# Pulmonary Embolism: Risk Stratification and Treatment

## Pathophysiology

### Mechanism

Venous thromboembolism originates from deep veins — most commonly the iliofemoral system — and embolizes to the pulmonary vasculature. The acute increase in pulmonary vascular resistance produces right ventricular pressure overload. The RV dilates, the interventricular septum bows into the left ventricle, LV filling is reduced, and cardiac output falls. Hypoxemia develops from ventilation-perfusion mismatch, shunting, and increased dead space. In massive PE, acute RV failure leads to obstructive shock and cardiac arrest.

### Risk Factors (Virchow Triad)

The three elements of Virchow's triad — stasis, endothelial injury, and hypercoagulability — remain the conceptual framework for PE risk. Stasis occurs with immobility, prolonged travel, paralysis, and hospitalization. Endothelial injury results from surgery, trauma, and central venous catheters. Hypercoagulability may be acquired (malignancy, pregnancy, oral contraceptives, antiphospholipid syndrome) or inherited (Factor V Leiden, prothrombin gene mutation).

## Clinical Presentation

### Signs and Symptoms

Dyspnea is the most common symptom, present in 70 to 80 percent of cases. Pleuritic chest pain occurs in 40 to 50 percent. Tachycardia and tachypnea are frequent but nonspecific. Cough and hemoptysis are less common. Syncope suggests massive PE with hemodynamic compromise. Unilateral leg swelling from concurrent DVT is present in 25 to 50 percent. The clinical presentation is highly variable and nonspecific — the diagnosis requires active suspicion. The classic triad of dyspnea, chest pain, and hemoptysis is present in fewer than 20 percent of cases.

## Risk Stratification for Diagnosis

### PERC Rule (Pulmonary Embolism Rule-Out Criteria)

The PERC rule should be applied only when clinical gestalt determines a low pretest probability (below 15 percent). All eight criteria must be negative to rule out PE without further testing: age under 50, heart rate under 100, SpO2 at or above 95 percent, no hemoptysis, no estrogen use, no prior DVT/PE, no unilateral leg swelling, and no surgery or trauma requiring hospitalization in the past 4 weeks. When all criteria are met, the PE risk is below 2 percent and no further workup is needed. PERC must not be applied to moderate or high pretest probability patients.

### Wells Score

The Wells score assigns points for clinical signs of DVT (3), PE as likely or more likely than an alternative diagnosis (3), heart rate above 100 (1.5), immobilization or surgery in the past 4 weeks (1.5), previous DVT/PE (1.5), hemoptysis (1), and active cancer (1). A score of 4 or below makes PE unlikely, and a D-dimer should be obtained. A score above 4 makes PE likely, and CTPA should be obtained directly.

| Criterion | Points |
|-----------|--------|
| Clinical signs of DVT | 3.0 |
| PE as likely or more likely than alternative diagnosis | 3.0 |
| Heart rate > 100 | 1.5 |
| Immobilization or surgery in past 4 weeks | 1.5 |
| Previous DVT/PE | 1.5 |
| Hemoptysis | 1.0 |
| Active cancer (treatment within 6 months) | 1.0 |
| **Score ≤ 4: PE unlikely** | **→ D-dimer** |
| **Score > 4: PE likely** | **→ CTPA** |

### YEARS Algorithm

The YEARS algorithm is a simplified approach using three items: clinical signs of DVT, hemoptysis, and PE as the most likely diagnosis. If no YEARS items are present and the D-dimer is below 1000 ng/mL, PE is excluded. If one or more YEARS items are present and the D-dimer is below 500 ng/mL, PE is excluded. Otherwise, CTPA is indicated. This approach reduces CT utilization by approximately 14 percent compared to standard Wells plus D-dimer.

### D-Dimer

D-dimer has high sensitivity (above 95 percent) but low specificity. Age-adjusted cutoffs (age multiplied by 10 ng/mL for patients over 50) improve specificity without losing sensitivity. D-dimer is elevated in many conditions including infection, malignancy, pregnancy, post-surgical states, and trauma. A negative D-dimer with low or moderate pretest probability effectively rules out PE. D-dimer should not be ordered in high pretest probability patients — they should go directly to imaging.

## Diagnostic Imaging

### CT Pulmonary Angiography (CTPA)

CTPA is the gold standard imaging modality with sensitivity and specificity both exceeding 95 percent for segmental and larger PE. It also identifies alternative diagnoses such as pneumonia, aortic dissection, and pericardial effusion. Limitations include radiation exposure, contrast allergy, renal insufficiency, and debated clinical significance of isolated subsegmental PE, which may not require anticoagulation in low-risk patients.

### Bedside Echocardiography / POCUS

Bedside echocardiography is not diagnostic for PE but identifies RV strain indicating hemodynamic significance. Key findings include RV dilation (RV-to-LV ratio greater than 1:1), RV free wall hypokinesis, and interventricular septal flattening (the D-sign). McConnell sign — RV free wall akinesis with apical sparing — is 60 percent sensitive and 94 percent specific. Echocardiography is particularly useful in unstable patients who cannot be transported to CT.

### Compression Ultrasound for DVT

A positive proximal DVT in a patient with symptoms consistent with PE may be sufficient for diagnosis and treatment initiation. It is particularly useful when CTPA is contraindicated due to renal failure, contrast allergy, or pregnancy.

### V/Q Scan

V/Q scanning is an alternative when CTPA is contraindicated. It is most useful when the chest X-ray is normal, which increases diagnostic yield. Results are reported as normal, low probability, intermediate probability, or high probability. Intermediate probability results are non-diagnostic and require further workup.

## Severity Classification

| Category | Hemodynamics | RV Dysfunction / Biomarkers | Mortality | Treatment |
|----------|-------------|----------------------------|-----------|-----------|
| Massive (High-Risk) | SBP < 90 for > 15 min, vasopressors, or arrest | Present | > 50% | Systemic thrombolysis + anticoagulation |
| Submassive (Intermediate-Risk) | Stable | RV dysfunction and/or elevated troponin/BNP | 3–15% | Anticoagulation ± thrombolytics if deteriorating |
| Low-Risk | Stable | Absent | < 1% | Anticoagulation (outpatient if sPESI = 0) |

### Massive PE (High-Risk)

Massive PE involves sustained hypotension (SBP below 90 for more than 15 minutes) or the need for vasopressors, pulselessness, or cardiac arrest. Mortality exceeds 50 percent without treatment.

### Submassive PE (Intermediate-Risk)

Submassive PE describes hemodynamically stable patients who have evidence of RV dysfunction (on echocardiography or CT) and/or elevated biomarkers (troponin, BNP). Mortality risk is 3 to 15 percent. Whether these patients benefit from thrombolytics remains the most active debate in the PE management literature.

### Low-Risk PE

Low-risk PE involves hemodynamically stable patients without RV dysfunction or biomarker elevation. Mortality is below 1 percent. These patients are candidates for outpatient management.

## Treatment

### Anticoagulation — Foundation of PE Treatment

Unfractionated heparin (80 U/kg bolus, then 18 U/kg/hr infusion) is preferred in massive PE because of its short half-life and reversibility if thrombolytics become necessary, and in patients with renal failure, morbid obesity, or those who are potential surgical candidates. Low-molecular-weight heparin (enoxaparin 1 mg/kg SC every 12 hours) is preferred for most hemodynamically stable PE due to predictable dosing and no need for monitoring. Direct oral anticoagulants can be started without parenteral bridging: rivaroxaban (15 mg BID for 21 days, then 20 mg daily) or apixaban (10 mg BID for 7 days, then 5 mg BID). DOACs are not appropriate for massive or high-risk submassive PE that may require thrombolysis.

### Systemic Thrombolysis

The indication for systemic thrombolysis is massive PE with hemodynamic instability. Alteplase at 100 mg IV over 2 hours is the most established protocol. Tenecteplase as a weight-based single bolus is logistically simpler and is being studied for PE. Half-dose tPA (50 mg over 2 hours) offers a lower bleeding risk with potentially equivalent efficacy — the MOPETT trial suggested benefit, and subsequent studies support comparable efficacy with reduced hemorrhage. Contraindications include active bleeding, recent surgery (within 3 weeks), prior intracranial hemorrhage, ischemic stroke within 3 months, and intracranial neoplasm. However, absolute contraindications may be overridden in truly massive PE with imminent death.

### Submassive PE — The Controversy

The standard of care for submassive PE is anticoagulation alone with close monitoring. The PEITHO trial showed that tenecteplase reduced hemodynamic decompensation in submassive PE but increased intracranial hemorrhage without a mortality benefit. Thrombolytics should be considered for submassive PE with progressive clinical deterioration despite anticoagulation, severe RV dysfunction (RV-to-LV ratio greater than 1.5), or high biomarker burden. Catheter-directed therapy delivers lower-dose thrombolytics directly to the clot and has growing evidence from the ULTIMA and SEATTLE II trials, though RCTs remain limited. Surgical embolectomy is reserved for patients with contraindications to thrombolytics or failed thrombolysis.

### Cardiac Arrest Due to PE

In PE-associated cardiac arrest, tPA 50 mg IV bolus is administered during CPR and can be repeated with another 50 mg in 15 minutes. CPR should continue for at least 60 to 90 minutes after thrombolytics to allow the drug to take effect. ECMO should be considered if available. Surgical embolectomy may be pursued if the patient achieves ROSC.

### Supportive Care

Volume resuscitation should be cautious (250-500 mL only) — excessive fluids worsen RV dilation and septal bowing, further compromising LV filling. Norepinephrine is the preferred vasopressor for RV-dependent shock. Intubation should be avoided if possible because positive pressure ventilation worsens RV failure; if intubation is necessary, low PEEP should be used while maintaining systemic vascular resistance. Supplemental oxygen should maintain SpO2 above 94 percent.

## Outpatient Management of Low-Risk PE

### sPESI (Simplified Pulmonary Embolism Severity Index)

The sPESI assigns points for age over 80, cancer, heart failure or chronic lung disease, heart rate at or above 110, SBP below 100, and SpO2 below 90 percent. A score of 0 indicates low risk with approximately 1 percent 30-day mortality, making the patient a candidate for outpatient management. The Hestia criteria provide additional safety screening for home discharge.

| sPESI Criterion | Points |
|----------------|--------|
| Age > 80 years | 1 |
| Active cancer | 1 |
| Heart failure or chronic lung disease | 1 |
| Heart rate ≥ 110 | 1 |
| SBP < 100 mmHg | 1 |
| SpO2 < 90% | 1 |
| **Score = 0: Low risk (~1% 30-day mortality)** | **Outpatient candidate** |
| **Score ≥ 1: Higher risk** | **Admit** |

### Outpatient PE Treatment

A DOAC is initiated in the ED (rivaroxaban or apixaban, neither requiring parenteral bridging). Close follow-up within 48 to 72 hours is arranged, with clear return precautions provided. Outpatient management is contraindicated if there is hemodynamic instability, RV dysfunction, high bleeding risk, poor follow-up access, or pregnancy.

<image>A clinical decision algorithm for the evaluation of suspected pulmonary embolism in the ED. The flowchart begins with clinical suspicion and pretest probability assessment. Low pretest probability leads to PERC rule evaluation; if PERC negative, PE is ruled out. If PERC positive or moderate pretest probability, age-adjusted D-dimer is ordered. Negative D-dimer rules out PE; positive D-dimer leads to CTPA. High pretest probability goes directly to CTPA. After diagnosis, severity classification branches into massive (thrombolytics plus anticoagulation), submassive (anticoagulation plus close monitoring plus or minus thrombolytics), and low-risk (outpatient DOAC if sPESI equals 0). Each pathway includes key decision points and treatments.</image>

<image>A bedside echocardiography image panel showing the findings of right ventricular strain in acute pulmonary embolism. Panel A shows a parasternal short-axis view with a dilated RV causing the interventricular septum to bow into the LV, creating the classic D-shaped LV (D-sign). Panel B shows an apical four-chamber view with a dilated RV (RV greater than LV diameter) and McConnell sign — akinesis of the RV free wall with preserved apical contractility highlighted with arrows. Panel C shows a subcostal view with a plethoric IVC greater than 2.1 cm with minimal respiratory variation, indicating elevated right atrial pressure. Each panel is labeled with measurements and diagnostic significance.</image>

## Clinical Pearls

PERC can only be applied when gestalt pretest probability is low — it is a rule-out tool, not a screening tool. Age-adjusted D-dimer (age multiplied by 10 ng/mL for patients over 50) improves specificity without losing sensitivity and should be routinely used. In massive PE with cardiac arrest, tPA should be given during CPR and resuscitation continued for at least 60 to 90 minutes. Submassive PE is not a blanket indication for thrombolytics — anticoagulation is the standard of care, with thrombolytics reserved for clinical deterioration. Aggressive fluid resuscitation should be avoided in PE because the failing RV cannot handle volume, and excess fluids worsen septal bowing and LV filling. Bedside echocardiography showing RV dilation in an unstable patient with suspected PE justifies empiric thrombolysis without CTPA. Low-risk PE (sPESI of 0) can be safely managed as outpatient with DOACs, avoiding unnecessary admissions. Half-dose tPA (50 mg) may offer comparable efficacy with less bleeding and is a reasonable approach when hemorrhage risk is elevated.

## References

- Konstantinides SV, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism. *Eur Heart J*. 2020;41:543-603.
- Kline JA, et al. PERC rule: clinical criteria to prevent unnecessary testing. *J Thromb Haemost*. 2004;2:1247-1255.
- Meyer G, et al. PEITHO Trial: Fibrinolysis for intermediate-risk pulmonary embolism. *NEJM*. 2014;370:1402-1411.
- Sharifi M, et al. MOPETT Trial: Moderate pulmonary embolism treated with thrombolysis. *Am J Cardiol*. 2013;111:273-277.
- van der Hulle T, et al. YEARS algorithm for suspected PE. *Lancet*. 2017;390:289-297.