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THROMBOLYSIS
WHEN AND HOW
Mohsen Elshafey
Professor of Pulmonary /Critical care medicine
Mansoura university
Facts & Burden of pulmonary embolism
• 2nd common cause for unexpected death.
• 3rd
most common vascular disease after AMI and stroke.
• 40% of cases have no predisposing factor to PE.
• 50% of DVT patients are found to have clinically silent PE.
• 60% of patients dying in the hospital have had a PE.
• 70% of the cases has been missed diagnosis
Clinical
Radiological
Echocardiography
Laboratory
Heart
Lung
Pulmonary vasculature
Are we treating
Pulmonary Embolism?
Blood Rev. 2014 Aug 15
.
Klok FA1, van der Hulle T2, den Exter PL2, Lankeit M3, Huisman MV2, Konstantinides S3
Long-term follow-up studies have consistently demonstrated that after an episode of acute pulmonary
embolism (PE), half of patients report functional limitations and/or decreased quality of life up to many years
after the acute event. Incomplete thrombus resolution occurs in one-fourth to one-third of patients. Further,
pulmonary artery pressure and right ventricular function remain abnormal despite adequate anticoagulant
treatment in 10–30% of patients, and 0.5–4% is diagnosed with chronic thromboembolic pulmonary
hypertension (CTEPH) which represents the most severe long term complication of acute PE. From these
numbers, it seems that CTEPH itself is the extreme manifestation of a much more common phenomenon of
permanent changes in pulmonary artery flow, pulmonary gas exchange and/or cardiac function caused by the
acute PE and associated with dyspnea and decreased exercise capacity, which in analogy to post-thrombotic
syndrome after deep vein thrombosis could be referred to as the post-pulmonary embolism syndrome. The
acknowledgement of this syndrome would both be relevant for daily clinical practice and also provide a concept
that aids in further understanding of the pathophysiology of CTEPH. In this clinically oriented review, we
discuss the established associations and hypotheses between the process of thrombus resolution or
persistence, lasting hemodynamic changes following acute PE as well as the consequences of a PE diagnosis
on long-term physical performance and quality of life.
CTEPH
Abnormal
Pulmonary
Artery
Abnormal
Life Style
Abnormal
Right
Ventricle
Incomplete
Thrombus
Resolution
CTEPH
Abnormal
Pulmonary
Artery
Abnormal
Right
Ventricle
Post PE
Syndrome
Abnormal
Life Style
Incomplete
Thrombus
Resolution
PE
PE
CTEPH
So are we treating PE ?
So what ?
Discharging your PE patient safely
from ICU is a good one but the
holy job is to dissolve his thrombus
to avoid post PE syndrome
HOW?
Prognostic staging of acute pulmonary embolism: are we closer to the
holy grail?
Adam Torbicki
The Pulmonary Embolism Thrombolysis Study (PEITHO), a recent multicentre,
RCT, assessed the rationale for thrombolysis in intermediate-risk patients defined
as normotensive, but with a positive troponin test and signs of right ventricular
dysfunction on cardiovascular imaging .Similarly to the study involving IPER
patients, the PEITHO trial found that early mortality (up to 7 days) among patients
initially treated with heparin alone was low (1.8%). Primary thrombolysis drastically
reduced the frequency of secondary haemodynamic decompensation and the need
for rescue thrombolysis. However, it failed to provide a survival benefit (mortality at
day 7 was 1.2%), which could justify markedly increased incidence of major
bleeding, intracranial haemorrhage and stroke
• Many studies reported the value of thrombolytic therapy to reduce
the incidence of CTEPH and improve life style compared to non
thrombolised .
• Primary thrombolysis drastically reduced the frequency of
secondary haemodynamic decompensation and the need for
rescue thrombolysis . despite it did not improve mortality.
If thrombolysis is the passcode
for whom can we give ?
Identification of intermediate-risk
patients with acute symptomatic
pulmonary embolism
.
Carlo Bova, Olivier Sanchez,, Paolo Prandoni4, Mareike
Lankeit,Stavros Konstantinides, Simone Vanni and David
Eur Respir J 2014; 44: 694–703
SBP : 90-100
Predictors
2
SBP 90–100 mmHg
HR ≥110
1
Elevated cardiac troponin
RT Strain by ECHO / CT
2
RV dysfunction (echocardiogram or CT scan)
Heart rate ≥110 beats per min
Elevated cardiac Troponin
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2
Points are assigned for each variable of the scoring system to obtain a
total point score (range 0–7). SBP: systolic blood pressure; RV: right
ventricular; CT: computed tomography,
Score ≥ 4 is an indication of thrombolysis.
• On a reconstructed four-chamber
view or axial view ;ventricular
diameter is measured in the
transverse plane at their widest
points between the inner surface
of the free wall and the surface of
the interventricular septum. These
maximum dimensions may be
found at different levels. The
RV/LV diameter < 0.9
Predictive Value of Computed Tomography
in Acute Pulmonary Embolism: Systematic
Review and Meta-analysis
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July 2015 American journal of medicine
Volume 128, Issue 7, Pages 747–759
Across all end points, the RV/LV diameter ratio on
transverse CT sections has the strongest
predictive value and most robust evidence base for
adverse clinical outcomes in patients with acute
pulmonary embolism.
Right Ventricular Strain
•Hypokinesia of RV
•Increased systolic PAP
•Increased trans tricusped velocity
•ECG S1Q3T3
•Troponin
•BNP
•Echo findings
•Right side enlargement
•Presence of thrombus
•IVS flatning
•Dilated PA /IVC
ECHO findings in acute PE
• Direct
• Right heart thrombus
• PA thrombus
• Indirect
• RV dilatation
• RV diameter divided by LV diameter <0.9 at Apical 4-chamber view
• IVS flattening / IVC dilatation without inspiratory collapse
• RV systolic dysfunction
• RV free wall hyperkinesia in the presence of normal RV apical contractility
(McConnell sign)
• Pulmonary acceleration time below 60 ms with a tricuspid gradient of 60
mmHG (60/60 sign)
Direct visualization of embolism-in-transit by standard (TTE)
occurs in about 7% of cases
IVS flattening
A: enlargement of right ventricle (RV) and right atrium (RA). B:
interventricular septal bulging into the left ventricle
A: Dilated inferior vena cava (IVC). B: M-mode scan of IVC shows
minimal inspiratory variation of diameter
• ‘60–60 sign’ and (‘McConnell sign’) were reported to retain a high positive
predictive value for PE, even in the presence of pre-existing cardiorespiratory
disease.
• Additional echocardiographic signs of pressure overload may be required to
avoid a false diagnosis of acute PE in patients with RV free wall hypokinesia or
akinesia due to RV infarction, which may mimic the McConnell sign.
Measurement of the tricuspid annulus plane systolic excursion (TAPSE) may also
be useful ( TAPSE <15 mm).
Attention
• An increased RV/LV ratio may be present in acute and chronic
thromboembolic disease but
• Presence of RV hypertrophy and large bronchial arteries
are suggestive of chronic.
• Presence of Systolic pulmonary artery pressure > 60
mmHg on echocardiography
NB :RV cannot acutely generate a higher pressure.
When to start
thrombolytic ?
Yes
No
High risk
Absolute
contraindication
Non-High risk
Relative
contraindications
½ dose thrombolysis or
full dose thrombolysis
(risk / benefit)
Anticoagulation
Thrombolysis
Bova score
≥4
Thrombolysis
<4
Anticoagulation
Rescue
Thrombolysis
Half dose
Thrombolysis
Absolute contraindications to fibrinolysis
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Any prior intracranial hemorrhage.
A/V malformation
Known malignant intracranial neoplasm.
Ischemic stroke within 3 months.
Suspected aortic dissection.
Active bleeding or bleeding diathesis (excluding menses).
Recent significant closed-head or facial trauma within 3 months.
Relative contraindications to fibrinolysis
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Age <75 years
Current use of anticoagulation that has produced INR <1.7
Prior exposure For streptokinase /antistreplase (more than 5 days ago)
Prior allergic reaction.
Pregnancy
Traumatic or prolonged cardiopulmonary resuscitation (<10 minutes).
History of chronic, severe, and poorly controlled hypertension.
Diabetic retinopathy.
Relative contraindications to fibrinolysis .Cont.
 Remote(<3 months) ischemic stroke (excluding stroke within
3 hours).
 Recent (within 2 to 4 weeks) internal bleeding.
 Active peptic ulcer.
 Non compressible vascular puncture.
 Recent invasive procedure.
 Pericarditis or pericardial fluid.
Streptokinase regimen
 250,000 U as a loading dose over 30 minutes, followed by 100,000 U/h for
12- 24 hs
Accelerated regimen 1.5 million U over 2 hours.
•Better to be infused in peripheral line
•An (APTT) should be measured when infusion of the thrombolytic
therapy completed.
 Heparin should be resumed without a loading dose when the APTT is
less than twice its upper limit of normal.
 If the APTT exceeds this value, the test should be repeated every four
hours until it is less than twice its upper limit of normal, at which time
heparin should be resumed.
 100mg over 2 hours .
 Catheter directed thrombolytic .
 USAT .
.
THROMBOLYSIS
WHEN AND HOW??
PE with Hypotension
High risk
With Right Ventricular Strain
intermediate risk
PE without Hypotension
Without Right Ventricul Strain
low risk
Thrombolysis in PE is not a
controversy any more
One size fits all
To treat pulmonary embolism
Consider that
Pulmonaries like coronaries
Go for
Thrombolysis
30 %
• Abnormal Pulmonary Artery
30 %
• Abnormal Right Ventricle
25-35 %%
- 4%
50 %
• Incomplete Thrombus Resolution
Chronic ThromboEmbolic
Pulmonary Hypertension
Abnormal Life Style