Acute Pulmonary Embolism
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Transcript Acute Pulmonary Embolism
Coenie Koegelenberg
Division of Pulmonology, Department of Medicine
Incidence according to two UK studies:
1 in 1000 per year
Incidence doubles for
each 10-year age
Post mortem studies:
Microemboli are found in 60 % of autopsies
30 % of all inpatient deaths (western world)
Immediate Mortality of untreated PE: 30%
With treatment: 2-8%
International Co-operative PE Registry1:
Three-Month Mortality = 17.5 %
1. Kniffin WD Jr, et al. The
epidemiology of diagnosed
pulmonary embolism and
deep venous thrombosis
in the elderly. Arch Intern
Med 1994;154:861-866.
Rudolf Karl Ludwig Virchow (1856)
"Thrombose und Embolie"
Stasis
Hypercoagulability
Vascular injury
Arterial obstruction
Release of vasogenic peptides
Neurogenic broncho- & vasoconstriction
Increase in pulm vasc resistance
Increased alveolar dead space
Shunt / V/Q mismatch due to
atelectasis & alveolar oedema
Increased Raw
Decreased lung compliance
Hypoxaemia
Increase in pulm vasc resistance
Increased alveolar dead space
Shunt / V/Q mismatch due to
atelectasis & alveolar oedema
Increased Raw
Decreased lung compliance
RV
Afterload
Increased RV afterload
Increased wall tension RV
Dilatation RV Tricuspid prolapse
RCA compressed Ischaemia
Dysrythmias
RV Failure / Dysfunction
RV Dysfunction
Important prognostic
Implications
Septal shift to left
Underfilling of LV
Fall is CO Blood pressure
LV myocardial ischaemia
Circulatory collapse
DEATH
Analysis of the four major PE registries:
RH hypokinesis
Mortality
Normal Systemic BP
Doubling of mortality at 14 days
& 3 times higher at one year !
Three large trails (incl. MAPPET1):
Similar relationship RV dysf and mortality
RV dysfunction = adverse outcome
1. Konstantinides S, et al. Comparison of alteplase versus heparin for resolution of
major pulmonary embolism. Am J Cardiol. 1998;82:966-970
Acute PE - Spectrum that ranges from:
Clinically unimportant / incidental
Minor emboli ± infarction
Large pulmonary emboli
Massive emboli
Acute PE - Spectrum that ranges from:
Clinically unimportant / incidental
Minor emboli ± infarction
Haemoptysis
Pleuritic pain
Pulmonary signs
Large pulmonary emboli
Dyspnoea
Massive emboli
Ischaemic pain
Collapse
Cardiac signs
Diagnostic difficulties!
Signs / symptoms non-specific
Only 25% of suspected cases
actually have pulmonary emboli1,2
1. Lee AY, Hirsh J. Diagnosis and treatment of venous thromboembolism.
Annu Rev Med. 2002;53:15-33.
2. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute
pulmonary embolism: results of the Prospective Investigation of Pulmonary
Embolism Diagnosis (PIOPED).JAMA. 1990;263:2753-2759.
Modified Wells score1 (“dichotomised”)
≤ 4 PE
“unlikely”
Score
> 4 PE
“likely”
1. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to
categorize patients’ probability of pulmonary embolism: increasing the model’s
utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83:416-420.
D-Dimer
Patho-physiological background
D-Dimer
SA Labs < 0.25 mg/l
Quantitative D-Dimer (ELISA) > 500 ng/ml
Present in > 95 % of patients with PE
High sensitivity (>96 %)
Low specificity (AMI, pneumonia, etc)
High negative predictive value (99.0%)
Useful in excluding PE in outpatients
Not to be used to “diagnose” PE
D-Dimer
Quantitative D-Dimer (ELISA) > 500 ng/ml
Not useful in inpatients1:
AUC of ROC Curves
0.8 for outpatients
0.5 for inpatients
1. Schreceqost JE, et al. Comparison of diagnostic accuracies in
outpatients and hospitalized patients of D-dimer testing for the
evaluation of suspected pulmonary embolism.
Clin Chem. 2003;49(9):1483-90
Combing Clinical Probability & D-Dimer
Christopher Study1 (n = 3,306)
Dichotomized Wells score ≤ 4
D-Dimer ≤ 500 ng/ml
Negative predictive value > 99.5%
Useful in excluding PE in outpatients
Safe to withhold treatment
1. Van Belle A, et al. Effectiveness of Managing Suspected Pulmonary Embolism
Using an Algorithm Combining Clinical Probability, D-Dimer Testing, and
Computed Tomography. JAMA 2006;295(2):172-179
ABG
Hypoxaemia
Hypocapnia
Not specific or sensitive1
Biochemistry
Troponin T/I
Brain natriuretic peptide (BNP)
Surrogate markers for RV dysfunction
1. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute
pulmonary embolism: results of the Prospective Investigation of Pulmonary
Embolism Diagnosis (PIOPED).JAMA. 1990;263:2753-2759.
ECG
Sinus tachycardia
New onset / Paroxysmal AF/Afl/SVT
Right heart strain:
Right atrial enlargement
Partial/complete RBBB
RVH
T-wave inversion ant chest leads (V1-V4)
Classic: SI, QIII, TIII (rare)
Differential Diagnosis
CXR
Often normal
Linear atelectasis
Small effusions
Focal oligaemia
Peripheral wedge-shape densities
Palla’s sign: enlarged right descending
pulmonary artery
CXR
Often normal
Linear atelectasis
Small effusions
Focal oligaemia
Peripheral wedge-shape densities
Palla’s sign: enlarged right descending
pulmonary artery
CXR
Often normal
Linear atelectasis
Small effusions
Focal oligaemia
Peripheral wedge-shape densities
Palla’s sign: enlarged right descending
pulmonary artery
CXR
Often normal
Linear atelectasis
Small effusions
Focal oligaemia
Peripheral wedge-shape densities
Palla’s sign: enlarged right descending
pulmonary artery
Echocardiography
Rapidly gaining importance (risk stratify)
40 % have abnormalities:
RV pressure overload
McConnel sign:
Regional RV dysfunction
Apical wall motion remains normal
Hypokinesis of free wall
Dif Diagnosis:
AMI, Aortic dissection,
Pericardial tamponade
Echocardiography
V/Q – Scan
Perfusion: Tc-99M
Ventilation: Xenon
Underperfusion ~ V/Q mismatch
V/Q – Scan
Greatest limiting factors:
Structural lung disease
Availability
Often non-diagnostic (60%!)1
Still useful: peripheral small/multiple PEs
1. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute
pulmonary embolism: results of the Prospective Investigation of Pulmonary
Embolism Diagnosis (PIOPED).JAMA. 1990;263:2753-2759.
V/Q – Scan
Diagnostic in the minority (41% in PIOPED)
High Probability
PE Diagnosed
Intermediate Probability
Low Probability
Normal Scan
P
T
P
Non-diagnostic
PE Excluded
Helical CT Pulmonary Angiography (CTPA)
First line / principal imaging!!!
Has superseded VQ scans
Widely available, performed rapidly
Also provides alternative diagnoses
Attention to protocol…
•Collimation, pitch, volume, field
•Tube amperage
•Contrast injection and timing
Helical CT Pulmonary Angiography (CTPA)
Multidetector Row Helical CT Systems
•Additional detectors
•Rapid scanning vascular bed
(4 slice 3 x faster than SDCT)
•Narrow collimation (1.25 mm)
•Increased spatial resolution
May combine with Helical CT Venography
(see later)
Helical CT Pulmonary Angiography (CTPA)
Findings of Acute PE
Intraluminal filling defect surrounded by
contrast
Ancillary findings that are suggestive:
•Expanded unopicified vessels
•Eccentric filling defects
•Peripheral wedge-shaped consolidation
•Oligaemia
•Pleural effusion
Helical CT Pulmonary Angiography (CTPA)
Helical CT Pulmonary Angiography (CTPA)
Helical CT Pulmonary Angiography (CTPA)
Helical CT Pulmonary Angiography (CTPA)
Helical CT Pulmonary Angiography (CTPA)
Helical CT Pulmonary Angiography (CTPA)
Helical CT Pulmonary Angiography (CTPA)
Saddle Embolism: pre- & post- thrombolysis
Helical CT Pulmonary Angiography (CTPA)
Helical CT Pulmonary Angiography (CTPA)
Pitfalls
•
•
•
•
•
Lymph nodes
Impacted bronchi
Pulmonary artery catheters
Pulmonary sarcomas
Technical: Respiratory motion
Improper contrast
Incorrect reconstruction algorithms
Helical CT Pulmonary Angiography (CTPA)
Diagnostic accuracy
• Large central emboli
• Segmental (up to 5th)
• Small subsegmental
Sensitivity = 100%
Specificity = 100%
Sensitivity = 95-98%
Specificity = 97%
Sensitivity ?
Specificity ?
Relevance of small emboli?
Diagnostic accuracy equal to angiography!
Gold standard?
Helical CT Pulmonary Angiography (CTPA)
Best evidence – PIOPED II Study1
• n = 1 090 (Outpatients)
• Investigated the diagnostic accuracy of
multidetector CTA alone and
combined CTA–CTV (CT Venography)
1. Stein PD, et al. Multidetector Computer Tomography for Acute
Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327
Helical CT Pulmonary Angiography (CTPA)
Best evidence – PIOPED II Study1
• Redefined the “reference standard”
Abnormal VQ scan
Abnormal venous ultrasonography
Abnormal digital subtraction angiography
Subsequent events (F/U 3 and 6 months)
1. Stein PD, et al. Multidetector Computer Tomography for Acute
Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327
Helical CT Pulmonary Angiography (CTPA)
Best evidence – PIOPED II Study1
• CTA
Sensitivity = 83%
Specificity = 96%
PPV = 96%
• CTA-CTV
Sensitivity = 90%
Specificity = 95%
NPV = 97%
1. Stein PD, et al. Multidetector Computer Tomography for Acute
Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327
Helical CT Pulmonary Angiography (CTPA)
Best evidence – PIOPED II Study1
• Both have a high PPV with concordant clinical
assessment, but
• Additional testing is necessary when clinical
probability is inconsistent
1. Stein PD, et al. Multidetector Computer Tomography for Acute
Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327
Pulmonary Angiography
Gold Standard? Challenged in PIOPED II
Can detect emboli as small as 1 – 2 mm
Diagnostic: filling defects
Secondary signs:
‘Cut-off’ of vessels
Segmental oligaemia
Prolonged arterial phase, slow filling
Tapering of vessels
Alt: Digital subtraction angiography
Pulmonary Angiography
Pulmonary Angiography
Main Indications
Diagnostic dilemmas
Prior to catheter embolectomy
Mortality: 0.5%1
1. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute
pulmonary embolism: results of the Prospective Investigation of Pulmonary
Embolism Diagnosis (PIOPED).JAMA. 1990;263:2753-2759.
MRI
Limited use
Gadolinium-enhanced MR angiography
Anatomical features
RV motion
Evaluation for DVTs
Duplex Doppler
Compression Ultrasound
Venogram (diagnostic dilemmas)
MRI
Evaluation for DVTs
Helical CT Venography (CTV)
Simultaneous with CT Chest (3 min)
Single contrast dose
Can detect proximal (IVC) thrombi
Direct sign: intraluminal filling defect
Indirect signs: non-opacified segments,
acute venous distention,
and prolonged arterial filling
Evaluation for DVTs
Helical CT Venography (CTV)
Poplitial DVT
Evaluation for DVTs
Helical CT Venography (CTV)
Pelvic DVT
Evaluation for DVTs
Helical CT Venography (CTV)
Sensitivity: 93-100%
> 95% studies are adequate
Limitations: PVD, orthopaedic hardware
venous catheters
Evidence: PIOPED II1
1. Stein PD, et al. Multidetector Computer Tomography for Acute
Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327
Christopher Study1
n = 3306
Diagnostic strategy:
Clinical info (Wells)
D-Dimer
CT
1. Van Belle A, et al. Effectiveness of Managing Suspected Pulmonary Embolism Using an
Algorithm Combining Clinical Probability, D-Dimer Testing, and Computed Tomography.
JAMA 2006;295(2):172-179
Christopher Study1
NPV = 99.5%
Algorithm completed and allowed decision
making in 97.9%
“Effective”
“…low risk for subsequent fatal and nonfatal
VTE”
1. Van Belle A, et al. Effectiveness of Managing Suspected Pulmonary Embolism Using an
Algorithm Combining Clinical Probability, D-Dimer Testing, and Computed Tomography.
JAMA 2006;295(2):172-179
PE?
Clinical Probability: Wells Score
≤4
>4
Imaging, e.g. CTPA
PE?
Clinical Probability: Wells Score
≤4
>4
D-Dimer
≤ 0.5
> 0.5
Pulmonary Embolism excluded
Imaging, e.g. CTPA
PE?
Imaging
CT
VQ
Principle investigation
Contrast allergy
Structural lung disease
Renal Impairment
Availability
Normal lungs
Speed
Multiple PEs
PE?
N
Imaging
Treat
PE
Non Diagn
1
1 Am J Respir Crit Care
Med1999;160:1043-1066
PE?
N
Imaging
PE
Non Diagn
Stable
Unstable
Treat
PE?
Imaging
PE
Non Diagn
Stable
Unstable
Treat
PE
Pulm Angio
N
N
PE?
Imaging
Treat
PE
Non Diagn
Stable
PE
Unstable
Pulm Angio
DVT
Bilat lower extrem eval
N
N
N
Risk
Risk Stratification
Stratification
High Risk
Hypotension
RV Strain
Hypoxia
Lower Risk
Hypotension
RV Strain
Hypoxia
Risk
Risk Stratification
Stratification
Lower Risk
High Risk
Secondary Therapy
Primary Therapy
Thrombolysis
Embolectomy
Heparin
Adjuvant Therapy
Oxygen
Inotropes
Warferin
IVC Filter
Hypotension
RV Strain
Hypoxia
Risk
Risk Stratification
Stratification
Lower Risk
High Risk
Secondary Therapy
Heparin
Adjuvant Therapy
Oxygen
Inotropes
Warferin
IVC Filter
Adjuvant Therapy
Manage respiratory failure
Oxygen
Mechanical ventilation
Improve right ventricular function
Inotropes (Dobutamine)
Heparin
Still cornerstone of acute management
Unfractionated Heparin IV ?
Low-molecular-weight Heparin SC ?
Heparin
2007 ACP Guidelines1
Pooled data from 11 reviews
Outcome and safety at six months
1. Snow V, et al. Management of Venous Thromboembolism. Ann Intern
Med 2007;146:204-210
Heparin
2007 ACP Guidelines1
LMWH >> UH for DVT
LMWH = UH for PE
Outpatient treatment is safe
1. Snow V, et al. Management of Venous Thromboembolism. Ann Intern
Med 2007;146:204-210
Heparin
2007 ACP Guidelines1
LMWH well established role in:
Recurrent DVTs (therapeutic INR)
Problematic INR
Malignancies
1. Snow V, et al. Management of Venous Thromboembolism. Ann Intern
Med 2007;146:204-210
Heparin
CLOT Study1
Large prospective study
LMWH vs. Warfarin
High risk (recurrent, cancer, etc.)
One year follow up
Safe and effective
Similar to 9 smaller studies
1. Lee AY, et al. Low-molecular-weight heparin versus a coumarin for
the prevention of recurrent venous thromboembolism in patients with
cancer. N Engl J Med. 2003;349:146-53.
Warfarin
Still the oral anticoagulant of choice
Commence after initiating Heparin
Takes at least five days to deplete FII
Aim for INR of 2.0 – 3.0
Lower INR (1.5)
Better than controls
Worse than INR > 2
Warfarin
Duration
Clear precipitant
3 Months
No apparent cause
6 Months
Thrombophylia
Lifelong
1st Episode
?
2nd Episode
> 1 Year
Newer anticoagulants
Many new drugs (PO/SC/IV) in pipeline
NO evidence as yet that they are
equivalent to LMW Heparin or Warfarin
Concerns:
Efficacy
Safety
Cost
Target
IIa
VIIa/TF
Drug
Hirudin
Route
IV
Stautus
Indication
Approved
Heparin-induced thrombocytopenia
Not
approved
Unstable angina and non-ST elevation MI
Bivalirudin
IV
Approved
Alternative to heparin in patients undergoing percutaneous coronary interventions
Argatroban
IV
Approved
Heparin-induced thrombocytopenia
H376/95
PO
Phase III
Thromboprophylaxis in patients undergoing elective hip or knee arthroplasty;
treatment of venous thrombosis
Phase II
Alternative to warfarin in patients with atrial fibrillation
TFPI
IV
Phase III
Sepsis
NAPc2
SC
Phase II
Thromboprophylaxis in patients undergoing elective knee arthroplasty
Va/VIIIa
APC
IV
Phase III
Sepsis
Xa
Pentasaccharide
SC
Phase III
Thromboprophylaxis in patients undergoing fractured hip, elective hip, or knee
surgery
Treatment of venous thrombosis
DX-9065a
IV
Phase II
Unstable angina
SNAC/heparin
PO
Phase III
Thromboprophylaxis in patients undergoing elective hip or knee arthroplasty
Xa/IIa
Idraparinux
Pentasaccharide (MW = 1,853 Daltons)
Long t½ (200 hours)
Selective factor Xa inhibitor
Given once weekly (2.5 mg SC)
Idraparinux
Matisse Trial1
Open label
Daily acc weight
Vs. UFH
1. Buller HR, et al. Subcutaneous fondaparinux
versus intravenous unfractionated heparin
in the initial treatment of pulmonary embolism.
N Engl J Med 2003;349:1695-1702
Idraparinux
Van Gogh PE1
Open label - weekly (3-6 months)
Vs. LMWH & Warfarin
Could not show non-inferiority
Mortality:
6.4% - Idraparinux
4.4% - LMW Heparin & Warfarin
1 Unpublished…
Idraparinux
Van Gogh PE
IVC Filters
Randomised trial by Razavi1
Filters vs. Filters + Warfarin
2 Year follow up
20.8% vs. 11.6% recurrence (p = 0.02)
Safe…
1 Razavi MK, et al. Initial clinical results of tenecteplase (TNK) in catheterdirected thrombolytic therapy. J Endovasc Ther. 2002;9:593-598
IVC Filters
Randomised trial by Decousus1
Filters vs. LMW Heparin
2 Year follow up
OR = 1.87 (also no mortality benefit)
No advantage proximal free-floating
thrombi
Safe…
1 Decousus H, et al. A clinical trial of vena caval filters in the prevention of
pulmonary embolism in patients with proximal deep-vein thrombosis.
N Engl J Med. 1998;338:409-415
IVC Filters
The evidence – summery:
Safe
No benefit vs. LMWH
Relatively useless without Warfarin
IVC Filters
Limited indications:
Active haemorrhage
Absolute C/I anticoagulation
VTE despite therapeutic INR
(better to use LMW Heparin)
Thrombolytic Therapy ~ Background
Faster clot lysis
Dissolves obstruction
May reverse RV failure
Dissolves much of source
Decrease risk of recurrence
Well tolerated PE
~ excellent prognosis
Risks:
~ major haemorrhage:
1.8 – 6.3%
~ ICH: 1.2%
Thrombolytic Therapy ~ Evidence
PE with circulatory collapse
Single study1
n = 8, BP < 90 mmHg
4 thrombolysed (all survived)
All 4 NOT thrombolysed died
BTS Guidelines & FDA approval
based on this single study!
1. Jerjes-Sanchez C, et al. Streptokinase and heparin versus heparin in massive
pulmonary embolism: a randomised controlled trial. J Tromb Thrombolysis
1995;2:227-229
Thrombolytic Therapy ~ Evidence
PE with circulatory collapse
Compare to AMI thrombolysis
> 20 000 patients (multiple trails)
Easier to diagnose
Subgroup definition
(<12 hr, ST Elev)
Symptoms to thrombolysis in PEs:
3.7 +/- 0.2 days (vs 12 hr)
Pharmaceutical industry ‘not interested’
Thrombolytic Therapy ~ Evidence
PE without circulatory collapse
Submassive pulmonary emboli
Much less evidence
Only 9 randomised studies, N < 500
Not adequately powered to show
statistical benefit in mortality
Thrombolytic Therapy ~ Evidence
PE with RV dysfunction &
No haemodynamic compromise
MAPPET-1 1
Retrospective analysis showed
trends towards survival benefit
Limitations of this study:
Non-randomized & Retrospective
1. Konstantinides S, et al. Comparison of alteplase versus heparin for resolution of
major pulmonary embolism. Am J Cardiol. 1998;82:966-970
Thrombolytic Therapy ~ Evidence
PE with RV dysfunction &
No haemodynamic compromise
MAPPET-3 1
Largest ever, n = 247
Specifically looked at patients with
confirmed PE and RV dysfunction
1. Konstantinides S, et al. Heparin plus alteplase compared with heparin alone in
patients with submassive pulmonary embolism. N Eng J Med 2002;347:1143-1150
Thrombolytic Therapy ~ Evidence
PE with RV dysfunction &
No haemodynamic compromise
MAPPET-3 1
Patients with haemodynamic
instability were excluded
Heparin +/- rTPA (random, <96hr)
1. Konstantinides S, et al. Heparin plus alteplase compared with heparin alone in
patients with submassive pulmonary embolism. N Eng J Med 2002;347:1143-1150
Thrombolytic Therapy ~ Evidence
PE with RV dysfunction &
No haemodynamic compromise
MAPPET-3 1
Primary end points:
In-hospital deaths
Escalation of therapy
Inotropes
Intubation
CPR
Embolectomy
1. Konstantinides S, et al. Heparin plus alteplase compared with heparin alone in
patients with submassive pulmonary embolism. N Eng J Med 2002;347:1143-1150
Thrombolytic Therapy ~ Evidence
PE with RV dysfunction &
No haemodynamic compromise
MAPPET-3 1
Secondary end points:
Recurrent PEs
Major bleeding
Ischaemic stroke
1. Konstantinides S, et al. Heparin plus alteplase compared with heparin alone in
patients with submassive pulmonary embolism. N Eng J Med 2002;347:1143-1150
Thrombolytic Therapy ~ Evidence
PE with RV dysfunction &
No haemodynamic compromise
MAPPET-3 1
Prematurely discontinued (IA)
Major advantage with TPA
Primary endpoints much higher in
placebo group (p = 0.006)
1. Konstantinides S, et al. Heparin plus alteplase compared with heparin alone in
patients with submassive pulmonary embolism. N Eng J Med 2002;347:1143-1150
Thrombolytic Therapy ~ Evidence
PE with RV dysfunction &
No haemodynamic compromise
MAPPET-3 1
Probability of 30-day event-free
survival much higher in rTPA
group (p = 0.005)
1. Konstantinides S, et al. Heparin plus alteplase compared with heparin alone in
patients with submassive pulmonary embolism. N Eng J Med 2002;347:1143-1150
Thrombolytic Therapy ~ Evidence
PE with RV dysfunction &
No haemodynamic compromise
MAPPET-3 1
Difference were due to higher
incidence of escalation of therapy
in placebo group:
24.6 % vs 10.2 % (p = 0.004)
1. Konstantinides S, et al. Heparin plus alteplase compared with heparin alone in
patients with submassive pulmonary embolism. N Eng J Med 2002;347:1143-1150
Thrombolytic Therapy ~ Evidence
PE with RV dysfunction &
No haemodynamic compromise
MAPPET-3 1
Mortality was low in both groups,
thus no mortality benefit…
No increase in fatal haemorrhage
1. Konstantinides S, et al. Heparin plus alteplase compared with heparin alone in
patients with submassive pulmonary embolism. N Eng J Med 2002;347:1143-1150
Thrombolytic Therapy ~ Evidence
PE with RV dysfunction &
No haemodynamic compromise
MAPPET-3 1
Authors concluded:
“…alteplase can improve the clinical course of
stable patients with submassive pulmonary
embolism…”
1. Konstantinides S, et al. Heparin plus alteplase compared with heparin alone in
patients with submassive pulmonary embolism. N Eng J Med 2002;347:1143-1150
Thrombolytic Therapy ~ Evidence
PE with Hypoxaemia
PE severity vs. PaO2 or P(A-a)O21
Linear relationship:
% pulm vasc obstructed and PO2
PaO2 < 6.7 ~ > 50% of vasc obstr
PaO2 < 8.0 ~ worse prognosis2
1. McIntyre KM, et al. The haemodynamic response to pulmonary embolism in
patients without prior cardio-pulmonary disease. Am J Cardiol 1971;28:288-294
2. Wicki J, et al. Predicting adverse outcome in patients with acute pulmonary
embolism: a risk scor. Thromb Haemost 2000;84:548-552
Thrombolytic Therapy ~ Evidence
PE with Hypoxaemia
Thrombolysis – small open study1
n=4
Average PaO2 = 7.81 (on max FiO2)
tPA
All 4 sats > 95 % next day
No major complications
1. Loebinger MR, et al. Thrombolysis in pulmonary embolism: are we under-using it?
Q J Med 2004;97:361-364
Thrombolytic Therapy ~ Evidence
PE with patent foramen ovale
Large PE & patent foramen ovale
Severe hypoxia due to R – L shunt
(R atrial hypertension)
Independent predictor of mortality1
1. Konstantinides S, et al. Patent foramen ovale is an important predictor of adverse
outcome in pateints with major pulmonary embolism. Circulation 1998;97:1946-1951
Thrombolytic Therapy ~ Controversy
For the ‘diehard’ EBM Clinician
Circulatory collapse (BP < 90) BTS
Sin. “Massive” PE FDA
Limited evidence, serious consideration1
RV dysfunction (no haemodynamic
compromise)
Respiratory failure (ventilatory support)
Respiratory failure & PFO
1. Konstantinides S. Should thrombolytic therapy be used in patients with pulmonary
embolism? Am J Cardiovasc Drugs. 2004;4:69-74
Thrombolytic Therapy ~ Controversy
For the ‘diehard’ EBM Clinician
Circulatory collapse (BP < 90) BTS
Sin. “Massive” PE FDA
Limited evidence ? Cost-effectiveness1
RV dysfunction (no haemodynamic
compromise)
Respiratory failure (ventilatory support)
Respiratory failure & PFO
1. Daniella J. Effectiveness and Cost-effectiveness of Thrombolysis in Submassive
pulmonary embolism. Arch Intern Med 2007;167:74-80
Thrombolytic Therapy ~ The agents
Streptokinase:
250 000 IU over 30 – 60 min
100 000 IU / hr for 24 hours
rTPA
10 mg stat (1-2 minutes)
90 mg (over 2 hours)
Maximum: 1.5 mg / kg (< 65 kg)
Neoplasms
Thrombophylias
Neoplasms
CXR
Abdominal +/- pelvic ultrasound
PSA
According to clinical setting…
Thrombophylia Screening:
Inherited / acquired defects in haemostasis
Predispose to venous / arterial thrombosis
Consider in patients with:
Recurrent DVTs
Venous thrombosis < 40 yr
Unusual DVTs (mesenteric)
Neonatal thrombosis
Recurrent miscarriages
Arterial thromboses with no PVD
Thrombophylia Screening:
Polycythaemia & Thombocythaemia
Activated Prot C resistance (Assay)
Factor V Leiden (Molecular)
Hyperhomocysteinaemia
AFL Syndrome / Anti-Cardiolipin ABs
ATIII Deficiency
Protein C
Protein S
Thrombophylia Screening:
Polycythaemia & Thombocythaemia
Activated Prot C resistance Common!
Factor V Leiden
Common!
Hyperhomocysteinaemia
Treatable!
AFL Syndrome
Intensive therapy!
ATIII Deficiency
Protein C
Rare!
Protein S
Thrombophylia Screening:
Polycythaemia & Thombocythaemia
Activated Prot C resistance Common!
Factor V Leiden
Common!
Hyperhomocysteinaemia
Treatable!
AFL Syndrome
Intensive therapy!
ATIII Deficiency
Protein C
Rare!
Protein S
Keep in mind:
ATIII, Prot C & S during acute event
Heparin ATIII
Warfarin Prot C & S
Pregnancy and OCP Prot S
ATIII, Prot C & S deficiencies are rare
Use the Wells score and D-Dimer to exclude
Spiral CT scanning is now well established
as the primary imaging modality
LMW Heparin and Warfarin are still the
agents of choice
IVC filters and newer drugs thus far
disappointing
Thrombolysis remains controversial