Pulmonary Infarction: Background, Pathophysiology, Etiology

In contrast with adults, most children (98%) diagnosed with pulmonary emboli have an identifiable risk factor or a serious underlying disorder. DVT is associated with a pulmonary embolism in 30-60% of cases. Thrombosis may also arise from intracardiac thrombi or intracerebral sinus thrombosis.

Acquired thrombosis has three broad etiological risk factors: (1) a relative stasis of blood flow due to either immobilization or the presence of a nidus on which a thrombus may form, (2) a prothrombogenic tendency (hypercoagulability), and (3) injury to a vascular wall. These three factors have been termed the Virchow triad.

The following conditions predispose to some or all of these factors for acquired thrombosis:

• Central venous catheters: This is one of the most common acquired risk factors for pediatric PE. In 1993, David et al reported that 21% of children with DVT, pulmonary emboli, or both had an indwelling central venous catheter. [6] Additional series report presence of central lines in as many as 36% of patients. [7] A clot may form as a fibrin sleeve that encases the catheter. When the catheter is removed, the fibrin sleeve is often dislodged, releasing a nidus for embolus formation. In another scenario, a thrombus may adhere to the vessel wall adjacent to the catheter.

• Surgery: Recent surgery and postsurgical immobilization are associated with approximately 15-29% of pulmonary embolism and DVT cases.

• Heart disease: Thrombi may be associated with dilated cardiomyopathy, a situation in which sluggish blood flow is combined with an enlarged cardiac chamber.

• Sickle cell disease: This condition often creates a diagnostic difficulty. A chest infection is often the presenting symptom. Hypoxemia, dehydration, and fever lead to intravascular sludging within pulmonary (among others) vasculature. This promotes a vicious cycle, further exacerbating local hypoxemia, ultimately leading to local tissue infarction. This process is further worsened by bone marrow infarction, which may cause release of fat emboli that lodge in the pulmonary circulation. [8]

• Trauma: Whether the increased risk of pulmonary embolism in trauma patients is independent of the role of immobilization and surgery is unclear. [9]

• Neoplasm: Pulmonary emboli have been reported to occur in association with solid tumors, leukemias, and lymphomas. This is probably independent of the indwelling catheters often used in such patients. [10]

• Hyperalimentation: A study reported that major thrombosis or pulmonary embolism was present in more than 33% of children treated with long-term hyperalimentation and that pulmonary embolism was the major cause of death in 30% of these children. Fat embolization may exacerbate this clinical picture. [11]

• Dehydration: Dehydration, especially hyperosmolar dehydration, is typically observed in younger infants with pulmonary emboli. [12]

• Inherited disorders of coagulation: In 1993, David et al reported that 5-10% of children with venous thromboembolic disease have inherited disorders of coagulation, such as antithrombin III, protein C, or protein S deficiency. [6] In 1997, Nuss et al reported that 70% of children with a diagnosis of pulmonary embolism have antiphospholipid antibodies or coagulation-regulatory protein abnormalities. [13] However, this was a small study in a population with clinically recognized pulmonary emboli; hence, its applicability to the broader pediatric population is uncertain.

• The systemic vasculitides are a heterogenous group of rare conditions which may infiltrate and occlude the pulmonary vessels leading to ischemia and infarction of the supplied tissue. [14]

Miscellaneous causes

Other causes of pulmonary embolism include the following:

• Obesity (BMI ≥ 25 kg/m2)

• Estrogen use, including oral contraceptives

• Pregnancy

• Pregnancy termination

• Nephrotic syndrome

• Ventriculoatrial shunt: The tip of the atrial shunt may act as a nidus for thrombus formation.

• Autoimmune disorders: These may be associated with antibodies that predispose to a hypercoagulable state.

In a retrospective review of pediatric patients presenting to a pediatric emergency department, the most common risk factors identified for pulmonary embolism were BMI ≥ 25 kg/m2, oral contraceptive use, and history of previous pulmonary embolism. [15]