Pulmonary Embolism

Definition
Pulmonary embolism (PE) is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream (embolism).


Epidemiology
For each 10-year increase in age, the incidence doubles.

Risk Factors
Advanced age
Obesity
Previous thromboembolism
Prolonged immobility
Hypercoagulable state

• Protein C, protein S, and antithrombin III deficiencies
• Activated protein C resistance (factor V Leiden)
• Hyperhomocysteinemia
• Prothrombin gene mutation
• Antiphospholipid antibody syndrome
• Lupus anticoagulant

Congestive heart failure
Primary pulmonary hypertension
Chronic obstructive pulmonary disease (COPD)
Malignancy
Stroke
Inflammatory bowel disease
Varicose veins
Pregnancy and postpartum period
Estrogen therapy such as oral contraceptives or hormone replacement therapy
Indwelling vascular devices
Surgery/postoperative
Trauma (especially spinal injuries and long bone fractures)
Severe burns

Pathophysiology

• Virchow's triad (contributors to the pathogenesis of venous thrombosis):
• Venous stasis
• Injury to the intima
• Changes in the coagulation properties of the blood
• Thrombosis mainly originates as a platelet nidus in the region of the venous valves located in the veins of the lower extremities.
• Further growth occurs by accretion of platelets and fibrin and progression to red fibrin thrombus, which may either break off and embolize or result in total occlusion of the vein.
• The endogenous thrombolytic system of the body leads to resolution.

Aetiology

• Venous stasis, endothelial injury, and hypercoagulability
• Deep vein thrombosis (DVT) is responsible for 95% of cases of PE.

Commonly Associated Conditions

• DVT
• Occult cancer (e.g., lung, gastrointestinal tract, breast, uterus, brain, prostate)
• Chronic medical conditions (CHF, obesity)

Presentation
History

• Acute unexplained dyspnea (73%)

• Cough (34%)

• Hemoptysis (23%)

• Pleuritic chest pain (44%)
• Anxiety and apprehension

Physical Exam

• Signs of DVT may or may not be present.
• Acute unexplained dyspnea (tachycardia, tachypnea 54%, focal wheeze)
• Hypoxia
• Distended neck veins/large A wave (14%)
• Heart: S3 gallop and increased P2 sound
• Lungs: may be clear or have decreased breath sounds due to pleural effusion
• Crackles (51%)
• Acute cor pulmonale (shock-systemic hypotension, syncope, cyanosis, right ventricular gallop, pleural friction rub, hemoptysis)

Differential diagnosis

• Pneumonia or bronchitis
• Myocardial infarction (angina pectoris)
• Pericarditis
• CHF
• Viral pleuritis
• Asthma
• Exacerbation of COPD
• Pulmonary edema
• Dissection of the aorta
• Rib fracture(s)
• Pneumothorax
• Musculoskeletal chest wall pain

Investigation

FBC	WCC- infection, anaemia, Platelet
PT, PTT	Hypercoagubility
D-Dimer	Def: D-dimer, a degradation product of crosslinked fibrin,which is elevated in plasma in the presence of an acute clot because of simultaneous activation of coagulation and fibrinolysis. A negative D-dimer result in a highly sensitive assay safely excludes PE in patients with a low or moderate clinical probability.
Spiral CT	In patients with a non-high clinical probability, a negative SDCT (single detector spiral CT) must be combined with negative CUS (compression venous ultrasonography) to safely exclude PE,
Compression ultrasonography (CUS)	Positive result in around 20% of patient with proximal DVT used either as a backup procedure to reduce the overall false-negative in SDCT
V/Q scan	Def: intravenous injection of technetium (Tc)-99 m labelled macroaggregated albumin particles, which block a small fraction of pulmonary capillaries and thereby enable scintigraphic assessment of lung perfusion at the tissue level. Normal V/Q scan excludes PE. Usually not done if CXR shows
pulmonary angiography	pulmonary angiography is a reliable but invasive test and is currently useful when the results of non-invasive imaging are equivocal. Whenever angiography is performed, direct haemodynamic measurements should be performed.
Basic	FBC, PT, PTT
ECG	ECG: Tachycardia, incomplete right bundle branch block, T wave inversions in V2 and V3, S1Q3T3 pattern
CXR	parenchymal infiltrates, pleural effusion, atelectasis, consolidation, prominent central arteries, focal oligemia (Westermark sign), wedge-shaped pleural density (Hampton hump), and/or elevated hemidiaphragm
Echo	Right ventricular strain and pulmonary hypertension, tricuspid regurgitation, septal flattening (reverse “D” sign)
Dopler	Color-flow Doppler imaging and compression ultrasonography are noninvasive tests for lower-extremity DVT
Stool guaiac	prior to initiating anticoagulation

Management
Diagnostic Strategies (Summarized from ECS 2008 Guideline)

Prediction Test	Well’s score Clinical Characteristic Score Previous pulmonary embolism or deep vein thrombosis + 1.5 Heart rate greater than 100 beats per minute + 1.5 Recent surgery or immobilization (within the last 30 d) + 1.5 Clinical signs of deep vein thrombosis + 3 Alternative diagnosis less likely than pulmonary embolism + 3 Hemoptysis + 1 Cancer (treated within the last 6 mo) + 1 Note: Clinical probability of PE: low 0–1; intermediate 2–6; high 7 or more Other test The Revised Geneva Score
Suspected high Risk PE (with shock / hypotension)	Emergency CT (recent study) CT is usually able to confirm PE A SDCT (Single detector CT) or MDCT (Multi-detector CT) showing a thrombus up to the segmental level can be taken as adequate evidence of PE in most instances Pulmonary angiography should be avoided because it carries a risk of mortality in unstable patients Echo The absence of echocardiographic signs of RV overload or dysfunction practically excludes PE as a cause of haemodynamic compromise If +ve CT: consider thrombolysis/ embolectomy, if -ve CT: search for other causes
Suspected non-high Risk PE	If pretest clinical probability is not high, then obtain high-sensitivity D-dimer. If positive, then perform diagnostic tests, such as Dopplers to rule out DVT and CT angiogram to rule out PE. If pretest clinical probability is high, then perform diagnostic tests.
Acute treatment	Anticoagulation with unfractionated heparin ASAP Correct hypotension to prevent progression of RV failure and death due -Vasopressive Dobutamine and dopamine may be used in patients with PE, low cardiac output and normal blood pressure Aggressive fluid challenge is not recommended Oxygen should be administered in patients with hypoxaemia Thrombolytic therapy in patients with high-risk PE presenting with cardiogenic shock and/or persistent arterial hypotension Surgical pulmonary embolectomy is a recommended therapeutic alternative in patients with high-risk PE in whom thrombolysis is absolutely contraindicated or has failed Catheter embolectomy or fragmentation of proximal pulmonary arterial clots may be considered as an alternative to surgical treatment in high-risk patients when thrombolysis is absolutely contraindicated or has failed
Long-term treatment	For patients with PE secondary to a transient(reversible) risk factor, treatment with a VKA is recommended for 3 months For patients with unprovoked PE, treatmentwith a VKA is recommended for at least 3 months Patients with a first episode of unprovoked PE and low risk of bleeding, and in whom stable anticoagulation can be achieved, may be considered for long-term oral anticoagulation For patients with a second episode of unprovoked PE, long-term treatment is recommended In patients who receive long-term anticoagulanttreatment, the risk/benefit ratio of continuing such treatment should be reassessed at regular intervals For patients with PE and cancer, LMWH should be considered for the first 3 –6 months . after this period, anticoagulant therapy with VKA or LMWH should be continued indefinitely or until the cancer is considered cured In patients with PE, the dose of VKA should be adjusted to maintain a target INR of 2.5(range 2.0–3.0) regardless of treatment duration
Thrombolysis	Approved regimens Streptokinase 250 000 IU as a loading dose over 30 min, followed by 100 000 IU/h over 12– 24 h Accelerated regimen: 1.5 million IU over 2 h Urokinase 4400 IU/kg as a loading dose over 10 min, followed by 4400 IU/kg/h over 12– 24 h Accelerated regimen: 3 million IU over 2 h rtPA 100 mg over 2 h or 0.6 mg/kg over 15 min (maximum dose 50 mg) Contraindications: Absolute Haemorrhagic stroke or stroke of unknown origin at any time Ischaemic stroke in preceding 6 months Central nervous system damage or neoplasms Recent major trauma/surgery/head injury (within preceding3 weeks) Gastrointestinal bleeding within the last month Known bleeding Relative Transient ischaemic attack in preceding 6 months Oral anticoagulant therapy Pregnancy or within 1 week post partum Non-compressible punctures Traumatic resuscitation Refractory hypertension (systolic blood pressure .180 mmHg) Advanced liver disease Infective endocarditis Active peptic ulcer
General prevention	Prophylactic therapy includes low-dose heparin, warfarin, LMWH, graduated-compression stockings, or leg compression devices. In high-risk individuals, t.i.d. dosing of unfractionated heparin is more effective prophylaxis than b.i.d. dosing.
In pregnancy	Incidence 5–50 times higher in pregnant vs. nonpregnant women Highest incidence of PE is during the postpartum period. Consider antiphospholipid antibody syndrome. Warfarin is teratogenic in 1st trimester. Treatment should be initiated with low molecular weight heparin (LMWH), a Factor Xa inhibitor, or IV unfractionated heparin. If VTE-positive during pregnancy, anticoagulation should be continued for a minimum total duration of 6 months and for at least 6 weeks postpartum.
Education	Limit foods and drugs that affect Coumadin (e.g., green leafy vegetables, proton pump inhibitors). Limit foods and drugs that affect Coumadin (e.g., green leafy vegetables, proton pump inhibitors).

Complications

• Pulmonary infarction
• Acute cor pulmonale
• CTEPH
• Recurrent DVT or PE, post-phlebitic syndrome
• Major hemorrhage associated with thrombolytics is 8%; incidence of intracerebral bleed is 2% and is fatal in 50% of cases.
• HIT (8-20% mortality)

Prognosis
Left untreated, high rate of mortality.

• Hospital mortality is <5%
• 5–15% of all in hospital deaths
• In 22% of cases, PE is not diagnosed before causing death.

Long-term prognosis determined by comorbid disease.

• Higher mortality rate in patients with + troponin and echocardiogram evidence of RV strain.