A clear understanding of the long-term consequences of pediatric pulmonary embolism (PE), a blood clot that blocks blood flow to an artery in the lungs, is limited, occurring in less than ∼ 10% of all cases and predominantly in neonates and adolescents. However, due to the fact that many cases of pediatric pulmonary embolism remain unrecognized, the exact incidence is unknown but is considered less common when compared with adults patients. In addition, while pediatric pulmonary embolism is distinct from adult PE, the medical literature regarding PE in children is relatively sparse. This is, in part, caused by the fact that most pediatric researchers face financial, regulatory, institutional, ethical, and career challenges, which place pediatric research at a distinct disadvantage compared to adult-focused medical research. As a result, the current guidelines for the management of pulmonary embolism in children are, therefore, mostly extrapolated from adult literature. [1][2][3]

Now, results from a single-center institution cohort study describe the long-term outcomes of PE in children. In this study by researchers from The Hospital for Sick Children (SickKids)* in Toronto, Canada, researchers used a local protocol that included clinical evaluation, chest imaging, echocardiography, pulmonary function tests, and cardiopulmonary exercise tests at follow-up, starting 3-6 months after acute PE.

Long-term effects
This study is the first one to comprehensively examine the long-term effects of pulmonary embolisms, or PEs, the most common and serious type of blood clots in the lungs in children, severe long-term complications were rare. The results show that the most common complications, shortness of breath and reduced exercise capacity, which are seen in about one-third of patients, were transient or could be alleviated by lifestyle changes such as greater physical activity. [4]

The study, based on 18 years of data, was published in the journal Blood, a journal of the American Society of Hematology (ASH). [4]

Thromboembolic PE in children: A serious condition
A pulmonary embolism (PE) is one of the most serious types of blood clot and, without immediate treatment, can be life-threatening. The most common type of PE is thromboembolic PE, which occurs when a blood clot in an arm or leg becomes dislodged and travels to the lungs.

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“This is the first study to examine the long-term functional outcomes of thromboembolic PE in children,” explained Laura Avila, MD, PhD, of The Hospital for Sick Children (SickKids) in Toronto, Canada, and lead author of the study.

Avila and her colleagues analyzed data for 150 children who, at a median age of 16, were diagnosed with and treated for a thromboembolic PE at SickKids between 2004 and 2022.

“We looked at a wider range of outcomes, including shortness of breath, exercise tolerance, and heart and lung function, than previous studies were able to do,” she said.

Avila said that the study findings are reassuring and show that the most severe long-term outcome in children who have had a PE – high blood pressure in the lungs due to chronic blood clots in the lungs – is rare and that focusing on a healthy lifestyle, including recommending regular physical activity, could help to prevent deconditioning, one of the most common reasons for reduced exercise capacity.

Promoting physical activity
“It’s so important to encourage a healthy lifestyle and develop strategies to promote physical activity in this population of children and teenagers,” she said, adding that nearly two out of three children with PE had one or more underlying conditions, such as autoimmune diseases, cancer, heart disease, or infectious diseases.

“Children at risk for blood clots tend to be those with serious illnesses who are inpatients at large, specialized hospitals,” Avila said.

By far the most common cause of blood clots among both children and adults in hospital settings is the use of a central venous catheter or central line. This is a long, flexible tube that’s used to deliver fluids, blood, or drugs to seriously ill hospitalized patients. The tube is threaded to the heart from a vein in the neck, chest, or arm. Using a central line reduces the need for needle sticks into a vein.

“Central lines help seriously ill patients survive, but their use can increase risk for blood clots,” Avila explained.

A study published in 2022 found that the rate at which children hospitalized in tertiary care institutions in the United States developed blood clots increased by 300% between 2001 and 2019.

Complications
SickKids began collecting data on the long-term complications of thromboembolic PE in children in 2004. Beginning at three to six months after their PE, children underwent a physical examination, a chest CT scan or a test of air and blood flow through the lungs, ultrasound examination of the heart (echocardiogram), lung function tests, and tests of their exercise capacity. Children made a median of three follow-up visits.

The study found that most children (61%) had an underlying health condition and 17% had more than one, including autoimmune diseases (22%), cancer (13%), infectious diseases (5%), and heart diseases (5%).

In the study, one patient developed the most severe long-term outcome, high blood pressure in the lungs due to old blood clots that limit blood flow into the lungs. Twenty-nine percent of patients had thickening of a blood vessel wall because of residual blood clots, 9% had a blood clot recurrence, and 5% died. Thirty-one percent (31%) had abnormal lung function tests, another 31% impaired exercise capacity, and 26% had shortness of breath with exertion or at rest; most of these abnormalities were transient. Patients with underlying conditions had higher rates of blood clot recurrence, more impairments of breathing or lung function, and poorer exercise capacity.

Most of the patients with shortness of breath had another condition, such as asthma or anxiety, that could explain their shortness of breath, Avila explained. The most common reason for impaired exercise capacity was inactivity resulting in lost muscle mass and general physical weakness.

Study limitation
One limitation of the study is that only half of the children who participated in the study completed exercise testing due to underlying conditions, lack of capacity, or for other reasons. Another limitation was the study’s relatively small size – although large for a pediatric study – and the low frequency of long-term problems meant that the researchers could not determine the effects of factors such as the severity of the pulmonary embolism, body mass index, age, and biological sex.

However, Avila concludes that these outcomes of the study give clearer expectations of potential longer-term effects of PE, offer reassurance, and allow clinicians to provide more informed patient and family counseling.

Note: * The Hospital for Sick Children (SickKids)* in Toronto, Canada is affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest center dedicated to improving children’s health in the country.

Reference
[1] Navanandan N, Stein J, Mistry RD. Pulmonary Embolism in Children. Pediatr Emerg Care. 2019 Feb;35(2):143-151. doi: 10.1097/PEC.0000000000001730. PMID: 30702542.
[2] Speer EM, Lee LK, Bourgeois FT, Gitterman D, Hay WW Jr, Davis JM, Javier JR. The state and future of pediatric research-an introductory overview : The state and future of pediatric research series. Pediatr Res. 2023 Jan 24:1–5. doi: 10.1038/s41390-022-02439-4. Epub ahead of print. PMID: 36694026; PMCID: PMC9873210.
[3] Dijk FN, Curtin J, Lord D, Fitzgerald DA. Pulmonary embolism in children. Paediatr Respir Rev. 2012 Jun;13(2):112-22. doi: 10.1016/j.prrv.2011.09.002. Epub 2011 Nov 21. PMID: 22475258.
[4] Bastas DM, Brandão LR, Vincelli J, Wilson D, Perrem L, Guerra V, Wong G, Bentley RF, Tole S, Schneiderman JE, Amiri N, Williams S, Avila L. Long-term Outcomes of Pulmonary Embolism in Children and Adolescents. Blood. 2023 Dec 22:blood.2023021953. doi: 10.1182/blood.2023021953. Epub ahead of print. PMID: 38134357.

Featured image Photo by Vitolda Klein on Unsplash. Used with permission.

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