Advances in pte management

1. RECENT ADVANCES IN MANAGEMENT
OF PULMONARY THROMBOEMBOLISM
DR ANUSHA CM

2. INTRODUCTION
• Venous thromboembolism (VTE), which encompasses deep vein
thrombosis and its most dangerous complication, acute pulmonary
embolism (PE), represents a major threat for the health, the well-
being and, under certain circumstances, the life of a large number of
patients worldwide.
• With its acute and long-term complications, VTE also poses a
substantial economic burden on national health systems

3. EPIDEMIOLOGY
• In epidemiological studies, annual incidence rates for PE range from
39115 per 100 000 population; for DVT, incidence rates range from
53162 per 100 000 population.
• Data show that the incidence of VTE is almost eight times higher in
individuals aged >_80 years than in the fifth decade of life

4. PREDISPOSING FACTORS
ESC 2019 Guidelines

6. Simplification of clinical prediction rules and age-
adjusted D-dimer cut-offs
• D-dimer cut-off values adjusted for age or clinical probability can be
used as an alternative to the fixed cut-off value.
• This is because the specificity of a positive D-dimer test in suspected
PE decreases steadily with age, to almost 10% in patients >80 years.
• Thus, using age-adjusted (instead of the conventional) cut-offs may
improve the performance of D-dimer testing in the elderly
European Heart Journal (2019) 00, 161

7. RISK STRATIFICATION
• Advanced age, major underlying conditions (cancer and cardiac or
respiratory disease), clinical signs of right ventricular dysfunction
(tachycardia and hypotension) and hypoxemia are the main clinical
determinants of the outcome of patients with PE.
• This has been summarized by the pulmonary embolism severity index
(PESI) and its simplified version (sPESI) to distinguish between
intermediate and low risk (of an adverse early outcome).

8. • Sustained hypotension, shock or even cardiac arrest is infrequent as
over 95 % of patients with acute PE appear hemodynamically stable
at presentation

9. Meyer et al. Ann. Intensive Care (2016) 6:19
The main strength : exclusion of an elevated risk for 30-day mortality (indicated by PESI classes I and II or by a
sPESI < 1)

10. • Right ventricular dysfunction (RVD) assessed by echocardiography or
spiral computed tomography angiography and biomarkers including
brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and
troponin, has been associated with an increased risk of death or PE-
related complications including death due to PE, cardiogenic shock
and recurrent PE in patients with normal blood pressure.

11. Eur Respir J 2014; 44: 1385–1390

12. DIAGNOSIS
• To suspect PTE in in every patient with dyspnoea or chest pain may lead to
high costs and complications of unnecessary tests.
• The Pulmonary Embolism Rule-out Criteria (PERC) comprise eight clinical
variables significantly associated with an absence of PE:
1. Age < 50 years
2. Pulse < 100 beats per minute
3. SaO2 >94%
4. No unilateral leg swelling
5. No haemoptysis
6. No recent trauma or surgery
7. No history of VTE
8. No oral hormone use.

14. DIAGNOSIS RECOMMENDATIONS
European Heart Journal (2019) 00, 161

17. Persisting uncertainty in subsegmental and
incidental PE
• The clinical significance of isolated subsegmental PE on CT pulmonary
angiography is controversial
• A single subsegmental defect does not have the same clinical
relevance as multiple, subsegmental thrombi.
• The positive predictive value is low and interobserver agreement is
poor at this distal level.
• Compression ultrasound of the leg veins helpful , as the exclusion of
proximal deep vein thrombosis in a patient with isolated
subsegmental PE would support a decision against anticoagulation
treatment; such cases should be managed on an individual basis,
taking into account the clinical probability and the bleeding risk.

18. Treatment and secondary prophylaxis of VTE
• The ‘‘standard’’ regimen of acute-phase treatment consists of
administering parenteral anticoagulation (unfractionated heparin, low
molecular weight heparin or fondaparinux) over the first 5–10 days.
• Parenteral heparin should overlap with the initiation of a vitamin K
antagonist
• This is accurately defined for low-risk and high-risk patients with PE.
• LMWH and fondaparinux are preferred over UFH for initial
anticoagulation in PE, as they carry a lower risk of inducing major
bleeding and heparin-induced thrombocytopenia.

22. Non-vitamin K antagonist oral
anticoagulants(NOAC)
• NOACs are small molecules that directly inhibit one activated
coagulation factor, which is thrombin for dabigatran and factor Xa for
apixaban, edoxaban, and rivaroxaban.
• Owing to their predictable bioavailability and pharmacokinetics,
NOACs can be given at fixed doses without routine laboratory
monitoring
• Compared with vitamin K antagonists (VKAs), there are fewer
interactions when NOACs are given concomitantly with other drugs.

23. • The results of the trials using the new oral anticoagulants (NOACs)
dabigatran, rivaroxaban, apixaban or edoxaban in the treatment of
VTE indicated, both individually and in a meta- analysis, that these
agents are non-inferior (in terms of efficacy) and possibly safer
(particularly in terms of major bleeding) than the standard
heparin/vitamin K antagonist regimen

31. Few unanswered questions regarding NOAC
1. How to measure the anticoagulant effect of NOAC?
• Unlike warfarin, NOACs do not require routine monitoring or dose
adjustment except in emergency situations where the drug exposure
assessment is required.
• Both aPTT and PT are qualitative indicators only and a normal aPTT or
PT suggests that haemostatic function is not impaired because of the
drug
• Quantitative tests for DTI and FXa inhibitors [thrombin clotting time
(TT), activated clotting time (ACT)] are sensitive tests to evaluate the
anticoagulant effects of dabigatran but are not routinely available in
hospitals
Journal of The Association of Physicians of India Vol. 64 , April
2016

32. 2. Switching between anticoagulant regimens
• Switching from VKAs to NOAC can be immediate if the INR is < 2.0
• It is also recommended to closely monitor INR within the first month
until stable values are attained (i.e. three consecutive measurements
between 2 and 3)
3. NOAC use in chronic kidney disease (CKD)
• Approximately 80 %, 33 %, and 25% of dabigatran,rivaroxaban, and
apixaban, respectively, are eliminated renally.
• ACC/AHA/ESC guidelines recommend yearly monitoring of renal
function (especially dabigatran)

33. 4.Management of bleeding complications
• Bleeding rates with NOACs are generally equal to or less than warfarin
bleeding rates.
• NOACs should be discontinued and assessment of hemodynamic
stability, degree of anticoagulation and severity of bleeding should be
done.
5. When to stop and restart NOACs in patients undergoing surgical
intervention?
• Common interventions with no clinically important bleeding risk can
be performed at trough NOAC concentration (i.e. 12 or 24 hours after
the last intake, depending on BID or QD regimen.

34. • Peri-operative NOAC interruption for dabigatran [1-2 days and 2-4
days depending upon CrCl in low and high bleeding risk respectively]
is more than rivaroxaban/ apixaban [1 and 2 days respectively for low
and high bleeding risk].
• Resumption o f NOAC depends on hemostasis, bleeding risk and
thromboembolic risk

35. VENACAVAL FILTERS
• Inferior vena cava (IVC) filters are designed to prevent the migration
of venous clots toward the pulmonary circulation
• It was first suggested by Trousseau in 1868.
• The ease of insertion of the new filters
by the percutaneous route and the
reportedly low complication rates have
increased their use and probably widened
the indications for their use.

37. Indication for IVC filter placement as per ACCP guidelines
• Acute VTE and contraindication to anticoagulation
• VTE despite anticoagulation
• Preoperatively in patients who have recent VTE ( <1 month ) and must
have anticoagulation interrupted for surgery
• In addition to anticoagulant therapy in patients with acute VTE
• Proximal DVT and poor cardiopulmonary reserve
• Free-floating proximal thrombus
• Thrombolysis with proximal DVT
• Primary prophylaxis in selected high-risk patients

38. • An RCT by Girard et.al , vena cava interruption using a definitive vena
cava filter was associated with an early reduction in the risk of
recurrent PE but with a late increase in recurrent deep vein
thrombosis without significant difference in the risk of recurrent
venous thromboembolism or death
Thrombosis and Haemostasis 111.4/2014

39. • The data supporting any and all indications for IVCF are limited.
• To date, only two randomized trials have been conducted on IVCF use
ie PREPIC-I and PREPIC-II

40. • According to this trial, in addition to heparin therapy, the use of a
permanent filter initially reduced the occurrence of symptomatic or
asymptomatic pulmonary embolism without major complications.
• However, no effect was observed on either immediate or long-term
mortality.
• In addition, after two years, the initial beneficial effect of filters was
counterbalanced by a significant increase in recurrent deep-vein
thrombosis, which could be related to thrombosis at the filter site.

41. PULMONARY EMOBOLISM AND PREGNANCY
• Acute PE remains one of the leading causes of maternal death in high-
income countries
• It increases during pregnancy and reaches a peak during the post-
partum period
• Venous compression ultrasonography may be considered in order to
avoid unnecessary irradiation, as a diagnosis of proximal deep vein
thrombosis confirms PE

42. RECOMMENDATIONS

43. PTE AND CANCER
• Overall risk is four times as great as in the general population
• Largest absolute numbers of VTE episodes occur in patients with lung,
colon and prostate cancer, the relative risk for VTE is highest in
multiple myeloma, brain, and pancreatic cancer
• Prophylactic anticoagulation is not routinely recommended during
ambulatory anticancer chemotherapy, with the exception of
thalidomide- or lenalidomide-based regimens in multiple myeloma
• For patients with PE and cancer, weight-adjusted subcutaneous low
molecular weight heparin should be considered for the first 3–6
months.
• Extended anticoagulation (beyond the first 3–6 months) should be
considered for an indefinite period, or until the cancer is cured.

44. CHRONIC THROMBOEMBOLISM
• It’s a disease caused by the persistent obstruction of pulmonary
arteries by organized thrombi, leading to flow redistribution and
secondary remodelling of the pulmonary microvascular bed.
• Reported with a cumulative incidence of between 0.1 and 9.1% in the
first 2 years after a symptomatic PE event.
• The diagnosis of CTEPH is based on findings obtained after at least 3
months of effective anticoagulation, to distinguish this condition from
acute PE

45. The diagnosis requires
• Mean PAP of >_25 mmHg
• Pulmonary arterial wedge pressure of <_15mmHg documented at
right heart catheterization in a patient with mismatched perfusion
defects on V/Q lung scan.
Specific diagnostic signs for CTEPH on multidetector CT angiography or
conventional pulmonary cineangiography include ring-like stenoses,
webs, slits, and chronic total occlusions

46. TREATMENT
1. Surgical treatment
i) Surgical PEA is the treatment of choice for operable CTEPH
• In contrast to surgical embolectomy for acute PE, treatment of CTEPH
necessitates a true bilateral endarterectomy through the medial layer
of the pulmonary arteries
• The majority of patients experience substantial relief from symptoms
and near-normalization of haemodynamics.
• General criteria include pre-operative New York Heart Association
(NYHA) functional class and the surgical accessibility of thrombi in the
main, lobar, or segmental pulmonary arteries.
• Post-operative ECMO is recommended as the standard of care in
PEA(pulmonary endarterectomy) centres

47. ii) Balloon pulmonary angioplasty
• an effective treatment for technically inoperable CTEPH
• It allows dilatation of obstructions down to subsegmental vessels, which
are inaccessible to surgery
2. Pharmacological treatment
• Optimal medical treatment for CTEPH consists of anticoagulants, as well as
diuretics and oxygen in cases of heart failure or hypoxaemia.
• Lifelong oral anticoagulation with VKAs is recommended, and also after
successful PEA or BPA.
• No data exist on the efficacy and safety of NOACs

48. THANK YOU