What is the pathophysiology of Pulmonary Embolism (PE)?

From the Guidelines

Pulmonary embolism (PE) is a life-threatening condition that occurs when a blood clot breaks free and travels through the bloodstream to lodge in the pulmonary arteries, creating a ventilation-perfusion mismatch and increasing pulmonary vascular resistance, which can lead to right ventricular strain and failure in severe cases, as noted in the European Society of Cardiology guidelines 1. The pathophysiology of PE involves the blockage of pulmonary arteries, leading to hypoxemia and increased pulmonary vascular resistance. Risk factors for PE include immobility, surgery, cancer, pregnancy, oral contraceptives, and inherited thrombophilias. The body's natural response to PE involves activating the fibrinolytic system to dissolve the clot, but this process can take weeks. Symptoms of PE result from both the mechanical obstruction and the inflammatory response to the clot, including dyspnea, chest pain, tachycardia, and hypoxemia.

Key Points

• The diagnosis of PE is often difficult to obtain and is frequently missed, with mortality in untreated PE approximately 30%, but with adequate anticoagulant treatment, this can be reduced to 2–8% 1.
• The classification of PE into massive and non-massive types is crucial for determining the appropriate treatment approach, with massive PE consisting of shock and/or hypotension, and non-massive PE being further subdivided into submassive and non-massive types based on echocardiographic signs of right ventricular hypokinesis 1.
• Treatment of PE focuses on anticoagulation with heparin initially, followed by oral anticoagulants like warfarin or direct oral anticoagulants (DOACs) for at least 3-6 months, with thrombolytic therapy reserved for hemodynamically unstable patients with massive PE.
• The use of inferior vena cava (IVC) filters is also an option for select patients with PE, particularly those with contraindications to anticoagulation or those who have recurrent PE despite anticoagulation, as noted in the ACR Appropriateness Criteria 1. The most effective treatment approach for PE is anticoagulation, which can reduce mortality from 30% to 2-8%, and should be initiated promptly in all patients with diagnosed PE, unless contraindicated 1.

From the Research

Pathophysiology of Pulmonary Embolism (PE)

• Pulmonary embolism (PE) is characterized by occlusion of blood flow in a pulmonary artery, typically due to a thrombus that travels from a vein in a lower limb 2
• The incidence of PE is approximately 60 to 120 per 100 000 people per year, with approximately 60 000 to 100 000 patients dying from PE each year in the US 2
• PE should be considered in patients presenting with acute chest pain, shortness of breath, or syncope 2

Clinical Presentation and Diagnosis

• The diagnosis of PE is determined by chest imaging 2
• In patients with a systolic blood pressure of at least 90 mm Hg, the following 3 steps can be used to evaluate a patient with possible PE: assessment of the clinical probability of PE, D-dimer testing if indicated, and chest imaging if indicated 2
• The clinical probability of PE can be assessed using a structured score or using clinical gestalt 2

Treatment and Management

• Anticoagulation is the cornerstone of acute pulmonary embolism (PE) therapy 3
• In patients with high or intermediate clinical probability of pulmonary embolism, anticoagulation should be initiated without delay while awaiting the results of diagnostic tests 4
• Low molecular weight heparins (LMWH) and fondaparinux are preferred over unfractionated heparin (UFH) in the initial anticoagulation of PE since they are associated with a lower risk of bleeding 4, 5
• Direct oral anticoagulants (DOACs) such as apixaban, edoxaban, rivaroxaban, or dabigatran, are noninferior for treating PE and have a 0.6% lower rate of bleeding compared to heparin combined with a vitamin K antagonist such as warfarin followed by warfarin alone 2
• Systemic thrombolysis is recommended for patients with PE and systolic blood pressure lower than 90 mm Hg, and is associated with an 1.6% absolute reduction of mortality 2
• Surgical pulmonary embolectomy (SPE) remains a vital option for select patients, particularly those who are not candidates for thrombolysis 6