Pulmonary Embolism

1
Pulmonary Embolism

• Todd A. May, M.D.
• Director, Family Practice Inpatient Service
• San Francisco General Hospital
• Associate Clinical Professor
• University of California, San Francisco

2
PE A Clinical Challenge

• Common 250,000 cases/year
• Mimics many other illnesses
• Potentially fatal (15)
• Treatment potentially dangerous
• No single reliable diagnostic test
• Under- and over-diagnosed

3
Diagnostic Testing

• No single noninvasive test is sufficiently
  sensitive or specific to diagnose or exclude PE
  in all patients
• No single test can reliably rule out PE
• Yep, that includes CT Angio (right?)

4
Clinical Approach

• Consider PE in DDx
• Stratify risk for PE (HP, initial lab)
• Select appropriate diagnostic test(s)
• Interpret results in clinical context
• Select therapy based on clinical status

5
Risk Factors

• General
• Hypercoagulability
• Stasis
• Vascular injury

6
Clinical Presentation

• 97 with PE have at least one of the following
• Dyspnea
• Tachypnea
• Pleuritic pain
• Presence should trigger initial suspicion

7
Clinical Presentation

• Symptoms
• Dyspnea, pleuritic chest pain
• Cough, hemoptysis, syncope
• Signs
• Tachypnea, tachycardia
• JVD, loud P2, TR murmur, rales
• Signs of DVT

8
Chest Radiograph
9
Electrocardiogram
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Oxygenation

• Pulse Oximetry (SpO2)
• Normal SpO2 does not exclude PE
• Interpret with RR
• ABG
• ? pO2 ? pCO2
• Increased A-a gradient

11
Risk Stratification

• Determine probability of PE
• Low
• Moderate
• High
• Overall clinical impression
• Models/scoring systems

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PE Probability Prediction Rule
13
D-Dimers

• Valuable screening test
• High sensitivity low specificity
• Helpful only if Negative
• Strong Negative Predictive Value-- Rules out PE
  when low probability
• Safe, noninvasive
• Rapid, inexpensive

14
D-Dimers

• Available assays
• Standard ELISA
• Latex agglutination
• Erythrocyte agglutination (SimpliRED)
• Turbidimetric assay (Liatest)
• Rapid ELISA (VIDAS)
• Immunofiltration (NycoCard)

15
V/Q Scan
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V/Q Lung Scan

• Normal V/Q Sensitivity 99
• Rules out PE
• High Prob V/Q Specificity 96
• Rules in PE
• But, gt60 nondiagnostic
• Takes gt2 hr to perform
• Not available at all times

17
V/Q Lung Scan
PIOPED. JAMA. 1990 2632753-59
18
Ultrasound for DVT

• Positive test
• Inability to compress femoral or popliteal vein
• Positive Predictive Value 97
• Negative test
• Full compressibility
• Negative Predictive Value 98
• Kearon et al. Ann Intern Med. 1998 1291044-49

19
Ultrasound and PE

• US DVT in 30-50 with PE
• Positive USconfirms PE
• Negative ultrasound
• PE less likely, but not excluded
• Sequential ultrasound
• Persistently negative ultrasound at 1-2 wks ? lt2
  DVT/PE at 6mos
• Hull et al. J. Thromb 1996 35-8.

20
CT Angiogram
21
CT Angiogram

• Benefits
• Available
• Direct image
• Alternative Dx
• Pelvic/leg veins

• Limitations
• IV contrast
• Expensive
• Patient cooperation
• Uncertain sens/spec

22
CT Angiogram

• Helical CT is a reliable imaging tool for
  excluding clinically important PE

Goodman LR et al. Radiology 2000215535-42.
23
CT Angiogram

• 1015 patients evaluated for PE
• Nonrandomized, not controlled
• Two diagnostic arms recommended
• Substantial differences between groups
• 285 patients with negative CT Angio
• 22 were treated anyway
• lt 2 risk of subsequent PE in 3 months
• Only 70 completed 3mo f/u!

24
CT Angiogram

• Prospective study of consecutive, nonselected
  patients in a Geneva ER included 299 with
  suspected PE
• 39 had confirmed PE
• High prob V/Q, US, or Angio
• CT Sensitivity 70
• CT Specificity 91
• Perrier et al. Ann Intern Med. 2001 13588-97

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CT Angiogram

• 35 false negative on CT
• 19 High prob V/Q
• 12 DVT on US
• 3 Angio
• 1 Dx at f/u
• CT should not be used alone for suspected PE,
  but combining tests improves accuracy and reduces
  need for angiography

26
CT Angiogram
27
CT Angiogram

• New Systematic Review
• 15 studies met criteria
• VTE after negative CT Angio
• NLR 0.07
• NPV 99.1
• The clinical validity of using CT to r/o PE is
  similar to that reported for pulmonary
  angiography

Quiroz R et al. JAMA 20052932012-17.
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Two Cases of Pulmonary Embolism as Shown on
Contrast-Enhanced 16-Slice Multidetector-Row
Computed Tomography
Goldhaber, S. Z. N Engl J Med 20053521812-1814
29
Multidetector-Row CT

• 756 consecutive pts 194 with PE
• 82 High Prob 78/82 CT, 1 US/-CT
• 674 Lower Prob
• 232 neg D-dimer ? no TE
• 109 CT
• 318 neg dimer and CT ? 3 TE at 3mo
• Neg CT plus Neg D-dimer 1 risk for TE at 3
  months

Perrier A et al. NEJM 20053521760-8.
30
CT Angiogram

• My Conclusions
• CT Angio is good and getting better
• Its not perfect, so dont over-rely on it
• Do additional testing if clinical suspicion is
  high
• Neg D-dimer plus neg MDR CT may be best to
  confidently r/o PE

31
MRI/MRA

• No radiation or contrast exposure
• Expensive
• Not uniformly available
• Limited data
• Role not established

32
Echocardiogram
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Pulmonary Angiogram

• Gold standard
• 98 Sensitive
• 97 Specific
• Complications
• Death 0.5
• Major non-fatal 1
• Minor 5

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Diagnostic Summary

• Determine pre-test probabilitybe selective when
  deciding to w/u
• D-Dimers to r/o PE if low prob.
• CT or V/Q (US first if DVT likely)
• Bilat. LE US if V/Q non-diagnostic and/or CT neg.
  and suspicion persists
• Then,
• Serial US if moderate/high prob.
• Angiogram if still high prob.

35
Treatment
36
Unfractionated Heparin

• Weight-based dosing (nomogram)
• IV bolus, then infusion
• Monitor PTT (1.5-2.0 x), CBC
• Continue ?4-5d and therapeutic on Warfarin for 2d
  (INRgt2.0)

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Low Molecular Weight Heparin

• Alternative regimen
• Better bioavailability, longer half-life, more
  predictable effect
• No monitoring of PTT (follow CBC)
• Contraindications renal failure (CrCllt30),
  weight extremes

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Warfarin

• Start when therapeutic on Heparin
• Monitor INR daily
• Goal INR 2.0-3.0 for 3-6 months

39
Duration of anticoagulation

• Identified precipitant 3 mos
• First idiopathic episode 6 mos
• Prolonged/indefinite
• ? 2 thrombotic episodes
• 1 spont. life-threatening episode
• Anti-phospholipid antibody syndrome, ATIII
  deficiency

40
Thrombolysis

• Massive PE
• Acute pulmonary hypertension
• RV dysfunction
• Systemic hypotension
• All age groups benefit
• Addition to Heparin therapy
• Various agents appear equivalent

41
Thrombectomy

• Surgical or transvenous (catheter)
• When thrombolysis unsuccessful or
  contraindicated, or
• Massive PE

42
Vena Cava Filters

• Indications
• Contraindication to anticoagulation
• Recurrent PE on anticoagulation
• Complications from anticoagulation
• Massive PE with poor reserve
• Problems with filter thrombosis

43
Prevention

• Identify and minimize risk factors
• Pneumatic compression devices
• S.Q. Heparin
• Unfractionated
• Low molecular weight

44
Thrombophilia evaluation

• Hypercoagulable states

45
Thrombophilia evaluation

• Why test for hypercoagulability?
• May affect intensity/duration of treatment
• Family counseling about risks
• Identify need for prophylaxis in higher risk
  situations

46
Risks of Venous Thrombosis
47
Thrombophilia evaluation

• Unprovoked thrombotic event and
• Age lt 45 yrs
• Recurrent event
• Family history of thrombosis
• Cerebral/visceral thrombosis
• Fetal demise
• 3 or more SABs

48
Thrombophilia evaluation

• First unprovoked event
• Provoked by pregnancy
• Provoked by OCs or HRT

49
Thrombophilia evaluation

• Testing caveats
• C, S, ATIII ? in acute thrombosis
• Heparin interferes with ATIII, lupus
  anticoagulant, Factor VIII, and some APC
  resistance tests
• Warfarin decreases C S

50
Thrombophilia evaluation

• Tests performed acutely
• Leiden Factor V (APC resistance)
• Prothrombin G20210A mutation
• Increased homocysteine
• Anti-cardiolipin antibodies

51
Thrombophilia evaluation

• Consider testing later
• Lupus anticoagulant
• Decreased Proteins C S
• Decreased Anti-thrombin III
• Increased Factor VIII

52
Summary

• Have index of suspicion for PE
• Develop clinical probability
• Interpret all tests in context of pre-test
  probability
• Selectively w/u for thrombophilia
• Choose therapy based on clinical status