Pulmonary Thromboembolism Disease Background

Introduction

Pulmonary embolism (PE) is the blockage of ≥1 pulmonary arteries in the lungs usually due to blood clots from the veins, especially the veins in the legs and pelvis. 

Epidemiology

Though the true incidence of pulmonary embolism is uncertain, it is estimated that it affects as much 1-3 per 1000, and that as much as a third of hospitalized patients are at risk of pulmonary embolism. It must be noted that the estimates of incidence of pulmonary embolism have been increasing and this might be due to the introduction of D-dimer testing and computed tomographic (CT) pulmonary. Overall, it is estimated that the incidence is higher in males than in females, and that it rises with increasing age. It is considered the third most common cause of cardiovascular death claiming up to 100,000 lives each year in the United States (US) alone. However, this may even be an underestimation as pulmonary embolism can result in an unexplained cardiac death. Despite the increasing incidence of pulmonary embolism, mortality rates are decreasing, reflecting the impact of the improvement in diagnosis and the initiation of early intervention and therapies.

Pathophysiology

The pathogenesis of pulmonary embolism is like the generation of thrombus, that is Virchow’s triad. This triad consists of stasis of blood flow, vascular endothelial damage, and hypercoagulability. Most pulmonary emboli arise from the lower extremity proximal veins (eg iliac, femoral, popliteal), with >50% of patients with deep vein thrombosis (DVT) have concurrent pulmonary embolism. Though the majority of thrombi from the calf vein resolves spontaneously, if untreated, as much as 1/3 of DVT will extend into the proximal veins where they have a greater potential to embolize.  

Pulmonary embolism occurs when the clot breaks off and travels into the pulmonary circulation where it causes a series of pathophysiologic processes to occur. Pulmonary emboli are usually multiple, involving the lower lobes more frequently than the upper, and affecting both lungs in most cases. Firstly, in the case of large emboli, these tend to obstruct the main pulmonary artery, causing a saddle embolus which, in turn, leads to cardiovascular compromise. On the other hand, smaller sized emboli block the peripheral pulmonary arteries, resulting in pulmonary infarction. Furthermore, due to the obstruction of the pulmonary bed, there is a mismatch in the ventilation to perfusion ratio thus resulting in impaired gas exchange.  Pulmonary vascular resistance (PVR) is increased in pulmonary embolism due to vascular obstruction with the thrombus and hypoxic vasoconstriction. In turn, increased PVR impedes right ventricular outflow and causes right ventricular dilatation. Finally, the combination of diminished flow from the right ventricle (RV) and RV dilatation reduces left ventricular preload, compromising cardiac output which then leads to systemic hypotension and hemodynamic instability. 

Risk Factors

Primary Risk Factors  

The primary risk factors for pulmonary embolism development are as follows:

• Antithrombin deficiency
• Protein C deficiency
• Thrombomodulin 
• Hyperhomocysteinemia
• Anticardiolipin antibody
• Prothrombin G20210A deficiency
• Factor XII deficiency 
• Factor V Leiden (APC-R) 
• Plasminogen deficiency
• Dysplasminogenemia 
• Congenital dysfibrinogenemia
• Excessive plasminogen activator 
• Protein S deficiency
• Positive history of proven venous thromboembolism 
• Trauma or fractures

Secondary Risk Factors  

The secondary risk factors for pulmonary embolism development are as follows:

• Surgery
• Advanced age
• Central venous catheters 
• Heart failure
• Pregnancy or puerperium
• Paresis
• Congenital heart disease 
• Long distance travel
• Stroke
• Hypertension
• Chronic venous insufficiency
• Obesity
• Smoking
• Oral contraceptives (eg Estrogen)
• Prosthetic surfaces
• Platelet abnormalities
• Crohn’s disease
• Lupus anticoagulant
• Nephrotic syndrome
• Malignancy with or without chemotherapy
• Hyperviscosity (polycythemia, Waldenstrom)

Classification

Massive Pulmonary Embolism  

Massive pulmonary embolism is defined as sustained hypotension and shock. It is also known as high-risk pulmonary embolism and is a medical emergency with a high mortality rate.  

Submassive Pulmonary Embolism  

Submassive pulmonary embolism involves either right ventricular (RV) dysfunction or myocardial injury without hemodynamic instability. It is also known as intermediate-risk pulmonary embolism.