2026 中国循证专家共识：儿童肺栓塞的管理

Abstract

Background Pulmonary thromboembolism is rare in children, but can be life-threatening. Timely diagnosis and treatment of pulmonary thromboembolism are crucial for reducing mortality associated with pulmonary thromboembolism in children. While guidelines for pulmonary thromboembolism in adults are available, guidelines for standardized diagnosis and management of pulmonary thromboembolism in children are not. This expert consensus aims to provide recommendations for the management of pulmonary thromboembolism in children based on the current best available evidence.

Data sources Following the World Health Organization Handbook for Guideline Development, the expert panel consisted of 30 members from different clinical areas. The panel identified clinical questions through systematic reviews and expert discussions, systematically reviewed evidence on pulmonary thromboembolism in children, and evaluated the quality of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Using the GRADE Evidence to Decision Framework, the panel made recommendations, considering the effects of interventions, resource use, values and preferences, equity, acceptability, and feasibility.

Results The epidemiology, classification, and pathophysiology characteristics are summarized. The expert panel developed 33 recommendations addressing 20 questions related to diagnosis steps, treatment approaches such as anticoagulant therapy, thrombolysis therapy, catheter-based interventional therapy, surgical embolectomy, multidisciplinary team, and treatment of patients with comorbidities, prognosis, education, as well as follow-up. Among these, 18 are weak recommendations based on very low quality evidence, and 15 are good practice statements.

Conclusions The expert panel provided recommendations for pulmonary thromboembolism in children based on available evidence, which was generally low in quality and volume. The panel urges further research on early identification and diagnosis strategies, preventive and therapeutic regimens, and long-term management for pulmonary thromboembolism.

World Journal of Pediatrics

Graphical abstract

# Management of pulmonary thromboembolism (PTE) in children: an evidence-based expert consensus

Background

$\bullet$ Pediatric PTE is rare but life-threatening $\bullet$ Timely diagnosis and treatment is essential $\bullet$ Pediatric guidelines or consensus are lacking

![graph TD\n A1[Data sources] --> A2[Systematic reviews]\n A1 --> A3[Expert discussions]\n A2 --> A4[Identified clinical questions]\n A2 --> A5[Systematically reviewed evidence]\n A2 --> A6[Evaluated evidence quality]\n A2 --> A7[Made recommendations]\n A4 --> A5\n A5 --> A6\n A6 --> A7\n A8[Results] --> A9[Diagnosis]\n A8 --> A10[Treatment]\n A8 --> A11[Prevention]\n A8 --> A12[Prognosis]\n A8 --> A13[Education]\n A8 --> A14[Follow-up]\n A9 --> A18[Anticoagulant therapy]\n A10 --> A19[Thrombolysis therapy]\n A11 --> A20[Catheeter-based interventional therapy]\n A12 --> A21[Surgical embolctomy]\n A13 --> A22[Treatment of patients with comorbidities]\n A14 --> A23[Other supportive treatments]\n A15[33 recommendations] --> A16[Establishment of a PERT]\n](1/parseimages/figure0e2e82ea3935432c944941fa9337a167_0_5.png) $\bullet$ Recommendations for pediatric PTE are provided despite low-quality evidence $\bullet$ Call for further research: early diagnosis, prevention, therapy, long-term management

Keywords Children · Diagnosis · Expert consensus · Management · Pulmonary thromboembolism · Treatment

Introduction

Pulmonary thromboembolism (PTE) is a cardiovascular condition caused by a thrombus obstructing the pulmonary artery or its branches [1]. PTE is rare in children, but can be life-threatening. Timely diagnosis and treatment of PTE are crucial for reducing mortality associated with PTE in children [2]. While guidelines for PTE in adults are available [3, 4], guidelines for the standardized diagnosis and management of PTE in children are not. This expert consensus aims to provide recommendations for the diagnosis and management (including treatment, assessment of prognosis, patient education, and follow-up) of children (<18 years of age) with PTE.

Data sources

The expert panel is composed of 30 members including content experts in pediatric respiratory, infection, hematology, critical care, cardiology, surgery, laboratory medicine, medical imaging, nursing, pharmacy, and methodologists (Supplementary material 1). We registered this evidence-based expert consensus in the Practice guideline REGistration for transPAREncy registry (registration number: PRE-PARE-2023CN922). The development and report followed the World Health Organization Handbook for Guideline Development [5], the Appraisal of Guidelines for Research and Evaluation II [6] and the Reporting Items for Practice Guidelines in Healthcare [7].

Through a systematic search of existing guidelines, systematic reviews, and original studies related to PTE in adults and children along with formal discussions, the expert panel identified 20 clinical questions. The systematic review team conducted systematic reviews to address these clinical questions and will report the detailed methodology and results in separate publications [8, 9]. The expert panel conducted an online consultation questionnaire to assess patient preferences regarding specific interventions, integrating insights from clinical practice experience.

Following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) framework, the expert panel formulated recommendations. The panel categorized the strength of recommendations as strong and weak [10]. In the absence of evidence from current studies and based on experience from the expert panel, good practice statements were developed [11].

# Overview of pulmonary thromboembolism

Definition

Pulmonary embolism (PE) refers to a group of diseases or clinical syndromes characterized by obstruction of the

World Journal of Pediatrics

pulmonary artery or its branches by various types of emboli [1]. PTE is the most common type of acute PE, caused by thrombosis originating from the venous system, the right heart chambers, or in situ within the pulmonary arterial system; this leads to obstruction of the pulmonary artery or its branches. The main pathophysiological features and clinical manifestations of PTE are pulmonary circulatory and respiratory dysfunction [12]. PTE accounts for more than 90% of PE [13]. Non-thrombotic PE is defined as the partial or total occlusion of the pulmonary circulation caused by different non-thrombotic embolic agents. These include cells (such as adipocytes, hematopoietic, amniotic, trophoblastic, or tumor cells), bacteria, fungi, parasites, foreign material, or gas [14]. PTE and deep venous thromboembolism (DVT) are collectively referred to as venous thromboembolism (VTE), as they share the same predisposing factors and represent two clinical manifestations of VTE at different sites and stages [1].

Epidemiology

Studies of children with PTE in the United States reported a prevalence of about 23 per 100,000 [15, 16], with two peaks occurring < 1 year old and > 15 years old [17–19]. Studies from the United States, Korea, and England revealed an increasing trend of PTE in children over the past decades [2, 20, 21]. The mortality rate of children with PTE was about 11.7% on average but with large variations between different countries [15, 16, 18, 22–24].

Risk factors for PTE in children can be categorized into hereditary and acquired. Hereditary factors include family history of VTE [23], specific gene mutations (i.e., V Leiden G1691A and G20210A gene mutations), congenital heart disease, elevated levels of human coagulation factors VIII/IX, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia, and positive for antiphospholipid antibodies [25]. Acquired factors include immobility, surgery, central or deep vein catheterization, history of VTE, obesity, heart disease, tumor, trauma, and infection. Some additional potential risk factors include a hypercoagulable state, pulmonary disease, vascular malformation, congestive heart failure, use of psycho-tropic medications, use of oral contraceptives [26], chemother-apy, shunted hydrocephalus, dehydration, shock [27], nephrotic syndrome [24] and dermatomyositis [19].

Classification

Based on classification criteria of PTE used in adults coupled with the experience of diagnosing PTE in children, the expert panel recommended the following classification

for PTE in children: (1) based on time of onset, PTE can be categorized into acute and chronic PTE. Acute PTE is mainly characterized by the sudden onset of pulmonary hypertension with hypoxemia, typically lasting no longer than six months [3]. Suspected acute PTE or acute exacerbation of chronic PTE is when pulmonary arterial pressure exceeds 40 mmHg [3]. Chronic PTE is defined as abnormal pulmonary blood flow distribution and pulmonary circulation hemodynamics that persist for ≥ 6 months without substantial improvement [28]. (2) Based on thrombus source, PTE can be categorized as PTE from the inferior vena cava pathway, PTE from the superior vena cava pathway, PTE from the right heart cavity, and PTE from the in-situ thrombus [12]. Most thrombi originate from deep veins of the lower extremities; thrombus from the right heart cavity or in-situ thrombus accounted for a smaller proportion. However, thrombi from the superior vena cava pathway have increased. This is mainly related to an increase in intraventricular chemotherapy in the internal jugular vein and subclavian vein catheterization, periph-ally inserted central venous catheters, or medium- and long-term catheters for intravenous chemotherapy [12]. (3) Based on pathogenesis, PTE can be categorized as idiopathic, secondary, and recurrent. (4) Based on the risk of pulmonary circulatory and respiratory dysfunction, PTE can be categorized as high-risk PTE, intermediate-risk PTE, and low-risk PTE [29, 30] (Table 1).

Pathophysiology

Thrombosis

Factors such as stagnant venous blood flow, vascular endothelial damage, and blood hypercoagulability contribute to the formation of thrombosis. Thrombi originating from the peripheral venous system may detach and migrate to the pulmonary artery, leading to PTE. In addition, focal inflammation and endothelial dysfunction of the pulmonary vasculature caused by pulmonary infectious diseases, pulmonary trauma, or pulmonary vasculitis can result in in-situ pulmonary thrombosis [31]. In recent years, the incidence of severe Mycoplasma pneumoniae (MP) pneumonia in children has increased. Moreover, the combination of MP pneumonia with PTE is more frequently reported [15, 32]. Thrombosis in these cases may be associated with direct MP invasion, indirect immune-mediated injury, vasculitis, and hypercoagulability [31].

Increased pulmonary vascular resistance and cardiac insufficiency

At the onset of PTE, thromboembolic obstruction of the pulmonary arterial bed can lead to increased pulmonary arterial

World Journal of Pediatrics

pressure. Anatomical obstruction with hypoxic vasoconstriction results in elevated pulmonary vascular resistance and reduced arterial compliance [1, 4, 12]. Increased pulmonary vascular resistance causes right ventricle (RV) dilatation, which impairs myocardial contractile properties. Elevated atrial pressure and volume increase ventricular wall tension and stretch cardiomyocytes. Prolonged atrial contraction, neurohumoral activation, and systemic vasoconstriction temporarily elevate pulmonary arterial pressure to stabilize systemic blood pressure. However, when RV diastolic pressure exceeds that of the left ventricle (LV), the interventricular septum deviates leftward, impairing LV filling. Meanwhile, reduced RV output results in diminished pulmonary venous return to the LV, further decreasing LV preload. These changes lead to compromised LV output, systemic hypotension, and shock [33].

Respiratory insufficiency

In the presence of hemodynamic instability, cardiac output decreases, leading to a reduction in mixed venous oxygen saturation. Pulmonary blood flow decreases at embolized sites while perfusion increases at unembolized sites, resulting in a ventilation-perfusion mismatch and ultimately hypoxemia. In about one-third of children, elevated right atrial pressure can cause reopening of the foramen ovale with subsequent right-to-left shunting, leading to severe hypoxemia. If the embolus occludes a small distal vessel, it may result in local hemorrhagic pulmonary atelectasis and alveolar hemorrhage, further impairing gas exchange [1, 4].

Chronic thromboembolic pulmonary hypertension

Following thromboembolic obstruction of the pulmonary artery, thrombus insolubility, organization, and pulmonary vascular remodeling can lead to vessel stenosis or occlusion. This results in increased pulmonary vascular resistance and a progressive rise in pulmonary arterial pressure, ultimately causing right ventricular hypertrophy and right heart failure, a condition known as chronic thromboembolic pulmonary hypertension (CTEPH).

Diagnosis of pulmonary thromboembolism

Question 1: What clinical manifestations should be suspected of pulmonary thromboembolism in children?

Recommendation

Symptoms in children: dyspnea or shortness of breath is the most common symptom. While dyspnea, chest pain,

and hemoptysis are the typical triad of pulmonary embo- lism, fewer than 30% of children present with this typical triad simultaneously. In addition, common symptoms in children include cough, syncope, tachycardia, and hypoxia. Other symptoms include fever, palpitations, other types of arrhythmias, and hypotension (very low quality, weak recommendation).

Physical signs in children: consider PTE when the following physical signs suddenly appear without apparent causes: (1) shortness of breath; (2) tachycardia; (3) changes in blood pressure or progression to shock; (4) cyanosis; (5) fever, mostly low; (6) jugular vein distension or pulsation; (7) wheezing and (or) moist rales on lung auscultation, occasionally with vascular murmurs; (8) corresponding signs of pleural effusions; (9) hyperactivity or splitting of the second heart sound at the pulmonary valve (P2 > A2), tricuspid systolic murmur (good practice statement).

Summary of the evidence

Clinical symptoms and physical signs of children with PTE are diverse and non-specific. Our meta-analysis showed that common clinical manifestations in children with PTE (including nonverbal children) are dyspnea, cough, chest pain, shortness of breath, and hemoptysis [15, 25, 34–42] (Supplementary Table S1). Nevertheless, the relatively small sample sizes for the typical triad, shortness of breath, and hemoptysis should be acknowledged, as this limitation may reduce the robustness of these findings.

Question 2: How can pulmonary thromboembolism be diagnosed initially in children?

Recommendation

Assess children with suspected PTE based on experience and clinical likelihood rating scales when available. For children with a high probability on clinical evaluation, a definitive diagnostic test may be considered. For those with a low clinical probability, D-dimer levels could be helpful. If the D-dimer level is below the thrombotic threshold, usually < 0.5 mg/L (fibrinogen equivalent units), acute PTE is less likely. If the D-dimer level is elevated, a definitive diagnostic test might be warranted (very low quality, weak recommendation).

Summary of the evidence

Studies on children with PTE demonstrated the poor sensitivity and specificity of existing clinical likelihood

World Journal of Pediatrics

|Classification|Definition| |---|---| |High-risk PTE|Persistent hypotension, defined as systolic blood pressure < the lower limit in the same age group (within 1 mon: < 60 mmHg; from 1 mon to 1 y old: < 70 mmHg; from 1 y old to 10 y old: < 70 + (age×2) mmHg; over 10 y old: < 90 mmHg) or need for vasoactive drug support or pulselessness or sustained heart rate < 60 beats/min with signs/ symptoms of shock or compensated (normotensive) shock| |Intermediate-risk PTE|Systolic blood pressure > the low limit in the same age group, but right ventricular dysfunction or myocardial necrosis, manifested by any of the following: right ventricular dilatation (echocardiogram or CT); echocardiography shows right ventricular systolic dysfunction; elevated troponin| |Low-risk PTE|Acute PTE and lack of clinical signs, symptoms and biomarkers defined as high- or intermediate-risk PTE|

PTE pulmonary thromboembolism, CT computer tomography

The original source of the classification can be found in Refs [29, 30]

rating scales (i.e., pulmonary thrombosis exclusion criteria and pediatric thrombosis decision rules) for the diagnosis of PTE [25, 42, 43]. Evidence showed [44, 45] that the use of a clinical likelihood rating score combined with D-pimer testing reduced the rate of missed PTE diagnosis (Supplementary Table S2). It should also be acknowledged that current evidence supporting the use of clinical likelihood rating scores is derived from studies of PE in adults, and their diagnostic utility in children with PTE may therefore be limited. However, due to the potential for misdiagnosis in D-dimer testing [46-51] (Supplementary Table 3), the expert panel suggested caution when interpreting D-dimer results.

Question 3: How can pulmonary thromboembolism be definitively diagnosed in children?

Recommendation

Where condition permits, perform computed tomography pulmonary angiography (CTPA) to confirm or exclude the diagnosis of PTE (very low quality, weak recommendation).

For children with suspected PTE and hemodynamic instability, if CTPA is unavailable or inappropriate: (1) perform bedside echocardiography. If increased right ventricular load and/or thrombus in the pulmonary artery or right ventricle is detected, diagnose PTE after ruling out other potential diseases. (2) Perform limb compression venous ultrasound. Confirm PTE if evidence of DVT is found. Once the clinical condition stabilizes, perform relevant tests to clarify the consideration (very low quality, weak recommendation).

For children with suspected PTE and stable hemodynamics where CTPA is contraindicated (i.e., iodine contrast agent allergy and renal insufficiency), consider alternative imaging options, including pulmonary ventilation/perfusion (V/Q) imaging and magnetic resonance

pulmonary arteriography (MRPA) (very low quality, weak recommendation).

Summary of the evidence

The plain chest radiography, a commonly used first-line examination, offers limited value in diagnosing PTE. About 80% of children with PTE present with abnormal chest radiographic findings, while 12%–24% may have normal results. The most common abnormalities include right heart enlargement (27%), pleural effusion (23%), pulmonary atelectasis (18%), and pulmonary consolidation (17%). Given that these findings are non-specific, PTE should be considered after ruling out other potential diagnoses.

CTPA has become the preferred method for pulmonary angiography in children with suspected PTE due to its high diagnostic accuracy. However, the diagnostic threshold setting for CTPA can affect its sensitivity and specificity in children with PTE [52]. Based on current evidence, the expert panel recommended less than 22 Hounsfield Units (HU) as the diagnostic threshold (Supplementary Table 4). Clinicians should be cautious when clinical probability is inconsistent with CTPA findings. In children with low clinical suspicion of PTE, a negative CTPA can rule out PTE, whereas a positive result warrants further investigation (especially if the thrombus is confined to a segmental or subsegmental vessel). In children with high or intermediate clinical suspicion of PTE, CTPA can confirm the diagnosis if it shows partial or complete low-density filling defects in pulmonary vessels at or above the segment level, or complete filling defects with non-visible distal vasculature. Indirect signs such as high-density wedge-shaped bands or discoid atelectasis in the pulmonary field, central pulmonary artery dilatation, and reduced or absent distal vascular distribution may also suggest PTE. For cases involving single or distal subsegmental PTE, further confirmation should

World Journal of Pediatrics

involve lower extremity venous ultrasound, V/Q scanning, or pulmonary angiography.

No evidence supported the use of MRPA in children with PTE. However, studies conducted in adult patients with PTE demonstrated high sensitivity and specificity for MRPA [53] (Supplementary Table 5). Various MRPA techniques can be used to evaluate the pulmonary vasculature. Time-resolved enhancement techniques offer a speed advantage, making this particularly suitable for imaging children.

Similarly, no relevant evidence supported the use of ventilation-perfusion (V/Q) imaging in children with PTE. However, the expert panel agreed that V/Q imaging was an established and reliable diagnostic method with significant advantages. It is safe, rarely triggers allergic reactions, and involves much lower radiation exposure compared to CTPA. The panel recommended V/Q imaging for children older than six years who could cooperate with respiratory maneuvers. Diagnostic criteria for PTE on V/Q imaging include a mismatch between perfusion and ventilation images, where tracer distribution in the perfusion image is sparse or defective, while the ventilation image shows no abnormalities.

Treatment of pulmonary thromboembolism

Question 4: Should anticoagulation be administered for children with pulmonary thromboembolism?

Recommendation

Administer anticoagulant therapy to children with symptomatic PTE (very low quality, weak recommendation). For children with asymptomatic PTE, consider anticoagulant therapy based on individual clinical condition (good practice statement).

In cases where children with PTE are not initially receiving anticoagulant therapy and radiologic monitoring reveals progression of thrombosis without adequate control of risk factors, initiate anticoagulation alongside relevant laboratory test results (good practice statement).

Summary of the evidence

In children with symptomatic DVT or PTE, the evidence was primarily from single-arm studies, reporting 3.6% (2/55, number of events/number of patients) of mortality [18] and 0.9% of major bleeding [95% confidence interval (CI) 0.0%–5.9%] [54–59] in the anticoagulant therapy group (Supplementary Table 6). Studies in children with symptomatic or asymptomatic PTE are also single-arm and reported 0.3% of PTE exacerbation

(95% CI 0.0%–2.1%) [54, 55, 60] and 1.7% of VTE recurrence (95% CI 1.0%–2.5%) in the anticoagulant therapy group. Only two studies compared anticoagulation with no anticoagulation. A cross-sectional study found anticoagulation is associated with a higher risk of major bleeding [risk ratio (RR) 4.09, 95% CI 0.19–86.09] [56–59]; however, the power to detect differences between groups was low due to the small sample size. An randomized clinical trial (RCT) in adults with PTE found that the mortality or recurrence of VTE is lower in adults who were anticoagulated than in those who were not [1.85% (1/54) vs. 26.3% (5/19), RR 0.07, 95% CI 0.01–0.57] [51] (Supplementary Table 6).

For children with asymptomatic PTE, the evidence was primarily from single-arm studies, making it difficult to compare the benefits and harms between anticoagulant therapy and no treatment (Supplementary Table 7). As a result, the expert panel considered that the decision to use anticoagulant therapy should depend on clinical condition.

In cases of children with PTE who were not receiving anti-coagulant therapy, and in whom radiologic monitoring showed thrombosis extension, no evidence showed whether anticoagulation should be initiated. Considering that anticoagulants provided preventive and therapeutic benefits, and most children with PTE and indications for anticoagulation would consider the potential benefits to outweigh the potential harms, the expert panel recommended starting anticoagulant therapy based on laboratory test results.

Question 5: How to choose anticoagulant drugs for children with pulmonary thromboembolism?

Recommendation

In children with symptomatic PTE, consider low molecular weight heparin (LMWH), unfractionated heparin (UFH), or Vitamin K antagonists (VKA) (very low quality, weak recommendation).

In children with PTE who do not respond to these treatments, antithrombin replacement therapy may be considered; however, antithrombin replacement therapy should not be considered as the first-line treatment option (very low quality, weak recommendation).

Summary of the evidence

In children with DVT or PTE, an RCT indicated that LMWH might increase the risk of minor bleeding (defined in the context of the primary underlying disorder and what was "usually" expected, such as, but not exclusive to, bruising or oozing around intravenous sites and surgical wounds, small amounts of blood from suctioning endotracheal tubes, small amounts of blood in urine or stool, and minor nose bleeds)

World Journal of Pediatrics

and any other bleeding compared to other anticoagulants, such as UFH or warfarin [61]. However, studies found no significant differences in mortality, incidence of PTE or DVT, overall bleeding rates [62] or major bleeding rates [61] (Supplementary Table 8). However, for the evidence for children with PTE, the power to detect differences between groups was low due to the small sample size. Studies in adults with DVT or PTE, which can provide indirect evidence, similarly found no significant differences between UFH and LMWH in terms of PTE, VTE recurrence, bleeding, or mortality, while LMWH was less costly [56, 63–65] (Supplementary Table 8).

In children with DVT or PTE, there were no significant differences in mortality, PTE exacerbation, or the incidence of major bleeding between LMWH and VKA [61] (Supplementary Table 9), but the power to detect differences between groups was low due to the small sample size. The expert panel agreed that anticoagulant selection should be based on the severity and remission of PTE. Parenteral administration is preferred for acute resuscitation; newer oral anticoagulants such as rivaroxaban and dabigatran may be considered for remission and maintenance bridging [66–68].

In children with VTE, we only found one study that compared children with PTE treated with combined antithrombin therapy or standard anticoagulant therapy. This study has not been published and showed that combined antithrombin therapy increased the time to therapeutic anti-Xa, increased cost and increased bleeding (14.3% vs. 3.9%; P = 0.55) [60]. We included additional studies in our meta-analysis to provide indirect information for the use of combined antithrombin therapy [69–76] (Supplementary Table 10); however, the power was limited due to the indirectness. In terms of major bleeding, our meta-analysis of indirect evidence from RCTs in children found no significant difference between combined antithrombin therapy and standard anticoagulant therapy. However, our meta-analysis of cohort children studies showed that antithrombin therapy was associated with an increased rate of major bleeding [70, 74–77] (Supplementary Table 10).

Question 6: How to determine the course of anticoagulant therapy for children with pulmonary thromboembolism?

Recommendation

Continue anticoagulant therapy for 3–12 months in children with PTE. Adjust duration based on etiology, clinical presentation, and imaging findings (good practice statement). Children with idiopathic VTE should receive anti-coagulant therapy for 6–12 months (very low quality, weak

recommendation). For children with recurrent idiopathic VTE, extend the duration of anticoagulant therapy (good practice statement). In children with secondary VTE, anticoagulant therapy should continue for at least three months if the risk factors have been resolved. If reversible risk factors persist, therapy should extend beyond three months until those risk factors are eliminated (very low quality, weak recommendation). For children with recurrent secondary VTE, continue anticoagulant therapy for more than three months if reversible risk factors remain, until those factors are resolved (good practice statement).

Monitor medication and coagulation parameters regularly throughout the course of therapy for children with PTE (good practice statement).

Summary of the evidence

In children with idiopathic DVT or PTE, studies did not demonstrate significant differences in VTE recurrence rates with varying durations of anticoagulant therapy [78] (Supplementary Table 11), but the power to detect differences between groups was low due to the small sample size.

For children with recurrent idiopathic PTE, clinical evidence remains limited. The expert panel emphasized the importance of assessing the risks of recurrence and bleeding and suggested consideration of long-term anticoagulant therapy with regular follow-up when indicated.

In children with secondary DVT or PTE, a single-center cohort study failed to detect differences in recurrence rates across different durations of anticoagulant therapy [78] (Supplementary Table 12). For children treated with LMWH or VKA for 3–6 months, a six-month follow-up RCT reported a VTE recurrence rate of 7.9% (6/76), a major bleeding incidence of 9.2% (7/76), and a mortality rate of 6.6% (5/76) [79] (Supplementary Table 12), but the power to detect differences between groups was low due to the small sample size. Based on these findings, the expert panel concluded that anticoagulant therapy should be individualized for children according to treatment outcomes and risk factor assessments.

For children with recurrent secondary PTE, the evidence was insufficient. The expert panel agreed to focus on identifying the causes of recurrence, assessing the risk of recurrence and bleeding, and continuing anticoagulant therapy until the primary disease was resolved or stabilized.

Furthermore, the expert panel concurred that for children with PTE, medication monitoring should occur throughout anti-coagulant therapy. For children with PTE receiving warfarin, limited clinical studies, alongside in vitro studies, suggested that the intensity of anticoagulation should be lower than in adults. Based on adult data, pediatric patients on warfarin therapy should maintain an international normalized ratio (INR) of 2.5 [80, 81]. For children with PTE treated with UFH, adjust the dosage to achieve an anti-Xa activity level between 0.35 and

World Journal of Pediatrics

0.70 IU/mL, or an activated partial thromboplastin time (aPTT) range that correlates with this anti-Xa range, or alternatively, a protamine titration range of 0.2–0.4 U/mL [82]. For neonates and children receiving once- or twice-daily LMWH, target anti-Xa activity should range from 0.5 to 1.0 U/mL for samples taken 4–6 hours after subcutaneous injection or 0.5 to 0.8 U/mL in a sample taken 2–6 hours after subcutaneous injection [81]. For children with PTE receiving rivaroxaban, adjust the dosage according to age and weight to match an equivalent adult dose of 20 mg. For children with PTE under six months who take rivaroxaban three times daily, after 30 consecutive days of treatment, the prothrombin time should be 1.35 [standard deviation (SD) 0.20] times the baseline; the aPTT should be 1.31 (SD 0.15) times the baseline and the anti-Xa activity should measure 118.12 (SD 82.08) µg/L [68].

Question 7: Should thrombolytic therapy be administered for children with pulmonary thromboembolism?

Recommendation

Consider thrombolytic therapy for children with high-risk PTE (i.e., hemodynamically unstable) who have no contraindications to thrombolysis (very low quality, weak recommendation).

Thrombolysis in intermediate-risk PTE in children could not be assessed due to a lack of evidence.

Summary of the evidence

For children with high-risk PTE, a systematic review found no significant differences between the active treatment and observation groups in the incidence of all-cause hospital mortality, PE-related mortality, fatal major bleeding, or nonfatal major bleeding [23, 35, 82]; however, the power to detect differences between groups was low due to the small sample size (Supplementary Table 13). For children with intermediate-risk PTE, a systematic review found no significant differences between the thrombolytic therapy group and the anticoagulant only or none group for nonfatal major bleeding. The incidence of all-cause hospital mortality (0/13 vs. 4/20), PE-related mortality (0/13 vs. 2/20), fatal major bleeding (0/13 vs. 1/2), and CTEPH (0/13 vs. 2/20) may be lower in thrombolytic therapy, but the evidence is insufficient for the small number of children [23, 35, 82]; however, the power to detect differences between groups was low due to the small sample size (Supplementary Table 13). In one study which did not differentiate PTE risk categories, combined anticoagulation and thrombolytic therapy was associated with a higher rate of major bleeding when compared to the anticoagulation only or none group [18]; however, indication bias is likely significant in this cohort, and the power to detect differences between groups was low due to the small sample size.

For children with VTE (without risk level stratification), most of the included studies only focused on combined thrombolytic therapy. Only one cohort study found that thrombolytic therapy may be associated with a higher incidence of major bleeding (1/9 vs. 0/13) and a lower incidence of PTS (1/9 vs. 8/13) compared with the anticoagulant only or none group; however, the power to detect differences between groups was low due to the small sample size [83].

Moreover, our meta-analysis showed that the influence on all-cause mortality, DVT, post-thrombotic syndrome (PTS), and the incidence of major bleeding is unclear [84–95] (Supplementary Table 13). Two cross-sectional studies reported outcomes in 14 children with PTE who underwent thrombolytic therapy, of whom three required additional interventions; seven experienced major bleeding; three died, and one developed pulmonary hypertension [18, 96] (Supplementary Table 13).

In the survey of preference of the expert panel, the expert panel concluded that most children with PTE and indications for thrombolytic therapy's potential benefits should outweigh the potential harms, and most children would prefer to receive thrombolytic therapy.

Question 8: How to select thrombolytic drugs for children with pulmonary thromboembolism with indications for thrombolysis?

Recommendation

For children with PTE, use tissue-type plasminogen activator (tPA) as the preferred agent for thrombolytic therapy. Consider urokinase and streptokinase as potential alternatives (good practice statement).

Summary of the evidence

Clinical research on the selection of thrombolytic agents for children with PTE remained limited. However, based on expert consensus, the panel agreed that tPA was the preferred thrombolytic agent due to its favorable balance of efficacy and safety. Urokinase and streptokinase were potential alternatives. The most commonly reported dosing regimen for tPA was 0.1–0.6 mg/kg/hour, with dosage reassessment typically conducted after six hours [80].

Question 9: Should catheter-based interventional therapy be considered for children with pulmonary thromboembolism?

Recommendation

Consider percutaneous catheter-based interventional therapy (i.e., catheter-directed thrombolysis or catheter-based thrombus aspiration) as an alternative to thrombolysis for

World Journal of Pediatrics

high-risk children with thrombus present in the pulmonary artery trunk or major branches and for those with a high risk of bleeding, contraindications to thrombolysis, or failure of thrombolysis or aggressive medical therapy (very low quality, weak recommendation).

For children with low-risk PTE, catheter-based interventions are generally not recommended. Instead, consider catheter-directed thrombolysis or catheter embolectomy based on factors such as vital signs, gas exchange, and the presence of contraindications (good practice statement).

Catheter-based interventional therapy in intermediate-risk PTE in children could not be assessed due to a lack of evidence.

Summary of the evidence

In children with PTE, a case series showed that catheter-directed thrombolysis could alleviate clinical symptoms with no reports of mortality, bleeding, or CTEPH. In children with high-risk PTE, our meta-analysis of two cohort studies showed no differences in all-cause hospital mortality and PE-related mortality between catheter-directed thrombolysis and systemic thrombolysis, and no fatal major bleeding, nonfatal major bleeding, or CTEPH occurred in catheter-directed thrombolysis; however, the power to detect differences between groups was low due to the small sample size (Supplementary Table 14). In children with intermediate-risk PTE, our meta-analysis found that no death, fatal major bleeding, nonfatal major bleeding, or CTEPH occurred in catheter-directed thrombolysis; however, the power to detect differences between groups was low due to the small sample size (Supplementary Table 14). In adults with PTE, several studies have also demonstrated that catheter-directed thrombolysis could effectively relieve clinical symptoms with a relatively low incidence of adverse events such as bleeding and death [18, 85, 88, 89, 97–100]; however, indication bias is likely significant in these studies (Supplementary Table 15). Due to a lack of clinical evidence on catheter embolectomy in children, the expert panel based its recommendations on clinical experience and expert consensus.

Question 10: Should surgical embolectomy be performed for children with pulmonary thromboembolism?

Recommendation

Consider surgical embolectomy for children with high-risk PTE under the following circumstances: (1) Treatment: failed or contraindicated anticoagulant or thrombolytic therapy. (2) Age: neonates or premature infants, in whom anticoagulant and thrombolytic therapy may carry an elevated risk

of bleeding. (3) Specific pulmonary anatomy: PTE occurring after palliative surgeries (such as the Blalock-Taussig shunt or Fontan procedure) in children with single ventricles. (4) Embolus characteristics: tumorous embolism or embolism accompanied by right ventricular thrombus (very low quality, weak recommendation).

Surgical embolectomy in intermediate-risk PTE in children could not be assessed due to a lack of evidence.

Summary of the evidence

Our pooled analysis included four case studies that involved eight children; seven underwent surgical embolectomy, of which four had PTE after palliative surgery (Fontan procedure) [101]; one with tumorous embolism [102], one with failure of anticoagulant or thrombolytic therapy [103] and one premature infant with a high risk of intracranial hemorrhage [104] (Supplementary Table 16).

A case-control study included five children, and one underwent surgical embolectomy due to failure of anticoagulant or thrombolytic therapy [105] (Supplementary Table 16).

Our pooled analysis included two cohort studies that included 87 children; seven underwent surgical embolectomy, of which five had tumorous embolism [23] and two had intracranial hemorrhage [18] (Supplementary Table 16).

However, the power of evidence was low due to the small sample size of the above studies.

In the survey of reference of expert panel, the panel agreed that most children with PTE with indications for surgical embolectomy would consider the potential benefits to outweigh the potential harms and that most children would prefer to receive surgical embolectomy.

Question 11: What other supportive treatments should be considered for children with pulmonary thromboembolism?

Recommendation

Provide appropriate respiratory and circulatory management for children with PTE (very low quality, weak recommendation).

Summary of the evidence

Limited evidence exists on respiratory and circulatory management in children with PTE. According to relevant guidelines for adults with PTE [106], respiratory management should include oxygen therapy and low tidal volume ventilation. For circulatory management, the primary focus should center on supporting blood pressure and adequate perfusion. Consider vasoactive agents as needed.

World Journal of Pediatrics

Question 12: Should a pulmonary embolism response team be established for children with acute pulmonary thromboembolism?

Recommendation

Consider the establishment of a pulmonary embolism response team (PERT) to manage acute PTE (very low quality, weak recommendation).

Summary of the evidence

A PERT typically comprises a multidisciplinary team involving various clinical specialties, such as emergency medicine, cardiology, respiratory medicine, cardiovascular surgery, critical care medicine, pharmacy, and radiology [107, 108]. The team is responsible for the initial assessment, diagnosis, treatment, outpatient care, and follow-up of patients with PTE [109].

One cohort study compared the health outcomes of children with PTE before and after PERT [108]. This study has shown that a PERT may increase the proportion of children who are eligible and receive reperfusion, shorten the time to echocardiogram, time to anticoagulation, and time to anti-coagulation order. Furthermore, there were consistently no significant differences in major bleeding rates or PE-related mortality. However, the power to detect differences between groups was low due to the small sample size.

In adults with PTE, cohort studies showed that the establishment of a PERT could increase the proportion of patients receiving advanced treatment, such as catheter-directed therapies [109] and improve reperfusion rates. In addition, PERT could shorten intensive care unit stay [110], triage-to-diagnosis time, diagnosis-to-treatment time, and diagnosis-to-reperfusion time [111]. Despite these benefits, no significant differences were consistently observed in major bleeding rates, overall mortality [109] or 30-day rehospitalization risk [112]. Findings on the impact of PERT on major bleeding rates, mortality, or in-hospital mortality were inconsistent among studies (Supplementary Table 17).

Treatment of pulmonary thromboembolism with comorbidities

Question 13: How to treat pulmonary thromboembolism combined with Mycoplasma pneumoniae pneumonia in children?

Recommendation

Children with MP pneumonia presenting with positive antiphospholipid antibodies, abnormal anticoagulant proteins, elevated D-dimer, lobular consolidation, and

pulmonary necrosis should be highly vigilant against PTE (very low quality, weak recommendation).

Children with pneumonia complicated with PTE should receive anticoagulant therapy. Consider thrombolytic therapy for high-risk PTE cases (very low quality, weak recommendation).

Summary of the evidence

PTE is more frequently associated with MP pneumonia in children than in adults. A case series of children with MP pneumonia combined with PTE showed that the onset of PTE did not necessarily align with the acute phase of MP infection. Moreover, symptoms such as dyspnea and chest pain during disease remission warranted careful evaluation [32]. The clinical presentation of MP pneumonia combined with PTE often mimics primary pulmonary conditions leading to potential under-recognition or mis- diagnosis [37].

Refractory MP pneumonia associated with positive antiphos-pholipid antibodies, abnormal anticoagulant protein levels, elevated D-dimer, and radiologic findings of lobular consolidation and pulmonary necrosis should prompt suspicion of thrombosis [37, 40, 113, 114]. Emboli can occur in any segment of the pulmonary artery but are most commonly found in the right pulmonary lobe or segmental arteries [113].

Case series for children with MP pneumonia complicated with PTE showed good effectiveness and safety for anticoagulation [37, 114–117]. Thrombolytic therapy might benefit some critically ill cases, but further multicenter, large-sample studies are needed for indications, administration routes, dosages, and duration of thrombolytic therapy for children [114] (Supplementary Table 18). However, the small sample size may have introduced variability into the results.

Question 14: How to treat pulmonary thromboembolism during the perioperative period in children?

Recommendation

For children with acute high-risk PTE during the periopera- tive period: (1) If PTE occurs within one week of surgery, thrombolytic therapy should generally be avoided due to the risk of bleeding. However, in life-threatening situations, such as cardiac arrest, thrombolytic therapy (i.e., tissue plas- minogen activator, tPA) or other treatments (i.e., interven- tional or surgical thrombectomy) may be considered. (2) If PTE occurs more than one week after surgery, thrombolytic therapy may be considered depending on clinical status and bleeding risk.

For children with PTE on anticoagulant therapy who require surgery: (1) For pediatric patients receiving warfarin

World Journal of Pediatrics

with a high risk of PTE recurrence and no significant bleeding tendency, discontinuation of warfarin and initiation of bridging anticoagulation about five days before surgery should be individualized. This should be based on factors such as recurrence history, underlying thrombophilia, recent thrombotic events, or the presence of malignancy. (2) For children receiving parenteral anticoagulation (i.e., UFH or LMWH) or bridging anticoagulation, discontinuation 4–6 hours before surgery may be appropriate. Continuing anticoagulant therapy may be considered for low-bleeding-risk procedures, such as minor oral, dermatologic, or cata-ract surgery (good practice statement).

Summary of the evidence

Evidence on the management of children with PTE during the perioperative period is limited, and the expert panel developed its recommendations based on clinical experience. Importantly, bridging anticoagulation is an important strategy during the perioperative period, using short-acting anticoagulants (UFH or LMWH) as a substitute for long-acting drugs (VKA). For children receiving long-term oral anticoagulants (i.e., warfarin) or antiplatelet therapy who require surgical or invasive procedures, discontinuation of antithrombotic medications preoperatively increases the risk of thromboembolism. Conversely, continuing such therapy during the perioperative period significantly increases the risk of postoperative bleeding. Bridging anticoagulation offers a balanced approach to mitigate both risks.

Question 15: How to treat pulmonary thromboembolism combined with renal impairment or renal failure in children?

Recommendation

For children with confirmed PTE and renal impairment (creatinine clearance 15–50 mL/minute): (1) apixaban, (2) rivaroxaban, and (3) LMWH for at least five days followed by edoxaban or dabigatran, provided creatinine clearance exceeds 30 mL/minute, are recommended. For children with confirmed PTE and renal failure (creatinine clearance < 15 mL/minute): (1) LMWH, (2) UFH, and (3) LMWH or UFH in combination with VKA for at least five days initially, or until the INR reaches at least 2.0 for two consecutive readings, followed by VKA alone, are recommended (good practice statement).

Summary of the evidence

For children with renal impairment or renal failure combined with PTE, studies showed that treatment with standard

anticoagulant bridging warfarin with UFH or LMWH was effective in relieving symptoms [118, 119] (Supplementary Table 20). However, the small sample size may have introduced variability into the results.

Prevention of pulmonary thromboembolism recurrence

Question 16: Should a venous filter be placed for children with pulmonary thromboembolism?

Recommendation

A venous filter should be avoided unless absolutely necessary. For children with high-risk PTE, contraindications to systemic anticoagulation, VTE in the lower extremities, and body weight ≥ 10 kg, placing a retrievable venous filter can be considered (very low quality, weak recommendation).

Summary of the evidence

In children with DVT or PTE, our meta-analysis showed a mortality rate of 8% (95% CI 0.0%–4.7%) in the inferior vena cava (IVC) filter group [120–127], and a previous guideline reported mortality ranging from 0% to 6% for children and adults with other conditions [128]. Besides, our meta-analysis did not find that major bleeding occurred in the IVC group [120, 121, 126, 127]. However, IVC filter placement might lead to adverse events such as venous thrombosis or failure to retrieve the filter due to adherent thrombus [18, 120–127] (Supplementary Table 19).

The expert panel agreed that, given the clinical benefits and technical challenges associated with venous filter placement, particularly in children, their use should be avoided unless absolutely necessary. Indications for venous filter placement include high-risk PTE, contraindications to systemic anticoagulation (i.e., bleeding tendencies or platelet dysfunction), and the presence of VTE in the lower extremities. In addition, consider individual patient and family preferences.

Question 17: When should venous filters be removed for children with pulmonary thromboembolism placed with venous filters?

Recommendation

Remove venous filters in children with PTE as soon as contraindications to anticoagulation are resolved and promptly resume anticoagulant therapy (good practice statement).

World Journal of Pediatrics

![graph TD\n A1[Symptoms] --> A2[History of risk factors]\n A1 --> A3[Physical examination]\n A2 --> A4[Suspected PTE]\n A3 --> A4\n A3 --> A5[Observe]\n A4 --> A6[Experience and clinical likelihood rating scales]\n A6 -->|High clinical probability| A7[Definitive diagnostic test]\n A6 -->|Low clinical probability| A8[D-dimer]\n A7 -->|≥0.5 mg/L| A7\n A7 -->|<0.5 mg/L| A10[Exclude]\n A8 --> A7\n A9[CTPA] -->|Available or inappropriate| A9\n A9 -->|Unavailable or inappropriate| A12[Stable hemodynamics]\n A9 -->|Unstable hemodynamics| A11[Bedside echocardiograph]\n A9 -->|Stable hemodynamics| A13[Pulmonary ventilation/perfusion]\n A9 -->|Stable hemodynamics| A14[Magnetic resonance pulmonary arteriography]\n A12 --> A13\n A12 --> A14\n](1/parseimages/figure6aa532f7ccb64322bf83c4c149c76672_0_1.png)

Summary of the evidence

No evidence specified the optimal timing for venous filter removal. The expert panel developed the recommendation based on experience and expert consensus.

Question 18: How to evaluate the prognosis for children with pulmonary thromboembolism?

Recommendation

Initial risk stratification in children with suspected or confirmed acute PTE should prioritize identifying high-risk patients at risk of early death by assessing for shock or persistent hypotension. For non-high-risk children without shock or persistent hypotension, a clinical prognostic risk score can differentiate between intermediate- and low-risk cases (good practice statement).

Summary of the evidence

Evidence on prognostic assessment in children with PTE was limited. Based on clinical experience, the expert panel

agreed to utilize a prognostic risk score, such as the Pulmonary Embolism Severity Index (PESI) [4], supplemented by clinical, imaging, and laboratory parameters related to PTE prognosis.

Question 19: How to conduct health education for children with pulmonary thromboembolism?

Recommendation

Encourage early mobilization in hemodynamically stable children with acute PTE, once adequate anticoagulation is achieved. Provide comprehensive medication and discharge education to children and their families to enhance medication adherence (good practice statement).

Summary of the evidence

No evidence addressed health education for children with PTE. The recommendation, based on clinical experience, emphasized the importance of early mobilization and education to optimize treatment outcomes and improve adherence.

World Journal of Pediatrics

![graph TD\n A1[Management] --> A2[Treatment]\n A1 --> A3[Prevention]\n A1 --> A4[Prognosis, education and follow-up]\n A2 --> A5[Anticoagulation]\n A2 --> A6[Thrombolytic therapy]\n A2 --> A7[Catheter-based interventional therapy]\n A2 --> A8[Surgical embolotherapy]\n A2 --> A9[Other supportive treatments and establishment of a PERT]\n A2 --> A10[Treatment of PTE with comorbidities]\n A3 --> A23[Venous filter]\n A5 --> A11[Symptomatic PTE]\n A5 --> A12[Asymptomatic PTE(based on individual clinical condition)]\n A5 --> A13[Progressive thrombus + uncontrolled risks]\n A5 --> A14[LMWH/UFH/VKA]\n A5 --> A15[If no response, antithrombin]\n A5 --> A16[Idiopathic VTE: 6-12 mon]\n A5 --> A17[Recurrent idiopathic VTE: extend therapy]\n A5 --> A18[Secondary VTE: ≥3 mon; extend if risk factors persist]\n A5 --> A19[Recurrent secondary VTE: continue until risk factors resolved]\n A6 --> A20[High-risk PTE & no contraindications]\n A6 --> A21[t-PA]\n A6 --> A22[If no response, urokinase/streptokinase]\n A7 --> A24[High-risk PTE with]\n A7 --> A25[Thrombus in the pulmonary artery trunk or major branches]\n A7 --> A26[High bleeding risk]\n A7 --> A27[Thrombolysis contraindications]\n A7 --> A28[Failure of thrombolysis or aggressive medical therapy]\n A8 --> A29[High-risk PTE with]\n A8 --> A30[Anticoagulation/thrombolysis fails]\n A8 --> A31[Neonate/premature(high bleeding risk)]\n A8 --> A32[Special anatomy]\n A8 --> A33[Tumor/RV thrombus]\n A9 --> A34[Myoclasmia pneumonia pneumonia]\n A9 --> A35[During the perioperative period]\n A9 --> A36[Renal impairment or renal failure]\n A10 --> A37[Myoclasmia pneumonia pneumonia]\n A10 --> A38[During the perioperative period]\n A10 --> A39[Renal impairment or renal failure]\n A23 --> A40[High-risk PTE with]\n A23 --> A41[Anticoagulation contraindication]\n A23 --> A42[VTE in the lower extremities]\n A23 --> A43[Weight ≥10 kg]\n A23 --> A44[Remove it once contraindications to anticoagulation are resolved]\n](1/parseimages/figure28941d7334ea4a9eae3167742bfcc557_0_1.png) Fig. 2 Flow chart of the process of management of PTE recommended in this evidence-based expert consensus. PTE pulmonary thromboembolism, LMWH low molecular weight heparin, UFH

Question 20: How long should the follow-up period be after anticoagulant therapy for children with pulmonary thromboembolism?

Recommendation

Monitor children with PTE who are eligible for long-term follow-up continuously after completing anticoagulant therapy. For those not eligible for long-term follow-up, monitor

unfractionated heparin, VKA Vitamin K antagonists, VTE venous thromboembolism, tPA tissue-type plasminogen activator, RV right ventricle, PERT pulmonary embolism response team

for at least three months after anticoagulant therapy. If relapse occurs, extend follow-up for at least three months after the recurrence (good practice statement).

Summary of the evidence

Evidence on the follow-up period for children with PTE was limited, and the expert panel developed the recommendation based on experience.

World Journal of Pediatrics

Conclusions

This expert consensus based on available evidence provides a detailed and comprehensive set of recommendations for clinicians involved in the diagnosis (Fig. 1) and management (Fig. 2) of PTE in children. It covers key aspects of PTE in children, including overviews, diagnostic strategies, treatments, and more.

During formulation, the expert panel conducted a systematic search on the epidemiology, diagnosis, treatment, and nursing of PTE in children. We found that clinical research evidence was insufficient, and the quality of that evidence was generally low. Most recommendations were based on reasonable extrapolation of data from clinical research on PTE in adults and the clinical experience of experts, considering the values and preferences of the children and their parents. The expert panel reached a consensus and formed a Statement of Good Practices.

The expert panel calls on clinicians and researchers to focus on PTE in children and to study early identification and diagnostic strategies, prevention and therapeutic regimens, and long-term management. Through in-depth exploration and rigorous research to improve the understanding of PTE in children, the expert panel hopes that we can provide more accurate and efficient clinical management strategies for children with PTE in the future.

Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s12519-025-00987-3.

Acknowledgements We want to thank Dr. Ying Gu from the Department of Nursing, Children's Hospital of Fudan University for her participation in the expert panel.

Author contributions Li-Nan Zeng, Ying-Xue Zou, Hai-Lin Zhang, Li-Na Chen, De-Hui Chen, Xin-Xin Chen, Xing Chen, Zhi-Min Chen, Xiao-Yan Dong, Liang Huang, Yi Ji, Yong-Mei Jiang, Zhi-Ping Li, En-Mei Liu, Shu-Hua Luo, Xiao-Feng Ni, Guang-Min Nong, Yun Peng, Su-Yun Qian, Tian-You Wang, Xin-Yu Yuan, Hao Zhang, Hong Zhang, Xiao-Bo Zhang, De-Yu Zhao, Shun-Ying Zhao, Xiu-Fang Zhao, and Kai-Yu Zhou contributed equally to this work. Li-Nan Zeng, Quan Lu, Ling-Li Zhang, Ying-Xue Zou, and Hai-Lin Zhang: conceptualization, data curation, formal analysis, writing-original draft. De-Hui Chen, Li-Na Chen, Xin-Xin Chen, Xing Chen, Zhi-Min Chen, Xiao-Yan Dong, Liang Huang, Yi Ji, Yong-Mei Jiang, Zhi-Ping Li, En-Mei Liu, Shu-Hua Luo, Guang-Min Nong, Yun Peng, Su-Yun Qian, Tian-You Wang, Xin-Yu Yuan, Hao Zhang, Hong Zhang, Xiao-Bo Zhang, De-Yu Zhao, Shun-Ying Zhao, Xiu-Fang Zhao, and Kai-Yu Zhou: formal analysis. Xiao-Feng Ni: data curation, formal analysis. Han-Min Liu: conceptualization, data curation, formal analysis, supervision, writing-review and editing.

Funding None.

Data availability The data are available as electronic supplementary material.

Declarations

Conflict of interest No financial or non-financial benefits have been received or will be received from any party related directly or indi-

rectly to the subject of this article. Zhi-Min Chen and Tian-You Wang are members of the Editorial Board of World Journal of Pediatrics. The manuscript was handled by other editors. Zhi-Min Chen and Tian-You Wang are not involved in the review process and decision of this manuscript.

Ethical approval Not applicable as this research did not directly involve human subjects or individual case details.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

References

1. Pulmonary Embolism and Pulmonary Vascular Disease Group of the Respiratory Disease Branch of the Chinese Medical Association, Pulmonary Embolism and Pulmonary Vascular Disease Committee of Chinese Association of Chest Physicians, National Pulmonary Embolism and Pulmonary Vascular Disease Prevention and Treatment Collaborative Group. Guidelines for the diagnosis, treatment, and prevention of pulmonary thromboembolism. CMJ. 2018:98:1060-87.

2. Carpenter SL, Richardson T, Hall M. Increasing rate of pulmonary embolism diagnosed in hospitalized children in the United States from 2001 to 2014. Blood Adv. 2018;2:1403–8.

3. Group JJW, Guidelines for the diagnosis, treatment and prevention of pulmonary thromboembolism and deep vein thrombosis (JCS 2009) - digest version -. Circ J. 2011;75:1258-81.

4. Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41:543-603.

5. World Health O. WHO handbook for guideline development. 2nd ed. Geneva: World Health Organization; 2014.

6. Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. Agree II: advancing guideline development, reporting and evaluation in health care. J Clin Epidemiol. 2010;63:1308–11.

7. Chen Y, Yang K, Muaršic A, Qaseem A, Meerpohl JJ, Flottorp S, et al. A reporting tool for practice guidelines in health care: the RIGHT statement. Ann Intern Med. 2017;166:128-32.

8. Ni XF, Liu JN, Zeng LN. 2025 The Prevelance and risk factors in children and adolescents with pulmonary embolisim: a systematic review and meta-analysis. BMJ open. In press.

9. Ni XF, Song X, Zeng LN. The role of clinical modeling/scoring and D-dimer in the initial diagnosis of suspected pulmonary thromboembolism in children: a systematic review and meta-analysis. BMJ open. This press.

10. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924-6.

World Journal of Pediatrics

11. Dewidar O, Lotfi T, Langendam MW, Parmelli E, Saz Parkinson Z, Solo K, et al. Good or best practice statements: proposal for the operationalisation and implementation of GRADE guidance. BMJ Evid-Based Med. 2023;28:189-96. 12. Pulmonary Vascular Disease Group of the Cardiology Branch of the Chinese Medical Association. Consensus on the Diagnosis and Treatment of Acute Pulmonary Embolism by Chinese Experts (2015). Chin J Cardiol. 2016;44:197-211 (in Chinese). 13. China Thrombosis and Hemostasis Society (CTHS) Guideline Committee. Guidelines for the Prevention and Treatment of Thrombotic Diseases in China. CMJ. 2018;98:2861-88 (in Chinese). 14. Jorens PG, Van Marck E, Snoeckx A, Parizel PM. Nonthrom-botic pulmonary embolism. Eur Respir J. 2009;34:452-74. 15. Agha BS, Sturm JJ, Simon HK, Hirsh DA. Pulmonary embolism in the pediatric emergency department. Pediatrics. 2013;132:663-7. 16. Sherrod BA, McClugage SG, Mortellaro VE, Aban IB, Rocque BG. Venous thromboembolism following inpatient pediatric surgery: analysis of 153, 220 patients. J Pediaturg Surg. 2019;54:63-9. 17. Stein PD, Kayali F, Olson RE. Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey. J Pediatr. 2004;145:563-5. 18. Biss TT, Brandão LR, Kahr WH, Chan AK, Williams S. Clinical features and outcome of pulmonary embolism in children. Br J Haematol. 2008;142:808-18. 19. Rashid A, Mansoor H, Ali SA, Nasir N. Paediatric thrombosis: a five-year experience from a tertiary care center of Pakistan. J Ayub Med Coll Abbottabad. 2022;34:263-8. 20. Hong J, Lee JH, Yhim HY, Choi WI, Bang SM, Lee H, et al. Incidence of venous thromboembolism in Korea from 2009 to 2013. PLoS ONE. 2018;13:e0191897. 21. Kempny A, McCabe C, Dimopoulos K, Price LC, Wilde M, Limbrey R, et al. Incidence, mortality and bleeding rates associated with pulmonary embolism in England between 1997 and 2015. Int J Cardiol. 2019;277:229-34. 22. Choi HS, Choi CW, Kim HM, Park HW. Venous thromboembolism in pediatric patients: a single institution experience in Korea. Blood Res. 2016;51:164-70. 23. Ross CE, Shih JA, Kleinman ME, Donnino MW. Pediatric massive and submassive pulmonary embolism: a single-center experience. Hosp Pediatr. 2020;10:272-6. 24. Sadiq MW, Ukrani RD, Arif A, Akbar I, Altaf S, Moiz B. Risk assessment and outcome of venous thromboembolism in pediatric population in an academic care center of a low-middle income country. Clin Appl Thromb Hemost. 2021;27:107029621995895. 25. Hangül M, Köse M, Pekcan S, Çalışkan Ü, Tokgöz H, Aslan AT, et al. Pulmonary embolism in childhood: a multicenter experience from Turkey. Balkan Med J. 2022;39:366-73. 26. Wolf S, Valerio L, Kucher N, Konstantinides SV, Klaassen ILM, van Ommen CH, et al. Acute pulmonary embolism in children and adolescents in the USA (2016 and 2019): a nationwide retrospective cohort study. Lancet Respir Med. 2025;13:393-402. 27. Buck JR, Connors RH, Coon WW, Weintraub WH, Wesley JR, Coran AG. Pulmonary embolism in children. J Pediatr Surg. 1981;16:385-91. 28. Daily PO, Dembitsky WP, Peterson KL, Moser KM. Modifications of techniques and early results of pulmonary thromboendarterec to my for chronic pulmonary embolism. J Thorac Cardiovasc Surg. 1987;93:221-33. 29. Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al. Management of massive and submasive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific

statement from the American Heart Association. Circulation. 2011;123:1788-830. 30. Ross PA, Abou-Zamazam A, Newth CJL. Height best predicts the optimal insertion length of orotracheal tubes in children. Intensive Care Med. 2024;2:6. 31. Gu SJ, Wen JL, Wang XY, Zhang LX, Li W, Qi X. Advances in the diagnosis and treatment of in situ pulmonary artery thrombosis. Zhonghua Jie He He Hu Xi Za Zhi. 2024;47:464-9 (in Chinese). 32. Wang W, Chang J, Zhang XJ, Cui J, Liu LP, Han ZY. Severe mycoplasma pneumoniae pneumonia complicated with pulmonary embolism in children: a clinical analysis. Chin Remedie Clin. 2021;21:3954-8 (in Chinese). 33. Bryce YC, Perez-Johnston R, Bryce EB, Homayoon B, Santos-Martin EG. Pathophysiology of right ventricular failure in acute pulmonary embolism and chronic thromboembolic pulmonary hypertension: a pictorial essay for the interventional radiologist. Insights Imaging. 2019;10:18. 34. Ma JR, Song HM, Xiao J, Tang XY, He YY, Wei M. Clinical analysis of 12 patients with pediatric antiphospholipid syndrome with pulmonary embolism. Zhonghua Er Ke Za Zhi. 2017;55:25-9 (in Chinese). 35. Pelland-Marcotte MC, Tucker C, Klaassen A, Avila ML, Amid A, AmirI N, et al. Outcomes and risk factors of massive and submassive pulmonary embolism in children: a retrospective cohort study. Lancet Haematol. 2019;6:14-53. 36. Lei YL, Li ZX, Tan J, Du XK, Shu C. Clinical analysis of 8 cases with pulmonary embolism in children. Zhonghua Shi Yong Er Ke Lin Chuang Za Zhi. 2020;35:852-5 (in Chinese). 37. Kang LL, Zhang SL, Zheng B, Sun LF, Shi SL. Features of the morphological distribution and outcome analysis of 9 cases of concurrent pulmonary artery embolism of mycoplasma pneumonia in children. J Clin Radiol. 2022;41:1331-5 (in Chinese). 38. Li X, Dong LL, Tang Y, Li M, Wang J. Clinical analysis of mycoplasma pneumoniae pneumonia complicated with pulmonary thromboembolism. Chin J Clin Med. 2021;28:328-32 (in Chinese). 39. Liu FQ, Zhang J, Chen X, Ding N, Dai FF, Wang K, et al. Clinical analysis and etiology factors of pulmonary embolism in 30 children. Zhonghua Shi Yong Er Ke Lin Chuang Za Zhi. 2022;37:1386-91 (in Chinese). 40. Yang K, Jia B, Yang PJ, Zhou J. Clinical and imaging characteristics of pulmonary embolism complicating Mycoplasma pneumoniae pneumonia. Physician Online. 2022;12:7-10 (in Chinese). 41. Chen LQ, Yin Ju, Xu BP, Duan XM, Wu RH, Shen KL. Clinical manifestations and genetic analysis of 5 cases with inherited thrombophilia. Zhonghua Shi Yong Er Ke Lin Chuang Za Zhi. 2022;37:934-8. 42. Ergenekon AP, Yilmaz Yegit C, Cenk M, Gulieva A, Kaloncu M, Selcuk M, et al. The utility of risk assessment tools for acute pulmonary embolism in children. Pediatr Pulmonol. 2023;58:55-60. 43. Schultz RF, Sharathkumar A, Kwon S, Doerfer K, Lales G, Bhat R. Implementation of automatic data extraction from an enterprise database warehouse (EDW) for validating pediatric VTE decision rule: a prospective observational study in a critical care population. J Thromb Thrombolsis. 2020;50:782-9. 44. Gibson NS, Sohe M, Kruip MJ, Tick LW, Gerdes VE, Bossuyt PM, et al. Further validation and simplification of the Wells clinical decision rule in pulmonary embolism. Thromb Haemost. 2008;99:229-34. 45. Douma RA, Gibson NS, Gerdes VE, Büller HR, Wells PS, Perrier A, et al. Validity and clinical utility of the simplified Wells rule for assessing clinical probability for the

World Journal of Pediatrics

exclusion of pulmonary embolism. Thromb Haemost. 2009;101:197–200. 46. Biss TT, Brandão LR, Kahr WH, Chan AK, Williams S. Clinical probability score and D-dimer estimation lack utility in the diagnosis of childhood pulmonary embolism. J Thromb Haemost. 2009;7:1633–8. 47. Hennelly KE, Baskin MN, Monuteuax MC, Hudgins J, Kua E, Commeree A, et al. Detection of pulmonary embolism in high-risk children. J Pediatr. 2016;178:214–8.e3. 48. Kanis J, Hall CL, Pike J, Kline JA. Diagnostic accuracy of the D-dimer in children. Arch Dis Child. 2018;103:832–4. 49. Kanis J, Pike J, Hall CL, Kline JA. Clinical characteristics of children evaluated for suspected pulmonary embolism with D-dimer testing. Arch Dis Child. 2018;103:835–40. 50. Sharaf N, Sharaf VB, Mace SE, Nowakick AS, Stoller JK, Carl JC. D-dimer in adolescent pulmonary embolism. Acad Emerg. Med. 2018;25:1235–41. 51. Wang CX. Clinical prediction score in the diagnosis and evaluation of pulmonary embolism in children. Master’s thesis. Jilin University; 2023 (in Chinese). 52. Sueyoshi E, Tsutsui S, Hayashida T, Ashizawa K, Sakamoto I, Uetani M. Quantification of lung perfusion blood volume (lung PBV) by dual-energy CT in patients with and without pulmonary embolism: preliminary results. Eur J Radiol. 2011;80:e505–9. 53. Stein PD, Chenevert TL, Fowler SE, Goodman LR, Gottschalk A, Hales CA, et al. Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism: a multicenter prospective study (PIOEPED III). Ann Intern Med. 2010;152:W142–3. 54. Streif W, Andrew M, Marzinotto V, Massicotte P, Chan AK, Julian JA, et al. Analysis of warfarin therapy in pediatric patients: a prospective cohort study of 319 patients. Blood. 1999;94:3007–14. 55. Bonduel M, Sciuccati G, Hepner M, Torres AF, Pieroni G, Froatro JP, et al. Acenocoumarol therapy in pediatric patients. J Thromb Haemost. 2003;1:1740–3. 56. Bidlingmaer C, Kenet G, Kurnik K, Mathew P, Manner D, Mitchell L, et al. Safety and efficacy of low molecular weight heparins in children: a systematic review of the literature and meta-analysis of single-arm studies. Semin Thromb Hemost. 2011;37:814–25. 57. Fiamoli V, Blatny J, Zapletal O, Kohlerova S, Janousova E. Treatment of deep vein thrombosis with continuous IV infusion of LMWH: a retrospective study in 32 children. Thrombosis. 2011;2011:981497. 58. Spoor N, Smiers FJ, van der Meer FJ, Hutten BA, van Ommen CH. Phenprocoumon and acenocoumarol treatment in paediatric patients. Thromb Haemost. 2012;108:1238–41. 59. O'Brien SH, Kulkarni R, Wallace A, Hamblin F, Burr S, Goldenberg NA. Multicenter dose-finding and efficacy and safety outcomes in neonates and children treated with dalteparin for acute venous thromboembolism. J Thromb Haemost. 2014;12:1822–5. 60. Andrew M, Marzinotto V, Massicotte P, Blanchette V, Ginsberg J, Brill-Edwards P, et al. Heparin therapy in pediatric patients: a prospective cohort study. Pediatr Res. 1994;35:78–83. 61. Massicotte P, Julian JA, Gent M, Shields K, Marzinotto V, Szechman B, et al. An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial. Thromb Res. 2003;109:85–92. 62. Nohe N, Flemmer A, Rümler R, Praun M, Auberger K. The low molecular weight heparin dalteparin for prophylaxis and therapy of thrombosis in childhood: a report on 48 cases. Eur J Pediatr. 1999;158:S134–9. 63. Argentina C, Ferreira MA, Sander GB, Moreira LB. Short-term therapy with enoxaparin or unfractionated heparin for venous

thromboembolism in hospitalized patients: utilization study and cost-minimization analysis. Value Health. 2011;14:S89-92. 64. Büller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, et al. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med. 2003;349:1695-702. 65. Hull RD, Raskob GE, Brant RF, Pineo GF, Elliott G, Stein PD, et al. Low-molecular-weight heparin vs heparin in the treatment of patients with pulmonary embolism. Ameri-can-Canadian Thrombosis Study Group. Arch Intern Med. 2000;160:229-36. 66. Halton J, Brandão LR, Luciani M, Bomgaars L, Chalmers E, Mitchell LG, et al. Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Lancet Haematol. 2021;8:e22-33. 67. Mitchell LG, Rōshammar D, Huang F, Albisetti M, Brandão LR, Bomgaars L, et al. Anticoagulant effects of dabigatran on coagulation laboratory parameters in pediatric patients: combined data from five pediatric clinical trials. Thromb Haemost. 2022;122:1573-83. 68. Monagle P, Lensing AWA, Thelen K, Martinelli I, Male C, Santamaría A, et al. Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies. Lancet Haematol. 2019;6:e500-9. 69. Fulia F, Cordaro S, Meo P, Gitto P, Gitto E, Trimarchi G, et al. Can the administration of antithrombin III decrease the risk of cerebral hemorrhage in premature infants? Biol Neonate. 2003;83:1-5. 70. Haussmann U, Fischer J, Eber S, Scherer F, Seger R, Gungor T. Hepatic Veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy. Haematologica. 2006;91:795-800. 71. Nieber A, Christensen M, Berens R, Wellner H, Mikhailov T, Tweddell JS. Antithrombin replacement during extracorporeal membrane oxygenation. Artif Organs. 2011;35:1024-8. 72. Petäjä J, Peltola K, Rautiainen P. Disappearance of symptomatic venous thrombosis after neonatal cardiac operations during antihrombin III substitution. J Thorac Cardiovasc Surg. 1999;118:955-6. 73. Schmidt B, Gillie P, Mitchell L, Andrew M, Caco C, Roberts R. A placebo-controlled randomized trial of antithrombin therapy in neonatal respiratory distress syndrome. Am J Respir Crit Care Med. 1998;158:470-6. 74. Stansfield BK, Wise L, Ham PB 3rd, Patel P, Parman M, Jin C, et al. Outcomes following routine antithrombin III replacement during neonatal extracorporeal membrane oxygenation. J Pediatr Surg. 2017;52:609-13. 75. Wong TE, Delaney M, Gernsheimer T, Matthews DC, Brogan TV, Mazor R, et al. Antithrombin concentrates use in children on extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2015;16:264-9. 76. Wong TE, Nguyen T, Shah SS, Brogan TV, Witmer CM. Antithrombin concentrate use in pediatric extracorporeal membrane oxygenation: a multicenter cohort study. Pediatr Crit Care Med. 2016;17:1170-8. 77. Corder A, Held K, Oschman A. Retrospective evaluation of antithrombin III supplementation in neonates and infants receiving enoxaparin for treatment of thrombosis. Pediatr Blood Cancer. 2014;61:1063-7. 78. Estepp JH, Smeltzer M, Reiss UM. The impact of quality and duration of enoxaparin therapy on recurrent venous thrombosis in children. Pediatr Blood Cancer. 2012;59:105-9. 79. Massicotte P, Julian JA, Gent M, Shields K, Marzinotto V, Szentchman B, et al. An open-label randomized controlled trial of low molecular weight heparin for the prevention of central venous

World Journal of Pediatrics

line-related thrombotic complications in children: the PROTEKT trial. Thromb Res. 2003:109:1-8. 80. Chalmers E, Ganesen V, Liesner R, Maroo S, Nokes T, Saunders D, et al. Guideline on the investigation, management and prevention of venous thrombosis in children. Br J Haematol. 2011;154:196-207. 81. Monagle P, Chan AKC, Goldenberg NA, Ichord RN, Journey-cake JM, Nowak-Göttl U, et al. (2012) Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis: American college of chest physicians evidence-based clinical practice guidelines. Chest. 141:e737S-e801S. 82. Ross C, Kumar R, Pelland-Marcotte MC, Mehta S, Kleinman ME, Thiagarajan RR, et al. Acute management of high-risk and intermediate-risk pulmonary embolism in children: a review. Chest. 2022;161:791-802. 83. Goldenberg NA, Durham JD, Knapp-Clevenger R, Manco-Johnson MJ. A thrombolytic regimen for high-risk deep venous thrombosis may substantially reduce the risk of postthrombotic syndrome in children. Blood. 2007;110:45-53. 84. Ansha DA, Patel KN, Montegna L, Nicholson GT, Ehrlich AC, Petit CJ. Tissue plasminogen activator use in children: bleeding complications and thrombus resolution. J Pediatr. 2016;171:e1-2. 85. Dandoy CE, Kukreja KU, Gruppo RA, Patel MN, Tarango C. Outcomes in children with deep vein thrombosis managed with percutaneous endovascular thrombolysis. Pediatr Radiol. 2015;45:719-26. 86. Darbari DS, Desai D, Arnaldez F, Desai K, Kallen J, Stroue J, et al. Safety and efficacy of catheter directed thrombolysis in children with deep venous thrombosis. Br J Haematol. 2012;159:376-8. 87. Farnoux C, Camard O, Pinquier D, Hurtaud-Roux MF, Sebag G, Schlegel N, et al. Recombinant tissue-type plasminogen activator therapy of thrombosis in 16 neonates. J Pediatr. 1989;133:137-40. 88. Gaballah M, Shi J, Kukreja K, Raffini L, Tarango C, Keller M, et al. Endovascular thrombolysis in the management of iliofemoral thrombosis in children: a multi-institutional experience. J Vasc Interv Radiol. 2016;27:524-30. 89. Goldenberg NA, Branchford B, Wang M, Ray C Jr, Durham JD, Manco-Johnson MJ. Percutaneous mechanical and pharmacometanical thrombolysis for occlusive deep vein thrombosis of the proximal limb in adolescent subjects: findings from an institution-based prospective inception cohort study of pediatric venous thromboembolism. J Vasc Interv Radiol. 2011;22:121-32. 90. Gupta AA, Leaker M, Andrew M, Massicotte P, Liu L, Benson LN, et al. Safety and outcomes of thrombolysis with tissue plasminogen activator for treatment of intravascular thrombosis in children. J Pediatr. 2001;139:682-8. 91. Knöfler R, Dinger J, Kabus M, Müller D, Lauterbach I, Rupprecht E, et al. Thrombolytic therapy in children—clinical experiences with recombinant tissue-plasminogen activator. Semin Thromb Hemost. 2001;27:169-74. 92. Leary SE, Harrod VL, de alarcon PA, Reiss UM. Low-dose systemic thrombolytic therapy for deep vein thrombosis in pediatric patients. J Pediatr Hematol Oncol. 2010;32:97-102. 93. Levy M, Benson LN, Burrows PE, Bentur Y, Strong DK, Smith J, et al. Tissue plasminogen activator for the treatment of thromboembolism in infants and children. J Pediatr. 1991;118:467-72. 94. Manco-Johnson MJ, Nuss R, Hays T, Krupski W, Drose J, Manco-Johnson ML. Combined thrombolytic and anticoagulant therapy for venous thrombosis in children. J Pediatr. 2000;136:446-53. 95. Newall F, Browne M, Savoia H, Campbell J, Barnes C, Monagle P. Assessing the outcome of systemic tissue plasminogen activator for the management of venous and arterial thrombosis in pediatrics. J Pediatr Hematol Oncol. 2007;29:269-73. 96. Zengin E, Sarper N, Yazal Erdem A, Odaman AI I, Sezgin Evim M, Yaral N, et al. Thrombolysis with systemic recombinant

tissue plasminogen activator in children: a multicenter retrospective study. Turk J Haematol. 2021;38:294-305. 97. Bloomer TL, El-Hayek GE, McDaniel MC, Sandvall BC, Liberman HA, Devireddy CM, et al. Safety of catheter-directed thrombolysis for massive and submassive pulmonary embolism: results of a multicenter registry and meta-analysis. Catheter Cardiovasc Interv. 2017;89:754-60. 98. Engelberger RP, Kucher N. Ultrasound-assisted thrombolysis for acute pulmonary embolism: a systematic review. Eur Heart J. 2014;35:758-64. 99. Kuo WT, Banerjee A, Kim PS, DeMarco FJ, Levy JR, Archini FR, et al. Pulmonary embolism response to fragmentation, embolectomy, and catheter thrombolysis (PERFECT) initial results from a prospective multicenter registry. Chest. 2015;148:667-73. 100. Piazza G, Hohlfelder B, Jaff MR, Ouriel K, Engelhardt TC, Sterling KM, et al. A prospective single-arm, multicenter trial of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis for acute massive and submassive pulmonary embolism: the SEAT-TLE II study. JACC Cardiovasc Interv. 2015;8:1382-92. 101. Lee SY, Baek JS, Kim GB, Kwon BS, Bae EJ, Noh CI, et al. Clinical significance of thrombosis in an intracardiac blind pouch after a Fontan operation. Pediatr Cardiol. 2012;33:42-8. 102. Cooper L, Moore C, Branchford B, Greffe B, Capocelli K, Kuder A, et al. Successful pulmonary artery embolectomy in a patient with a saddle Wilms tumor embolus. Pediatr Blood Cancer. 2012;58:806-9. 103. Maraj S, Bajpai E, Crespo G, Doshi K, Langan N, Jacobs LE, et al. Undefined hypercoaguable state associated with massive right ventricular thrombus and embolism in a previously healthy 17-year-old male. Echocardiography. 2003;20:439-42. 104. Forbes TJ, Rosenthal GL, Reul GR, Ott DA, Feltes TF. Risk factors for life-threatening cavopulmonary thrombosis in patients undergoing bidirectional superior cavopulmonary shunt: an exploratory study. Am Heart J. 1997;134:865-71. 105. Snow V, Qaseem A, Barry P, Hornbake ER, Rodnick JE, Tobolic T, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146:204-10. 106. Barnes G, Giri J, Courtney DM, Naydenov S, Wood T, Rosovsky R, et al. Nuts and bolts of running a pulmonary embolism response team: results from an organizational survey of the National PERT™ consortium members. Hosp Pract. 2017;45:76-80. 107. Dang MP, Cheng A, Garcia J, Lee Y, Parikh M, McMichael ABV, et al. Bringing PERT to pediatrics: initial experience and outcomes of a pediatric multidisciplinary pulmonary embolism response team (PERT). Chest. 2025;167:851-62. 108. Rosovsky R, Chang Y, Rosenfield K, Channick R, Jaff MR, Weinberg I, et al. Changes in treatment and outcomes after creation of a pulmonary embolism response team (PERT), a 10-year analysis. J Thromb Thrombolysis. 2019;47:31-40. 109. Jen WY, Kristanto W, Teo L, Phua J, Yip HS, MacLaren G, et al. Assessing the impact of a pulmonary embolism response team and treatment protocol on patients presenting with acute pulmonary embolism. Heart Lung Circ. 2020;29:345-53. 110. Wright C, Elbadawi A, Chen YL, Patel D, Mazzillo J, Acquisto N, et al. The impact of a pulmonary embolism response team the efficiency of patient care in the emergency department. J Thromb Thrombolysis. 2019;48:331-5. 111. Xenos ES, Davis GA, He Q, Green A, Smyth SS. The implementation of a pulmonary embolism response team in the management of intermediate- or high-risk pulmonary embolism. J Vasc Surg Venous Lymphat Disord. 2019;7:493-500. 112. Jia CY, Yang KH, Sun LF. Clinical, CT, and CTPA features of pediatric pneumonia-associated pulmonary embolism. Zhongguo Zhong Xi Yi Jie He Ying Xiang Xue Za Zhi. 2023;21:324-6.

World Journal of Pediatrics

113. Song SX, Xu YS. Clinical analysis of 9 cases of mycoplasma pneumoniae pneumonia complicated with pulmonary embolism in children and literature review. J Shandong Univ (Health Sci). 2023;61:96–103 (in Chinese). 114. Fu Y, Zhang TQ, Dong CJ, Xu YS, Dong HQ, Ning J. Clinical characteristics of 14 pediatric mycoplasma pneumoniae pneumonia associated thrombosis: a retrospective study. BMC Cardiovasc Disord. 2023;23:1. 115. Han C, Zhang T, Zheng J, Jin P, Zhang Q, Guo W, et al. Analysis of the risk factors and clinical features of Mycoplasma pneumoniae pneumonia with embolism in children: a retrospective study. Ital J Pediatr. 2022;48:153. 116. Sheng CQ, Yang CF, Ao Y, Zhao ZY, Li YM. Mycoplasma pneumoniae pneumonia with pulmonary embolism: a study on pediatric cases in Jilin province of China. Exp Ther Med. 2021;21:201. 117. Suri D, Ahluwalia J, Saxena AK, Sodhi KS, Singh P, Mittal BR, et al. Thromboembolic complications in childhood nephrotic syndrome: a clinical profile. Clin Exp Nephrol. 2014;18:803–13. 118. Lv YL, Guan N, Ding J, Yao Y, Xiao HJ, Zhong XH, et al. Spectrum of thrombotic complications and their outcomes in Chinese children with primary nephrotic syndrome. Ital J Pediatr. 2020;46:182. 119. Reed RA, Teitelbaum GP, Stanley P, Mazer MJ, Tonkin IL, Rollins NK. The use of inferior vena cava filters in pediatric patients for pulmonary embolus prophylaxis. Cardiovasc Intervent Radiol. 1996;19:401–5. 120. Cahn MD, Rohrer MJ, Martella MB, Cutler BS. Long-term follow-up of Greenfield inferior vena cava filter placement in children. J Vasc Surg. 2001;34:820–5.

121. Chaudry G, Padua HM, Alomari AI. The use of inferior vena cava filters in young children. J Vasc Interv Radiol. 2008;19:1103-6. 122. Raffini L, Cahill AM, Hellinger J, Manno C. A prospective observational study of IVC filters in pediatric patients. Pediatr Blood Cancer. 2008;51:517-20. 123. Kukreja KU, Gollaudi J, Patel MN, Johnson ND, Racadio JM. Inferior vena cava filters in children: our experience and suggested guidelines. J Pediatr Hematol Oncol. 2011;33:334-8. 124. Blevins EM, Glanz K, Huang YS, Raffini L, Shinohara RT, Witterer C. A multicenter cohort study of inferior vena cava filter use in children. Pediatr Blood Cancer. 2015;62:2089-93. 125. Rottenstreich A, Revel-Vilk S, Bloom AI, Kalish Y. Inferior vena cava (IVC) filters in children: a 10-year single center experience. Pediatr Blood Cancer. 2015;62:1974-8. 126. Guzman AK, Zahra M, Trerotola SO, Raffini LJ, Itkin M, Keler MS, et al. IVC filter retrieval in adolescents: experience in a tertiary pediatric center. Pediatr Radiol. 2016;46:534-40. 127. Monagle P, Cuello CA, Augustine C, Bonduel M, Brandão LR, Capman T, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism. Blood Adv. 2018;2:3292-316. 128. Maraj S, Bajpai E, Crespo G, Doshi K, Langan N, Jacobs LE, et al. Undefined hypercoaguable state associated with massive right ventricular thrombus and embolism in a previously healthy 17-year-old male. Echocardiography. 2003;20:439-42.

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Authors and Affiliations

Li-Nan Zeng$^{1}$,$^{2}$,$^{3}$,$^{4}$ · Ying-Xue Zou$^{5}$ · Hai-Lin Zhang$^{6}$ · Li-Na Chen$^{7}$ · De-Hui Chen$^{8}$ · Xin-Xin Chen$^{9}$ · Xing Chen$^{10}$ · Zhi-Min Chen$^{11}$ · Xiao-Yan Dong$^{12}$ · Liang Huang 1$^{1,2}$, · Yi Ji $^{13}$ · Yong-Mei Jiang$^{14}$ · Zhi-Ping Li$^{15}$ · En-Mei Liu$^{16}$ · Shu-Hua Luo$^{7}$ · Xiao-Feng Ni$^{1}$,$^{2}$,$^{3}$,$^{4}$ · Guang-Min Nong$^{17}$ · Yun Peng$^{18}$ · Su-Yun Qian$^{19}$ · Tian-You Wang$^{20}$ · Xin-Yu Yuan$^{21}$ · Hao Zhang$^{22}$ · Hong Zhang$^{23}$ · Xiao-Bo Zhang$^{24}$ · De-Yu Zhao$^{25}$ · Shun-Ying Zhao$^{26}$ · Xiu-Fang Zhao$^{32}$,$^{27}$ · Kai-Yu Zhou$^{3,7}$ · Quan Lu$^{12}$ · Ling-Li Zhang$^{1,2,3,4,28}$ · Han-Min Liu$^{3}$,$^{29,30,31,32}$

☑ Quan Lu luquan-sh@vip.sina.com

☑ Ling-Li Zhang zhanglingli@scu.edu.cn

☑ Han-Min Liu liuhm@scu.edu.cn

$^{1}$ Department of Pharmacy/Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University; Children's Medicine Key Laboratory of Sichuan Province, Chengdu, China

$^{2}$ NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation, Chengdu, China

$^{3}$ Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China

$^{4}$ West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China

$^{5}$ Department of Pulmonology, Tianjin Children's Hospital (Children's Hospital of Tianjin University), Tianjin, China

$^{6}$ Department of Pediatric Respiratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China

7 Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

$^{8}$ Department of Pediatrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

9 Heart Center, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China

$^{10}$ Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China

11 Department of Pulmonology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China

12 Department of Pulmonology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

World Journal of Pediatrics

13 Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China 14 Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China 15 Department of Clinical Pharmacy, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China 16 Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China 17 Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China 18 Department of Radiology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China 19 Pediatric Intensive Care Unit, Beijing Children's Hospital, Capital Medical University, Beijing, China 20 Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China 21 Department of Radiology, The Affiliated Children's Hospital, Capital Institute of Pediatrics, Beijing, China 22 Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China 23 Department of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

24 Department of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China 25 Department of Respiratory Medicine, Children's Hospital of Nanjing Medical University, Nanjing, China 26 Department of Respiratory Disease, Beijing Children's Hospital, Capital Medical University, Beijing, China 27 Department of Nursing, West China Second University Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China 28 Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China 29 Department of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, China NHC Key Laboratory of Chronobiology (Sichuan University), Chengdu, China 30 NHC Key Laboratory of Chronobiology (Sichuan University), Chengdu, China 31 The Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, Sichuan University and School of Life Sciences of Fudan University, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China 32 Sichuan Birth Defects Clinical Research Center, West China Second University Hospital, Sichuan University, Chengdu, China