result in
1.Surfactant dysfunction
2.Changes in vascular permeability
3.Functional intrapulmonary shunting
Pulmonary Vasoconstriction • Pulmonary vasoconstriction appears to play a definite but
secondary role
Vasoconstriction is partly mediated by
1. Hypoxemia
2. Serotonin
3. Prostaglandins
PATHOPHYSIOLOGY
• After occlusion of the PA, areas of the lung are ventilated
but not perfused, resulting in wasted ventilation contributing
to hyperventilation
• Depletion of alveolar surfactant within hours after the
embolic event results in diminished lung volume and
compliance
• Diminished lung volume and possibly lowered airway PCO2
may induce bronchoconstriction
PATHOPHYSIOLOGY • In acute PE the thrombi begin to lyse immediately after
reaching the lung.
• Usually, lysis is complete within several weeks.
• Massive emboli may cause death within minutes or
hours
• Recurence can cause progressive pulmonary arterial
obstruction
Risk Factors
• Advanced age
• Immobilization
• Surgery
• Stroke
• History of VTE
• Malignancy
• Obesity
• Heart failure
• Atrial fibrillation
• M.I
• Varicose veins
• Heavy smoking
• Hypertension
• Estrogen therapy
Idiopathic VTE • Factor V leiden mutation
• Antithrombin III, protein C, or protein S deficiency
• Antiphosphholipid Antibody Syndrome
• Hyperviscosity syndromes
• Occult malignancy
1. VTE the presenting sign of pancreatic or prostate cancers
2. VTE occurs late in the course of patients with breast,
lung, uterine, or brain malignancies
Signs & Symptoms PE (n = 131)
• Observation Rate
Dyspnea 77%
Chest pain 55%
Cyanosis 18%
Hemoptysis 13%
Syncope 10%
Arch Intern Med 1991; 151:933
CLINICAL MANIFESTATIONS
• The majority of patients with PE have an
underlying clinical predisposition
• Less than 10% of the patients have no obvious
cause for DVT at the time of presentation
• 56% of patients with symptomatic DVT may
have asymptomatic PE
• Diagnostically confusing syndromes (confusion, unexplained fever, wheezing, resistant heart failure, or unexplained arrhythmias)
• Transient shortness of breath and tachypnea
• Pulmonary infarction (pleuritic pain, cough, hemoptysis, pleural effusion, and pulmonary infiltrate)
• Right-sided heart failure with shortness of breath and tachypnea
• Cardiovascular collapse with hypotension and syncope
• The classic triad in less than 20% of patients of dyspnea, chest pain, and hemoptysis.
The most common symptoms • 73% Dyspnea
• 66% Pleuritc Pain
• 43% Cough
• 33% Leg Swelling
• 30% Leg Pain
• 15% Hemoptysis
• 12% Palpitations
• 10% Wheezing
• 5% Angina-Like pain
The most common signs • Tachypnea (70%)
• Rales (51%)
• Tachycardia (30%),
• A fourth heart sound (24%)
• Loud P2 (23%)
• Fever, usually < 38.9°C (14%)
• Circulatory collapse (8%)
• Cyanosis
• Wheezing
Thrombophlebitis
D.D: Rupture of a Baker’s cyst
Variable Point Score
Heart Failure +1
Prior DVT +1
Hypoxaemia +1
DVT on US +1
The Bounameaux PE Point Score (The Geneva Risk Score)
Vicki J et.al Thromb Haemost 2000; 84: 548-552
SBP < 90mmHg +1
Cancer +2
predicts death 2 >Score of
recurrent VTE, or major bleed at 3 months
LABORATORY ABNORMALITIES
Routine laboratory findings are
nonspecific
• Leukocytosis
• Elevated ESR
• Elevated serum LDH
• Elevated Plasma D-dimer
Arterial blood gases
• Hypoxemia > 80%
• Hypocapnia
• Hypercapnia and a combined respiratory and metabolic
acidosis in massive PE
• Normal A-a gradient for oxygen, up to 6%
BLOOD ACTIVATION
fibrinogen fibrin monomers fibrin clot
thrombin
F XIII
F XIIIa
plasmin
FDP fibrinogen
degradation products
D-Dimers (XDP)
D-Dimer is exclusively from fibrin clot
D D
D-Dimer for PE diagnosis
Overview of 9 trials (n = 908)
ELISA assay; 38% have positive scans/PA grams
Sensitivity Specificity PPV NPV
97% 45% 50% 94%
Thromb Haemostas 1994; 71:1-6
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
Electrocardiography • ECG is often abnormal (70% in patients
without preexisting cardiovascular disease)
• The findings are insensitive and nonspecific
• ECG changes are typically transient
• Serial tracings are often helpful
The most common abnormalities • Sinus tachycardia
• Atrial fibrillation
• Atrial flutter
• SVT
• Right ventricular strain
• Rt. axis deviation
• RBBB
• S1Q3T3
• T-wave inversion in the precordial leads
Sinus Tachycardia
RVH with Right Axis Deviation
S1Q3T3
Chest Radiography The most common finding is
Normal CXR
The most frequent abnormalities: • Atelectasis
• Elevated diaphragm
• Pleural effusion
• Pulmonary oligaemia
• Wedge-shaped pulmonary infarction
Atelectasis
Pulmonary
Infarction
Pulmonary
Infiltration
Pleural
Effusion
Ventilation/Perfusion Lung Scanning It was the most frequently used test to diagnose PE
The relationships between lung scanning and clinical assessment are:
• Normal
• Near Normal
• Low probability
• Intermediate probability
• High probability
V/Q Scan
• Normal perfusion lung scan virtually excluded
the diagnosis of pulmonary embolism
• Near normal scans marginal defects, not fully
normal scans
• High probability lung scan indicated a high
likelihood of emboli
•The combination of pre lung
scan clinical probability
assessment and lung scan
probability assessment are
complementary for the
diagnosis of PE
High probability lung scans
are insensitive for PE
Scan interpretation
Sensitivity (%)
Specificity (%)
High 41 97
59% of patients with PE have non-high probability scans
JAMA 1990; 263:2753-9
Perfusion Scan
• This perfusion scan shows multiple segmental perfusion defects at:
• The right apex
• The right base anterior
• The right base posterior
Perfusion Scan
This perfusion scan
demonstrates:
1. Blockage of almost
the entire left lung
2. Segmental defects on
the right lung
Perfusion Ventilation
Pulmonary Angiogram
It is undertaken if surgery is considered in acute massive PE
• It is the gold standard in the diagnosis of PE
• Two diagnostic criteria of PE
1. Intra-arterial filling defects
2. Complete obstruction (abrupt cutoff) of pulmonary
arterial branches
Pulmonary Angiogram
• Filling defect within the
interlobar branch of the
right pulmonry artery.
• This defect extended
into the middle lobe.
Pulmonary Angiogram
Spiral CT • Major advantage of Spiral CT is speed:
• Often the patient can hold their breath for the entire study, reducing motion artifacts.
• Allows for more optimal use of intravenous contrast enhancement.
• Spiral CT is quicker than the equivalent conventional CT permitting the use of higher resolution acquisitions in the same study time.
• Contraindicated in cases of renal disease.
• Sensitive for PE in the proximal pulmonary arteries, but less so in the distal segments.
CT Angiogram • Quickly becoming the test of choice for initial evaluation of a
suspected PE.
• CT unlikely to miss any lesion.
• CT has better sensitivity, specificity and can be used directly to screen for PE.
• CT can be used to follow up “non diagnostic V/Q scans.
CT Angiogram
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 (McConnell’s sign)
Echocardiogram suggesting a PE Diastole on the left, systole on the right
D sign: Secondary to high PA pressure
Lower Extremity Tests
• Assessment for DVT is helpful in the evaluation of
patients with intermediate clinical and scan probabilities
for pulmonary emboli
• Color-flow Doppler with compression ultrasound has
high sensitivity and specificity for the detection of a first
episode of proximal venous thrombosis
• Venography is the gold standard in the diagnosis of DVT
Venography for suspected PE
Venography Pulmonary angiography
Positive Negative
Positive 29 11
Negative 12 22
Total 41 33
Hull et al. Ann Intern Med 1983; 98:891
Prophylaxis
• The choice and intensity of prophylactic measures are
determined by clinical factors that predispose to venous
stasis and thromboembolism
Prophylactic Regimens
• Low-dose Unfractionated Heparin (LDUH)
• Low Molecular Weight Heparin (LMWH)
• Dextran infusion
• Warfarin
• Intermittent pneumatic compression (IPC)
• Graded compression elastic stockings
• Aspirin does not help prevent VTE in general
surgical patients.
Thromboprophylaxis
Treatment
Supportive Treatment
• Analgesics are given if pleuritic pain is severe
• Although anxiety is often prominent, sedatives should
be prescribed cautiously
• Continuous O2 should be given, usually by mask or
cannula
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 pts need adjustments Kidney dz, pregnancy, massive obesity may need
anti factor Xa monitoring
• Usefulness questioned as correlation with antithrombotic effect not clear
Heparin Treatment • IV loading dose of heparin 80 - 100 U/kg
• Heparin is given at a rate to keep the APTT at 1.5 to 2
times control [60 – 90]
• APTT may be checked q 6 h after treatment is initiated
• The maintenance dose by continuous infusion is usually
10 to 50 U/kg/h
• Generally PE patients need high doses of Heparin
Warfarin Therapy
• Oral warfarin may be initiated on the second day of
heparin therapy
• Warfarin and heparin should overlap for 5 to 7 days,
allowing warfarin to take effect
• The duration of anticoagulant therapy is adjusted
individually
• In some patients anticoagulation may be discontinued 3
to 6 months
• In others long-term or lifelong anticoagulant therapy is
required
Newer agents
• Fondaparinux
• Synthetic pentasaccharide with anti-Xa activity
• Once daily
• No adjustments
• No risk of HIT
Thrombolytic Therapy
• When massive PE is uncomplicated by hypotension or when
systolic BP can be maintained at 90 to 100 mm Hg with moderate
dosage of a vasopressor. Streptokinase, urokinase, and tPA
enhance the conversion of plasminogen to plasmin
Pulmonary Embolectomy • Should be considered when systolic BP is < 90 mm Hg,
urine output is < 20 mL/h, and PaO2 is < 60 mm Hg for as
long as 1 h after massive PE.
• Angiographic confirmation of PE is strongly advised before
embolectomy
• Inferior vena caval interruption and IV heparin therapy
generally follow the embolectomy
Inferior Vena Cava Umbrella
considered in certain situations
1. When anticoagulation is contraindicated
2. Emboli recur despite adequate anticoagulation
3. For septic pelvic thrombophlebitis with emboli only
when antibiotics and heparin fail
4. When pulmonary embolectomy is performed
Review
A 50-year-old man presents with a painful, swollen leg that occurred over 2
days. He smokes two packs of cigarettes per day, and he is moderately
overweight. He recalls striking his calf against a coffee table 3 days before
and suffered an abrasion. His temperature is 100.5°F, and the leg is visibly
swollen to the groin with moderate erythema. Pulses are normal. Which of
the following statements is correct?
• (A) Absence of palpable cords and a negative Homans’ sign make DVT
unlikely
• (B) The fever and erythema make a diagnosis of DVT very unlikely
• (C) The patient may be started on heparin anticoagulation immediately
• (D) Because there is no evidence of pulmonary embolism, the patient
may be started on coumadin alone
• (E) A venogram must be performed within 24 h
The answer is C • A patient with four or more risk factors has a high probability for
deep venous thrombosis (DVT). It is reasonable to start
anticoagulation with heparin or LMWH pending confirmation
with diagnostic studies. Coumadin should never be started alone
because it can cause a transient hypercoagulable state that
promotes thrombus propagation and embolization. Homans’ sign
has no clinical predictive value. A mild fever is consistent with
DVT, as is redness. Although venography was once the gold
standard test, duplex ultrasonography is currently favored.
All of the following statements are TRUE
about PE EXCEPT • (A) The risk for embolism from proximal DVT is highest in the
first week
• (B) The majority of the patients with PE have at least one risk
factor
• (C) Tachypnea is defined as a RR of greater than 16 breaths per
minute
• (D) Syncope is the presenting complaint in up to 5 percent of
cases
• (E) The right lower lobe is the most common part of the lung
involved
The answer is D. • PE presents with a syncopal episode up to 15 percent of the time.
Altered mental status and generalized seizures may also be the
presenting complaint, especially in the elderly. The most common
presenting symptoms are chest pain and dyspnea (up to 85
percent); anxiety occurs in more than 50 percent of PE patients.
Tachypnea (RR 16) is seen in more than 98 percent of all cases,
and tachycardia (resting HR 100) is seen in up to 44 percent of all
patients. Other signs are variable. The risk for embolism from
proximal DVT is highest in the first week of its formation.
Which one of the following has the highest
sensitivity for pulmonary embolism?
• (A) A high-probability ventilation-perfusion radionuclear scan
• (B) A medium-probability ventilation-perfusion radionuclear scan
• (C) A low-probability ventilation-perfusion radionuclear scan
• (D) Transesophageal echocardiography (TEE)
• (E) Dynamic (spiral) computed tomography (CT)
The answer is E
• The sensitivity of spiral CT for pulmonary embolism has been
reported at 86 to 91 percent. It exceeds that of V/Q scans and
TEE. Its specificity is nearly as good as that of a high-probability
V/Q scan. High- and medium-probability V/Q scans have a
higher specificity than low-probability scans. Their sensitivity
however, is significantly lower than that of dynamic CT.
Which one of the following V/Q findings (coupled with the
clinical description) is LEAST suggestive of pulmonary
embolism?
• (A) Multiple matched defects between ventilation and perfusion
scans with a low clinical index of suspicion
• (B) One moderately sized mismatched defect between ventilation
and perfusion scans with a low clinical index of suspicion
• (C) Bilateral mismatched defects between ventilation and
perfusion scans with a moderate clinical index of suspicion
• (D) A low-probability scan with a high clinical index of suspicion
• (E) An intermediate-probability scan with a low clinical index of
suspicion
The answer is A • Results of V/Q scanning must be used in conjunction with pretest
probability (clinical suspicion) to assess the likelihood of
pulmonary embolism. A mismatched defect between ventilation
and perfusion scans is most consistent with a pulmonary
embolism, and the scan would be read as moderate or high
probability. Bilateral mismatched defects between ventilation and
perfusion scans suggest a high probability of recurrent pulmonary
emboli. Many pulmonary diseases can cause ventilation and
perfusion abnormalities. These include COPD, pneumonia, and
chronic fibrosis. The V/Q scan is “low probability” when
matched, but no unmatched, defects are present. There is only
about a 4 percent incidence of pulmonary embolism if a low-
probability V/Q scan is coupled with a low clinical suspicion.
A 19-year-old normal nonsmoking woman has a
moderately severe pulmonary embolism while on oral
contraceptive pills. Which of the following is the most
likely predisposing factor?
• (A) Abnormal factor V
• (B) Abnormal protein C
• (C) Diminished protein C level
• (D) Diminished protein S level
• (E) Diminished antithromin III level
The answer is A • Many patients who develop pulmonary thromboembolism have an underlying
inherited predisposition that remains clinically silent until they are subjected to
an additional stress, such as the use of oral contraceptive pills, surgery, or
pregnancy. The most frequently inherited predisposition to thrombosis is so-
called activated protein C resistance. The inability of a normal protein C to carry
out its anticoagulant function is due to a missense mutation in the gene coding for
factor V in the coagulation cascade. This mutation, which results in the
substitution of a glutamine for an arginine residue in position 506 of the factor V
molecule, is designated the factor V Leiden gene. Based on the Physicians Health
Study, about 3% of healthy male physicians carry this particular missense
mutation. Carriers are clearly at an increased risk for deep venous thrombosis and
also for recurrence after the discontinuation of warfarin. The allelic frequency of
factor V Leiden is more common than are all other identified inherited
hypercoagulable states combined, including deficiencies of protein C, protein S,
and antithrombin III and disorders of plasminogen.
Thank You
Dr. Raed Abu Sham’a