ACUTE

1
ACUTE PULMONARY EMBOLISM
An Update On
Diagnosis Treatment
Coenie Koegelenberg Division of Pulmonology,
Department of Medicine
2
Background
ð Incidence according to two UK studies ð 1 in
1000 per year ð Incidence doubles for each
10-year ñ age ð Post mortem studies ð
Microemboli are found in 60 of autopsies ð 30
of all inpatient deaths (western world)
3
Background
ð Immediate Mortality of untreated PE 30 ð
With treatment 2-8 ð 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 1994154861-866.
4
Background

ð Rudolf Karl Ludwig Virchow (1856) "Thrombose
und Embolie" ð Stasis ð Hypercoagulability
ð Vascular injury
ð Stasis ð Hypercoagulability ð Vascular
injury
5
Pathophysiology
ð Arterial obstruction ð Release of vasogenic
peptides ð Neurogenic broncho-
vasoconstriction
6

Pathophysiology
ð Increase in pulm vasc resistance ð Increased
alveolar dead space ð Shunt / V/Q mismatch due
to atelectasis alveolar oedema ð Increased
Raw ð Decreased lung compliance
Hypoxaemia
7

Pathophysiology
ð Increase in pulm vasc resistance ð Increased
alveolar dead space ð Shunt / V/Q mismatch due
to atelectasis alveolar oedema ð Increased
Raw ð Decreased lung compliance
RV
Afterload
8

Pathophysiology

• ð Increased RV afterload
• ð Increased wall tension RV
• ð Dilatation RV è Tricuspid prolapse
• ð RCA compressed è Ischaemia
• ð Dysrythmias
• ð RV Failure / Dysfunction

9

Pathophysiology
Important prognostic
Implications

• ð RV Dysfunction
• ð Septal shift to left
• ð Underfilling of LV
• ð Fall is CO è ò Blood pressure
• ð LV myocardial ischaemia
• ð Circulatory collapse
• ð DEATH

10

Pathophysiology
ð Analysis of the four major PE registries ð
RH hypokinesis ð Normal Systemic
BP ð Doubling of mortality at 14 days
3 times higher at one year ! ð Three large
trails (incl. MAPPET1) Similar relationship
RV dysf and mortality ð RV dysfunction
adverse outcome 1. Konstantinides S, et al.
Comparison of alteplase versus heparin for
resolution of major pulmonary embolism. Am J
Cardiol. 199882966-970
Mortality
11

Presentation
ð Acute PE - Spectrum that ranges from ð
Clinically unimportant / incidental ð Minor
emboli infarction ð Large pulmonary
emboli ð Massive emboli
12

Presentation
ð Acute PE - Spectrum that ranges from ð
Clinically unimportant / incidental Haemop
tysis ð Minor emboli infarction Pleuritic
pain Pulmonary signs ð Large pulmonary
emboli Dyspnoea Ischaemic pain ð
Massive emboli Collapse Cardiac signs

13

Presentation
ð Diagnostic difficulties! ð Signs / symptoms
non-specific ð Only 25 of suspected cases
actually have pulmonary emboli1,2 1. Lee
AY, Hirsh J. Diagnosis and treatment of venous
thromboembolism. Annu Rev Med.
20025315-33. 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. 19902632753-2759.
14

Presentation
ð Modified Wells score1 (dichotomised)
1. Wells PS, Anderson DR, Rodger M, et al.
Derivation of a simple clinical model to
categorize patients probability of pulmonary
embolism increasing the models utility
with the SimpliRED D-dimer. Thromb Haemost.
200083416-420.
4 PE unlikely gt 4 PE likely
Score
15

Special Investigations
ð D-Dimer ð Patho-physiological background
16

Special Investigations

• ð D-Dimer
• ð Quantitative D-Dimer (ELISA) gt 500 ng/ml
• ð Present in gt 95 of patients with PE
• ð High sensitivity (gt96 )
• ð Low specificity (AMI, pneumonia, etc)
• ð High negative predictive value (99.0)
• ð Useful in excluding PE in outpatients
• ð Not to be used to diagnose PE

SA Labs lt 0.25 mg/l
17

Special Investigations
ð D-Dimer ð Quantitative D-Dimer (ELISA) gt 500
ng/ml ð Not useful in inpatients1 ð 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. 200349(9)1483-90
18

Special Investigations

• ð Combing Clinical Probability D-Dimer
• ð Christopher Study1 (n 3,306)
• ð Dichotomized Wells score 4
• ð D-Dimer 500 ng/ml
• ð Negative predictive value gt 99.5
• ð Useful in excluding PE in outpatients
• ð 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 2006295(2)172-179

19

Special Investigations
ð ABG ð Hypoxaemia ð Hypocapnia ð Not
specific or sensitive1 ð Biochemistry ð
Troponin T/I ð Brain natriuretic peptide (BNP)
ð 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. 19902632753-2759.
20

Special Investigations

• ð ECG
• ð Sinus tachycardia
• ð New onset / Paroxysmal AF/Afl/SVT
• ð Right heart strain
• ð Right atrial enlargement
• ð Partial/complete RBBB
• ð RVH
• ð T-wave inversion ant chest leads (V1-V4)
• ð Classic SI, QIII, TIII (rare)
• ð Differential Diagnosis

21

Special Investigations
ð CXR ð Often normal ð Linear atelectasis ð
Small effusions ð Focal oligaemia ð Peripheral
wedge-shape densities ð Pallas sign enlarged
right descending pulmonary artery
22

Special Investigations
ð CXR ð Often normal ð Linear atelectasis ð
Small effusions ð Focal oligaemia ð Peripheral
wedge-shape densities ð Pallas sign enlarged
right descending pulmonary artery
23

Special Investigations
ð CXR ð Often normal ð Linear atelectasis ð
Small effusions ð Focal oligaemia ð Peripheral
wedge-shape densities ð Pallas sign enlarged
right descending pulmonary artery
24

Special Investigations
ð CXR ð Often normal ð Linear atelectasis ð
Small effusions ð Focal oligaemia ð Peripheral
wedge-shape densities ð Pallas sign enlarged
right descending pulmonary artery
25

Special Investigations
ð Echocardiography ð Rapidly gaining
importance (risk stratify) ð 40 have
abnormalities ð RV pressure overload ð
McConnel sign Regional RV
dysfunction Apical wall
motion remains normal
Hypokinesis of free wall ð Dif Diagnosis
AMI, Aortic dissection,
Pericardial tamponade
26

Special Investigations
ð Echocardiography
27

Special Investigations
ð V/Q Scan ð Perfusion Tc-99M ð
Ventilation Xenon ð Underperfusion V/Q
mismatch
28

Special Investigations

• ð V/Q Scan
• ð Greatest limiting factors
• ð Structural lung disease
• ð Availability
• ð Often non-diagnostic (60!)1
• ð 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.
  19902632753-2759.

29

Special Investigations

• ð V/Q Scan
• ð Diagnostic in the minority (41 in PIOPED)
• High Probability PE
  Diagnosed
• Intermediate Probability
• 
  Non-diagnostic
• Low Probability
• Normal Scan PE
  Excluded

PTP
30

Special Investigations

• ð Helical CT Pulmonary Angiography (CTPA)
• ð First line / principal imaging!!!
• ð Has superseded VQ scans
• ð Widely available, performed rapidly
• ð Also provides alternative diagnoses
• ð Attention to protocol
• Collimation, pitch, volume, field
• Tube amperage
• Contrast injection and timing

31

Special Investigations

• ð Helical CT Pulmonary Angiography (CTPA)
• ð 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
• ð May combine with Helical CT Venography
• (see later)

32

Special Investigations

• ð Helical CT Pulmonary Angiography (CTPA)
• ð Findings of Acute PE
• ð Intraluminal filling defect surrounded by
  contrast
• ð Ancillary findings that are suggestive
• Expanded unopicified vessels
• Eccentric filling defects
• Peripheral wedge-shaped consolidation
• Oligaemia
• Pleural effusion

33

Special Investigations
ð Helical CT Pulmonary Angiography (CTPA)

34

Special Investigations
ð Helical CT Pulmonary Angiography (CTPA)

35

Special Investigations
ð Helical CT Pulmonary Angiography (CTPA)

36

Special Investigations
ð Helical CT Pulmonary Angiography (CTPA)

37

Special Investigations
ð Helical CT Pulmonary Angiography (CTPA)

38

Special Investigations
ð Helical CT Pulmonary Angiography (CTPA)
39

Special Investigations
ð Helical CT Pulmonary Angiography (CTPA)
Saddle Embolism pre- post- thrombolysis
40

Special Investigations
ð Helical CT Pulmonary Angiography (CTPA)

41

Special Investigations

• ð Helical CT Pulmonary Angiography (CTPA)
• ð Pitfalls
• Lymph nodes
• Impacted bronchi
• Pulmonary artery catheters
• Pulmonary sarcomas
• Technical Respiratory motion
• Improper contrast
• Incorrect reconstruction algorithms

42

Special Investigations

• ð Helical CT Pulmonary Angiography (CTPA)
• ð Diagnostic accuracy
• Large central emboli Sensitivity 100
• Specificity 100
• Segmental (up to 5th) Sensitivity 95-98
• Specificity 97
• Small subsegmental Sensitivity ?
• Specificity ?
• Relevance of small emboli?
• Diagnostic accuracy equal to angiography!
• Gold standard?

43

Special Investigations

• ð Helical CT Pulmonary Angiography (CTPA)
• ð Best evidence PIOPED II Study1
• n 1 090 (Outpatients)
• Investigated the diagnostic accuracy of
  multidetector CTA alone and
• combined CTACTV (CT Venography)

1. Stein PD, et al. Multidetector Computer
Tomography for Acute Pulmonary Embolism. N
Engl J Med 2006354(22)2317-2327
44

Special Investigations

• ð Helical CT Pulmonary Angiography (CTPA)
• ð 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 2006354(22)2317-2327
45

Special Investigations

• ð Helical CT Pulmonary Angiography (CTPA)
• ð 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 2006354(22)2317-2327
46

Special Investigations

• ð Helical CT Pulmonary Angiography (CTPA)
• ð 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 2006354(22)2317-2327
47

Special Investigations

• ð Pulmonary Angiography
• ð Gold Standard? Challenged in PIOPED II
• ð Can detect emboli as small as 1 2 mm
• ð Diagnostic filling defects
• ð Secondary signs
• ð Cut-off of vessels
• ð Segmental oligaemia
• ð Prolonged arterial phase, slow filling
• ð Tapering of vessels
• ð Alt Digital subtraction angiography

48

Special Investigations
ð Pulmonary Angiography
49

Special Investigations

• ð Pulmonary Angiography
• ð Main Indications
• ð Diagnostic dilemmas
• ð Prior to catheter embolectomy
• ð Mortality 0.51
• 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.
  19902632753-2759.

50

Special Investigations
ð MRI ð Limited use ð Gadolinium-enhanced
MR angiography ð Anatomical features ð RV
motion
51

Special Investigations

ð Evaluation for DVTs ð Duplex Doppler ð
Compression Ultrasound ð Venogram
(diagnostic dilemmas) ð MRI
52

Special Investigations

• ð Evaluation for DVTs
• ð Helical CT Venography (CTV)
• ð Simultaneous with CT Chest (3 min)
• ð Single contrast dose
• ð Can detect proximal (IVC) thrombi
• ð Direct sign intraluminal filling defect
• ð Indirect signs non-opacified segments,
  acute venous distention,
• and prolonged arterial filling

53

Special Investigations

• ð Evaluation for DVTs
• ð Helical CT Venography (CTV)

Poplitial DVT
54

Special Investigations

• ð Evaluation for DVTs
• ð Helical CT Venography (CTV)

Pelvic DVT
55

Special Investigations

• ð Evaluation for DVTs
• ð Helical CT Venography (CTV)
• ð Sensitivity 93-100
• ð gt 95 studies are adequate
• ð Limitations PVD, orthopaedic hardware
• venous catheters
• ð Evidence PIOPED II1

1. Stein PD, et al. Multidetector Computer
Tomography for Acute Pulmonary Embolism. N
Engl J Med 2006354(22)2317-2327
56

Diagnostic Pathway

• ð Christopher Study1
• ð n 3306
• ð 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
2006295(2)172-179
57

Diagnostic Pathway

• ð Christopher Study1
• ð NPV 99.5
• ð Algorithm completed and allowed decision
• making in 97.9
• ð Effective
• ð 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
2006295(2)172-179
58

Practical Approach
PE?
Clinical Probability Wells Score
4
gt 4
Imaging, e.g. CTPA

59

Practical Approach
PE?
Clinical Probability Wells Score
4
gt 4
D-Dimer
Imaging, e.g. CTPA
0.5
gt 0.5

Pulmonary Embolism excluded
60

Practical Approach
PE?
Imaging
?
CT
VQ
Contrast allergy Renal Impairment Normal lungs
Multiple PEs
Principle investigation Structural lung
disease Availability Speed
61

Practical Approach
PE?
Treat
Imaging
N
PE
Non Diagn
1
1 Am J Respir Crit Care Med19991601043-1066
62

Practical Approach
PE?
Treat
Imaging
N
PE
Non Diagn
Stable
Unstable
63

Practical Approach
PE?
Treat
Imaging
N
PE
Non Diagn
PE
Stable
Unstable
Pulm Angio
N
64

Practical Approach
PE?
Treat
Imaging
N
PE
Non Diagn
PE
Stable
Unstable
Pulm Angio
N
DVT
Bilat lower extrem eval
N
65

Management
Hypotension RV
Strain
Hypoxia

• Risk Stratification

• Risk Stratification

Lower Risk
High Risk
66

Management
Hypotension RV
Strain
Hypoxia

• Risk Stratification

• Risk Stratification

Lower Risk
High Risk
Secondary Therapy
Primary Therapy
Heparin Warferin IVC Filter
Thrombolysis Embolectomy
Adjuvant Therapy
Oxygen Inotropes
67

Management
Hypotension RV
Strain
Hypoxia

• Risk Stratification

• Risk Stratification

Lower Risk
High Risk
Secondary Therapy
Heparin Warferin IVC Filter
Adjuvant Therapy
Oxygen Inotropes
68

Treatment

ð Adjuvant Therapy ð Manage respiratory
failure ð Oxygen ð Mechanical
ventilation ð Improve right ventricular
function ð Inotropes (Dobutamine)
69
Treatment
ð Heparin ð Still cornerstone of acute
management ð Unfractionated Heparin IV ? ð
Low-molecular-weight Heparin SC ?
?
70
Treatment
ð Heparin ð 2007 ACP Guidelines1 ð
Pooled data from 11 reviews ð Outcome and
safety at six months
1. Snow V, et al. Management of Venous
Thromboembolism. Ann Intern Med
2007146204-210
71
Treatment
ð Heparin ð 2007 ACP Guidelines1 ð LMWH
gtgt UH for DVT ð LMWH UH for PE ð
Outpatient treatment is safe
1. Snow V, et al. Management of Venous
Thromboembolism. Ann Intern Med
2007146204-210
72
Treatment
ð Heparin ð 2007 ACP Guidelines1 ð LMWH
well established role in Ø Recurrent DVTs
(therapeutic INR) Ø Problematic INR Ø
Malignancies
1. Snow V, et al. Management of Venous
Thromboembolism. Ann Intern Med
2007146204-210
73
Treatment
ð Heparin ð CLOT Study1 ð Large
prospective study ð LMWH vs. Warfarin ð
High risk (recurrent, cancer, etc.) ð One year
follow up ð Safe and effective ð 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. 2003349146-53. 1
74
Treatment
ð Warfarin ð Still the oral anticoagulant of
choice ð Commence after initiating Heparin
ð Takes at least five days to deplete FII ð
Aim for INR of 2.0 3.0 ð Lower INR (1.5)
ð Better than controls ð Worse than INR gt 2
75
Treatment
ð Warfarin ð Duration
3 Months
Clear precipitant
1st Episode
6 Months
No apparent cause
Lifelong
Thrombophylia
?
gt 1 Year
2nd Episode
76
Treatment
ð Newer anticoagulants ð Many new drugs
(PO/SC/IV) in pipeline ð NO evidence as yet
that they are equivalent to LMW
Heparin or Warfarin ð Concerns ð
Efficacy ð Safety ð Cost
77

Treatment

Target Drug Route Stautus Indication
IIa Hirudin IV 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
VIIa/TF 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 surgeryTreatment of venous thrombosis
DX-9065a IV Phase II Unstable angina
Xa/IIa SNAC/heparin PO Phase III Thromboprophylaxis in patients undergoing elective hip or knee arthroplasty
78
Treatment
ð Idraparinux ð Pentasaccharide (MW 1,853
Daltons) ð Long t½ (200 hours) ð Selective
factor Xa inhibitor ð Given once weekly (2.5
mg SC)
79
Treatment
ð Idraparinux ð Matisse Trial1 ð Open
label ð Daily acc weight ð Vs. UFH 1.
Buller HR, et al. Subcutaneous fondaparinux
versus intravenous unfractionated heparin in
the initial treatment of pulmonary embolism.
N Engl J Med 20033491695-1702
80
Treatment
ð Idraparinux ð Van Gogh PE1 ð Open
label - weekly (3-6 months) ð Vs. LMWH
Warfarin ð Could not show non-inferiority ð
Mortality 6.4 - Idraparinux 4.4 - LMW
Heparin Warfarin 1 Unpublished
81
Treatment
ð Idraparinux ð Van Gogh PE
82
Treatment

• ð IVC Filters
• ð Randomised trial by Razavi1
• ð Filters vs. Filters Warfarin
• ð 2 Year follow up
• ð 20.8 vs. 11.6 recurrence (p 0.02)
• ð Safe
• 1 Razavi MK, et al. Initial clinical results of
  tenecteplase (TNK) in catheter-
• directed thrombolytic therapy. J Endovasc
  Ther. 20029593-598

83
Treatment

• ð IVC Filters
• ð Randomised trial by Decousus1
• ð Filters vs. LMW Heparin
• ð 2 Year follow up
• ð OR 1.87 (also no mortality benefit)
• ð No advantage proximal free-floating
• thrombi
• ð 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. 1998338409-415

84
Treatment

• ð IVC Filters
• ð The evidence summery
• ð Safe
• ð No benefit vs. LMWH
• ð Relatively useless without Warfarin

85
Treatment

• ð IVC Filters
• ð Limited indications
• ð Active haemorrhage
• ð Absolute C/I anticoagulation
• ð VTE despite therapeutic INR
• (better to use LMW Heparin)

86
Treatment
ð Thrombolytic Therapy Background
Well tolerated PE excellent prognosis
Risks major haemorrhage 1.8 6.3
ICH 1.2
Faster clot lysis Dissolves obstruction May
reverse RV failure Dissolves much of
source Decrease risk of recurrence
87
Treatment
ð Thrombolytic Therapy Evidence ð PE with
circulatory collapse ð Single study1
ð n 8, BP lt 90 mmHg ð 4 thrombolysed
(all survived) ð All 4 NOT thrombolysed died
ð 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 19952227-229
88
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with circulatory collapse
• ð Compare to AMI thrombolysis
• ð gt 20 000 patients (multiple trails)
• ð Easier to diagnose
• ð Subgroup definition
• (lt12 hr, ST Elev)
• ð Symptoms to thrombolysis in PEs
• ð 3.7 /- 0.2 days (vs 12 hr)
• ð Pharmaceutical industry not interested

89
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE without circulatory collapse
• ð Submassive pulmonary emboli
• ð Much less evidence
• ð Only 9 randomised studies, N lt 500
• ð Not adequately powered to show
• statistical benefit in mortality

90
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with RV dysfunction
• No haemodynamic compromise
• ð MAPPET-1 1
• ð Retrospective analysis showed
• trends towards survival
  benefit
• ð 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.
  199882966-970

91
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with RV dysfunction
• No haemodynamic compromise
• ð MAPPET-3 1
• ð Largest ever, n 247
• ð 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
20023471143-1150
92
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with RV dysfunction
• No haemodynamic compromise
• ð MAPPET-3 1
• ð Patients with haemodynamic instability were
  excluded
• ð Heparin /- rTPA (random, lt96hr)

1. Konstantinides S, et al. Heparin plus
alteplase compared with heparin alone in patients
with submassive pulmonary embolism. N Eng J Med
20023471143-1150
93
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with RV dysfunction
• No haemodynamic compromise
• ð MAPPET-3 1
• ð Primary end points
• Ø In-hospital deaths
• Ø 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
20023471143-1150
94
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with RV dysfunction
• No haemodynamic compromise
• ð MAPPET-3 1
• ð Secondary end points
• Ø Recurrent PEs
• Ø Major bleeding
• Ø Ischaemic stroke

1. Konstantinides S, et al. Heparin plus
alteplase compared with heparin alone in patients
with submassive pulmonary embolism. N Eng J Med
20023471143-1150
95
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with RV dysfunction
• No haemodynamic compromise
• ð MAPPET-3 1
• ð Prematurely discontinued (IA)
• Ø Major advantage with TPA
• ð 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
20023471143-1150
96
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with RV dysfunction
• No haemodynamic compromise
• ð MAPPET-3 1
• ð 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
20023471143-1150
97
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with RV dysfunction
• No haemodynamic compromise
• ð MAPPET-3 1
• ð 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
20023471143-1150
98
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with RV dysfunction
• No haemodynamic compromise
• ð MAPPET-3 1
• ð Mortality was low in both groups,
• thus no mortality benefit
• ð 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
20023471143-1150
99
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with RV dysfunction
• No haemodynamic compromise
• ð MAPPET-3 1
• ð 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
20023471143-1150
100
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with Hypoxaemia
• ð PE severity vs. PaO2 or P(A-a)O21
• ð Linear relationship
• pulm vasc obstructed and
  PO2
• ð PaO2 lt 6.7 gt 50 of vasc obstr
• ð PaO2 lt 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
197128288-294 2. Wicki J, et al. Predicting
adverse outcome in patients with acute pulmonary
embolism a risk scor. Thromb Haemost
200084548-552
101
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with Hypoxaemia
• ð Thrombolysis small open study1
• ð n 4
• ð Average PaO2 7.81 (on max FiO2)
• ð tPA
• ð All 4 sats gt 95 next day
• ð No major complications

1. Loebinger MR, et al. Thrombolysis in pulmonary
embolism are we under-using it? Q J Med
200497361-364
102
Treatment

• ð Thrombolytic Therapy Evidence
• ð PE with patent foramen ovale
• ð Large PE patent foramen ovale
• ð Severe hypoxia due to R L shunt
• (R atrial hypertension)
• ð 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 1998971946-1951
103
Treatment
ð Thrombolytic Therapy Controversy ð For the
diehard EBM Clinician ð Circulatory
collapse (BP lt 90) Sin. Massive PE ð
Limited evidence, serious consideration1 ð RV
dysfunction (no haemodynamic
compromise) ð Respiratory failure
(ventilatory support) ð Respiratory failure
PFO
ü BTS
ü FDA
1. Konstantinides S. Should thrombolytic therapy
be used in patients with pulmonary embolism?
Am J Cardiovasc Drugs. 2004469-74
104
Treatment
ð Thrombolytic Therapy Controversy ð For the
diehard EBM Clinician ð Circulatory
collapse (BP lt 90) Sin. Massive PE ð
Limited evidence ? Cost-effectiveness1 ð RV
dysfunction (no haemodynamic
compromise) ð Respiratory failure
(ventilatory support) ð Respiratory failure
PFO
ü BTS
ü FDA
1. Daniella J. Effectiveness and
Cost-effectiveness of Thrombolysis in Submassive
pulmonary embolism. Arch Intern Med
200716774-80
105
Treatment
ð Thrombolytic Therapy The agents ð
Streptokinase ð 250 000 IU over 30 60
min ð 100 000 IU / hr for 24 hours ð rTPA
ð 10 mg stat (1-2 minutes) ð 90 mg (over
2 hours) ð Maximum 1.5 mg / kg (lt 65 kg)
106
Screening
ð Neoplasms ð Thrombophylias
107
Screening
ð Neoplasms ð CXR ð Abdominal /- pelvic
ultrasound ð PSA ð According to clinical
setting
108
Screening
ð Thrombophylia Screening ð Inherited /
acquired defects in haemostasis ð Predispose
to venous / arterial thrombosis ð Consider
in patients with ð Recurrent DVTs ð Venous
thrombosis lt 40 yr ð Unusual DVTs (mesenteric)
ð Neonatal thrombosis ð Recurrent miscarriages
ð Arterial thromboses with no PVD
109
Screening

• ð Thrombophylia Screening
• ð Polycythaemia Thombocythaemia
• ð Activated Prot C resistance (Assay)
• ð Factor V Leiden (Molecular)
• ð Hyperhomocysteinaemia
• ð AFL Syndrome / Anti-Cardiolipin ABs
• ð ATIII Deficiency
• ð Protein C
• ð Protein S

110
Screening

• ð Thrombophylia Screening
• ð Polycythaemia Thombocythaemia
• ð Activated Prot C resistance Common!
• ð Factor V Leiden Common!
• ð Hyperhomocysteinaemia Treatable!
• ð AFL Syndrome Intensive therapy!
• ð ATIII Deficiency
• ð Protein C
  Rare!
• ð Protein S

111
Screening

• ð Thrombophylia Screening
• ð Polycythaemia Thombocythaemia
• ð Activated Prot C resistance Common!
• ð Factor V Leiden Common!
• ð Hyperhomocysteinaemia Treatable!
• ð AFL Syndrome Intensive therapy!
• ð ATIII Deficiency
• ð Protein C
  Rare!
• ð Protein S

112
Screening

• ð Keep in mind
• ð ATIII, Prot C S ò during acute event
• ð Heparin ò ATIII
• ð Warfarin ò Prot C S
• ð Pregnancy and OCP ò Prot S
• ð ATIII, Prot C S deficiencies are rare

113
Take Home Messages
Diagnosis
ð Use the Wells score and D-Dimer to exclude
ð Spiral CT scanning is now well established
as the primary imaging modality
114
Take Home Messages
Treatment
ð LMW Heparin and Warfarin are still the agents
of choice ð IVC filters and newer drugs thus
far disappointing ð Thrombolysis remains
controversial
115
The End