Pulmonary Infarction

Loschner first described pediatric pulmonary embolism (PE) in the 1860s. Deep venous thromboses (DVT) and pulmonary emboli are relatively rare phenomena in pediatric practice; however, when they do occur, they are associated with significant morbidity and mortality. Because of the rarity of pulmonary emboli in children, they are probably underdiagnosed.[1, 2, 3, 4] For the same reason, much of the information pertaining to diagnosis and management of pulmonary embolism has been derived from adult practice.[5]

A specific diagnosis that should be mentioned because of its prevalence is sickle cell disease. Prompt recognition and management of pulmonary problems may lead to a decreased rate of pulmonary complications.

Most pulmonary emboli derive from a free-floating thrombus. In rare situations, extension of an existing pulmonary thrombus may result in pulmonary infarction. Many materials and substances may form emboli and move to the pulmonary circulation; these include fat, tumor, septic emboli, air, amniotic fluid, and injected foreign material.

The size of a pulmonary embolism determines at which points in the pulmonary vasculature it lodges. After the embolus lodges, it occludes the vessel, reducing distal blood flow to the area directly supplied by the vessel. The degree of obstruction of the pulmonary circulation directly affects the resulting pathophysiology.

In all cases of pulmonary embolism, ventilation/perfusion (V/Q) mismatch occurs to some degree, in which continued ventilation of lung units without circulation is present. Oxygenation is usually not affected by the V/Q mismatch, in contrast with V/Q mismatch that arises from obstruction of airways and lung parenchyma. Impaired oxygenation in the context of suspected pulmonary embolism implies a massive obstruction.

An increase in effective alveolar dead space is a direct result of the V/Q mismatch. Ventilation (carbon dioxide removal) is usually compensated for by tachypnea.

In cases in which the pulmonary embolus is large, a sudden increase in pulmonary artery pressure may lead to right ventricular strain and right heart failure. A sudden rise in the right ventricular pressure may cause a leftward shift of the intraventricular septum, which may impair left ventricular filling and output (classic obstructive shock).

Reflex bronchoconstriction is often associated with pulmonary embolism. This increases the work of breathing and decreases pulmonary compliance. Pulmonary infarction is also associated with diminished surfactant levels, which may contribute to the increased work of breathing and diminished oxygenation.

Children with pulmonary emboli often have a serious underlying condition that predisposes them to embolus development and may worsen their clinical outcome. Some of the more common underlying conditions include the following:

• Sickle cell disease

• Nephrotic syndrome

• Cancer

• Chemotherapy

• Inherited hypercoagulable state

• Vasculitis

In sickle cell disease, an initial trigger (often infection) exacerbated by dehydration (eg, due to fever, tachypnea, or decreased intake) leads to sickling of RBCs within small blood vessels of the lung and other organs. This precipitates a cycle of relative deoxygenation that further exacerbates the sickling tendency, leading to small vessel occlusion and, ultimately, infarction of areas of the pulmonary parenchyma. Allied to this sequence is the tendency of many patients with sickle cell disease to have a component of reactive airways disease, which may further decrease oxygenation.

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]

United States data

Pulmonary embolism is a rare disorder in pediatric practice. In 1993, David et al identified 308 children reported in the medical literature from 1975-1993 with DVT of an extremity, pulmonary embolism, or both.[6] In 1986, Bernstein reported 78 episodes of pulmonary embolism per 100,000 hospitalized adolescents.[16] Unselected autopsy studies in children estimate the incidence of pulmonary embolism from 0.05-3.7%.

International data

Canadian data derived from 15 tertiary care centers show a frequency of 0.86 events per 10,000 pediatric hospital admissions for patients aged 1 month to 1 year.[17] Frequency of pulmonary embolism in developed countries has been increasing when compared with historical data. This increase in frequency is linked with the increased use of central venous lines in the pediatric population.[18] The overall frequency is still considerably less than that seen in adults.

Race-, sex-, and age-related demographics

No data outlining variations in pulmonary embolism prevalence by race are available.

Some authors have reported a female-to-male ratio of 2:1. Others have found that this ratio is reversed.

Given the rarity of pulmonary embolism in childhood, no definitive data identify age as an independent risk factor for pulmonary embolism. The frequency of pulmonary embolism has a bimodal distribution, with peaks in the neonatal period and adolescence.

Morbidity/mortality

Morbidity may include pulmonary hypertension, right ventricular failure and cor pulmonale, paradoxical embolization to the systemic circulation in patients with intracardiac defects, and side effects of medications used to treat pulmonary embolism.[16, 19, 9]

In a case series and literature review of massive pediatric pulmonary embolism, children with massive PE had higher rates of mortality and were more likely to have the PE diagnosed postmortem.[20]

No data are available regarding the risk of recurrence of pulmonary embolism in children.

Separating mortality attributable to pulmonary embolism from that due to conditions that may be associated with pulmonary embolism, such as trauma and surgery, is difficult.

The data regarding death from pulmonary embolism in children are conflicting. Various authors suggest that pulmonary embolism contributes to the death of affected children in approximately 30% of cases.[21] Others, however, have reported pulmonary embolism as a cause of death in fewer than 5% of affected children.[22] As in adults, the mortality rate is highest in the period immediately following embolization. If no major cardiovascular sequelae are present, a full recovery may be anticipated without complications.

The importance of adherence to the treatment regimen should be repeatedly stressed. The patient should be instructed regarding what to do in the event of any bleeding complications. Because most patients are administered warfarin upon discharge from the hospital, they must be advised regarding potential interactions between warfarin and other medications.

Risk factors for the development of pulmonary embolism should be discussed, including the following:

• Pregnancy

• Oral contraceptive pill use

• Termination of pregnancy

• Smoking

For patient education resources, see the Lungs Center, as well as Pulmonary Embolism and Sickle Cell Disease.

Classic symptoms of pulmonary embolism (PE) are rarely encountered. The frequency with which the diagnosis is missed in both adults and children is striking. Adding to the clinical dilemmas is the fact that few symptoms are sensitive or specific for pulmonary embolism. In adult series, clinical diagnosis has a sensitivity of 85% but a specificity of 38%, reflecting the vast differential diagnosis found in both adults and children. Symptoms vary according to the severity of the pulmonary embolism and the presence of underlying conditions. Pulmonary emboli of small-to-moderate size are generally asymptomatic. Case series of pediatric emergency department presentations for PE showed that the most common risk factors included BMI > 25, oral contraceptive use, and previous history of thrombus without PE.[15]

Respiratory symptoms

Pleuritic chest pain is reported to occur in as many as 84% of children and adults with pulmonary emboli. Its presence suggests that the embolus is located more peripherally and, thus, may be smaller.

Tachypnea and dyspnea are observed in as many as 60% of adult patients with pulmonary emboli but are generally less frequent in children.

Cough is present in approximately 50% of children with pulmonary emboli. Hemoptysis is a feature in a minority of children with pulmonary emboli, occurring in about 30% of cases.

Other symptoms

A feeling of apprehension is a manifestation of arousal of the sympathetic system. Sweating and syncope are rarely present.

Risk factors to elicit on history taking

Obtain a detailed history of any previous pulmonary embolism/thromboembolism, oral contraceptive use, recent pregnancy, termination of pregnancy, drug history, and family history.

Sickle cell disease

Patients with sickle cell disease may present with manifestations of sickle cell anemia other than acute chest syndrome. These may include anemia, sequestration crisis, pain crisis, stroke, and priapism.

The use of physical findings as a diagnostic aid in suspected cases of pulmonary embolism brings the same problems as are outlined in History. Many physical findings are typically less marked than they are in adults, presumably because children have greater hemodynamic reserve and, thus, are better able to tolerate the significant hemodynamic and pulmonary changes.

Pulmonary findings include the following:

• Tachypnea is a feature in almost 50% of children with pulmonary emboli.

• Crackles are heard in a minority of cases.

• Cyanosis and hypoxemia are not prominent features of pulmonary embolism. If present, cyanosis suggests a massive embolism leading to a marked V/Q mismatch and systemic hypoxemia. Some case reports have described massive pediatric pulmonary embolism with normal saturation.

• A pleural rub is often associated with pleuritic chest pain and indicates an embolism in a peripheral location in the pulmonary vasculature.

• Signs that indicate pulmonary hypertension and right ventricular failure include a loud pulmonary component of the second heart sound, right ventricular lift, distended neck veins, and hypotension. An increase in pulmonary artery pressure is reportedly not evident until at least 60% of the vascular bed has been occluded.

Cardiovascular findings include the following:

• A gallop rhythm signifies ventricular failure.

• Peripheral edema is a sign of congestive heart failure.

• Various heart murmurs may be audible, including a tricuspid regurgitant murmur signifying pulmonary hypertension.

Other signs include the following:

• Fever is an unusual sign that is nonspecific.

• Diaphoresis is a manifestation of sympathetic arousal.

• Signs of other organ involvement in patients with sickle cell disease would be elicited, such as sequestration crisis, priapism, anemia, and stroke.

Complications of pulmonary embolism include the following:

• Death

• Hemorrhage

• Heparin-induced thrombocytopenia

• Thrombophlebitis

Arterial or capillary blood gas measurements

Arterial blood gas findings are often normal. However, a calculated alveolar-arterial oxygen gradient may be elevated.

Abnormal findings are nonspecific and may include hypoxemia, hypocarbia or hypercarbia, and respiratory alkalosis that reflects dyspnea and anxiety or respiratory acidosis that reflects a V/Q mismatch.

Hypercarbia with hypoxemia is a poor prognostic sign and indicates a massive pulmonary embolism (PE).

Metabolic acidosis is occasionally observed and is a sign of poor cardiac output. In the case of pulmonary embolism with obstructive shock, venous oxygen saturation is decreased.

D-dimer levels

Two methods measure D-dimer levels, a qualitative assay and a quantitative enzyme-linked immunosorbent assay (ELISA). The ELISA is usually performed only if the result of the qualitative test is positive.

D-dimer levels are elevated (>500 ng/mL) in 90% of adults with pulmonary emboli. Although D-dimers measurement is a very sensitive test, its specificity is only on the order of 50%. Because of the poor specificity, positive D-dimers measurements are generally not helpful in diagnosis. In addition, the use of D-dimers in children is not well studied. A small pediatric series reported that D-dimers findings are negative in 40% of patients.[22] A more recent retrospective series reported an elevated D-dimer in 86% of patients at presentation.[7]

CBC count

The WBC count may be slightly elevated. Hemoglobin and hematocrit are reduced in children with sickle cell disease who present with acute chest syndrome.

Hypercoagulation panel

A hypercoagulation workup should be performed if no obvious cause for embolic disease is apparent. This may include screening for conditions such as antithrombin III deficiency, protein C or protein S deficiency, lupus anticoagulant, homocystinuria, occult neoplasm, and connective tissue disorders.

Assessment of risk factors for pulmonary embolism should guide the use of imaging studies. This has been well established in literature guiding the use of V/Q scans. Emerging literature suggests that similar analysis should be used to guide the use of computed tomography (CT) scanning and CT angiography.

Chest radiography

Radiographic findings are abnormal in as many as 70% of cases. Problems of low sensitivity and specificity complicate its use as a diagnostic tool.

Chest radiography is useful to rule out other differential diagnoses; it is a necessary adjunct to the interpretation of the V/Q scan.

The most common radiographic changes include infiltrates, atelectasis, and pleural effusions. Effusions are bilateral in 10% of cases. Signs that are said to be characteristic include Westermark sign, an area of focal hypoperfusion, and Hampton hump, a peripheral wedge-shaped density above the diaphragm. Evidence of a dilated pulmonary artery is occasionally observed.

CT scanning and CT pulmonary angiography

Many diagnostic algorithms have been suggested to facilitate the evaluation of the patient with suspected pulmonary embolism. The widespread availability of CT has evoked much interest in the use of this modality to diagnose pulmonary embolism. Most centers now use CT angiography as an initial step in the workup of pulmonary embolism.

The embolism appears as a low-density filling defect within the pulmonary artery.

One study found that 1% of patients with pulmonary embolism had negative findings on helical CT scanning.[23] Small emboli are more likely to be missed, particularly if they are peripherally located. Hence, the negative predictive value is of the order of 99%, which does not substantially differ from that found with V/Q scanning or pulmonary angiography.

Radiopaque intravenous contrast should be used with caution in patients with possible renal impairment.

Multidetector CT (MDCT) scanning has increased in popularity in recent years. MDCT techniques may reduce the volume of contrast and may improve diagnosis of pulmonary embolism, especially by trainees.[24]

Ventilation/perfusion (V/Q) scanning

This noninvasive scan delineates both regional lung ventilation and perfusion. Note that a normal finding on V/Q scanning does not rule out pulmonary embolism. However, multiple V/Q scans with normal findings suggest that, if a pulmonary embolism is present, it is clinically unimportant. A problem that commonly arises is which test to perform first because confusion may stem from overlap of radioactive signals. Generally, if only one scan can be performed, the perfusion scan is thought to provide more useful information.

A sample of aggregated albumin labeled with radioactive technetium is administered intravenously and lodges in the pulmonary capillary bed. The patient is placed in a supine position to ensure optimal blood flow to the lung apices and, thus, reduce the risk of a false-positive result. The gamma rays emitted by the technetium are revealed by a gamma camera. Areas of decreased perfusion, which suggest a pulmonary embolism, are observed as areas of decreased radiation emission.

The ventilation scan is usually performed by having the patient inhale radiolabeled xenon (Xe) 133. Areas of decreased ventilation are revealed as areas of decreased radioactivity. The ventilation scan is compared with the perfusion scan. An area with normal ventilation but decreased perfusion is consistent with a diagnosis of pulmonary embolism. An area of diminished ventilation is consistent with a large number of diagnoses.

A V/Q scan is usually reported in terms of probability of pulmonary embolism (ie, high, intermediate, moderate, low). A high-probability scan is defined as having two or more areas with segmental defects on a perfusion scan with a normal finding on a ventilation scan. V/Q scan reporting is based on adult risk stratification (Prospective Investigation of Pulmonary Embolus Diagnosis [PIOPED] study).[25]

Forty percent of adults with a high clinical index of suspicion for pulmonary embolism and a low-probability V/Q scan are found to have a pulmonary embolism based on angiography findings. No similar data are available for children. Children generally have a more homogenous perfusion scan; thus, deficits in perfusion are more likely to represent real or significant pulmonary embolism compared with adults.

Magnetic resonance imaging (MRI)

Few data are available regarding the use of MRI in children suspected of having a pulmonary embolism. Its use should be considered investigational at this time. Studies in adults suggest that MR technology has limited sensitivity for distal pulmonary embolism and is not a viable alternative to CT.[26]

Deep venous thromboses (DVT) imaging studies

The possibility of DVT should be considered. Most adults with a pulmonary embolism have a coexisting DVT; whether this holds true for children is unknown. The presence of a DVT may provide indirect evidence of a pulmonary embolism when the V/Q scan is a low-probability scan. Like pulmonary embolism, the reliability of clinical diagnosis of DVT is suboptimal. In a pediatric series, 18% of patients with clinically suspected DVT actually had a DVT confirmed radiologically.

The three methods used for the diagnosis of DVT are as follows:

• Doppler ultrasonography is based on the principle that ultrasonic waves reflected from blood traveling at different velocities vary in frequency. The change of frequency (ie, change in blood velocity) reflects the degree of obstruction.

• Impedance plethysmography is based on the principle that the electrical impedance of a limb is related to the blood volume in that limb. A pneumatic cuff adjusts the pressure on the limb to be measured. An increase in blood volume within that limb signifies an obstruction (ie, DVT). No data are available regarding its use in children.

• Venography is the criterion standard for diagnosing DVT. With the advent of noninvasive imaging, it has become less common in pediatric practice.

Echocardiography

Echocardiography (ECHO) provides useful information. It may allow diagnosis of other conditions that may be confused with pulmonary embolism, such as pericardial effusion.

ECHO allows visualization of the right ventricle and assessment of the pulmonary artery pressure.

This imaging modality serves a prognostic function; the mortality rate is almost 10% in the presence of right ventricular dysfunction and 0% in the absence of right ventricular dysfunction.

ECHO may be used to identify the presence of right-chamber emboli and upper extremity DVT

Electrocardiogram (ECG) findings may be normal. ECG is helpful to rule out other conditions in the differential diagnosis.

ECG changes found in pulmonary embolism include sinus tachycardia, T-wave inversion, S1 Q3 T3 pattern, right axis deviation, right bundle branch block, and P pulmonale (ie, a tall P wave representing an enlarged right atrium).

Angiography is the criterion standard for diagnosing pulmonary embolism. It detects emboli as small as 1 mm. A positive test result is defined as an intraluminal filling defect that is visible in more than one radiographic view.

The usual indication for pulmonary angiography is an equivocal finding on a V/Q scan with a high index of suspicion for pulmonary embolism, especially in a patient at high risk for complications from therapy (ie, anticoagulation, thrombolysis); another indication are instances in which an embolectomy is considered.

Complications, apart from mortality, include hemorrhage, infection, arrhythmias, and great vessel or myocardial perforation. Patients at highest risk are those with right ventricular dysfunction or elevated pulmonary artery pressures. The mortality risk in adults is less than 0.5% in series from large centers. No similar data on children are available.

Medical therapy centers on providing initial cardiopulmonary support, anticoagulation to prevent clot extension, and thrombolysis in the rare event of pulmonary embolism (PE) that leads to massive cardiorespiratory failure. When able, acquired risk factors such as central venous lines should be addressed. Much of the information regarding treatment of pulmonary embolism in children has been derived from that on adults.

Deciding how to treat a venous thrombosis that may lead to a pulmonary embolism is difficult. A survey of Canadian pediatric intensivists reported four patient factors commonly used to determine if a venous thrombosis was clinically important: clinical suspicion of a pulmonary embolism, symptoms, detection of thrombosis on clinical examination, and presence of an acute or chronic cardiopulmonary comorbidity that affects the patient's ability to tolerate a pulmonary embolism.[17]

Anticoagulation

Anticoagulation should be started in patients without contraindications (active bleeding). Systemic anticoagulation should be started with unfractionated or low molecular weight heparin (LMWH) to achieve an antifactor Xa level of 0.5-1 U/mL or, in the case of unfractionated heparin, activated partial thromboplastin time (aPTT) levels of twice the control value. Therapy should continue for 5-10 days.

Long-term anticoagulation should continue with LMWH for as long as 6 months to achieve a target antifactor Xa level of 0.5-1 U/mL. Alternatively, oral therapy with warfarin can be used to achieve an international normalized ratio (INR) of 2-3. If oral therapy is used, dosing should begin with initial systemic anticoagulation, with discontinuation of heparin on day 5.

Studies suggest that attempts to achieve a higher INR with warfarin are associated with an increased risk of bleeding without commensurately reducing the risk of new clot formation; therefore, aiming for an INR of 2-3 is recommended. Levels of more than 3 are generally unnecessary. Patients with the antiphospholipid syndrome may require INRs of more than 3.

Thrombolysis

Thrombolysis should be considered only if a large embolus is present in the pulmonary vasculature or in the setting of potential cardiac or pulmonary failure. Small case series have shown that systemic thrombolytic therapy can be safely used in pediatric patients with high risk venous thromboses.[27] Catheter-directed thrombolysis in centers with the appropriate expertise may be an alternative approach with lower risk of hemorrhage.[28] Potential benefit must be weighed against the significant risk of bleeding.

Supportive care

Pharmacologic support of the cardiovascular system may be necessary. Pressors, inotropic agents, and selective pulmonary vasodilators may be required in cases of obstructive shock from PE. Mechanical ventilation may be necessary both to provide respiratory support and as adjunctive therapy for a failing circulatory system. Extracorporeal membrane oxygenation (ECMO) has successfully been used to bridge patients who have suffered cardiac arrest or who are peri-arrest to definitive management.[29]

Children with sickle cell disease who present with pulmonary symptoms require treatment with a macrolide and cephalosporin antibiotic. Their clinical status should be closely monitored in order to anticipate those children who may develop acute chest syndrome.[8, 30]

Transfusion with packed RBCs (either simple or exchange) improves oxygenation immediately, helping to break the vicious cycle outlined above.

Transfer

Transfer to an appropriate institution for further workup and therapy. Generally, this is a tertiary center in view of the rarity of embolic disease in children.

Surgical interventions in the management of pulmonary embolism consist primarily of embolectomy. Inferior vena cava filters have been used to prevent recurrent emboli, but few data are available regarding their use in children.

Embolectomy

Case reports and retrospective series support the use of surgical embolectomy in children centers with the appropriate resources and expertise.[1, 2] Consider embolectomy in the setting of massive cardiac failure when time is insufficient for natural or pharmacologic thrombolysis or if thrombolysis is contraindicated.

Very few cases of embolectomy in infants and neonates have been described in the literature. Kalanti et al reported a successful emergency surgical embolectomy in a 10-day-old preterm neonate who experienced sudden cardiorespiratory collapse.[2]

Vena caval filters

Otherwise known as Greenfield filters, these are placed surgically in the inferior vena cava (IVC) and prevent further emboli from reaching the pulmonary circulation. Indications for IVC filters include a contraindication to anticoagulation and recurrent PE despite adequate anticoagulation.

Historically, IVC filters have been limited to larger adolescent patients. Filter placement in younger patients has increased with the development of retrievable filters but is still limited to large centers with specific technical expertise.[31]

Complications include migration of the filter, sepsis, and misplacement of the filter.

Consider consultations with the following specialists:

• Intensivist: A critical care specialist should be consulted in any case of pulmonary embolism with cardiorespiratory compromise.

• Pulmonologist: A pulmonologist is often consulted before the true diagnosis is made because of the nonspecific nature of the symptoms.

• Cardiologist: Consultation with a cardiologist is warranted to rule out a cardiac etiology for the presenting symptoms and signs and to perform ECHO and pulmonary angiography.

• Cardiothoracic surgeon: If embolectomy is considered, consultation with a cardiac surgeon is mandatory.

• Hematologist: A hematologist can suggest an appropriate workup for a procoagulant defect and can recommend an anticoagulation regimen. Consultation with a hematologist is essential in children with sickle cell disease. A free clinical consultation service for complex cases of thromboembolism in children is available for clinicians by calling The Pediatric Thrombosis Program at 1-800-NO-CLOTS (1-800-662-5687).

No specific diet is contraindicated. However, excessive weight should be avoided in those with a history of pulmonary embolism.

Activity should not be limited. Mobilization should be encouraged in those with a history of pulmonary embolism or those at risk of having a pulmonary embolism. Patients taking anticoagulants should avoid high-impact sports.

Anticipate patients at risk. Any child with a risk factor may develop a pulmonary embolism (PE). See Etiology. Methods to reduce risk include early mobilization, thromboembolic stockings, and prophylactic use of subcutaneous LMWH.

Current standard of care does not call for thromboprophylaxis in critically ill children without DVTs.[32] Practice with adolescent patients is mixed with a large minority routinely prophylaxing critically ill adolescents.

Females of childbearing age should be advised regarding the increased risk of thromboembolic disease during pregnancy. Women who are sexually active should be offered appropriate contraceptive advice. Those who wish to become pregnant should be referred to an obstetrician skilled in the management of hypercoagulable disorders during pregnancy.

PT should be measured on a regular basis; the goal is an INR of 2-3.

The length of treatment depends on the presence of risk factors. If no underlying risk factors are present, therapy can be stopped within 1-2 months. If risk factors are present, especially anticardiolipin antibodies, therapy should continue for at least 4-6 months.

The American Society of Hematology (ASH) released their updated recommendations on the management of venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [PE]) in October 2020.[33] Select recommendations are outlined below.

Strong Recommendations

For patients with PE and hemodynamic compromise, it is recommended that thrombolytic therapy followed by anticoagulation be used over anticoagulation alone.

For patients with DVT and/or PE who have completed primary treatment and will continue vitamin K antagonist (VKA) therapy as secondary prevention, it is recommended that an international normalized ratio (INR) range of 2.0 to 3.0 be used over a lower INR range (eg, 1.5-1.9).

For patients with a recurrent unprovoked DVT and/or PE, indefinite antithrombotic therapy is recommended over stopping anticoagulation after completion of primary treatment.

Conditional Recommendations

Initial management

For patients with DVT and/or PE, the ASH guideline panel suggests using direct oral anticoagulants (DOACs) over VKAs. No single DOAC is suggested over another.

In most patients with proximal DVT, anticoagulation therapy alone is suggested over thrombolytic therapy in addition to anticoagulation.

For patients with PE with echocardiography and/or biomarkers that are compatible with right ventricular dysfunction but without hemodynamic compromise (submassive PE), anticoagulation alone is suggested over the routine use of thrombolysis in addition to anticoagulation.

For patients with extensive DVT in whom thrombolysis is considered appropriate, the ASH guideline panel suggests using catheter-directed thrombolysis over systemic thrombolysis.

For patients with PE in whom thrombolysis is considered appropriate, systemic thrombolysis is suggested over catheter-directed thrombolysis.

For patients with proximal DVT and significant preexisting cardiopulmonary disease, as well as for patients with PE and hemodynamic compromise, use of anticoagulation alone is suggested rather than anticoagulation plus insertion of an inferior vena cava (IVC) filter.

Primary treatment

For primary treatment of patients with DVT and/or PE, whether provoked by a transient risk factor or by a chronic risk factor or unprovoked, using a shorter course of anticoagulation for primary treatment (3-6 months) is suggested over a longer course of anticoagulation for primary treatment (6-12 months).

Secondary prevention

To guide the duration of anticoagulation for patients with unprovoked DVT and/or PE, the ASH guideline panel suggests against routine use of prognostic scores, D-dimer testing, or ultrasonography to detect residual vein thrombosis.

Indefinite antithrombotic therapy is suggested over anticoagulation cessation after completion of primary treatment for the following:

• Patients with DVT and/or PE provoked by a chronic risk factor
• Patients with unprovoked DVT and/or PE

For patients with DVT and/or PE who have completed primary treatment and will continue to receive secondary prevention, use of anticoagulation is suggested over aspirin.

For patients with DVT and/or PE who have completed primary treatment and will continue with a DOAC for secondary prevention, the ASH guideline panel suggests using a standard-dose DOAC or a lower-dose DOAC.

Recurrent events

For patients with breakthrough DVT and/or PE during therapeutic VKA treatment, the ASH guideline panel suggests using low-molecular-weight heparin (LMWH) over DOAC therapy.

For patients who develop DVT and/or PE provoked by a transient risk factor and have a history of previous unprovoked VTE or VTE provoked by a chronic risk factor, indefinite antithrombotic therapy is suggested over stopping anticoagulation after completing primary treatment.

For patients who develop DVT and/or PE provoked by a transient risk factor and have a history of a previous VTE also provoked by a transient risk factor, anticoagulation cessation after completion of primary treatment is suggested over indefinite antithrombotic therapy.

Other

For patients with DVT and/or PE with stable cardiovascular disease (CVD) who initiate anticoagulation and were previously taking aspirin for cardiovascular risk modification, it is suggested that aspirin be suspended over continuing it for the duration of anticoagulation therapy.

For patients with DVT, with or without an increased risk for postthrombotic syndrome (PTS), the ASH guideline panel suggests against the routine use of compression stockings.

Additional Resources

For more information, please go to Venous Thromboembolism (VTE), Deep Venous Thrombosis (DVT), and Pulmonary Embolism (PE).

For more Clinical Practice Guidelines, please go to Guidelines.

Anticoagulants are the treatment of choice in most children with pulmonary emboli. Thrombolytics are rarely used. To date, little data are available regarding the use of LMWH in children with thromboembolic disease; however, numerous studies have described the efficacy of LMWH in thromboembolic disease.

A review that compared the use of LMWH with standard unfractionated heparin (UFH) in the treatment of venous thromboembolic disease in adult patients concluded that therapy with LMWH is associated with a decreased risk of major hemorrhage and a decreased mortality rate.[34] Benefits of using LMWH include a lower overall cost, the convenience of twice-daily subcutaneous injections, decreased requirement for laboratory monitoring, and a more favorable antithrombotic-to-hemorrhagic ratio.

Duration of therapy must be individualized. One review recommends that in adult patients with transient risk factors (ie, surgery, immobilization, estrogen administration), therapy less than 3 months may be sufficient; however, no studies are available to validate this statement. Patients with slowly resolving or persistent risk factors should be treated for at least 3 months.

Previous studies have confirmed that longer duration of therapy is associated with decreased risk of disease recurrence. Adult patients with idiopathic thrombosis benefit most, although the relevance of comparing these patients with children (most of whom have identifiable risk factors) is uncertain. Patients with genetic thrombophilic states (factor V Leiden) may benefit from longer courses of therapy. Individuals with recurrent embolic disease should be treated for at least 12 months and possibly longer.

Class Summary

Inhibition of thrombin prevents extension of the thrombus, thus allowing recanalization of the blood vessel over time, and reduces the risk of further embolization. Anticoagulation does not lyse the clot per se. It merely allows the body time to lyse the clot while reducing the risk of subsequent embolization.

Heparin, unfractionated

Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

Warfarin (Coumadin)

Reduces production of vitamin K–dependent clotting factors. Allows anticoagulation on an outpatient basis. Generally should be commenced shortly after initiating heparin, and their use should overlap by 5-10 d; adjust dosage to maintain INR of 2-3.

Enoxaparin (Lovenox)

Has become first-line therapy in many patients with thromboembolism. Prevents DVT, which may lead to PE in patients undergoing surgery who are at risk for thromboembolic complications. Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases inhibition of factor Xa. Average duration of treatment is 7-14 d.

Class Summary

These convert plasminogen to plasmin, leading to clot lysis. Thrombolytic agents are rarely used in pediatric practice. Their use should be considered investigational and should be restricted to patients with severe pulmonary or cardiovascular compromise. If thrombolysis is being considered, the diagnosis of pulmonary embolism should first be confirmed by pulmonary angiography. Newborns may be relatively resistant to thrombolytics because of their lack of fibrinogen activity.

Streptokinase (Kabikinase, Streptase)

Acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots, as well as fibrinogen and other plasma proteins. Increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 h takes place with IV infusion of streptokinase.

Alteplase (Activase)

Also called tissue plasminogen activator (TPA). Produced naturally by vascular endothelium; however, the therapeutic agent is derived using recombinant technology. Binds tightly to fibrin, thus activating plasminogen, which results in clot lysis. With ongoing shortage of urokinase, more studies are emerging for use in pediatrics.