Description

• PE is the most serious presentation of venous thromboembolism (VTE).
• Classified based on severity:
  • Low-risk PE: acute and absence of clinical markers of adverse prognosis
  • Submassive PE: no systemic hypotension, but there is either myocardial necrosis (elevated troponin) or right ventricle (RV) dysfunction (RV dilation or systolic dysfunction on echocardiography [echo], RV/LV ratio >1 on computed tomography [CT], elevation of B-type natriuretic peptide [BNP] or N-terminal pro-BNP, or consistent electrocardiogram [ECG] changes)
  • Massive PE: hemodynamic instability with sustained hypotension; pulselessness; or persistent bradycardia, cardiogenic shock, acute manifesting RV failure

Epidemiology

Third leading cause of vascular death (after MI and stroke); case fatality rates vary (1–60%); ~11% at 2 weeks

Incidence

• Approximately 30 to 80/100,000, with higher incidence in African Americans and lower in Asians; >100,000 cases annually in the United States
• Incidence increases with age, most occurring at 60 to 70 years of age.
• 250,000 hospitalizations per year in the United States, 10–60% in hospitalized patients (highest risk for orthopedic and cancer patients; 1:1,000 pregnancies)

Prevalence
Within hospitalized patients: 17.3% prevalence of PE in hospitalized adults who were admitted for first episode of syncope (between 2012 and 2014) (1)

Etiology and Pathophysiology

• Venous stasis, endothelial damage, and changes in coagulation properties generate thrombus formation.
• Thrombus causes increased pulmonary vascular resistance, impaired gas exchange, and decreased pulmonary compliance. RV failure due to pressure overload is usually the primary cause of death.
• The most common source (85%) of PE is proximal lower extremity deep vein thrombosis (DVT).

Genetics

• Factor V Leiden: most common thrombophilia; +5.5% in Caucasian, 2.2% in Hispanics, 1.2% in African American, 0.5% in Asian; associated with 20% of VTE
• Prothrombin G20210A: 3% of Caucasians; rare in African American, Asian, and Native American; 6% in patients with VTE
• Rarely, deficiencies in protein C, S, and antithrombin

Risk Factors

• Older age, obesity, prolonged immobilization, surgery (total hip and knee arthroplasty, hip fracture cancer), major trauma, joint replacement, spinal cord injury, active cancer, hormonal replacement therapy, pregnancy/puerperium, previous thrombosis, antiphospholipid syndrome, genetics
• Oral contraceptive is the most frequent risk factor in women.

General Prevention

• Low VTE risk: early ambulation after surgery, compression stockings, and intermittent pneumatic compression
• Use of thromboprophylaxis in COVID-19 infection is not commonly done but may be considered in those at high risk (prior VTE, recent surgery, limb immobilization, recent trauma, etc.).
• Hip or knee arthroplasty (high VTE risk): ≥10 days prophylaxis with low-molecular-weight heparin (LMWH), fondaparinux, apixaban, dabigatran, rivaroxaban, or low-dose unfractionated heparin (UFH)
• Spinal cord injury, hip fracture surgery, and trauma surgery (high VTE risk): 28 to 35 days with LMWH, fondaparinux, UFH, or vitamin K antagonists (VKA)
• Long-distance travel (>8 hours): hydration, walking, avoidance of constrictive clothing and frequent calf exercises, compression stockings below knee
• Patients with factor V Leiden and G20210A prothrombin gene mutation with no previous thrombosis do not need prophylaxis.

Commonly Associated Conditions

COVID-19 infection, cancer, sepsis, illnesses leading to hospitalizations, surgery