Martin Johnson

Glasgow, UK
 Assessment of
risk

Low risk Hospital vs home

Thrombolysis
Intermediate –
high risk
Alternatives to
thrombolysis

Treatment of Acute PE -
Anticoagulate with DOACs Anticoagulation
IVC filters
not possible

Right heart
thrombi
Special cases

Pregnancy
Duration of
anticoagulation

Investigation for
underlying cause
 Fixed dose
No monitoring
Few drug-drug or drug-food interactions

ACCP 2016
Van der Hulle J Thromb Hemostasis 2014
 D
R
R Major bleeding
A
E
Overall

Non-fatal bleeding at a
critical site

Non-major bleeding

Non-fatal ICH

Major GI bleeding

Fatal bleeding

Van der Hulle J Thromb Hemostasis 2014

2016
Apixaban
Rivaroxaban
Edoxaban
 DOACs VKAs
Most people Higher INR
Antiphospholipid syndrome
Mechanical heart valves
CrCl < 15 ml/min
Weight < 120kg / BMI < 40 Weight > 120kg / BMI > 40
LMWH
Cancer (first 6/12)
Pregnancy
Severe liver disease
Weight > 120kg / BMI > 40

Leentjens BJCP 2017, Martin J Thromb Haem 2016

 Assessment of
risk

Low risk Hospital vs home

Thrombolysis
Intermediate –
high risk
Alternatives to
thrombolysis

Treatment of Acute PE -
Anticoagulate with DOACs Anticoagulation
IVC filters
not possible

Right heart
thrombi
Special cases

Pregnancy
Duration of
anticoagulation

Investigation for
underlying cause
 • All cause mortality
• Recurrent VTE
• Major bleeding

Echo
Troponin
Bova
DVT

Low sPESI High

PESI CTPA
HESTIA
Home H-FABP
Thrombolysis
management GRACE or similar
BNP
PROTECT
PREP
FAST

Intermediate - low Intermediate - high

Hospital management
Jimenez Intern Emerg Med 2016
 Only bedside
parameters needed
(PROTECT)

PESI, sPESI, HESTIA

Intermediate Risk

Troponin

Echo,
CTPA, BNP

• Systemic
• CDT

Barrios Seminars Resp Crit Care Med 2017

 Assessment of
risk

Low risk Hospital vs home

Thrombolysis
Intermediate –
high risk
Alternatives to
thrombolysis

Treatment of Acute PE -
Anticoagulate with DOACs Anticoagulation
IVC filters
not possible

Right heart
thrombi
Special cases

Pregnancy
Duration of
anticoagulation

Investigation for
underlying cause
No recurrence of
VTE or major
bleeding on
treatment in home-
managed patients
 Assessment of
risk

Low risk Hospital vs home

Thrombolysis
Intermediate –
high risk
Alternatives to
thrombolysis

Treatment of Acute PE -
Anticoagulate with DOACs Anticoagulation
IVC filters
not possible

Right heart
thrombi
Special cases

Pregnancy
Duration of
anticoagulation

Investigation for
underlying cause
 Retrospective USA
n=3668

Desai AJM 2017

 Normotensive
n=1006 RV dysfunction (echo/CT and +ve troponin)

< 7 days

Guy PEITHO NEJM 2014

Konstantinides JACC 2017
 Thrombolyse in
intermediate-high risk PE
only if haemodynamic
decompensation occurs

Konstantinides JACC 2017

Jimenez Thorax 2018
Jimenez Thorax 2018
 Inhaled NO Half dose
(iNOPE trial) thrombolysis

What if systemic
thrombolysis
fails or is
Supportive
contraindicated?
(ventilation, Catheter
inotropes, directed
antibiotics, thrombolysis
ECMO, RVAD)

Mechanical
Surgical
disruption by
embolectomy
catheter
ESC Guidelines 2014
 pre
 Ultrasound aids thrombolysis
by increasing thrombus
permeability & penetration of
thrombolytic agent

 One catheter in each lower lobe

PA (through 6F femoral
sheaths)
24 hours
post
 rtPA infused bilaterally at
1mg/hr for 5hrs then 0.5mg/hr
for 15 hours; maximal dose
20mg

Kucher Circulation 2014

101 consecutive patients with
massive or submassive PE

Outcomes
• Haemodynamics / RV strain
• Survival to discharge
• Procedure related problems
• Major bleeding

No (%)
No (%)
No (%) SUNSET-sPE – ongoing RCT USAT vs CDT
 Assessment of
risk

Low risk Hospital vs home

Thrombolysis
Intermediate –
high risk
Alternatives to
thrombolysis

Treatment of Acute PE -
Anticoagulate with DOACs Anticoagulation
IVC filters
not possible

Right heart
thrombi
Special cases

Pregnancy
Duration of
anticoagulation

Investigation for
underlying cause
PREPIC: RCT in cases of proximal DVT of anticoagulation for at least 3/12 ± IVC filter

PREPIC Circulation 2005

Use IVC filters
• where anticoagulation
is contraindicated
(preferably retrievable)
• where there are
recurrent PTE despite
anticoagulation
Time from filter insertion to retrieval
Successful - 60 days (range 3–537)
Failed - 59 days (range 5–262)

Success rate of attempted retrieval at

first attempt – 85%

Tse Diag & Intervent Rad 2017

 Assessment of
risk

Low risk Hospital vs home

Thrombolysis
Intermediate –
high risk
Alternatives to
thrombolysis

Treatment of Acute PE -
Anticoagulate with DOACs Anticoagulation
IVC filters
not possible

Right heart
thrombi
Special cases

Pregnancy
Duration of
anticoagulation

Investigation for
underlying cause
Type A thrombus
Type B thrombus
Serpiginous, associated Type C thrombus
with PE Immobile, no associated Straddling PFO
PE Mobile, mass-like
Thrombolysis High risk of systemic
Anticoagulate
Surgical embolectomy embolisation
Surgical embolectomy
Surgical embolectomy
Shock index = HR/BP 30 day mortality NOT related to clot
characteristics
RIETE registry, Spain

Barrios AJM 2017

 Assessment of
risk

Low risk Hospital vs home

Thrombolysis
Intermediate –
high risk
Alternatives to
thrombolysis

Treatment of Acute PE -
Anticoagulate with DOACs Anticoagulation
IVC filters
not possible

Right heart
thrombi
Special cases

Pregnancy
Duration of
anticoagulation

Investigation for
underlying cause
 Warfarin is teratogenic in the first trimester &
causes neural abnormalities at any time; no data on
DOACs
 use LMWH
 For high risk PE
 Thrombolysis can be used in pregnancy – major bleeding
rate 8.5%
 In peripartum period, mechanical methods are preferred

 If PE is within a month of delivery a retrievable IVC

filter should be inserted
Condliffe Thorax 2012, RCOG Guideline 2007, Sousa Gomes 2018
 Assessment of
risk

Low risk Hospital vs home

Thrombolysis
Intermediate –
high risk
Alternatives to
thrombolysis

Treatment of Acute PE -
Anticoagulate with DOACs Anticoagulation
IVC filters
not possible

Right heart
thrombi
Special cases

Pregnancy
Duration of
anticoagulation

Investigation for
underlying cause
  At least 3 months

3 months is a reasonable
Boutitie BMJ 2011 timepoint to ask whether
anticoagulation should be
temporary or indefinite
 Simple question -

 Risk of recurrent VTE vs risk of bleeding

 What is an
acceptable
level of risk
at 1 year?

5% in first
year off
treatment?
International Society of Thrombosis
and Haemostasis 2010

Kearon 2010
 Risk of VTE recurrence
at 1 year

Surgical transient risk factor 1%

Temporary
Non-surgical transient risk factor 4%
anticoagulation
Unprovoked distal DVT 4%

Unprovoked PE

Active cancer 15% Indefinite

Multiple previous unprovoked VTE 15% anticoagulation

Donadini 2011, Kearon 2011, Iorio 2010, Boutitie 2011, ACCP 2016
 Risk of VTE recurrence
at 1 year

Surgical transient risk factor 1%

Non-surgical transient risk factor 4%
Unprovoked distal DVT 4%

Unprovoked PE 10%

Active cancer 15%

Multiple previous unprovoked VTE 15%

Donadini 2011, Kearon 2011, Iorio 2010, Boutitie 2011, ACCP 2016
 Risk of VTE recurrence At 5 years
at 1 year

Surgical transient risk factor 1%

Non-surgical transient risk factor 4%
Unprovoked distal DVT 4%

Unprovoked PE 10% 30%

Active cancer 15%

Multiple previous unprovoked VTE 15%

Donadini 2011, Kearon 2011, Iorio 2010, Boutitie 2011, ACCP 2016
 Risk of VTE recurrence At 5 years At 10 years
at 1 year

Surgical transient risk factor 1%

Non-surgical transient risk factor 4%
Unprovoked distal DVT 4%

Unprovoked PE 10% 30% 50%

Active cancer 15%

Multiple previous unprovoked VTE 15%

Donadini 2011, Kearon 2011, Iorio 2010, Boutitie 2011, ACCP 2016
 Single unprovoked PE – allcomers 10% 1 year risk of
recurrence

ACCP 2016
 Single unprovoked PE – allcomers 10% 1 year risk of
recurrence

 What factors increase risk of recurrence?

 D-dimer +ve at end of treatment or at 1 month after
stopping (2 x risk)
 Male sex (1.75 x risk)

ACCP 2016
Tosetto et al.
Tosetto et al.

DASH Score Annual Risk

≤1 3.1%
2 6.4%
>2 12.3%
 Klok et al.

VTE-BLEED Score Annual Risk

<2 2.8%
≥2 12.6%

Outperformed HAS-BLED
 Shall we anticoagulate indefinitely?

Risk of bleeding
Low Intermediate High
First unprovoked VTE Weak yes Weak yes Strong no
Second unprovoked VTE Strong yes Weak yes Weak no

ACCP 2016
 Assessment of
risk

Low risk Hospital vs home

Thrombolysis
Intermediate –
high risk
Alternatives to
thrombolysis

Treatment of Acute PE -
Anticoagulate with DOACs Anticoagulation
IVC filters
not possible

Right heart
thrombi
Special cases

Pregnancy
Duration of
anticoagulation

Investigation for
underlying cause
 LIMITED SCREENING vs LIMITED SCREENING + CT
 Blood tests  As limited + CT abdo / pelvis
 CXR  Virtual colonoscopy / gastroscopy
 Biphasic enhanced CT of liver
 Screening for breast, cervical &
 Parencymal pancreatography
prostate  Virtual cystoscopy
n=854; 1 year follow-up Number %
Number of cancer cases at 1 year 33 3.9%
No missed by limited screening 4/14 29%
No missed by limited screening + CT a/p 5/19 26%

No difference in cancer-related mortality at 1 year

 Assessment of
risk

Low risk Hospital vs home

Thrombolysis
Intermediate –
high risk
Alternatives to
thrombolysis

Treatment of Acute PE -
Questions?
Anticoagulate with DOACs Anticoagulation
IVC filters
not possible

Right heart
thrombi
Special cases

Pregnancy
Duration of
anticoagulation

Investigation for
underlying cause