This article discusses pneumothorax, pneumomediastinum, and pulmonary embolism in pediatric practice. Although children appear to have better outcomes than adults, the risk factors are substantial. Topics covered include the pathophysiology incidence, presentation, diagnosis, and management of these diseases.
This article discusses pneumothorax (PTX), pneumomediastinum, and pulmonary embolism (PE); including incidence, presentation, diagnosis, and management of each.
Pneumothorax
Pneumothorax (PTX) is defined as the presence of gas in the potential space between the visceral and parietal pleura. It can be classified into two causal categories.
The first, spontaneous PTX, occurs in the absence of trauma. These pneumothoraces (PTXs) can be further broken down into primary and secondary classifications. A primary spontaneous PTX occurs in a patient with either no or subclinical underlying lung disease. Often attributed to ruptured apical blebs, primary spontaneous PTX is often associated with smoking in adults, but can also be seen in healthy children. A secondary spontaneous PTX occurs as a complication of a chronic or acute underlying pulmonary disease process.
The second, traumatic PTX, occurs via blunt or penetrating mechanisms. Rib fractures may or may not be present. Traumatic PTX takes place when air enters the pleural space from pulmonary, esophageal, chest wall, or tracheobronchial tree injuries. Iatrogenic PTX is an important subset that can occur secondary to medical procedures such as thoracentesis, central venous cannulation, and mechanical ventilation.
The most concerning adverse outcome of traumatic and iatrogenic PTX is progression to a tension PTX. This occurs when the lung or airway defect acts as a one-way valve, allowing air to flow into the pleural cavity without a means of escape. As the volume of air increases, the pressure leads to vascular compromise of the heart and great vessels. The circulatory system decompensates from mechanical impingement on blood flow and hypoxia due to respiratory compromise. Tension PTX in the absence of trauma is relatively rare and is associated with spontaneous PTX in 1% to 3% of cases.
Incidence, Risk Factors, and Mortality
In the United States the incidence of spontaneous PTX is approximately 7.4 to 18 cases per 100,000 boys and 1.2 to 6 cases per 100,000 girls, with a male-to-female ratio of about 2:1. This ratio appears to be reversed, however, below the age of 9 years. Mean age at presentation has been reported to be 14 to 15.9 years, with one pediatric cohort reporting mean age at diagnosis of 13.8 years. It appears to present most typically in tall, thin males with low body mass index. Mortality is considered low in children.
Although the incidence of secondary PTX in children is not well described, those with asthma and cystic fibrosis are considered at particular risk. The probability of PTX is thought to increase as the lung function decreases, and the mortality is considered higher because of decreased reserve of the ill lung. Infectious causes such as Pneumocystis jirovecii pneumonia in immune disorders and necrotizing pneumonias (anaerobic gram-negative or staphylococcal) are associated with a higher incidence of PTX. Individuals with underlying connective tissue disease, such as Marfan syndrome, Ehlers-Danlos, and ankylosing spondylitis, are also at higher risk.
In the setting of thoracic trauma, PTX occurs in one-third of pediatric cases, with the majority of these having associated intrathoracic and extrathoracic injuries, and only one-third occurring in isolation. In a review of 1533 victims of thoracic trauma listed in the National Pediatric Trauma Registry database, the incidence of isolated PTX in blunt and penetrating trauma was similar, 24% (306:1288) and 23% (52:230) respectively. Of note, PTX not complicated by hemothorax was present in 30% (58:228) of blunt and 0% (0:228) of penetrating trauma patients who died in this series.
Iatrogenic PTX is an unfortunate consequence of medical procedures. A recent review found that 57% of the procedures that lead to PTX at a teaching hospital were performed under emergent conditions. The most frequent procedure types were central venous catheterization (43.8% of iatrogenic PTX), thoracentesis (20.1%), and barotrauma due to mechanical ventilation (9.1%). The internal jugular and subclavian approaches to central venous access are considered to have the highest risk of PTX. A systematic review reported an overall incidence of PTX resulting from thoracentesis of 6%, with 34.1% of these requiring chest tube insertion. The introduction of real-time ultrasound guidance has been shown to reduce the incidence of PTX for both central venous access and thoracentesis in adults. A recent meta-analysis of the pediatric literature of ultrasound-guided central venous access, however, failed to show any statistical difference in adverse outcomes.
Presentation, Physical Examination Findings, and Differential Diagnosis
Children with spontaneous PTX typically present with a sudden onset of unilateral thoracic pain and dyspnea while at rest. Valsalva maneuvers such as lifting or straining have also been implicated. In a chart review, 100% of patients presented with chest pain and 42% with dyspnea. Children presenting after 24 hours may have little to no pain. Patients with secondary spontaneous PTX can present in greater cardiopulmonary distress. Vital signs may include tachycardia, tachypnea with hypoxia, and hypotension in the most severe cases. Physical examination findings depend on the size of the PTX; many small air collections are undetected, whereas findings in large PTXs often include decreased breath sounds, vocal fremitus, and hyperresonance to percussion on the affected side.
Traumatic PTX has a wide spectrum of presentation. As in primary PTX, vital signs and symptomatology will depend on the size of the PTX. Physical examination findings that can differentiate tension PTX from simple traumatic PTX include neck vein distension, tracheal deviation away from the affected side, and cyanosis. Patients often present in moderate to severe distress, and tachycardia, hypotension, and oxygen desaturation are also seen.
Diagnostic Imaging
The plain radiograph, or chest x-ray (CXR), is the primary radiographic test to screen for PTX. Diagnosis is made by visualization of the visceral pleural margin, with the absence of lung markings peripheral to the pleural line. The sensitivity of CXR in the detection of PTX has been reported as high as 80%. When clinically feasible, an upright CXR is the procedure of choice for suspected PTX, although a lateral decubitus view may also be diagnostic ( Fig. 1 ). Inspiratory and expiratory views are reported to be equally sensitive in detection of PTXs, so the routine use of expiratory views for detection of PTX is not recommended. In many patients, especially those presenting with multiple trauma, an upright CXR cannot be performed. Supine anteroposterior (AP) CXR is unreliable at detecting PTX, with a sensitivity of 36% to 48% in some studies. Some may exhibit the deep sulcus sign ( Fig. 2 ), which represents lucency of the lateral costophrenic angle extending toward the hypochondrium and giving the deepened lateral costophrenic angle a sharp, angular appearance. Unfortunately, CXRs frequently underestimate the size of PTXs.
The introduction and increased availability of CT scam has changed the ability of physicians to evaluate for PTX. Because it is the most sensitive and specific modality in the clinical setting, chest CT scan has become the reference standard for the diagnosis of PTX. Traumatic PTXs not detected on supine AP CXR but seen on CT scan are a fairly recent phenomenon approximated to be present in 5% of all injured patients. In a pediatric cohort of blunt trauma patients the incidence was found to be 3.7%. Referred to in the trauma literature as “occult PTXs,” their clinical relevance is a subject of debate as management guidelines have not been clearly delineated. The literature describing the benefit of chest CT scan in the evaluation of primary and secondary PTX also appears to be unclear. The increased sensitivity of CT scan, however, has been used to predict the risk of recurrence and to justify and plan surgical intervention.
With the increased use and acceptance of the Focused Assessment with Sonography in Trauma (FAST) examination, ultrasound has become more readily available at the bedside. Techniques for detecting PTXs using ultrasound and its efficacy have been reported. A recent literature review reported a sensitivity between 86% to 98% and specificity between 97% to 100%. When compared with the sensitivity of supine CXR between 28% to 75% in this series, it appears the ultrasound will play a major role in evaluation of traumatic PTX in the near future.
Management
Initial treatment of the child with PTX should include prompt administration of oxygen, intravenous access, and placement on oximetry and cardiac monitors. Patients with suspected tension PTX and significant respiratory distress require immediate and aggressive intervention even before a CXR is obtained. A large-bore needle or intravenous catheter should be inserted on the ipsilateral side at the second intercostal space at the midclavicular line ( Fig. 3 A , B). If the needle fails to evacuate enough air to stabilize the patient, emergent thoracostomy will be required. There is no evidence that a chest tube with a larger diameter will be more effective in the treatment of any PTX than a smaller size ( Table 1 ).
| Weight, kg | Chest Tube Size, French |
|---|---|
| 3–5 | 10–12 |
| 6–9 | 12–16 |
| 10–11 | 16–20 |
| 12–14 | 20–22 |
| 15–18 | 22–24 |
| 19–22 | 24–28 |
| 23–30 | 24–32 |
| >32 | 32–40 |
Pigtail catheters are smaller bore catheters inserted using the Seldinger technique. These catheters have been shown to offer a safe and effective alternative to larger bore chest tubes in children. It must be remembered that tube thoracostomy is not a benign procedure, with an adverse event rate as high as 21%. Complications of tube thoracostomy include injuries to thoracic or abdominal organs, empyema, bleeding, re-expansion pulmonary edema, pain, chest tube occlusion, and residual pneumothorax.
Eighty percent of PTXs of less than 15% have no persistent air leak, and the rate of recurrence in such patients managed with observation alone is lower than in those treated with chest tubes. The asymptomatic patient with primary PTX of less than 15% may be observed for 3 to 6 hours, and then discharged home with close follow-up if a repeat CXR shows no progression of the PTX. Patients with poor social situations or unreliable follow-up should be admitted.
In the setting of primary (spontaneous) PTX, symptomatic patients and patients with PTX of 15% or greater should be admitted. Mildly symptomatic patients may be observed with or without the administration of high-flow oxygen via a nonrebreather mask. Oxygen may increase the rate of PTX reabsorption, with a fourfold effect demonstrated in the presence of PTX greater than 30%. The duration of therapy is dependent on resolution of symptoms and reabsorption of the PTX, usually between 1.25% and 2.2% of hemithoracic volume every 24 hours. There is no evidence that invasive intervention improves the associated chest pain, which is more appropriately managed with analgesia.
Larger and more significantly symptomatic primary PTXs should undergo re-expansion. Simple needle aspiration is recommended as first-line therapy by the British Thoracic Society, whereas the American College of Chest Physicians guidelines consider simple aspiration to be “appropriate rarely in any clinical circumstance” and recommend tube thoracostomy as primary management.
Admission should be strongly considered in all cases of secondary spontaneous PTX. Hemodynamically stable patients with small secondary PTX may be observed as inpatients without invasive intervention. Clinically unstable patients, patients with respiratory distress, and patients with large PTXs should undergo tube thoracostomy. Patients with persistent air leaks or recurrent PTX should be referred for surgical intervention such as video-assisted thoracoscopy.
All patients with traumatic PTX should be considered to be at risk for cardiopulmonary decompensation and should be admitted. Penetrating PTXs and large blunt trauma PTXs are treated with tube thoracostomy. As stated previously, treatment of the small occult PTX remains controversial. Concern exists that these PTXs can expand, especially in the ventilated patient, leading to tension PTX. The available literature for children and adults, however, appears to support the position that these patients may be safely observed regardless of mechanical ventilation and rarely require tube thoracostomy.
Pneumomediastinum
Pneumomediastinum is defined as air in the mediastinum and should be included in the differential diagnosis of acute chest pain. The anatomic borders of the mediastinum are as follows: superior, thoracic inlet; inferior, diaphragm; posterior, thoracic spine; and anterior, sternum ( Fig. 4 ). Pneumomediastinum may affect any or all of these spaces.
Classification of pneumomediastinum stems from its cause. Secondary or acquired pneumomediastinum generally occurs as a result of thoracic or abdominal surgery, foreign body ingestion, cardiac catheterization, or endotracheal intubation and mechanical ventilation. Other medical procedures predisposing to mediastinal emphysema include dental, endotracheobronchial and endoesophageal procedures. Severe cases may result from trauma to the chest or neck with disruption of the tracheobronchial tree.
Spontaneous pneumomediastinum occurs in the absence of the above causes, and often occurs as a result of infections or asthma. Asthma is the most common underlying condition, with up to 35% of cases associated with asthma and other obstructive pulmonary diseases. Infectious causes include bronchiolitis, bronchitis, viral pneumonia, and retropharyngeal abscesses. Valsalva maneuvers such as coughing, screaming, deep breathing with physical activity, or vomiting are frequent causes of spontaneous pneumomediastinum. Diabetic ketoacidosis has been associated with the development of spontaneous pneumomediastinum, possibly as a result of associated vomiting. Inhaled drug use is another important risk factor for developing this condition.
The most common mechanism resulting in pneumomediastinum is thought to be alveolar rupture, resulting in tracking of free air toward the hilum of the affected lung, into the mediastinum and upwards into the subcutaneous space of the upper chest and neck. Rupture or perforation of the esophagus or large airways can also result in the characteristic clinical picture.
Incidence
Whereas its true incidence is unknown, it has been reported in an estimated 1 per 14,000 individuals between 14 and 29 years of age. The incidence has a bimodal peak, occurring more frequently in children between 6 months and 3 to 4 years of age and in adolescents, and in 1 per 20,000 patients presenting to emergency departments with exacerbations of asthma. Tall, thin adolescent boys are more commonly affected.
Presentation
Patients typically complain of retrosternal chest pain that increases with respirations, dyspnea, and neck pain. The history may reveal the presence of sore throat, coughing or vomiting, low-grade fevers, dysphagia, and dysphonia. A history of risk factors and predisposing conditions may also be elicited. Physical examination findings include subcutaneous emphysema (air in the subcutaneous tissues of the chest and neck), often with visible neck edema; palpable crepitus is diagnostic. Precordial crepitus auscultated during systole (Hamman’s sign) indicates the presence of subcutaneous emphysema and is pathognomonic for pneumomediastinum. Patients may also present with torticollis as a result of cervical subcutaneous air.
The differential diagnosis for pneumomediastinum includes pericarditis and pneumothorax, both of which present with dyspnea and chest pain; however, respiratory distress in PTX is often more pronounced than in pneumomediastinum. Hamman’s sign, neck edema, and torticollis are not usually seen in pneumothorax. Pericarditis differs from pneumomediastinum and PTX in that the severity of chest pain sometimes varies with position (increased pain when supine and decreased in a seated position while leaning forward). Auscultation may reveal a friction rub, a finding distinct to pericarditis.
Diagnosis
Plain radiographs remain the gold standard for diagnosing pneumomediastinum. Anterior and lateral views of the chest including the neck are usually sufficient to demonstrate typical findings. The anterior view may reveal a continuous diaphragm sign, which is a lucency that extends between the pericardium and diaphragm. A vertical line of lucency surrounding the left side of the trachea, heart, and aortic arch may also be visualized on the anterior view ( Fig. 5 ). The spinnaker sail sign, superior and lateral elevation of the thymus, is often seen in infants. Lateral views may demonstrate retrocardiac, pericardiac, periaortic, and peritracheal lucency. PTX may coexist with pneumomediastinum.
High-resolution chest CT scan is not routinely necessary to diagnose pneumomediastinum, but is recommended when history and physical examination raise clinical suspicion of esophageal perforation. Boerhaave’s syndrome, which is esophageal rupture resulting from forceful vomiting, is the most common cause of esophageal perforation. The diagnosis is strongly indicated by the presence of Mackler’s triad: (1) history of violent vomiting, (2) chest pain, and (3) subcutaneous emphysema on examination. Perforation of the esophagus may also result from ingestion of a foreign body ( Fig. 6 A , B). Barium swallow or esophagoscopy, though not indicated to diagnose pneumomediastinum, should also be obtained in this instance to identify disruption of the esophageal wall. It is preferable to obtain both studies as contrast studies may not indicate the diagnosis alone.
Management of pneumomediastinum primarily consists of supportive care, including rest, pain control, cough suppression, and avoidance of Valsalva and other aggravating factors. Most cases will resolve without sequelae over 3 to 15 days. Most cases may be managed in the outpatient setting. Admission criteria include hypoxia, significant respiratory distress, esophageal perforation, and severity requiring surgical intervention. Definitive treatment consists of treating the underlying cause. In the instance of marked hypoxia or respiratory distress requiring mechanical ventilation, a collar mediastinotomy (release incisions made in the infraclavicular region) should be performed.
Complications of pneumomediastinum are rare and include laryngeal compression, pseudotamponade, mediastinitis in the setting of esophageal perforation, and tension pneumomediastinum or pneumothorax. These complications generally require surgical management. Pneumomediastinum is rarely fatal. A few case reports demonstrate increased mortality in children with serious chronic pulmonary disease and in a group of children in a developing country with measles.
Pneumomediastinum
Pneumomediastinum is defined as air in the mediastinum and should be included in the differential diagnosis of acute chest pain. The anatomic borders of the mediastinum are as follows: superior, thoracic inlet; inferior, diaphragm; posterior, thoracic spine; and anterior, sternum ( Fig. 4 ). Pneumomediastinum may affect any or all of these spaces.
Classification of pneumomediastinum stems from its cause. Secondary or acquired pneumomediastinum generally occurs as a result of thoracic or abdominal surgery, foreign body ingestion, cardiac catheterization, or endotracheal intubation and mechanical ventilation. Other medical procedures predisposing to mediastinal emphysema include dental, endotracheobronchial and endoesophageal procedures. Severe cases may result from trauma to the chest or neck with disruption of the tracheobronchial tree.
Spontaneous pneumomediastinum occurs in the absence of the above causes, and often occurs as a result of infections or asthma. Asthma is the most common underlying condition, with up to 35% of cases associated with asthma and other obstructive pulmonary diseases. Infectious causes include bronchiolitis, bronchitis, viral pneumonia, and retropharyngeal abscesses. Valsalva maneuvers such as coughing, screaming, deep breathing with physical activity, or vomiting are frequent causes of spontaneous pneumomediastinum. Diabetic ketoacidosis has been associated with the development of spontaneous pneumomediastinum, possibly as a result of associated vomiting. Inhaled drug use is another important risk factor for developing this condition.
The most common mechanism resulting in pneumomediastinum is thought to be alveolar rupture, resulting in tracking of free air toward the hilum of the affected lung, into the mediastinum and upwards into the subcutaneous space of the upper chest and neck. Rupture or perforation of the esophagus or large airways can also result in the characteristic clinical picture.
Incidence
Whereas its true incidence is unknown, it has been reported in an estimated 1 per 14,000 individuals between 14 and 29 years of age. The incidence has a bimodal peak, occurring more frequently in children between 6 months and 3 to 4 years of age and in adolescents, and in 1 per 20,000 patients presenting to emergency departments with exacerbations of asthma. Tall, thin adolescent boys are more commonly affected.
Presentation
Patients typically complain of retrosternal chest pain that increases with respirations, dyspnea, and neck pain. The history may reveal the presence of sore throat, coughing or vomiting, low-grade fevers, dysphagia, and dysphonia. A history of risk factors and predisposing conditions may also be elicited. Physical examination findings include subcutaneous emphysema (air in the subcutaneous tissues of the chest and neck), often with visible neck edema; palpable crepitus is diagnostic. Precordial crepitus auscultated during systole (Hamman’s sign) indicates the presence of subcutaneous emphysema and is pathognomonic for pneumomediastinum. Patients may also present with torticollis as a result of cervical subcutaneous air.
The differential diagnosis for pneumomediastinum includes pericarditis and pneumothorax, both of which present with dyspnea and chest pain; however, respiratory distress in PTX is often more pronounced than in pneumomediastinum. Hamman’s sign, neck edema, and torticollis are not usually seen in pneumothorax. Pericarditis differs from pneumomediastinum and PTX in that the severity of chest pain sometimes varies with position (increased pain when supine and decreased in a seated position while leaning forward). Auscultation may reveal a friction rub, a finding distinct to pericarditis.
Diagnosis
Plain radiographs remain the gold standard for diagnosing pneumomediastinum. Anterior and lateral views of the chest including the neck are usually sufficient to demonstrate typical findings. The anterior view may reveal a continuous diaphragm sign, which is a lucency that extends between the pericardium and diaphragm. A vertical line of lucency surrounding the left side of the trachea, heart, and aortic arch may also be visualized on the anterior view ( Fig. 5 ). The spinnaker sail sign, superior and lateral elevation of the thymus, is often seen in infants. Lateral views may demonstrate retrocardiac, pericardiac, periaortic, and peritracheal lucency. PTX may coexist with pneumomediastinum.
High-resolution chest CT scan is not routinely necessary to diagnose pneumomediastinum, but is recommended when history and physical examination raise clinical suspicion of esophageal perforation. Boerhaave’s syndrome, which is esophageal rupture resulting from forceful vomiting, is the most common cause of esophageal perforation. The diagnosis is strongly indicated by the presence of Mackler’s triad: (1) history of violent vomiting, (2) chest pain, and (3) subcutaneous emphysema on examination. Perforation of the esophagus may also result from ingestion of a foreign body ( Fig. 6 A , B). Barium swallow or esophagoscopy, though not indicated to diagnose pneumomediastinum, should also be obtained in this instance to identify disruption of the esophageal wall. It is preferable to obtain both studies as contrast studies may not indicate the diagnosis alone.
Management of pneumomediastinum primarily consists of supportive care, including rest, pain control, cough suppression, and avoidance of Valsalva and other aggravating factors. Most cases will resolve without sequelae over 3 to 15 days. Most cases may be managed in the outpatient setting. Admission criteria include hypoxia, significant respiratory distress, esophageal perforation, and severity requiring surgical intervention. Definitive treatment consists of treating the underlying cause. In the instance of marked hypoxia or respiratory distress requiring mechanical ventilation, a collar mediastinotomy (release incisions made in the infraclavicular region) should be performed.
Complications of pneumomediastinum are rare and include laryngeal compression, pseudotamponade, mediastinitis in the setting of esophageal perforation, and tension pneumomediastinum or pneumothorax. These complications generally require surgical management. Pneumomediastinum is rarely fatal. A few case reports demonstrate increased mortality in children with serious chronic pulmonary disease and in a group of children in a developing country with measles.
Pulmonary embolism
Although pulmonary embolism (PE) occurs rarely in children as compared with adults, its incidence has increased in recent years, with a current documentable incidence of between 0.86 and 5.3 cases per 10,000 hospital admissions. This increase is expected to continue for a number of reasons, including increased survival of children with previously fatal disease conditions that increase PE risk, and increased use of central venous catheters, a known risk factor for PE development. The true incidence is almost certainly much greater than reported for a number of reasons, including lower index of suspicion on the part of physicians treating children, lower reliability of screening algorithms in children than in adults, and masking of symptoms by other ongoing disease processes. In a recent literature review, 12 of 20 (60%) of children with massive PE died suddenly, with diagnosis made only at autopsy.
Despite these factors, PE remains much less common in children than in adults. Possible protective mechanisms in children may include reduced capacity to generate thrombin and increased antithrombic potential of blood vessel walls compared with adults. PE incidence in children is bimodal, with peaks in infancy and in adolescence.
PE severity can be roughly divided into three groups. In the first, the PE is small and well tolerated clinically, without hemodynamic instability. The second group consists of patients with sufficient obstruction of flow in the pulmonary arterial bed to produce pulmonary hypertension and right ventricular strain from afterload, but without systemic hypotension. The third group involves massive PE, which has been defined as PE associated with systemic hypotension, shock, syncope, or cardiac arrest, or as obstruction equivalent to loss of flow to two or more lobar arteries resulting in acute right heart failure and cardiogenic shock.
Risk Factors
Ninety-five percent of venous thromboembolic events (VTE) in children are associated with serious medical conditions such as cancer, surgery or trauma, congenital heart disease, and collagen vascular disease. Virchow’s triad delineates three types of risk factors for VTE: alterations in blood flow, endothelial injury, and hypercoagulability ( Table 2 ).
| Alterations in Blood Flow (Venous Stasis) | Vascular Endothelial Injury | Thrombophilic (Hypercoagulable) States |
|---|---|---|
| Immobilization | Central venous catheters | Cancer or chemotherapy |
| Surgery | Trauma | Nephrotic syndrome |
| Venous malformations | Infection | Genetic disorders (protein C, S, antithrombin deficiencies) |
| Blood flow obstruction (May-Thurner syndrome) | — | Estrogen |
| — | — | Acquired disorders (lupus) |
The development of deep vein thrombosis (DVT) is influenced by these factors and can result in PE, either by embolization or by direct extension through the inferior or superior vena cava. Recent studies have found an incidence of DVT in 55% to 72% of pediatric patients with documented PE.
One of the most frequent VTE-PE risk factors in children is the presence of a central venous catheter (CVC), particularly when the CVC is infected. The presence of malignancy is also a significant factor separately from its common association with CVCs, due to both inherent hypercoagulability state and embolization or direct extension of tumor material; the latter has been shown in one study to cause 40% of PEs in children. Other risk factors include congenital heart disease and cardiac surgery, especially involving right heart bypass surgery such as the Fontan procedure, other recent surgery, and immobilization.
Sepsis and other forms of infection are also risk factors for PE, particularly septic PEs arising from localized infections. These may include suppurative otitis media, pyomyositis and other soft tissue infections, osteomyelitis, and Lemierre syndrome (jugular venous thrombosis associated with anaerobic infection of the head and neck). The most frequent causative organism is Staphylococcus aureus , except in the case of Lemierre syndrome, which is commonly caused by Fusobacterium necrophorum or is polymicrobial.
Thrombophilia (hypercoagulability) has a large number of causes, both genetic and acquired; they may be present in combination, further increasing the risk of VTE-PE ( Table 3 ).
