Pulmonary Embolism (PE) and Deep Venous Thrombosis (DVT) are two clinical presentations of venous thromboembolism (VTE). Deep venous thrombosis is the most common condition that may lead to pulmonary embolism and its diagnosis and treatment is discussed elsewhere.
Pulmonary embolism is the obstruction of the pulmonary artery or its branches by a thrombus or a different object originated in a distant area (embolus). Anatomically, it can be unilateral or bilateral, saddle, lobar, segmental or sub segmental.
The overall incidence of PE is around 112 cases per 100.000 individuals and around 70% of patients with PE may have a DVT that can be detected in the limbs.
SYMPTONS AND SIGNS:
PE can either be asymptomatic or present with a wide variety of symptoms. It can be acute, subacute or chronic. Patients may complain of dyspnea on exertion or at rest, chest pain, fatigue, shortness of breath, palpitations, lightheadedness, pre-syncope, or syncope. Other patients may already unconscious due to shock or sudden death.
Signs may include tachycardia, tachypnea, respiratory distress, jugular venous distension, rales, decreased breath sounds, fever, increased intensity of P2, and sometimes hypotension and cardiac arrest.
A patient with PE is considered to be unstable if SBP is <90 mmHg or if the SBP drops more than 40 mmHg from baseline in 15 minutes and there is no other explanation.
Since history and physical examination may be very non-specific, an algorithm that involves pretest probability, D-dimer testing and imaging is the most useful way to diagnose PE.
To assess the pretest probability, the Wells score for PE is useful:
|Parameter||Points if present|
|Signs and symptoms of DVT||+3|
|Alternative diagnosis less likely than PE||+3|
|Surgery in the past month or immobilization||+1.5|
|Previous PE or DVT||+1.5|
|Cancer (in the past 6 months)||+1|
|Three tier Model interpretation||Risk category|
|0 or 1||Low risk|
|2 - 6||Moderate risk|
|> 6||High risk|
|Two tier model interpretation||Risk category|
|<= 4||PE Unlikely|
|>= 5||PE likely|
The two tier model has been used in most recent studies and guidelines. A Wells score >4 is likely for PE. A score <=4 is unlikely.
Patients with an unlikely PE should have undergo D-dimer testing. If D-dimer is negative with an unlikely score, PE is excluded. If the D-dimer is positive, an imaging method should be used.
Patients with a likely PE do not need D-dimer testing and should receive imaging test right away. The best initial test is computed tomography pulmonary angiography (CTPA). Other imaging methods include ventilation/perfusion scanning (V/Q scanning), magnetic resonance pulmonary angiography and catheter-based contrast angiography.
Echocardiography is an important test and can be used in unstable patients in which the diagnosis has not been established yet. New right ventricular strain, increased RV size, hypokinesis, decreased RV function, tricuspid regurgitation or visible thrombus are all relevant findings.
Other tests may be useful in excluding alternative diagnoses.
CBC may show leukocytosis. ESR, LDH and AST may be elevated. Kidney function tests are important particularly in patients that may need contrast exams. ABG may show hypoxemia, increase in the A-a gradient or respiratory alkalosis due to low CO2. Troponins may be elevated and can be associated with worse prognosis.
Chest x-ray may be completely normal or have changes that are not specific, such as effusions. Other changes such as Westermark`s sign (oligemia in an area of the lung) or Hampton`s hump (a triangle-shaped opacity with the base pointing to the pleural surface, indicative of necrosis) may also be present.
EKG can show sinus tachycardia, arrhythmias, right bundle branch block, right axis deviation, inferior Q-waves, anterior ST-segment changes, and the McGiin-White sign (S1Q3T3 – large S wave in lead I, Q wave in lead III and inverted T wave in lead III).
Lower extremity ultrasound is important to rule out DVT.
After diagnosis, the pulmonary embolism severity index (PESI) may be used to classify the severity of the PE and decide between outpatient and inpatient treatment (and maybe even between just anticoagulation or thrombolytics). The PESI index is:
Prognostic variables and risk stratification of the Pulmonary Embolism Severity Index (PESI)
|Age||Points = Age|
|Cancer (previous or active)||+30|
|Chronic lung disease||+10|
|SBP <100 mmHg||+30|
|Respiratory rate >= 30pm||+20|
|Altered mental status||+60|
|Oxygen saturation <90% (with or without supplemental O2).||+20|
|Risk classes||Points||Risk stratification|
|Class I||<= 65||Very low risk|
|Class II||66-85||Low risk|
|Class III||86-105||Intermediate risk|
|Class IV||106-125||High risk|
|Class V||>125||Very high risk|
Initially patients should be evaluated regarding their hemodynamic status. Oxygen supplementation should be provided to keep SO2 >= 90%.
Stable patients may receive additional testing to confirm the diagnosis and, after that, receive anticoagulation. If the patient is stable and has low risk of bleeding and complications, anticoagulation can be done outpatient. Patients with higher risk should be admitted for inpatient initial anticoagulation and monitoring. Anticoagulation should be continued for at least three months (and in cases of recurrent VTE or persistent risk factors, it may continue to up to 6-12 months or indefinitely).
For outpatient treatment: Rivaroxaban (XARELTO) 15 mg twice daily for 21 days, followed by 20 mg qDay after that.
For inpatient treatment: Enoxaparin (LOVENOX) 1mg/kg/dose SC q12hr OR 1.5mg/kg/day.
For inpatient/outpatient treatment: Warfarin: Start with 2 to 5mg qDay and monitor INR, adjusting accordingly (target INR 2-3). Use it with enoxaparin or another parenteral agent for the first 3-5 days.
In patients with confirmed or presumptive (due to history, physical examination, pretest probability and/or bedside echocardiographic findings) acute PE and hypotension that does not respond to fluid ressuscitation, thrombolytics should be given through a peripheral IV line.
Alteplase (tPA) (ACTILYSE) – 100 mg IV over two hours OR
Streptokinase – 250,000 U IV over 30 minutes, then 100.000 U/hour for 24 hours. Be aware of reactions (hypotension, anaphylaxis, asthma).
Urokinase (ABBOKINASE) – 4400 U/kg IV over 10 minutes, then 4400 units/kg/hour for 12 hours.
Patients that do not respond to IV thrombolysis or patients with high risk of bleeding may benefit from catheter-directed thrombolysis or embolectomy (surgical or by catheter).
If anticoagulation is contraindicated, the patient should receive an IVC filter.
REFERENCES & FURTHER READING:
- 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J (2014) 35 (43): 3033-3073.
- Wells PS, Anderson DR, Rodger M, et. al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000 Mar;83(3):416-20.
- Ouellette DR. Pulmonary Embolism Treatment & Management. Medscape Updated: Jun 22, 2016.
- Jaff MR et al. Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension. Circulation. 2011;123:1788-1830.
- Jaber WA et al. Acute Pulmonary Embolism: With an Emphasis on an Interventional Approach. JACC 2016: 67(8).
- Guidelines on the diagnosis and management of acute pulmonary embolism. European Heart Journal (2008)29, 2276–2315.
- Dentali F et al. Pulmonary embolism severity index accurately predicts long-term mortality rate in patients hospitalized for acute pulmonary embolism. Journal of Thrombosis and Haemostasis, 11: 2103–2110.