Long-term outcomes of pulmonary embolism in children and adolescents.

ABSTRACT: Knowledge regarding the long-term consequences of pulmonary embolism (PE) in children is limited. This cohort study describes the long-term outcomes of PE in children who were followed-up at a single-center institution using a local protocol that included clinical evaluation, chest imaging, echocardiography, pulmonary function tests, and cardiopulmonary exercise tests at follow-up, starting 3 to 6 months after acute PE. Children objectively diagnosed with PE at age 0 to 18 years, who had ≥6 months of follow-up were included. Study outcomes consisted of PE resolution, PE recurrence, death, and functional outcomes (dyspnea, impaired pulmonary or cardiac function, impaired aerobic capacity, and post-PE syndrome). The frequency of outcomes was compared between patients with/without underlying conditions. In total, 150 patients were included; median age at PE was 16 years (25th-75th percentile, 14-17 years); 61% had underlying conditions. PE did not resolve in 29%, recurrence happened in 9%, and death in 5%. One-third of patients had at least 1 documented abnormal functional finding at follow-up (ventilatory impairments, 31%; impaired aerobic capacity, 31%; dyspnea, 26%; and abnormal diffusing capacity of the lungs to carbon monoxide, 22%). Most abnormalities were transient. When alternative explanations for the impairments were considered, the frequency of post-PE syndrome was lower, ranging between 0.7% and 8.5%. Patients with underlying conditions had significantly higher recurrence, more pulmonary function and ventilatory impairments, and poorer exercise capacity. Exercise intolerance was, in turn, most frequently because of deconditioning than to respiratory or cardiac limitation, highlighting the importance of physical activity promotion in children with PE.

Physical activity for children with deep vein thrombosis and pulmonary embolism on anticoagulation: a scoping review.

Context: There are no clear pediatric guidelines on the return to physical activity following deep vein thrombosis (DVT) or pulmonary embolism (PE), particularly while being treated with anticoagulation. Objective: This scoping review aimed to examine the current literature on physical activity beyond simple ambulation for patients with DVT/PE being treated with anticoagulation. Data Sources: An electronic search for articles in MEDLINE, Epub Ahead of Print, In-Process, and Other Non-Indexed Citations, Daily (1946 to April 4, 2022), and Embase+Embase Classic (1946 to 2022, week 13) was conducted. Study Selection: (1) Patients of any age with DVT/PE, treated with anticoagulation; (2) studies of any design providing information on physical activity (ie, sport, exercise) while on anticoagulation; and (3) studies in English. Data Extraction: Data from eligible studies obtained included the study design, population, disease characteristics, and information on physical activity participation. Results: A total of 26 eligible studies were included. Only 2 studies were specific to children. Studies recommend a gradual return to participation in noncontact or low-risk activities after the first 3-4 weeks of anticoagulation, with close monitoring of symptoms. Participation in contact sports and activities is typically delayed until after anticoagulants are discontinued. However, personalized anticoagulation with intermittent dosing schedules has been proposed for athletes after the first 3 months of anticoagulation treatment. Conclusions: Physical activity participation guidelines for children with DVT/PE being treated with anticoagulation are needed, and the evidence currently available is limited. Largely based on evidence from adult patients, we present evidence-informed options to facilitate clinician recommendations for returning to activity.

Unraveling the pathophysiology of lower-limb postthrombotic syndrome in adolescents: a proof-of-concept study.

A better understanding of the pathophysiology of pediatric postthrombotic syndrome (PTS) is needed to develop strategies to treat this condition. We investigated calf pump function, exercise capacity, balance in power output, and changes in limb muscle oxygen saturation (SmO2) and fluid content during exercise in 10 pediatric patients with unilateral lower-limb PTS, and in age- and sex-matched controls (1:1-1:2 ratio). Outcomes were investigated using bioimpedance spectroscopy, torque-sensing pedals, and near-infrared spectroscopy during incremental- and constant-load cycling tests. The median age at participation was 17 years (25th-75th percentile, 15-18 years); 68% of participants were females. The median CAPTSure score in the affected leg of affected participants was 35 points (25th-75th percentile, 24-46 points), indicating moderate/severe PTS; 20% of patients had a history of central venous catheter-related thrombosis. Increasing PTS severity was associated with higher calf pump venous volume and higher ejection volume, leading to compensated calf pump performance. We found no evidence of PTS impact on exercise capacity. Leg contribution to power output was similar in affected and unaffected legs. However, the PTS-affected legs showed lower SmO2 during active cycling and recovery with increasing PTS severity, indicating impaired microvascular function in the muscle. These findings suggest that PTS severity is associated with impaired blood flow, presumably from elevated venous pressure during and after exercise. The fact that microvascular function is impaired in young patients with PTS underscores the relevance of developing strategies to mitigate the effects of this chronic vascular disease to minimize its deleterious effects as children grow older.

Functional impact of pediatric postthrombotic syndrome.

BACKGROUND: Postthrombotic syndrome (PTS) is the most common complication of deep vein thrombosis (DVT) in children. OBJECTIVES: We aimed to assess the impact of pediatric PTS on functioning as assessed by movement ability, mobility, functional disability, and physical activity levels in children after diagnosis of limb DVT. METHODS: Patients aged 8-21 years in follow-up care after objectively documented limb DVT were prospectively recruited in this cross-sectional study. Measures of functioning (outcomes) included self-reported questionnaires that assessed: 1) movement ability, measured with the Movement Ability Measure-Computer Adaptive Test version; 2) mobility, evaluated with the Computer Adaptive Test version of the Patient-Reported Outcomes Measurement Information System Pediatric Physical Functioning, Mobility domain; 3) functional disability, evaluated with the Functional Disability Inventory; and 4) physical activity levels, evaluated with the Godin Leisure-Time Exercise Questionnaire. The main predictor was PTS severity, which was assessed using the index for the Clinical Assessment of PTS in children. The association between PTS and outcomes was analyzed using linear models. RESULTS: Eighty-seven patients (median age, 16 years; 25th-75th percentile, 15-18 years; 56% boys) were enrolled. Adjusted for age, sex, and underlying condition, increasing PTS severity was associated with lower current movement ability, a wider gap between current vs preferred movement ability, lower mobility, and slightly higher functional disability scores. There was a nonsignificant effect of PTS severity on moderate-strenuous physical activity. CONCLUSION: In children, increased PTS severity is associated with lower movement ability and impaired mobility. Reducing the gap between the patients' current vs preferred movement ability is a relevant aspect of PTS management in children.

Can thrombophilia predict recurrent catheter-related deep vein thrombosis in children?

The role of thrombophilia testing in predicting catheter-related deep vein thrombosis (DVT) after an incident (ie, first) catheter-related DVT in children remains unclear. The present study investigated the association between thrombophilia and recurrent catheter-related DVT. Children with thrombophilia testing, performed according to the clinician's judgment and the family's preference, and a history of objectively confirmed catheter-related DVT were included in the study. Recurrent catheter-related DVT after placement of a new catheter was the main outcome. Thrombophilia was classified as minor, major, or none. Analysis was conducted using mixed effect logistic regression. A total of 245 patients had 1,365 catheters inserted; 941 of these catheters were placed after the incident catheter-related DVT. Anticoagulants as treatment or prophylaxis were administered in 78.1% of inserted catheters for at least 50% of the time they were in place. Minor thrombophilia was found in 12.7% of patients, whereas major thrombophilia was seen in 8.2% of children. The incidence rate of recurrent events was 0.23/100 catheter-days (95% confidence interval, 0.19-0.28 catheter-days); 34.3% (95% confidence interval, 28.6%-40.0%) of patients requiring a new catheter after their incident thrombotic event had at least 1 recurrent event. The incidence proportion of bleeding complications was 4.6/100 patients receiving anticoagulation. Young age of the patient at the time of catheter insertion and lack of administration of treatment or prophylactic doses of anticoagulant were predictive of recurrent events. In contrast, thrombophilia was not predictive of recurrent catheter-related DVT during subsequent catheter insertions among tested patients. Our findings suggest that thrombophilia testing to predict recurrence in these patients may be unnecessary.