What is pulmonary embolism and how is it treated?

Pulmonary Embolism: Comprehensive Overview

Definition and Epidemiology

Pulmonary embolism (PE) is a life-threatening condition caused by obstruction of pulmonary arteries, most commonly by thrombus from deep vein thrombosis, but also by fat, air, amniotic fluid, septic material, tumor cells, or foreign bodies. 1

• PE represents the third leading cause of cardiovascular mortality globally 2
• Annual incidence exceeds 100,000 cases in France, 65,000 in England and Wales, and 60,000 in Italy 2
• In the United States, approximately 370,000 patients are affected annually, with 60,000-100,000 deaths per year 3
• The incidence rate is approximately 60-120 per 100,000 people per year 3
• Untreated PE carries approximately 30% mortality, which drops to 2-8% with adequate anticoagulation 2
• Autopsy studies reveal PE prevalence of 12-15% in hospitalized patients, unchanged over three decades 2

Pathophysiology and Hemodynamic Impact

Right ventricular failure from acute pressure overload is the primary cause of death in severe PE. 1

• Abrupt increase in pulmonary vascular resistance leads to right ventricular dilation and dysfunction 1
• Systemic hypotension compromises coronary perfusion to the overloaded right ventricle, potentially causing right ventricular ischemia 1
• The ICOPER study demonstrated 3-month cumulative mortality of 17.5% in acute PE 2
• Sustained hypotension defines massive PE with 90-day mortality of 52.4% versus 14.7% in normotensive patients 1

Risk Stratification and Classification

PE should be classified based on hemodynamic stability into massive, submassive, and non-massive categories to guide treatment decisions. 2

Massive PE

• Defined by shock and/or hypotension (systolic blood pressure <90 mmHg or pressure drop of 40 mmHg for >15 minutes) 2
• Must exclude new-onset arrhythmia, hypovolemia, or sepsis as causes 2
• Requires immediate intervention with thrombolysis or embolectomy 2

Submassive PE

• Non-massive PE with echocardiographic signs of right ventricular dysfunction 2
• This subgroup has different prognosis than non-massive PE with normal RV function 2
• Risk stratification tools help identify these patients 2

Non-massive PE

• Hemodynamically stable patients without RV dysfunction 2
• Most patients in this category do well with anticoagulation alone 2

Clinical Presentation and Diagnosis

Pre-hospital Assessment

Clinical prediction scores are highly recommended in the pre-hospital setting to determine PE likelihood. 2

Wells' Rule (Simplified):

• Previous PE or DVT (1 point)
• Heart rate >100 beats/min (1 point)
• Surgery or immobilization within past 4 weeks (1 point)
• Hemoptysis (1 point)
• Active cancer (1 point)
• Clinical signs of DVT (1 point)
• Alternative diagnosis less likely than PE (1 point)
• PE unlikely: 0-1 criteria; PE likely: ≥2 criteria 2

Revised Geneva Score:

• Includes age >65 years, heart rate thresholds, previous PE/DVT, surgery/fracture, hemoptysis, active cancer, unilateral leg symptoms 2
• PE unlikely: 0-2 points; PE likely: ≥3 points 2

Diagnostic Approach in Stable Patients

In patients with systolic blood pressure ≥90 mmHg, use a three-step approach: assess clinical probability, perform D-dimer testing if indicated, and obtain chest imaging if indicated. 3

• Very low risk patients (age <50 years, heart rate <100/min, oxygen saturation >94%, no recent surgery/trauma, no prior VTE, no hemoptysis, no unilateral leg swelling, no estrogen use) require no further testing 3
• Low or intermediate probability patients with D-dimer <500 ng/mL have post-test PE probability <1.85% and can be excluded without imaging 3
• High probability patients (>40% probability) should proceed directly to chest imaging without D-dimer testing 3
• D-dimer thresholds can be refined in patients ≥50 years old and those with low likelihood 3

ECG Findings

• Most frequent signs are sinus tachycardia or atrial fibrillation 2
• Right ventricular overload signs (T wave inversion V1-V4, QR pattern in V1, S1Q3 pattern, right bundle branch block) typically seen in severe cases 2

Echocardiography

• Point-of-care echocardiography can demonstrate right ventricular enlargement and D-shaped left ventricle in high-risk PE 2
• Echocardiographic findings in shocked patients with suspected PE are sufficient to initiate reperfusion therapy 2
• Mobile right heart thrombi are associated with significantly increased early mortality 2

Treatment Strategies

Anticoagulation for Stable PE (Non-massive)

Direct oral anticoagulants (DOACs) such as apixaban, edoxaban, rivaroxaban, or dabigatran are first-line therapy for hemodynamically stable PE, as they are noninferior to heparin/warfarin and have 0.6% lower bleeding rates. 3

FDA-approved anticoagulation regimens:

• Heparin: Indicated for prophylaxis and treatment of venous thrombosis and PE 4

  • Initial dose: 5,000 units IV, followed by 10,000-20,000 units subcutaneously every 8-12 hours 4
  • Monitor aPTT to maintain 1.5-2 times normal 4
  • Periodically monitor platelet counts for heparin-induced thrombocytopenia 4

• Warfarin: Indicated for prophylaxis and treatment of venous thrombosis and PE 5

  • Typically initiated after heparin bridging 5

Duration of anticoagulation:

• Minimum 3 months for objectively confirmed PE 6
• Indefinite anticoagulation increasingly considered due to heightened recurrence risk after cessation and overall safety of DOACs 6
• Recurrent PE occurs in 8.3% of patients, with 45% mortality in this group 7

Early Discharge Protocol

Early discharge with rivaroxaban is effective and safe in acute low-risk PE, with symptomatic recurrence rate sufficiently low to support this approach. 2

Eligibility criteria for early discharge:

• Absence of hemodynamic instability 2
• No right ventricular dysfunction or intracardiac thrombi 2
• No serious comorbidity 2
• Up to 2 nights hospital stay permitted 2
• Major bleeding occurred in only 1.2% of patients 2

Thrombolysis for Massive PE

In patients with PE and systolic blood pressure <90 mmHg, systemic thrombolysis is recommended and reduces absolute mortality by 1.6% (from 3.9% to 2.3%). 3

Critical considerations:

• Thrombolysis should be administered without delay in massive PE 2
• Alarmingly, only a minority of hemodynamically unstable patients receive this recommended treatment 2
• In presence of mobile right heart thrombus on echocardiography, no further diagnostic tests needed before initiating therapy 2

Interventional and Surgical Options

Catheter-based interventions and surgical embolectomy are options when thrombolysis is contraindicated or has failed. 2

• Two pharmacomechanical devices recently FDA-cleared for PE treatment 2
• Benefits of active thrombus removal increase with PE severity 2
• Harms of thrombolytic strategies increase with patient-specific bleeding risk factors 2
• Catheter-based embolectomy harms driven more by patient comorbidities 2

Management of Right Heart Thrombi

Mobile right heart thrombi are associated with significantly increased early mortality and require immediate therapy. 2

• Thrombolysis and embolectomy are both probably effective 2
• Anticoagulation alone appears less effective 2
• Optimal treatment remains controversial due to absence of controlled trials 2

Special Considerations and Complications

Heparin-Induced Thrombocytopenia (HIT)

HIT is a life-threatening immunological complication occurring in 1-3% of patients on unfractionated heparin and ~1% on LMWH. 2

• Caused by IgG antibodies against platelet factor 4-heparin complex 2
• Typically occurs 5-14 days after heparin exposure, or earlier with re-exposure 2
• Paradoxically causes high risk of venous and arterial thromboembolism despite thrombocytopenia 2
• No formally proven cases reported with fondaparinux 2
• Treatment requires immediate heparin discontinuation and alternative anticoagulation 2
• Monitoring platelet counts essential for early detection 2

Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

CTEPH is a rare but severe long-term complication developing in approximately 3.8% of patients within 2 years after symptomatic PE. 2, 1

Pulmonary thromboendarterectomy selection criteria:

• NYHA functional class III or IV symptoms 2
• Preoperative pulmonary vascular resistance >300 dyn·s·cm⁻⁵ 2
• Surgically accessible thrombi in main, lobar, or segmental pulmonary arteries 2
• Absence of severe comorbidity 2

Surgical outcomes:

• Perioperative mortality 4% with PVR <900 dyn·s·cm⁻⁵, 20% with PVR >1200 dyn·s·cm⁻⁵ 2
• 3-year survival rate approximately 80% after successful surgery 2
• Functional results excellent and sustained over time 2

Non-Thrombotic PE

While thrombotic PE is most common, clinicians must recognize non-thrombotic causes requiring specific management approaches. 1

Septic embolism:

• Most commonly from right-sided endocarditis in IV drug users 1
• Also from infected catheters, pacemaker wires, septic thrombophlebitis 1
• Presents with fever, cough, hemoptysis 1
• Treatment: antibiotics targeting responsible organism, occasional surgical source removal 1

Fat embolism:

• Common with pelvic/long bone fractures, prosthetic joint placement 1
• Clinical syndrome 12-36 hours post-injury: altered mental status, respiratory distress, petechial rash 1
• Treatment primarily supportive as often self-limiting 1

Venous air embolism:

• Lethal volume estimated 200-300 ml (3-5 ml/kg) at 100 ml/s 1
• Management: prevent further air entry, left lateral decubitus head-down positioning, hemodynamic support 1

Amniotic fluid embolism:

• Rare (1/8,000-1/80,000 pregnancies) but catastrophic 1
• High maternal (80%) and fetal (40%) mortality 1

Tumor embolism:

• Seen in up to 26% of autopsies but rarely identified pre-mortem 1
• Most common with prostate, breast, hepatoma, stomach, pancreatic cancers 1
• Limited treatment success with chemotherapy 1

Foreign body embolism:

• Broken catheters, guidewires, vena cava filters, coils, stent components 1
• Increasing incidence with widespread interventional techniques 1
• Management: intravascular retrieval when possible to prevent thrombosis and sepsis 1

Prognosis and Long-term Outcomes

When properly diagnosed and treated, PE is an uncommon cause of death, with most deaths due to underlying diseases. 7

• Only 2.5% of treated patients died from PE in prospective follow-up 7
• 23.8% of PE patients died within one year, primarily from underlying conditions 7
• Most frequent causes of death: cancer (34.7%), infection (22.1%), cardiac disease (16.8%) 7

Risk factors for one-year mortality:

• Cancer (relative risk 3.8) 7
• Left-sided congestive heart failure (relative risk 2.7) 7
• Chronic lung disease (relative risk 2.2) 7

Critical Pitfalls to Avoid

• Never delay thrombolysis in massive PE while awaiting additional diagnostic tests 2
• Do not miss HIT by failing to monitor platelet counts during heparin therapy 2
• Avoid intramuscular heparin administration due to frequent hematoma formation 4
• Do not transfer unstable patients to non-surgical centers for imaging when aortic dissection probability is high 2
• Recognize that many hemodynamically unstable PE patients are undertreated with thrombolysis 2
• Do not assume all PE is thrombotic—consider non-thrombotic causes in appropriate clinical contexts 1