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1. Acute Pulmonary Embolism
David Maldonado MD
Mayo Clinic
Rochester, MN, USA

2. Agenda
• Pathophysiology
• Risk Factors and Epidemiology
• Diagnosis
• Treatment
• Prophylaxis and Prevention
• Proposed Algorithms

3. Acute Pulmonary Embolism
• Part of a spectrum of venous thrombotic disease
• Severity from asymptomatic to sudden death
• Often occurs without prior warning
• Signs and symptoms are nonspecific and
therefore diagnosis often delayed or missed
• Treatments are effective in reducing risk of death
• Hospital-based prevention can reduce frequency

4. Tapson VF. N Engl J Med.
2008 Mar 6;358(10):1037-
52

5. Incidence
• 1 DVT/PE per 1,000 patient visits
• PE found in 10% of autopsies
• 83% of patients who died of PE also
had LE DVT on autopsy.
• Only 20% had LE symptoms
• Only 3% had undergone evaluation
for DVT/PE prior to death.
Sandler DA, Martin JF. J R Soc Med. 1989
Apr;82(4):203-5
Silverstein MD et al,
Arch Intern Med.
1998 Mar
23;158(6):585-93.

6. Risk Factors
• ACQUIRED:
• Older age
• Postoperative (joint replacement, hip fracture,
cancer surgeries)
• Trauma or spinal cord injury
• Malignancy
• Pregnancy, Oral contraceptives, Estrogen
• Prior venous thrombosis
• Obesity
• HEREDITARY:
• Protein C or S deficiency, Protein C resistance
• Antithrombin III deficiency
• (Factor V Leiden or Prothrombin mutation)

7. Age
Silverstein MD et al, Arch
Intern Med. 1998 Mar
23;158(6):585-93.

8. Thrombotic Risk in Asia
Is it Different?
• Obesity less common
• According to United Nations, only 10% older
than 65, vs 20-30% in Europe and U.S.
• Asian diet may reduce risk
• Factor V Leiden and Prothrombin mutation
absent
• Joint replacement surgery less common
Ho CH, et al. Am J Hematol 2000; 63:
74-8

9. SMART Study Group
• Analysis of published studies
• Malaysia, Thailand, Hong Kong, Korea, Singapore,
Taiwan, and Japan
• Postoperative thrombosis
• General surgery 13%
• Hip replacement 16%
• Knee replacement 50%
• Pulmonary embolus
• Total 2%
• Autopsy studies 6%
Leizorovicz A et al., Int J Angiol 2004; 13:
101-8

10. SMART Study
• Large (2420 patients), prospective, multinational
study
• Bangladesh, India, Indonesia, Malaysia, Pakistan,
Philippines, Singapore, South Korea, Taiwan, and
Thailand
• Orthopedic surgery patients treated without DVT/PE
prophylaxis
• Rate of symptomatic DVT/PE 1.2-2.3%
• Risk factors: History of venous thrombosis, CHF,
varicose veins
Leizorovicz A et al. J Thromb Haemost. 2005
Jan;3(1):28-34.

11. AIDA Study
(Venography)
Piovella F, et al., J Thromb Haemost
2005; 3: 2664-70

12. Diagnosis
• History
• Physical Examination
• Imaging Studies
• Laboratory Studies

13. Symptoms from History
• Dyspnea 73%
• Pleuritic pain 66%
• Cough 37%
• Leg swelling 28%
• Leg pain 26%
• Hemoptysis 13%
• Palpitations 10%
• Wheezing 9%
Stein PD et al., Chest 1991; 100:
598-608

14. Signs on
Physical Examination
• Tachypnea 70%
• Rales 51%
• Tachycardia 30%
• S4 24%
• Loud P2 23%
• Diaphoresis 11%
• Fever 7%
• Wheeze 5%
• Homan’s sign 4%
Stein PD et al., Chest 1991; 100: 598-
608

15. Wells, Ann Int Med, 2001;
135:98

16. Imaging Studies
• Chest X-ray
• Ventilation-perfusion (V/Q) Scan
• Contrast-enhanced CT Arteriography
• Magnetic Resonance Imaging (MRI)
• Echocardiography
• Lower Extremity Doppler Ultrasound
• Standard Pulmonary Angiography

17. Chest X-Ray
• Cannot diagnose or exclude PE
• Suggestive but infrequent signs
• Westermark’s Sign
• Hampton’s Hump
• Non-specific Signs
• Atelectasis
• Pleural Effusion
• Infiltrate
• Elevated Hemidiaphragm

18. Westermark’s Sign Hampton’s Hump

19. Ventilation-Perfusion (V/Q) Scan
• Interpretable best in the absence of
other underlying cardiopulmonary
disease
• Normal V/Q rules out PE
• High probability scan effectively rules
in PE and warrants treatment
• All other combinations require
further clinical judgement regarding
decision to treat

20. Contrast-Enhanced CT
Arteriography
• Faster than V/Q
• Visualization of other thoracic structures
• Emboli in main, lobar, and segmental
pulmonary arteries readily seen
• In patients suspected of PE who have
negative CT arteriography, the risk of
DVT/PE in 3 months 0.5%
• False positive studies very unusual
Swensen SJ et al., Mayo Clin Proc
2002; 77: 130-8

22. • MRI – can detect PE but speed, availability,
and cost currently prohibitive
• Echocardiography – findings of right heart
dysfunction suggestive of acute PE
• Lower Extremity Doppler Ultrasound –
consider in patients unable to tolerate
other diagnostic imaging
• Pulmonary Angiography – Major
complication rate 1-5%, Mortality 0.5-1.0%

23. Laboratory Studies
• Arterial Blood Gas –
• Neither sensitive nor specific
• Does not assist in diagnosis
• D-dimer (ELISA) - 96-98% sensitivity
• When negative in a patient with low-medium
suspicion, imaging not required
• In a patient of high PE suspicion, D-dimer
should not be used
• Troponin –
• Elevated levels often found in those who go
on to develop complications
• Brain Natriuretic Peptide –
• Compliments D-dimer and Troponin

24. EKG

25. Treatment
• Anticoagulation
• Thrombolytics
• Embolectomy
• Prophylaxis

26. Parenteral Anticoagulation to
Treat Acute PE
• Low Molecular Weight Heparin
• Unfractionated Heparin
• Pentasaccharide Fondaparinux
• Decrease clot burden without
thrombolysis
• Improve survival
• Should be started prior to imaging if
suspicion is high
• Lepirudin or Argatroban if HIT develops

27. Anticoagulation after
hospitalization
• While in hospital on parenteral
anticoagulation, warfarin should be
initiated with a target INR 2.0 to 3.0
• Duration depends on scenario
• Transient risk factor 3-6 months
• Idiopathic 6-12 months
• Malignancy (LMWH) indefinite
• Protein C/S, AT3 6-12 months
• 2 or more episodes indefinite
Buller HR et al., Chest2004;126:401S-
428S.)

28. Thrombolysis
• Tissue plasminogen activator (t-PA),
streptokinase, urokinase
• Accepted for PE with cardiogenic shock
• Data insufficient in submassive PE
• Elevated troponin and echocardiographic
RV failure may warrant thrombolysis
• Contraindications: recent trauma or major
surgery, bleeding, pregnancy,
intracranial/spinal/ocular disease

29. 03:30

30. Embolectomy
• Catheter-based Mechanical Embolectomy
• Surgical Embolectomy
• Not supported by evidence for most PE’s
• Mortality 20-70% for surgical embolectomy
• Only in “selected highly compromised patients
who are unable to receive thrombolytic
therapy or whose critical status does not allow
sufficient time to infuse thrombolytic therapy”
Buller HR et al.,
Chest2004;126:401S-428S.)

31. Prevention/Prophylaxis
• All hospitalized patient should be
considered and need assessed
• Medical prophylaxis superior to
mechanical
• LMWH superior to UFH in knee or hip
replacement, trauma, and spinal cord
injury
• LMWH equivalent to UFH in medical
inpatients

32. Potential Diagnostic Algorithm
• Low/moderate suspicion D-dimer
• D-dimer normal No treatment
• D-dimer abnormal CT Angio
• CT Angio normal No treatment
• CT Angio reveals PE Treatment
• CT Angio non-diagnostic Doppler U/S
• Doppler U/S normal No treatment
• Doppler U/S abnormal Treatment
• (No treatment still need DVT/PE prophylaxis as
inpatients)

33. High Suspicion Algorithm
• Consider treatment prior to testing with CT Angio
• CT Angio normal or nondiagnostic Doppler U/S
• CT Angio reveals PE Treatment
• Doppler U/S normal V/Q scan
• Doppler U/S reveals DVT Treat as PE
• V/Q scan low probability No treatment
• V/Q scan positive or indeterminate Treat

34. Treatment Algorithm
• Anticoagulation contraindicated IVC Filter
• All others LMWH or heparin
(Echo troponin, BNP)
• Echo, troponin, BNP abnormal Consider lytics
• Clinical shock Thrombolytics
• Thrombolytics contraindicated Embolectomy