Venous thrombosis and thromboembolism (VTE) in children: Risk factors, clinical manifestations, and diagnosis

INTRODUCTION — The incidence of venous thromboembolism (VTE; which includes venous thrombosis and/or pulmonary embolism [PE]) during childhood is considerably lower than that seen in adults; however, VTE is increasingly recognized in the pediatric population as a complication of contemporary health care.

This review summarizes the available information on the incidence, risk factors, clinical manifestations, and diagnosis of VTE in children beyond the neonatal period, excluding VTE in the central nervous system. Other aspects of VTE are discussed in separate topic reviews:

●Treatment, prevention, and outcome of noncerebral VTE in children (see "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome")

●VTE in the newborn (see "Neonatal thrombosis: Clinical features and diagnosis" and "Neonatal thrombosis: Management and outcome")

●VTE in children with cancer (see "Thromboembolism in children with cancer")

●Cerebral venous thrombosis (see "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis" and "Cerebral venous thrombosis: Treatment and prognosis")

INCIDENCE — Estimates of the incidence of VTE in the general pediatric population range from 0.14 to 0.21 per 10,000 children per year [1,2]. Among hospitalized pediatric patients, the incidence of VTE is approximately 0.2 to 1 percent [3-6]. Pulmonary embolism (PE) accounts for approximately 15 percent of VTE episodes [7]. Rates of VTE and PE are highest among children with underlying medical conditions, such as malignancy and cardiac disease [3-5]. One study reported a fivefold higher incidence of VTE among children admitted to tertiary children's hospitals compared with community hospitals, which likely reflects the greater risk associated with more complex care [4].

In a prospective registry study in the Netherlands, the majority of VTE episodes (85 percent) occurred in the hospital setting and nearly all patients (98 percent) had at least one underlying risk factor [1]. In this study, one-third of the cases were associated with a central venous catheter (CVC).

In two studies using data from the Pediatric Health Information System administrative database (2001 to 2007 and 2008 to 2019), the annual rate of VTE among hospitalized children has risen from 0.3 percent in 2001 to 1.1 percent in 20019 [3,6]. These studies were unable to determine whether this increase represented a true increase in the frequency of VTE or improved detection of VTE.

In a national registry study from Denmark, rates of pediatric VTE were highest among infants and adolescents [2]. Most affected patients (87 percent) had at least one underlying condition or trigger for VTE; one-third were found to have underlying thrombophilia (eg, factor V Leiden mutation, antithrombin deficiency, protein C or S deficiency, antiphospholipid antibodies). Use of estrogen-containing contraceptives was an important risk factor for VTE among adolescent girls (80 percent of girls with VTE used contraceptives, as compared with 27 percent in the general population).

RISK OF VTE IN CHILDREN VERSUS ADULTS — The risk of VTE is substantially lower in children compared with adults. Several factors may protect children from VTE, contributing to the relatively low incidence of VTE throughout childhood:

●Children less commonly develop diseases causing damage to the vascular endothelium (eg, diabetes, dyslipidemias, hypertension).

●Children are less frequently exposed to acquired prothrombotic risk factors (eg, oral contraceptives, hormone replacement therapy, pregnancy and puerperium, smoking, malignancy, orthopedic surgery).

●As compared with adults, children have lower plasma concentrations of all vitamin K-dependent factors and almost all contact factors, as well as reduced capacity to generate thrombin [8,9].

●The capacity to inhibit thrombin is enhanced throughout childhood due to increased plasma concentrations of the thrombin inhibitor alpha-2-macroglobulin [8-10].

Risk factors and the epidemiology of VTE in adults are discussed separately. (See "Overview of the causes of venous thrombosis" and "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Epidemiology'.)

RISK FACTORS — Risk factors for VTE are summarized by Virchow's triad: endothelial injury, stasis, and hypercoagulability [11].

In children, the most common risk factor for VTE is the presence of a central venous catheter (CVC). Other risk factors include inherited hypercoagulable state, infection, trauma, immobility, malignancy, and chronic inflammatory conditions (table 1).

Central venous access devices — Approximately one- to two-thirds of VTEs in children are associated with CVCs [1,5,12]. CVCs are often necessary in the short- and long-term medical management of pediatric patients (eg, for administration of parenteral nutrition, chemotherapy, intensive fluid therapy, vasoactive infusions, or prolonged antibiotic therapy).

Indwelling CVCs are thrombogenic because they present a foreign intravascular surface, damage vessel walls, and disrupt blood flow. (See "Central venous catheters: Overview of complications and prevention in adults".)

Several factors may influence the risk of CVC-associated VTE, including [13-20]:

●Type of catheter – In most studies, peripherally inserted central catheters (PICCs) appear to carry a higher risk of VTE compared with other types of CVCs, with rates ranging from 1 to 9 percent for PICCs versus 0.5 to 3 percent for other CVCs [13-16]. However, some studies reported comparable or lower rates of VTE for PICCs compared with other catheter types [17,18].

●Location of the catheter – VTEs can occur in the upper venous system (in association with CVCs inserted through the jugular or subclavian vein) or in the lower extremities (in association with CVCs placed in the femoral vein) [19,20]. In some studies, the risk of VTE appears to be higher with upper extremity CVCs compared with lower extremity [13,19]; while other studies found similar rates of VTE regardless of location [14].

●Size of catheter – The risk of VTE is increased when the diameter of the catheter is large relative to the size of the vessel.

●Number of lumens – The risk of VTE appears to be increased with multi-lumen compared with single-lumen catheters.

●Concomitant thrombophilic conditions – Patients with underlying thrombophilic conditions (eg, cancer, trauma, infection) are at higher risk of developing CVC-associated VTE. (See 'Other risk factors' below.)

Inherited thrombophilia — Studies in adults have demonstrated a strong association between inherited thrombophilia and VTE. However, the impact of these disorders on the development of VTE during childhood remains poorly defined and controversial [21-25]. As discussed above, several factors may protect individuals with IT from developing VTE during childhood. (See 'Risk of VTE in children versus adults' above.)

The ITs for which the pathogenic link is most clearly established include (table 2):

●Factor V Leiden mutation (see "Factor V Leiden and activated protein C resistance")

●Prothrombin G20210A mutation (see "Prothrombin G20210A")

●Antithrombin deficiency (see "Antithrombin deficiency")

●Protein C deficiency (see "Protein C deficiency")

●Protein S deficiency (see "Protein S deficiency")

In children with VTE, the reported prevalence of IT varies greatly, ranging from approximately 10 to 60 percent, depending on the population studied and the tests used [2,26-34]. The prevalence is highest in children with unprovoked VTE and lowest in patients with CVC-associated VTE [33].

The approach to testing for IT in children with VTE is summarized in the algorithm (algorithm 1) and discussed in a separate topic review. (See "Thrombophilia testing in children and adolescents", section on 'Children with venous thromboembolism'.)

Other risk factors — Other risk factors that are frequently associated with VTE in children include (table 1) [35,36]:

●Age – The incidence of pediatric VTE according to age shows two peaks, one in infancy and the second in adolescence. The first peak reflects the increased risk of VTE in preterm infants, largely due to the presence of invasive catheters. (See "Neonatal thrombosis: Clinical features and diagnosis".)

●Infection – Children with severe systemic bacterial infections are at increased risk of developing VTE. This can occur with any pathogen, but it is particularly well described in meningococcal infections. (See "Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis" and "Clinical manifestations of meningococcal infection".)

VTE can also occur as a complication of systemic viral infections. This is particularly well described for coronavirus disease 2019 (COVID-19) [37]. (See "COVID-19: Hypercoagulability" and "COVID-19: Management in children", section on 'Supportive care for all patients'.)

●Malignancy – VTE can occur as a complication of any pediatric malignancy. VTE is particularly common in children with acute lymphoblastic leukemia who are treated with asparaginase. This is discussed separately. (See "Thromboembolism in children with cancer" and "Treatment of acute lymphoblastic leukemia/lymphoma in children and adolescents", section on 'Induction chemotherapy'.)

●Congenital heart disease – The risk is VTE is particularly high in patients with single-ventricle physiology and those who have undergone surgical repair involving placement of a conduit or prosthetic valve. (See "Management of complications in patients with Fontan circulation", section on 'Thrombosis' and "Antithrombotic therapy for mechanical heart valves".)

●Trauma – The risk of VTE increases following major traumatic injury; however, the risk in children is substantially lower compared with adult trauma patients. In reports from large trauma registries and administrative databases, the rates of VTE in pediatric trauma patients were quite low (0.03 to 0.4 percent); however, these studies may underestimate the true incidence [38,39]. In one study of 1934 pediatric patients managed at a level I trauma center, VTE occurred in 1.2 percent [40]. The risk was highest among patients with a major vascular injury (14 percent) and those requiring orthopedic surgery (5 percent). (See "Venous thromboembolism risk and prevention in the severely injured trauma patient", section on 'Risk factors'.)

●Estrogen-containing contraceptives – The risk of VTE associated with estrogen-containing contraceptives is discussed separately. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Venous thromboembolism'.)

●Nephrotic syndrome – The risk of thrombosis in children with nephrotic syndrome is discussed separately. (See "Complications of nephrotic syndrome in children", section on 'Thromboembolism'.)

●Inflammatory bowel disease (IBD) – Patients with IBD have an approximately two- to threefold higher risk of VTE compared with individuals without IBD, and the risk increases substantially during disease flares [41,42]. This is discussed in greater detail separately. (See "Clinical manifestations and complications of inflammatory bowel disease in children and adolescents", section on 'Venous thromboembolism'.)

●Systemic lupus erythematosus and antiphospholipid syndrome – The risk of thrombosis in children with systemic lupus erythematosus and antiphospholipid syndrome is discussed separately. (See "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis", section on 'Thromboembolic' and "Clinical manifestations of antiphospholipid syndrome".)

●Vascular abnormalities – Certain vascular malformations and anatomic abnormalities carry an increased risk of thrombosis (eg, May-Thurner syndrome, Paget-Schroetter syndrome/thoracic outlet syndrome, inferior vena cava atresia). (See "May-Thurner syndrome" and "Primary (spontaneous) upper extremity deep vein thrombosis".)

●Other risk factors in hospitalized patients – Additional risk factors may be considered in determining the need for thromboprophylaxis in hospitalized patients (eg, prolonged immobility, critical illness, duration of mechanical ventilation). This is discussed separately. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Primary prophylaxis'.)

These risk factors are characterized by either a protein-losing state, inflammatory state, or vascular disruption, which are consistent with Virchow's triad describing VTE risk. (See "Overview of the causes of venous thrombosis", section on 'Virchow triad'.)

CLINICAL MANIFESTATIONS — Clinical manifestations of VTE in children vary, depending on the location of the thrombus and degree of vessel occlusion.

Central venous line — Central venous catheter (CVC)-related VTE can present with any of the following [43-49]:

●Asymptomatic (most cases)

●Repeated loss of CVC patency

●CVC-related sepsis

●Swelling and discoloration of the related limb

●Facial swelling and other signs of superior vena cava syndrome

●Prominent collateral circulation in the skin over the chest, back, neck, and face

●Pulmonary embolism (PE)

●Stroke (in children with right-to-left cardiac shunting)

●Chylothorax

In a systematic review of 16 cohort studies, which included 1279 children with CVCs, approximately 20 percent of patients had at least one documented VTE, most of which (75 percent) were asymptomatic [26].

Deep vein thrombosis — Clinical manifestations of deep vein thrombosis (DVT) vary depending on the location. Non-CVC-related DVT can occur in any venous system but most commonly present in the lower extremities, especially in the iliac, femoral, and/or popliteal veins.

●Lower extremity DVT – Lower extremity DVT manifests with unilateral leg, buttock, inguinal, and/or abdominal pain associated with swelling and/or reddish or purple discoloration of the legs. Larger calf diameter in the affected leg compared with the contralateral leg may also be noted. Homans' sign (calf pain on passive dorsiflexion of the foot) is unreliable for signaling the presence of DVT in children [50].

●Upper extremity DVT – Outside of the setting of CVC-related VTE, upper extremity DVT is rare in children. Upper extremity DVT manifests with unilateral swelling and discoloration of the arm and hand [50]. Swelling of the face may be noted if the thrombus extends into the superior vena cava. Patients may complain of pain in the affected arm and/or discomfort in the neck, shoulder, or axilla. Effort-related upper extremity DVT (Paget-Schroetter syndrome) is a rare condition that typically affects young, healthy individuals, most commonly males [51]. It is discussed in greater detail separately. (See "Primary (spontaneous) upper extremity deep vein thrombosis".)

Pulmonary embolism — PE is rare in children but should be considered in the differential diagnosis of cardiorespiratory deterioration in critically ill children [52-54]. PE can manifest with pleuritic chest pain, tachypnea, cough, tachycardia, acute dyspnea, hypoxia, and sudden collapse. Clinical signs of DVT may also be present. Most commonly, however, the clinical manifestations of PE in children, especially young children, are nonspecific and often mimic the clinical symptoms of the underlying disease. (See "Causes of acute respiratory distress in children".)

Though PE is rare in children, its reported incidence has increased since the early 2000s [7]. It is uncertain whether the increase represents a true increase in the frequency of PE or an increase in the detection of PE. (See 'Incidence' above.)

Commonly reported risk factors for PE in children include presence of a CVC, trauma, immobility, recent surgery, use of estrogen-containing contraceptives, inflammatory conditions, malignancy, heart disease, dehydration, and obesity [7,55-59].

The majority of PEs in children are nonmassive (ie, without any hemodynamic effects). In one study of 170 children with PE, 71 percent were nonmassive and 29 percent were massive or submassive [60]. Compared with patients with nonmassive PE, those with massive or submassive PE were somewhat younger (median age 12.5 versus 14.4 years) and more likely to have a CVC (59 versus 40 percent) or underlying cardiac condition (33 versus 14 percent). There were 11 PE-related deaths in this cohort (6 percent), all of which occurred in patients with massive or submassive PE.

Other venous thrombosis

●Renal vein thrombosis (RVT) - In children, RVT most commonly occurs secondary to nephrotic syndrome and renal transplantation [61-63]. The author of this topic review has also seen RVT as the presenting manifestation of systemic lupus erythematosus; however, this is uncommon [64]. (See "Complications of nephrotic syndrome in children", section on 'Thromboembolism' and "Kidney transplantation in children: Complications", section on 'Vascular thrombosis' and "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'Clinical manifestations'.)

RVT most often has an insidious onset and produces no symptoms referable to the kidney. In this case, the RVT may first come to attention when the patient presents with a complication resulting from extension or embolism (eg, PE or symptomatic lower extremity DVT if the thrombus extends into the inferior vena cava). When findings referable to the kidney are present, they may include hematuria, proteinuria, anuria, and vomiting. (See "Renal vein thrombosis in adults", section on 'Clinical features'.)

In neonates, RVT is the most prevalent non-catheter-related VTE, accounting for approximately 10 percent of all thromboembolic events in newborns [65]. RVT in neonates is discussed separately. (See "Neonatal thrombosis: Clinical features and diagnosis", section on 'Renal vein thrombosis'.)

●Portal vein thrombosis (PVT) - Children may develop PVT secondary to liver transplantation, infections, splenectomy, sickle cell disease, chemotherapy, or antiphospholipid syndrome [66-71]. PVT may manifest acutely with symptoms of an acute abdomen, particularly in adolescents [72], or may be asymptomatic for long periods of time until symptoms reflecting chronic portal hypertension occur (eg, splenomegaly or gastrointestinal bleeding secondary to esophageal varices) [73]. (See "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management".)

In neonates, PVT is most often related to umbilical catheterization and sepsis [74]. Neonatal PVT is discussed in a separate topic review. (See "Neonatal thrombosis: Clinical features and diagnosis", section on 'Portal vein thrombosis'.)

●Cerebral venous thrombosis – Cerebral venous thrombosis is discussed separately. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".)

DIAGNOSIS — Ultrasonography is the preferred initial diagnostic study in most children with suspected venous thrombosis. Noncompressibility of the vein with or without visible intraluminal thrombus confirms the diagnosis. Alternative imaging modalities are available (eg, contrast venography, contrast magnetic resonance venography [MRV], computed tomography [CT] venography); however, they are rarely necessary. The exception is suspected pulmonary embolism (PE), for which CT pulmonary angiography (CTPA) is the imaging modality of choice.

Duplex ultrasonography is the preferred initial test because it is noninvasive, readily available, does not require sedation, and does not expose the child to ionizing radiation. Though data are limited in children, studies in adults indicate that compression ultrasonography has an acceptable sensitivity and specificity for the diagnosis of venous thrombosis. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Diagnostic ultrasonography suspected first DVT' and "Catheter-related upper extremity venous thrombosis in adults", section on 'Duplex ultrasonography'.)

The diagnostic approach varies somewhat depending on the location of the suspected thrombus [75]:

●Catheter-associated thrombosis – Patients with signs or symptoms of large vessel thrombosis (eg, swelling and/or discoloration of the related limb) should be evaluated with duplex ultrasound. For mechanical catheter problems, instillation of intravenous contrast into the lumen of the catheter under fluoroscopy may readily demonstrate the presence of thrombus at the tip of the catheter. (See "Catheter-related upper extremity venous thrombosis in adults".)

●Lower extremity – Compression ultrasonography is recommended for initial evaluation of deep vein thrombosis (DVT) in the lower extremities. If ultrasonography is normal and the clinical suspicion of DVT remains high, the study can be repeated after a week [75]. In children with suspected proximal extension of femoral DVT, MRV is the appropriate diagnostic study. CT is a reasonable choice if MRV is not available; however, CT has the disadvantage of exposing the child to radiation.

●Upper extremity – The initial assessment of the peripheral upper extremity, axillary, subclavian, and internal jugular veins should be performed with ultrasonography; however, this modality may be relatively insensitive for detection of central intrathoracic VTE. Ultrasonography can yield false-negative results due to the position of the clavicles (which hinder the view of the distal subclavian veins) and the thoracic cage (which hinders compression of veins in a central location) [76]. Assessment of the central veins for VTE can be performed using MRV, CT, or contrast venography; we prefer MRV because it does not expose the child to radiation.

In patients with non-catheter-related upper extremity DVT, a diagnosis of thoracic outlet syndrome (also referred to as Paget-Schroetter syndrome or "effort" thrombosis) should be considered. Establishing this diagnosis may require specialized imaging techniques, as discussed in detail separately. (See "Primary (spontaneous) upper extremity deep vein thrombosis".)

●PE – CTPA is the imaging modality of choice for diagnosis of PE in children [77]. Clinical tools commonly used in adult patients to assess the pretest probability of PE (eg, Wells score and D-dimer measurements) do not appear to perform well in children [55,56]. In a retrospective cohort study, D-dimer and Wells score were not useful in discriminating between children with versus without radiographically confirmed PE [56].

Other imaging studies that are sometimes used in the evaluation for PE include ventilation perfusion scans and magnetic resonance pulmonary angiography. Use of these modalities is generally limited to instances in which CTPA is contraindicated, not available, or inconclusive. These modalities have the advantage of avoiding ionizing radiation; however, they are more time-consuming and young children generally require sedation.

Echocardiography can be useful to provide support for the diagnosis of PE and to provide prognostic information (eg, it may demonstrate right ventricular strain, which is an indicator of poor prognosis). However, it is insensitive and nonspecific for diagnosing PE since many patients with PE have normal echocardiography and because right ventricular strain can be seen in many other conditions. (See "Echocardiographic assessment of the right heart".)

The diagnosis of PE in adult patients is discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

THROMBOPHILIA TESTING — Once the diagnosis of VTE has been made, it may be appropriate to test for underlying inherited or acquired thrombophilias. The utility of thrombophilia testing depends on the clinical circumstance. Thrombophilia testing is generally not warranted in patients presenting with a first episode of VTE associated with a central venous catheter (CVC). Our approach to thrombophilia testing is summarized in the algorithm (algorithm 1) and discussed in greater detail separately. (See "Thrombophilia testing in children and adolescents".)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of VTE depends on the location of the thrombus:

●Deep vein thrombosis (DVT) – Mimics of upper or lower extremity DVT include other conditions that present with swelling, erythema/discoloration, and tenderness of the extremity:

•Baker's cyst (see "Popliteal (Baker's) cyst")

•Cellulitis (see "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis")

•Musculoskeletal injury (see "Calf injuries not involving the Achilles tendon" and "Approach to acute knee pain and injury in children and skeletally immature adolescents")

•Lymphangitis or lymph obstruction (see "Lymphangitis")

•Superficial thrombophlebitis (see "Superficial vein thrombosis and phlebitis of the lower extremity veins")

The history and physical examination findings can often distinguish DVT from these conditions, though ultrasonography is ultimately required to make the diagnosis.

●Pulmonary embolus (PE) – The differential diagnosis of PE in children includes other entities that present with chest pain (table 3), dyspnea, and hypoxia. The approach to children with these complaints is reviewed separately. (See "Causes of nontraumatic chest pain in children and adolescents" and "Causes of acute respiratory distress in children" and "Approach to cyanosis in children".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Thrombotic diseases in infants and children".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Venous thrombosis and thromboembolism (VTE; including venous thrombosis and pulmonary embolism [PE]) are relatively uncommon in children, with an estimated annual incidence of approximately 0.2 per 10,000 children. Rates of VTE are highest among children with underlying medical conditions, such as malignancy and cardiac disease. The risk of VTE is substantially lower in children compared with adults because several protective factors are present during childhood. (See 'Incidence' above and 'Risk of VTE in children versus adults' above.)

●Risk factors for VTE – Important risk factors for VTE in pediatric patients include (table 1) (see 'Risk factors' above):

•Central venous catheters (CVCs) – In children, approximately one- to two-thirds of VTEs are associated with the use of CVCs. Indwelling CVCs are thrombogenic because they present a foreign intravascular surface, damage vessel walls, and disrupt blood flow. (See 'Central venous access devices' above.)

•Inherited thrombophilia (IT) – The association between IT and VTE in children is less well established than in adults. In children with VTE, the reported prevalence of IT ranges from 10 to 60 percent. The most common IT disorders include factor V Leiden; prothrombin G20210A mutation; and deficiencies of antithrombin, protein C, and protein S. The approach to testing for IT in children who have had a VTE episode is summarized in the algorithm (algorithm 1) and discussed separately. (See "Thrombophilia testing in children and adolescents", section on 'Children with venous thromboembolism'.)

•Other conditions – Other conditions that are associated with increased VTE risk in children include infection, malignancy, congenital heart disease, trauma, surgery (particularly cardiac and orthopedic surgery), obesity, estrogen-containing contraceptives, protein-losing conditions (eg, nephrotic syndrome, inflammatory bowel disease [IBD]), and autoimmune conditions (eg, systemic lupus erythematosus). (See 'Other risk factors' above.)

●Clinical manifestations – Clinical manifestations of VTE in children depend on the location of the thrombus and degree of vessel occlusion (see 'Clinical manifestations' above):

•CVC-related VTE – CVC-related VTEs are usually asymptomatic. When symptoms are present, they may include (see 'Central venous line' above):

-Repeated loss of CVC patency

-CVC-related sepsis, swelling, and discoloration of the related limb

-Facial swelling and other symptoms of superior vena cava syndrome

-Prominent collateral circulation in the skin over the chest, back, neck, and face

-PE

-Stroke (in patients with right-to-left cardiac shunt)

-Chylothorax

•Deep vein thrombosis (DVT) – Non-CVC-related DVTs can occur in any venous system but most commonly present in the lower extremities, especially in the iliac, femoral, and/or popliteal veins. VTE in the lower extremities manifests with leg, buttock, inguinal, and/or abdominal pain associated with swelling and reddish or purple discoloration of the legs. (See 'Deep vein thrombosis' above.)

•PE – The clinical manifestations of PE can manifest with pleuritic chest pain, tachypnea, cough, tachycardia, acute dyspnea, hypoxia, and sudden collapse. A high index of clinical suspicion is warranted in children with risk factors for PE, including obesity, contraceptive use, trauma, CVC, and immobility. (See 'Pulmonary embolism' above.)

●Diagnosis – Ultrasonography is the preferred initial diagnostic study in most children with suspected venous thrombosis. Noncompressibility of the vein with or without visible intraluminal thrombus confirms the diagnosis. Alternative imaging modalities are available (eg, contrast venography, contrast magnetic resonance venography [MRV], computed tomography [CT] venography); however, they are rarely necessary. CT pulmonary angiography (CTPA) is the imaging modality of choice for diagnosis of PE in children. (See 'Diagnosis' above.)

●Differential diagnosis – The differential diagnosis of VTE depends on the location of the thrombus. Mimics of upper or lower extremity DVT include other conditions that present with swelling, erythema/discoloration, and tenderness of the extremity (eg, Baker's cyst, cellulitis, musculoskeletal injury, lymphangitis, and superficial thrombophlebitis). The differential diagnosis of PE in children includes other entities that present with chest pain (table 3), dyspnea, and hypoxia. (See 'Differential diagnosis' above.)