RESPIRATORY CONDITIONS

Pulmonary Embolism

Etiology and Risk Factors

Venous thromboembolism includes deep-vein thrombosis and pulmonary embolism.

Virchow’s triad describes the major mechanisms promoting venous thrombosis:

• Venous stasis
• Endothelial injury
• Hypercoagulability

Risk factors include:

• Recent surgery
• Trauma
• Immobilization
• Hospitalization
• Active malignancy
• Prior venous thromboembolism
• Estrogen exposure
• Pregnancy and the postpartum period
• Inherited or acquired thrombophilia
• Central venous devices
• Severe medical illness
• Obesity
• Increasing age
• Inflammatory disease

The presence of a risk factor changes pretest probability but does not establish the diagnosis. PE can also occur without an obvious provoking factor (Huynh et al., 2026; Sisson et al., 2019).

Pathophysiology

A thrombus that enters the venous circulation travels through the right side of the heart and lodges in a pulmonary artery or one of its branches.

The immediate respiratory effect is loss of perfusion to ventilated alveoli. These lung units become high ventilation-perfusion regions or alveolar dead space. The patient increases minute ventilation, commonly producing hypocapnia and respiratory alkalosis (Norris, 2020; Sisson et al., 2019).

Hypoxemia may result from:

• Ventilation-perfusion mismatch
• Redistribution of blood toward low ventilation-perfusion regions
• Reduced mixed venous oxygen content
• Atelectasis
• Right-to-left shunting in selected patients

Large or multiple emboli increase pulmonary vascular resistance. Acute right-ventricular pressure overload can cause right-ventricular dilation, reduced contractility, interventricular septal shift, reduced left-ventricular filling, decreased cardiac output, hypotension, obstructive shock, and death (Sisson et al., 2019).

Pulmonary infarction is not inevitable because lung tissue receives blood from both the pulmonary and bronchial circulations. Infarction is more likely when cardiopulmonary reserve or collateral blood flow is impaired.

Clinical Manifestations

Presentations vary considerably.

Possible findings include:

• Sudden or unexplained dyspnea
• Pleuritic chest pain
• Tachypnea
• Tachycardia
• Hypoxemia
• Cough
• Hemoptysis
• Syncope or presyncope
• Anxiety
• Signs of deep-vein thrombosis
• Hypotension or shock in high-risk PE

A normal lung examination does not exclude PE. No single symptom, physical finding, electrocardiographic pattern, or arterial blood gas result is sufficiently reliable to confirm or exclude the diagnosis (Ma & Lucey, 2012; Prabhu, 2012; Sisson et al., 2019).

Diagnostic Evaluation

Evaluation should follow a structured assessment of hemodynamic stability and pretest probability.

Immediate Stability Assessment

Identify:

• Hypotension
• Shock
• Severe hypoxemia
• Syncope
• Altered mental status
• Signs of acute right-ventricular failure
• Cardiac arrest

Hemodynamic instability changes the urgency, testing pathway, and potential need for reperfusion therapy.

Clinical Probability

History and examination are used to estimate whether PE is unlikely, intermediate, or likely. A validated clinical decision rule may support this assessment, but it does not replace clinical judgment.

D-Dimer

A negative high-sensitivity D-dimer can help exclude PE when pretest probability is sufficiently low or intermediate. A positive result is nonspecific and requires further evaluation.

D-dimer commonly rises with age, inflammation, malignancy, pregnancy, trauma, surgery, and hospitalization. It should not be used as a general screening test in patients whose probability is already high.

Imaging

Computed tomography pulmonary angiography directly evaluates the pulmonary arteries and is commonly used for definitive imaging.

A ventilation-perfusion scan may be considered when computed tomography contrast is unsuitable or another clinical circumstance favors nuclear imaging.

Compression ultrasonography can identify deep-vein thrombosis and may contribute to decision-making, particularly when chest imaging is delayed or unsuitable.

Additional Testing

Depending on severity and presentation, evaluation may include:

• Electrocardiography
• Chest radiography
• Cardiac biomarkers
• Echocardiography
• Arterial blood gas analysis
• Laboratory assessment before anticoagulation

These tests help assess severity, alternatives, and complications. None independently excludes PE.

Expected Findings

Potential findings include:

• Hypoxemia
• Decreased PaCO₂
• Respiratory alkalosis
• Elevated alveolar-arterial oxygen gradient
• Tachycardia
• Signs of right-heart strain
• Elevated cardiac biomarkers in right-ventricular injury
• Filling defect on pulmonary vascular imaging
• Deep-vein thrombosis on compression ultrasonography

Chest radiography may be normal or show nonspecific abnormalities. Its primary value is often identifying an alternative explanation for symptoms.

Differential Diagnosis

Acute Coronary Syndrome

Both PE and acute coronary syndrome may cause chest pain, dyspnea, diaphoresis, electrocardiographic changes, and biomarker elevation. Pleuritic pain and thromboembolic risks support PE, while ischemic symptoms and coronary findings support acute coronary syndrome. Either condition may present atypically (Prabhu, 2012).

Pneumonia

Pneumonia is more likely with fever, productive cough, focal findings, and a compatible infiltrate. PE may cause low-grade fever, leukocytosis, or pulmonary opacity, so these findings do not exclude it.

Pneumothorax

Pneumothorax can cause abrupt pleuritic pain and dyspnea. Unilateral diminished breath sounds and pleural air on imaging support the diagnosis.

Heart Failure or Pulmonary Edema

Orthopnea, paroxysmal nocturnal dyspnea, diffuse congestion, edema, and cardiac dysfunction support heart failure. PE can also precipitate right-sided dysfunction and biomarker elevation.

Asthma or COPD Exacerbation

Wheezing and dyspnea may occur with either obstructive lung disease or PE. Abrupt symptoms, disproportionate hypoxemia, pleuritic pain, syncope, or thromboembolic risk should prompt evaluation beyond an assumed exacerbation.

Treatment and Management

Treatment depends on hemodynamic status, clot burden, right-ventricular function, bleeding risk, comorbidities, and the balance between recurrent thrombosis and treatment-related bleeding.

Anticoagulation

Anticoagulation is the primary treatment for most patients with confirmed PE and may be started before definitive confirmation when clinical probability is high, testing is delayed, and bleeding risk is acceptable.

Potential options include:

• Unfractionated heparin
• Low-molecular-weight heparin
• Fondaparinux
• Direct oral anticoagulants
• Warfarin in selected circumstances

Selection depends on renal and hepatic function, pregnancy, malignancy, drug interactions, bleeding risk, procedural plans, access, and the need for rapid reversal or titration (Huynh et al., 2026).

Reperfusion and Advanced Intervention

Patients with PE-associated shock or persistent hemodynamic instability may require urgent reperfusion therapy. Options can include systemic fibrinolysis, catheter-directed intervention, or surgical embolectomy. The decision requires rapid assessment of bleeding risk, contraindications, available expertise, and the cause of instability (Huynh et al., 2026; Norris, 2020).

Supportive Care

Supportive management may include:

• Oxygen for hypoxemia
• Ventilatory support when required
• Careful hemodynamic support
• Treatment of dysrhythmias or cardiac arrest
• Monitoring for right-ventricular failure and bleeding

Excessive fluid administration can worsen right-ventricular dilation and impair left-ventricular filling in severe PE. Hemodynamic interventions should be individualized.

Complications and Red Flags

Urgent escalation is required for:

• Hypotension
• Shock
• Syncope with ongoing instability
• Severe hypoxemia
• Acute right-ventricular failure
• Cardiac arrest
• Recurrent embolism
• Major bleeding during anticoagulation

Long-term complications include recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension.

Clinical Reasoning Priorities

Begin with stability, then determine clinical probability. Testing should follow that probability rather than beginning automatically with D-dimer or computed tomography.

An apparently mild oxygen-saturation abnormality does not establish low risk. Right-ventricular strain, hypotension, syncope, biomarker elevation, and reduced cardiopulmonary reserve may indicate greater clinical severity.

Before selecting anticoagulation, evaluate renal function, hepatic function, pregnancy status, bleeding risk, drug interactions, adherence, affordability, and the likelihood of upcoming procedures.

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References

Huynh, N. S., Cantrell, M., & Lee, J. C. (2026). Venous thromboembolism. In M. A. Chisholm-Burns, T. L. Schwinghammer, P. M. Malone, J. M. Kolesar, K. C. Lee, & P. B. Bookstaver (Eds.), Pharmacotherapy principles & practice (7th ed., pp. 387–447). McGraw-Hill.

Ma, I., & Lucey, C. R. (2012). Dyspnea. In M. C. Henderson, L. M. Tierney Jr., & G. W. Smetana (Eds.), The patient history: An evidence-based approach to differential diagnosis (2nd ed., pp. 286–297). McGraw-Hill Medical.

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.

Prabhu, S. D. (2012). Chest pain. In M. Henderson, L. M. Tierney Jr., & G. W. Smetana (Eds.), The patient history: An evidence-based approach to differential diagnosis (2nd ed., pp. 306–322). McGraw-Hill Medical.

Sisson, T. H., Claar, D., Chesnutt, M. S., & Prendergast, T. J. (2019). Pulmonary disease. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw-Hill.