ISNU PRADJOKO

PULMONOLOGY DEPARTEMENT and RESPIRATORY MEDICINE

MEDICAL FACULTY of AIRLANGGA UNIVERSITY

RSUD dr. SOETOMO ACADEMIC HOSPITAL.

SURABAYA

PULMONARY EMBOLISM

KONAS SOLO 2019

INTRODUCTION

• Pulmonary embolism partial or total obstruction of

pulmonary artery circulation or branches due to

embolism or other thrombus embolism blocked blood

flow.

• Pulmonary embolism: increased pulmonary artery

pressure secondary pulmonary hypertension.

• Resulting in right ventricular hypertrophy right heart

failure (cor pulmonale).

• Difficult diagnosis broad clinical spectrum

(Burrowes, 2011; Ghaye et all, 2006; Heit, 2013)

INTRODUCTION (2)

• Severity: size of embolism,

location, population, degree of

occlusion, previous

cardiopulmonary disorders.

• The patient comes in an

advanced condition.

EPIDEMIOLOGY

• Epidemiological data of pulmonary embolism difficult to

determine (asymptomatic).

• United States: 50,000 cases/year, 1 case/1,000 people/year.

• Sudden death in 20-34% of cases.

• Insidensi kematian meningkat seiring dengan usia tua (usia

>40 tahun).

(Cohen, 2007; Gruber, 2008; Konstatinides, 2014; Simon , 2010)

ETIOLOGY AND RISK FACTORS

• Penyebab emboli paru semula belum jelas autopsi

trombus pada pembuluh darah.

• Tumor emboli, amnion, air, fat, bone marrow, septic focus (in

endocarditis).

Virchow Triage

Slow Blood Flow (Stasis)

Vascular Wall Damage

Hypercoagulation

(Hwang, 2013)

RISK FACTORS

Slow blood flow (stasis)

• Long period of bed rest

• Obesity

• Varicose veins

• Congestive heart failure

• Slow-flowing blood gives more chance to clot (thrombus).

(Gruber, 2008; Kostadima, 2007)

RISK FACTORS (2)

Vascular Wall Damage

• Surgery orthopedic surgery, neurosurgery, abdominal piston,

pelvis, kidney transplant or TCV surgery.

• Blood vessel trauma (injections, cardiac catheterization).

• Trauma Trauma of the lower limb and/or pelvis, spinal cord

with paralysis, head trauma, vascular trauma, use of mechanical

ventilation for more than 3 days.

• Combustio.

(Gruber, 2008; Yung, 2008)

RISK FACTORS (3)

Hypercoagulation

• Malignancies pancreatic cancer, lymphoma, brain cancer,

hepatocellular carcinoma, leukemia, colorectal cancer.

• Splenectomy with thrombocytosis.

• Use of oral contraceptives (estrogen).

• Heparin-induced thrombocytopenia.

• Disseminated intravascular coagulation (DIC).

• Pregnancy.

( Gruber, 2008; Konstatinides, 2014; Kostadima, 2007; Yung, 2008)

PATHOPHYSIOLOGY

• Vasoconstriction

• ↑ lung vascular resistance

• Pulmonal HT right heart failure Hemodynamic

Disorder

• Hypoxemia

• Ventilation – Inadequate perfusion O2 ↓

• Terminal bronchi constriction ↑ Dead Space Atelectasys

Gas Exchange Disorder

(Alexander, 2010; Hwang, 2013; Konstatinides, 2014; Hwang, 2013)

Thrombus Journey

Loose vein thrombus

Thromboembolism will follow

venous flow and enter the

pulmonary artery circulation

Pulmonary artery

blockage

Increased pulmonary

artery pressure

Vasoconstrictor release

(serotonin)

Pulmonary artery hypertension

Right ventricular pressure

Fedullo PF, 2005.

Impaired ventricular filling

Cardiac output

Lung infarction

Ischemia, cardiogenic shock,

and death

CLINICAL APPEARANCE

• Dispnea, hemoptoe, wheezing, chest pain.

• Chest pain pleural irritation due to pulmonary infarction.

• Anamnesa family history of venous thromboembolism,

accompanying medical conditions, and treatment history.

• Scoring system Well’s score helps diagnosing PE.

(Gruber, 2008; Hwang, 2013; Konstatinides, 2014)

DIAGNOSIS

• Clinical symptoms sudden shortness of breath, chest pain

(pleuritic pain) or hemoptysis suspicion of pulmonary

embolism/pulmonary infarction.

• ECGs in leads V1-V4 have T-wave inversions in anterior leads

right ventricular hypertrophy, pulmonary thromboembolism.

• Deep S-waves in Lead I, Q-waves in Lead III, and inversion of

T-waves in Lead III.

• Conduction and rhythm disorders atrial fibrillation/right

bundle branch block acute pulmonary embolism.

(Konstatindes, 2014; Kostadima, 2007; Yung, 2008)

Well’s Scoring System for PE

Variabel Score

Clinical signs and symptoms of deep vein

thrombosis

3.0

Other differential diagnosis 3.0

Pulse rate more than 100 times per minute 1.5

Immobilization or surgery in the past 4 weeks 1.5

Previous history of DVT or pulmonary

embolism

1.5

Hemoptysis 1.0

Cancer (getting treatment in the last 6 months

or getting palliative management)

1.0

A score of 0-1 might have a low embolism, a score of 2-6 might have a

moderate embolism, and a score of >6 might have a high embolism.

Goldhaber SZ. Braunwald’s heart disease. 2012; Gandara E, Wells PS, 2010.

Geneva Scoring System for PE

Variabel Total Score

Aged >65 years 1

Previous history of PE or DVT 3

Surgery or fracture in 1 month 2

Active malignancy 2

Unilateral lower limbs pain 3

Hemoptysis 2

Pain in deep vein palpation, in the lower limbs

accompanied by unilateral edema

4

Pulse rate 75–94 times per minute 3

Pulse rate >95 times per minute 5

A score of 0-3 might be low (less than 8%), a score of 4-10 might be moderate

(less 28%), and a score of >10, likely high (approximately 74%).

Goldhaber SZ. Braunwald’s heart disease. 2012; Gandara E, Wells PS, 2010.

(Kostadima, 2007)

CHEST X-RAYs

Hampton’s Hump

Triangle radio-opaque

area, with hilar apex

appearance. It means

pulmonary infarction area

distal of thrombus.

(Kostadima, 2007)

Palla’s Sign

Descending pulmonal

artery enlargement.

Westermark’s Sign

Decreased pulmonary

vascular pattern in

defect area.

PE Diagnostic Examination

Examination

Type

Description

Chest x-rays • Non-specific, normal appearance 25%

• Mild pleural effusion, high-level diaphragm, atelectasis, cardiomegali ,

lung edema .

• Hampton hum sign (35%) effusion-like opacity (parenkim infarction)

Chest CT scan • Accurate for detecting thrombus, especially in the central and large.

CT Pulmonary

Angiography

(CTPA)

• Sensitive and specific, the gold standard of pulmonary embolism.

• Detect thrombus directly in the pulmonary artery and measure the diameter

of the right ventricle/left ventricle.

Echocardio-

graphy

• Right ventricular dilatation, tricuspid regurgitation, pulmonary hypertension,

inferior vena cava dilatation.

PE Diagnostic Examination

Examination

Type

Description

Blood

examination

• Routine blood tests and blood chemistry are not typical.

• BGA PO2 down, PCO2 can be normal or slightly down,

sensitivity and specificity of BGA as a diagnostic support for

pulmonary embolism is relatively low.

• D-dimer by ELISA method high sensitivity (94%), less

specificity (45%).

• The specificity of the ELISA D-dimer for pulmonary embolism

increases if the D-dimer/fibrinogen ratio is >1,000.

ECG • Getting rid of the possibility of acute myocardial infarction.

• The most common ECG patterns sinus tachycardia, mild ST-

and T-wave abnormalities.

PE Diagnosis Procedure

Goldhaber SZ. Braunwald’s heart disease. 2012.

PE Management Procedure

without Shock or Hypotension

Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D et al, 2014.

PE Management Procedure

with Shock or Hypotension

Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D et al, 2014.

Pulmonary Embolism Diff. Dx.

• Pneumonia or bronchitis

• Infarct miocard

• Pericarditis

• Congestive heart failure

• Idiopatic pulmonal hypertension

• Asthma bronchiale, COPD exaserbation

• Lung edema

• Aorta disection

• Lung carcinoma

• Rib fracture

• Pneumothorax

• Musculosceletal pain.

• Anxiety-hysteria)

• Pleuritis

Goldhaber SZ. Braunwald’s heart disease. 2012; Fedullo PF, Tapson VF, 2003.

Management of Pulmonary Embolism and DVT

Anticoagulant

Unfractionated Heparin

LMWH

Warfarin

New generation Oral Anticoagulan

Thrombolitic

Streptokinase

rt-PA

Urokinase

Surgical

Thrombectomy

Embolectomy

Non Phararmaclogy

Bed rest

Compression stocking

Unfractionated Heparin

• Mechanism: Increasing AT III effects and releasing TFPI

• Side effects: Bleeding and thrombocytopenia.

• Heparin can be stopped after 4-5 days of combination with warfarin if INR>2.0.

Dosis awal Bolus 80 unit/kgBB kemudian 18

unit/kg/jam dengan infus

APTT <35 detik ( <1 kali kontrol) Bolus 80 unit/kgBB kemudian 4

unit/kg/jam dengan infus

APTT 35-45 detik (1,2 -1,5 kali kontrol) Bolus 40 unit/kgBB kemudian 2

unit/kg/jam dengan infus

APTT 46-70 detik (1,5 - 2,3 kali kontrol) Tidak ada perubahan

APTT 71-90 detik (2,3 - 3,0 kali kontrol) Kecepatan infus diturunkan 2

unit/kgBB/jam

APTT >90 detik (>3 kali kontrol) Hentikan infus selama 1 jam lalu turunkan

kecepatan infus rata-rata 3 unit/kgBB/jam

Scarvelis D, Wells P, 2006; Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, et, 2012.

Low-Molecular-Weight Heparin (LMWH)

Biological half-life > unfractionated heparin

Does not require laboratory monitoring

Combination with wafarin for 4-5 days stopped if INR>2

DVT therapy dose 1 mg/kg 2x/day or 1.5mg/kg 1x/day.

Side effects of thrombocytopenia and osteoporosis LMWH <<UFH

Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D et al, 2014; JCS Guidelines 2009; Scarvelis D, Wells P,

2006; Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, et al , 2012.

LMWH Regimen and Dosage

Medicine Dosage

Enoxaparin 1 mg/kg bodyweight divided into 2 doses per day

Dalteparin 200 UI/kg bodyweight once a day

Tinzaparin 175 UI/kg bodyweight once a day

Nadroparin 6150 UI divided into 2 doses for 50-70 kg of bodyweight

4100 UI divided into 2 doses for <50 kg of bodyweight

9200 UI divided into 2 doses for >70 kg of bodyweight

Reviparin 4200 UI divided into 2 doses for 44-60 kg of bodyweight

3500 UI divided into 2 doses for 35-45 kg of bodyweight

6300 UI divided into 2 doses for >60 kg of bodyweight

Fondaparinux 7.5 mg once a day for 50-100 kg of bodyweight

5 mg once a day for 35-45 kg of bodyweight

10 mg once a day for >100 kg of bodyweight

Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, et al , 2012

Warfarin

Acute anticoagulation

The standard dose of warfarin is 5 mg/day, the dose is adjusted every three to seven days to get an INR value of between 2-3

Dosage is monitored with prothrombin time or INR

For uncomplicated DVT, 3-6 months of therapy

Contraindications: Cerebral hemorrhage, trauma and surgery

Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, et al, 2008; Scarvelis D, Wells P,

2006.

Thrombolytic

• Breaking newly formed blood clots and restoring

venous patency faster than anticoagulants.

• Thrombolytic therapy in acute episodes of DVT

can reduce the risk of recurrence.

Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, et al, 2008;

Scarvelis D, Wells P, 2006.

Thrombolytic

Regimen Dosage

Streptokinase The initial dose is 250,000 IU in 30 minutes,

followed by a dose of 100,000 IU/hour for 12 to

24 hours.

Accelerated regiment: 1.5 million IU in 2 hours.

Urokinase An initial dose of 4,400 IU/kg in 10 minutes,

followed by a dose of 4,400 IU/kg/hour in 12-24

hours.

Accelerated regiment: 3 million IU in 2 hours.

Recombinant tissue

plasminogen activator

(rtPA)

Initial dose of 100 mg in 2 hours or 0.6 mg/kg in

15 minutes.

Maximum dose: 50 mg.

Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, et al, 2008.

Contraindications to the administration of

fibrinolytic therapy

Absolute Contraindications Relative Contraindications

Hemorrhagic stroke or stroke with

unknown causes Transient ischemic attack in the past 6

months

Ischemic stroke in the past 6 months Use of oral anticoagulant therapy

Damage to the central nervous system

or neoplasms Pregnancy or 1 week postpartum state

Major trauma, head surgery or trauma

within the past 3 weeks Refractory hypertension with systolic

blood pressure >180 mmHg

Gastrointestinal bleeding within the last

1 month Advanced liver disease

Active hemorrhage Infective endocarditis

Active peptic ulcer

Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, et al ; 2012.

Thrombectomy and Embolectomy Open surgical thrombectomy therapy is recommended for:

1. Acute iliofemoral DVT

2. Thrombolytic contraindications

3. Thrombolytic therapy and mechanical thrombectomy failure

4. Lesions are inaccessible to the catheter

5. Thrombus is difficult to break

6. Anticoagulant contraindications

• Post-surgery heparin is given for 5 days, continued for 6 months

• For the best results, surgery should be performed within 7 days after the onset of DVT

Percutaneous embolectomy technique with catheterization can only be done if the blocked part is the main artery

Embolectomy in small arterial branches has a risk of perforation and damage to the structure of blood vessels

Scarvelis D, Wells P, 2006; Jaber WA, Fong P, Weisz G, et al, 2016.

New Generation of Oral Anticoagulant

There are several types of new generation drugs from anticoagulants

They are Dabigatran, Rivaroxaban, Apixaban and Edoxaban

Rivaroxaban inhibiting Xa factor

Rivaroxaban is well tolerated in adult patients rapid onset and high bioavailability (80%) and half-life of 4-12 hours has the same effectiveness as LMWH, enoxaparin, fondaparinux and warfarin in preventing recurrent venous thromboembolism

Does not require laboratory monitoring

Weitz JI, Hirsh J, Samama MM, 2012; Chen T, Lam S., 2009.

Chest X-rays

1 Mei 2016 5 Mei 2016

May 1, 2016

Left pneumonia and central lung

mass with pneumonic reaction.

May 14, 2016

Mass-like lesions in the left hilar are

reduced, calcification in the right and left

hilar remains and mild cardiomegaly.

14 Mei 2016

PROGNOSIS

PESI (PULMONARY EMBOLISM SEVERITY INDEX)

•

Predictors Score

Demographic characteristics Age (year) Male

Age +10

Comorbid diseases Ca (previous or now) Heart failure Chronical lung disease

+30 +10 +10

Clinical appearent Pulse ≥100x/menit Sistolic pressure <100 mmHg Respiratori rate ≥30x/menit Temperature <360C Disorientation, letargic, stupor, coma Oxygen saturation <90% (with/without O2)

+20 +30 +20 +20 +60 +20

(Dentali, 2013)

Class of Risk Score Stratification of Risk

I ≤65 Very Low

II 66 - 85 Low

III 86 - 105 Medium

IV 106 - 125 High

V >125 Very High

(Dentali, 2013)

TAKE HOME MESSAGES

• Pulmonary embolism pulmonary artery obstruction caused

by movement of emboli/thrombus.

• Risk factors immobilisation, obesity, surgery, trauma,

malignancy, oral contraception and chemotherapy.

• Clinical symptoms variation complex diagnosis.

• Dx Well’s score + advanced diagnostic finding.

• Management anticoagulant and thrombolytic.

• Prognose is good if in good management. Bad prognose if in

advanced stage.

XIE -XIE