Pulmonary Embolism: Latest Diagnostic & Management Strategies
Michael D. McGoon, MD
The VTE Continuum and Goals of Intervention
Proximal DVT
Risk of VTE
Distal (calf) DVT
Pulmonary Embolism
Death
Recurrence
Post-thrombotic syndrome
CTEPH
25%
50%
3.8% after 2 years Pengo, NEJM 2004
7% in 6 months
17% in 1 year; 28% in 5 years
See also Kearon Cl: Natural History of Venous Thromboembolism; Circulation 2003;107:I-22 - I-30
Venous Thromboembolism: PE - The Scope of the Problem (2004)
30% mortality if untreated (vs 2-8%)
10 -15% of deaths in acute care hospitals
100 - 200,000 deaths yearly (US)
> 50% are undiagnosed
<30% of fatal PE cases have prior DVT suspicion
Venous Thromboembolism: Risk Factors (Relative Risk)
Obesity, smoking, hypertension (2-3)
Oral contraceptives, estrogen modulators (5)
Cancer, acute illness in hospital (5-10)
Thrombophilia
Antithrombin III deficiency (5-50)
Homozygous factor V Leiden mutation (80)
Major trauma or surgery (200)
Venous Thromboembolism: Demographics of Risk (2004)
Brest District, France
Olmsted County, MN
US Hospital Survey (2004)
Afr Am, Whites
Population
VTE Incidence
1.22 – 1.83/1000
DVT 0.48 – 1.24
PE 0.34 – 0.69
US Hospital Survey (2004) AJC 2004;93:1194-1197
Asians, PI’s
Hong Kong 2004
0.23/1000
DVT 0.17 - 0.20
PE 0.039 – 0.05
Lower prevalence of Factor V Leiden and other thrombophilias in Asians
Deep Vein Thrombosis Evaluation of Suspected DVT (2004)
Clinical Probability
Low
High
D-dimer
No DVT
DVT
Duplex
US
Duplex
US
D-dimer
No DVT
Serial
US
Based on Circulation 2004, 109, I-9
pos
neg
pos
neg
neg
pos
neg
pos
neg
pos
Pulmonary Embolism Diagnosis - Ventilation Perfusion Scintigraphy
Normal scan essentially rules out PE
Sensitivity of “high-probability” scan is 41%
Everything in between is indeterminate
By 2001, less used than CT angio
Identifies PE in 14 - 44% of indeterminate VQ scans
Accurate to the segmental level
Can diagnose other intrathoracic diseases; can be combined with leg CT venography
Excellent outcome without anticoagulation after negative CT angio
Swenson et al, Mayo Clinic Proceedings 77:130-138, 2002
Faster, cheaper, less invasive, more widely available than pulmonary angio
Pulmonary Embolism Diagnosis - CT Angiography
Pulmonary Embolism Diagnosis - MR Angiography
No need for IV iodinated contrast material
Pulmonary vascular imaging may be combined with MR venography of the legs and pelvis (DVT)
Lower spatial resolution, longer acquisition time, more costly, less available than CT
Pulmonary Embolism Diagnosis - Pulmonary Angiography
Gold standard for the diagnosis of PE
Problems
Mortality <1%, morbidity 2-5%.
Disagreements in interpretation of results
False-positive results from non-embolic disorders, e.g., mediastinal disorder
Incomplete or nondiagnostic result in 4%.
Establish Pretest Probability; Image
CT or VQ normal
CT or VQ equivocal;
Prob low or mod
Duplex US
PE
No PE
CT or VQ equivocal; Prob high
CT or VQ high; prob...
Duplex US
PE
Pulm Angio
No PE
pos
neg
pos
neg
pos
neg
low
Mod or
high
Pulmonary Embolism Diagnosis (2004) - Algorithm
Treatment of VTE Mechanical Prophylaxis
Graduated compression stockings reduce DVT 72% after non-orthopedic surgery
Intermittent pneumatic compression devices prevent venous stasis and stimulate endogenous fibrinolysis
Treatment of VTE Traditional Anticoagulants
Unfractionated Heparin
Indirect thrombin inhibitor (requires antithrombin)
Accelerates inhibition of factor Xa and thrombin >1000X
Coumarins
Reduce Vitamin K dependent thrombin substrates, e.g. prothrombin
“Direct thrombin inhibitor”
Treatment of VTE Low Molecular Weight Heparins
Generally as effective as heparin
Less protein and endothelial binding
More predictable, longer half-life
Less bleeding
One/day dose without lab monitoring
Types
Enoxaparin (Lovenox) Dalteparin (Fragmin)
Ardeparin (Normiflo) Nadroparin (Fraxiparin)
Tinzaparin (Innohep) Reviparin (Clivarine)
Treatment of VTE Factor X Inhibitors
Fondaparinux (Arixtra)
Synthetic heparin pentasaccharide
Low risk of bleeding and HIT
=LMWH in DVT Buller: AIM 140:867;2004
= UFH in PE Matisse Inv: NEJM 349:1695;2003
FDA approved: prevention of DVT after hip fx (more effective than LMWH), knee/hip replacement
Treatment of VTE Direct Thrombin Inhibitors
Hirudin (lepirudin), Argatroban, Bivalirudin
Independent of antithrombin
For use in patients with heparin-induced thrombocytopenia
Ximelagatran (Exanta)
Oral, with rapid onset of action
= LMWH + warf after DVT JACC 2000;36:1336 (THRIVE)
Reduces recurrent VTE when used for 18 months after 6 months warfarin NEJM 349;1713,2003 (THRIVE III)
Risk of liver toxicity (4-10%)
Treatment of VTE Pharmacologic Prophylaxis
Post-operative patients
Fondaparinux (ortho) > LMWH > low dose UFH
Medical patients (acutely ill or long hospitalization)
LMWH – reduces risk for DVT or PE at 14, 21 and 110 days
Samama et al: NEJM 1999;341:793-800 (MEDENOX Study)
Leizorovicz et al: Circulation 2004;110:874-9 (PREVENT Study)
Treatment of VTE 2004
Anticoagulation contraindicated?
IVC Filter
Hx of HIT?
DTI (lepirudin)
Factor X Inhib (Fondaparinux)
Hospitalize for DVT?
Extensive iliofemoral DVT
Risk of bleeding
Admit
Heparin/LMWH or DTI, and warfarin
Long-term anticoagulation
Suspect PE?
High Risk PE?
Thrombolysis or Embolectomy
yes
no
yes
no
yes
no
yes
End
Recent Useful Reviews
Circulation, vol 109, 12 (supplement); March 30, 2004 Diagnosis of VTE
Circulation, vol 110, 9 (supplement); August 31, 2004 Treatment of VTE
CHEST, vol 126, 3 (supplement); September 2004 Antithrombotic and Thrombolytic Therapy Evidence-based Guidelines
Treatment of VTE IVC Filter
Indications
When anticoagulation cannot be used or doesn’t work
With surgical embolectomy or pulmonary endarterectomy
14% of DVT’s receive filter in US
Goldhaber et al, AJC 2004;93:259
5% Risk of PE; RR 2.6 rehospitalization for DVT recurrence
Consider retrievable filter for temporary need
Treatment of VTE Thrombolytic Treatment
Indications
Massive PE/hemodynamic instability
Free-floating RV thrombus or PFO
Limb-threatening DVT
More rapid thrombolysis than heparin alone
Reduces need to escalate therapy
No proven mortality benefit except in highest risk
1-3% risk of intracranial bleed
Treatment of VTE Pulmonary Embolectomy
Indications
Massive PE/Hemodynamic instability
Failure or contraindication for thrombolysis
Experienced cardiac surgical team available
Venous Thromboembolism: Demographics of Risk
450 - 600,000 episodes/year in US
Stein et al: Regional Differences in Rates of Diagnosis and Mortality of Pulmonary Thromboembolism; AJC 2004;93:1194-1197
Pulmonary Embolism Presentation
Asymptomatic (5%)
About 50% of DVT patients with PE - asymptomatic
70-90% of post-op patients with PE - asymptomatic
No symptoms of VTE in 1/2 of pts with chronic thromboembolic pulmonary hypertension
Syndrome of “uncomplicated” PE (22%)
Often atypical, s