Acute Pulmonary Embolism, highlights of a Kauvery Post Graduate Lecture

Belinda Anet

Consultant – Pulmonary Medicine, Kauvery Hospital, Tirunelveli

Introduction

Pulmonary embolism – obstruction of the pulmonary artery or one of its branches by a material (thrombus, tumor, air, or fat) that originated elsewhere in the body.

Epidemiology

Third most common acute cardiovascular syndrome (after myocardial infarction and stroke)
Annual incidence rates for PE – 39 to 115 per 100 000 population
Incidence of VTE – eight times higher in individuals aged >_80 years

Source of emboli

Lower extremity	Pelvic veins	Upper extremity
Calf venous plexus	Pregnancy	Central venous catheters
Popliteal vein	Pelvic thrombophlebitis	Intravascular cardiac devices
Femoral vein	Pelvic surgery	Thoracic outlet obstruction
		Paget schrotter syndrome

Source of emboli

Etiologies

Stasis	Injury	Hypercoagulability
Immobility	Trauma	Malignancy
Bed rest	Surgery	Anticardiolipin antibody
Anesthesia		Nephrotic syndrome
Congestive heart failure/cor pulmonale		Essential thrombocytosis
Prior venous thrombosis		Estrogen therapy
		Paroxysmal nocturnal hemoglobinuria
		Disseminated intravascular coagulation
		Protein C and S deficiencies
		Antithrombin III deficiency

Clinical features

Diagnostic tests

D-dimer
Chest X ray
CTPA
V/Q scan
TTE
USG doppler

Classical ECG of Pulmonary Embolism

Sinus tachycardia
S1Q3T3 pattern
Right bundle branch block
T wave inversion in V1,2,3.

D-dimer

ELISA method preferred, sensitivity >95%
Negative predictive value in low and intermediate risk probability
Age adjusted cut-off: age * 10 mg/L, for patients aged >50 years
Not recommended in patients with high clinical probability – does not safely exclude PE.

Chest X-ray

Fleischner sign: enlarged pulmonary artery (20%)
Hampton hump: peripheral wedge of airspace opacity and implies lung infarction (20%)
Westermark sign: regional oligemia and highest positive predictive value (10%)
Pleural effusion (35%) – pleural effusions in pulmonary embolism
Palla sign: enlarged right descending pulmonary artery
Chang sign: dilated right descending pulmonary artery with sudden cut-off

CTPA

Method of choice for imaging the pulmonary vasculature in patients with suspected PE.
PIOPED II study – sensitivity of 83% and specificity of 96%.

CTPA	Positive	Negative
Low risk	Low PPV	High NPV
Intermediate risk	High PPV	High NPV
High risk	High PPV	Low NPV

Example Images

V/Q scan

Tracers: xenon-133 gas, krypton-81 gas, technetium-99m-labelled aerosols, or technetium-99m-labelled carbon microparticles
Lower-radiation and contrast medium sparing procedure, so preferred in
- Out patients with low clinical probability
- Young females
- Pregnant
- Contrast medium anaphylaxis
- Renal failure

Example Image

Transthoracic echocardiography

Doppler scan

DVT was found in 70% of patients with proven PE.

Biomarkers

Troponin I/T
Fatty acid binding protein – >6 ng/ml
N terminal proBNP – >_600 ng/L
Lactate – >2mmol

Diagnostic algorithm

Treatment

Supportive measures

Respiratory support	Hemodynamic support
Supplemental oxygen SpO2<90%	IV fluids
Non invasive ventilation	Vasopressors and inotropes
Invasive mechanical ventilation	Mechanical circulatory support
	Advanced life support in cardiac arrest

Risk Adjusted Management Strategies

Reperfusion therapy

Thrombolysis

Contraindications to Thrombolysis

Absolute	Relative
History of haemorrhagic stroke or stroke of unknown origin	Transient ischaemic attack in previous 6 months
Ischaemic stroke in previous 6 months	Oral anticoagulation
Central nervous system neoplasm	Pregnancy or first post-partum week
Major trauma, surgery, or head injury in previous 3 weeks	Non-compressible puncture sites
Bleeding diathesis	Traumatic resuscitation
Active bleeding	Refractory hypertension (systolic BP >180 mmHg)
	Advanced liver disease
	Infective endocarditis
	Active peptic ulcer

Percutaneous Catheter-Directed Treatment

Catheter-directed thrombolysis
Ultrasound-assisted catheter-directed thrombolysis
Aspiration thrombectomy
Rheolytic thrombectomy

Surgical embolectomy

	Thombolysis	Embolectomy
30 day mortality	15%	3%–7.9%
Recurrence	More	Less
Risk of stroke and re-intervention	7.9%	2.8%

Initial anticoagulation

Low molecular weight heparin

Active cancer
Pregnancy
Warfarin, dabigatran, or edoxaban is chosen as the agent for long-term use
Therapeutic anticoagulation cannot be given via the oral route (malabsorption)
Dose: 1 mg/kg BD or 1.5 mg/kg OD
Creat cl <30 ml/min – 1mg/kg OD

Advantages

Greater bioavailability
Duration of the anticoagulant effect is longer – once or twice daily administration
Fixed dosing is feasible because the anticoagulant response (anti-Xa activity) correlates well with body weight
Laboratory monitoring – not necessary (correlation between anti-Xa activity and bleeding or recurrent thrombosis is poor)
Lower risk of heparin-induced thrombocytopenia (HIT)
Use as an outpatient therapy

Fondaparinux

Weight	Dose
<50 kg	5 mg
50-100 kg	7.5 mg
>100 kg	10 mg

IV unfractionated heparin

CrCl <30 mL/minute
Acute reversal of anticoagulation will be needed (eg, procedure or at increased risk of bleeding)
Hemodynamic instability
Pregnancy

Therapeutic level of heparin

Target aPTT ratio range – 1.5 to 2.5 times the control
Corresponds to a heparin level of 0.3 to 0.7 units/mL, when measured by an anti-Xa assay

Direct factor Xa and thrombin inhibitors

Given within 6 to 12 hours following the last dose of subcutaneous LMW heparin when administered as a twice daily regimen

Contraindicated in:

Severe renal insufficiency
Pregnancy
Who requires thrombolytic therapy

Warfarin

Should be started along with heparin from day 1
Min of 5 days of LMWH is given
Normal adult 5 mg starting dose
Frail adult, malnourished, elderly, liver disease – 2.5 mg
Target INR 2-3
Titrate dose accordingly

Maintenance therapy

Drug	Dose
Dabigatran	150 mg BD
Apixaban	10 mg BD for seven days followed by 5 mg BD (2.5 mg BD for extended treatment beyond six months)
Endoxaban	60 mg OD
Rivoroxaban	15 mg BD for 21 days followed by 20 mg OD

Trials of non-vitamin K antagonist oral anticoagulants in venous thromboembolism

Drug	Trial	Regimens	Duration	Efficacy outcome	Safety outcome
Dabigatran	RECOVER	Parenteral anticoagulant for ≥5 days followed by dabigatran 150 mg BID vs. parenteral anticoagulant/warfarin	6 months	Recurrent VTE or fatal PE: 2.4% on dabigatran 2.1% on warfarin	Major bleeding: 1.6% on dabigatran 1.9% on warfarin
Rivaroxaban	EINSTEIN PE	Rivaroxaban (15 mg BID for 3 weeks, then 20 mg OD) vs. enoxaparin/warfarin	3, 6, or 12 months	2.1% on rivaroxaban 1.8% on warfarin	10.3% on rivaroxaban 11.4% on warfarin
Apixaban	AMPLIFY	Apixaban (10 mg BID for 7 days, then 5 mg BID) vs. standard	6 months	2.3% on apixaban 2.7% on warfarin	0.6% vs 1.8%

Duration

Minimum 3 months for all patients

IVC filters

Indication

Absolute contraindication to anticoagulant treatment
Recurrent PE despite adequate anticoagulation
Primary prophylaxis in patients with a high risk of VTE.

Absolute contraindications to anticoagulation include

Active bleeding
Severe bleeding diathesis
Recent, planned, or emergency high bleeding-risk surgery/procedure
Major trauma
Acute intracranial hemorrhage (ICH)

Relative contraindications to anticoagulation include: Recurrent bleeding from multiple gastrointestinal telangiectasia’s

Intracranial or spinal tumours
Large abdominal aortic aneurysm with concurrent severe hypertension
Stable aortic dissection
Recent, planned, or emergent low bleeding-risk surgery/procedure

Summary

Age adjusted D-dimer cut off is preferred
Validated scores combining clinical, imaging, and laboratory prognostic factors may be considered to further stratify PE severity.
When oral anticoagulation is initiated in a patient with PE who is eligible for a NOAC, a NOAC is the recommended form of anticoagulant treatment.
ECMO may be considered, in combination with surgical embolectomy or catheter-directed treatment, in refractory circulatory collapse or cardiac arrest
Indefinite treatment with a VKA is recommended for patients with antiphospholipid antibody syndrome.
Extended anticoagulation should be considered for patients with no identifiable risk factor for the index PE event.
Extended anticoagulation should be considered for patients with a persistent risk factor other than antiphospholipid antibody syndrome.
Extended anticoagulation should be considered for patients with a transient/reversible risk factor for the index PE event
NOACs are not recommended during pregnancy or lactation.
Routine clinical evaluation is recommended 3-6 months after acute PE.

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Acute Pulmonary Embolism, highlights of a Kauvery Post Graduate Lecture