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