New Recommendations Provide a Framework for Better Decision-Making 

When children are hospitalized with an illness or after experiencing severe trauma or undergoing surgery, the required immobilization and invasive, life-saving treatments they receive can put them at risk for a medical condition that triggers the blood to clot too easily. This can lead to the development of blood clots in the veins, called venous thromboembolism (VTE), which can have significant short-term and long-term consequences for pediatric patients.

Pediatric VTE is considered rare in healthy children but is being seen increasingly in children who are hospitalized. In fact, hospital-acquired VTE is the second most common cause of preventable harm in children, yet until now there has been little consensus on strategies for VTE prevention, and what that care should involve, prompting new clinical guidelines to improve prevention and care.

Recently, the American Society of Hematology (ASH) and the International Society on Thrombosis and Haemostasis (ISTH) released comprehensive clinical practice guidelines on anticoagulant prophylaxis, or preventative measures, in non-cardiac pediatric patients at risk of VTE. Noting a scarcity of quality data on VTE in pediatric patients, an expert panel co-chaired by a Johns Hopkins All Children’s pediatric hematologist developed the evidence-based guidelines following a rigorous review process and published them in the peer-reviewed ASH journal, Blood Advances.

The new guidelines are intended to help clinicians more thoroughly weigh the benefits and risks of VTE prevention in pediatric patients.

What Is Pediatric VTE?

A simple definition of VTE is the formation of blood clots in in the deep veins of the body, called deep vein thrombosis or DVT — including those that have traveled to the arteries of the lungs, called pulmonary embolism or PE). Commonly seen in elderly adult patients, VTE can be caused by long periods of immobility during travel or a hospital stay, certain medications, surgery or injuries that trigger the blood to clot too easily.

In children who are hospitalized, those with chronic medical conditions, being treated in the pediatric intensive care unit (PICU), getting a central line or undergoing long surgeries, the condition is becoming more common. Potential complications of VTE can include rare but serious lung and heart damage from pulmonary embolism, the long-term pain and swelling of post-thrombotic syndrome (due to poor functioning of veins after damage from a blood clot), and an overall reduced quality of life due to the greater lifetime burden in children compared with older adults. 

Who is Most at Risk for Pediatric VTE?

• Cancer patients
• ICU patients
• Surgical patients
• Trauma patients
• Children with central lines
• Patients on parenteral nutrition (the administration of nutrients directly into the bloodstream via a central vein catheter).
• Children with conditions like antiphospholipid syndrome (APS), an autoimmune disorder where the immune system creates faulty antibodies that attack cells, causing the blood to clot inappropriately in veins and arteries.

Understanding a Vulnerable and Complex Patient Group

Marisol Betensky, M.D., M.P.H., an associate professor of Pediatrics in the Division of Hematology at the Johns Hopkins University School of Medicine and a pediatric hematologist in the Johns Hopkins All Children’s Cancer & Blood Disorders Institute in St. Petersburg, Florida, co-chaired the ASH-ISTH panel developing the new practice guidelines. As director of the hospital's pediatric thrombosis program, Betensky has treated many patients with complex thrombotic disorders. Following residency and fellowship at the Children's Hospital of Philadelphia, Betensky came to Johns Hopkins All Children’s nearly 10 years ago to work under the mentorship of Neil Goldenberg, M.D., Ph.D., associated dean for research at Johns Hopkins All Children’s and an internationally recognized expert in pediatric thrombosis.

Betensky says the panel’s recommendations will provide a more complete, evidence-based framework to help clinicians refine their decision-making when caring for this vulnerable and medically complex patient group. Prior to the work of this panel of more than 30 researchers, much of the medical and scientific thinking around VTE prevention in pediatric patients was applied from an adult patient population with generally less varied and complex risk profiles. That’s why Betensky says she is particularly grateful for the pediatric patients and families who participated in the research performed to date on VTE prevention in children and who continue to partner with medical professionals to help refine the care children receive when they are admitted to the hospital, require surgery or are chronically ill.

Addressing VTE’s ‘Stacking’ Risk Factors

According to Betensky, healthy kids will rarely develop VTE, but those who are hospitalized, after severe trauma to the pelvis or legs for example, can have multiple VTE risk factors leading to short-or-long-term complications. In this scenario, the child would require surgery, followed by a potentially long stay in the pediatric ICU and a period of immobilization, which itself can be traumatic to a growing young body accustomed to being in seemingly perpetual motion. These and other risk factors, she says, can add up.

“We know that being hospitalized for more than three days is a risk factor for thrombosis. Then there’s surgery. We know that surgeries greater than 30 minutes with general anesthesia are a risk factor. Then there's ‘critical illness’ — the types of severe conditions that require often life-saving care in a pediatric intensive care unit. So, it’s easy to see how, for kids, the risk factors stack on top of each other until reaching the threshold for thrombosis,” Betensky says.

Paradoxically, invasive life-sustaining or medically stabilizing interventions during a lengthy hospital stay, like the insertion of a central line to administer medications or long-term parenteral nutrition, can elevate the risk of blood clots.

Emphasizing the far-reaching impact of the new practice guidelines, Goldenberg says, "These new guidelines, of which a Johns Hopkins All Children’s Thrombosis Program director and internationally recognized pediatric thrombosis researcher serves as lead author among a multinational multidisciplinary group of experts, will inform clinical care on thrombosis prevention in young patients for years to come. Johns Hopkins All Children’s Hospital, Johns Hopkins University, and the field of pediatric thrombosis are fortunate to have Dr. Betensky's expertise and leadership in improving the care and outcomes for the growing numbers of children at risk for thrombosis in the hospital and in our communities."

How Can VTE be Prevented?

VTE prevention (also known as prophylaxis) can be accomplished through various pharmacological or mechanical measures.

Pharmacological agents are the same anticoagulant medications that are used to treat VTE when it occurs, but typically employed at lower doses or a reduced frequency of administration, for prevention purposes. They include (among other medications) heparin-based agents like enoxaparin (Lovenox) and direct oral anticoagulants, such as rivaroxaban (Xarelto) and apixaban (Eliquis).

Mechanical measures may include devices that promote blood flow and/or reduce blood stasis (impaired blood circulation), such as compression stockings, intermittent pneumatic compression devices with cuffs on the legs that inflate and deflate, or venous foot pumps.

Because preventive approaches with anticoagulants carry some risk, the need for clear and pediatric-specific practice recommendations is critical.

New Guidelines for Better Clinical Decision-Making

The guideline panel noted a scarcity of high-quality data on anticoagulant prophylaxis for pediatric VTE, and that, despite the emergence of VTE as “a significant cause of morbidity in children, particularly among hospitalized patients and those with chronic medical conditions,” existing prophylaxis guidelines were based largely on data from adult patients.

The panel agreed on 12 recommendations for the administration of anticoagulant prophylaxis to children at risk of developing VTE. A summary of their conditional recommendations includes guidance on administering preventive care to children at risk:

• In children with solid-tumor cancer including Hodgkin lymphoma, trauma or a critical illness, universal anticoagulant prophylaxis is not recommended.
• In children with antiphospholipid syndrome or those on long-term total parenteral nutrition, anticoagulant prophylaxis is conditionally recommended.
• In each recommendation, the panel identified subgroups of patients that may benefit from prophylactic anticoagulation such as patients with acute lymphoblastic leukemia receiving asparaginase therapy or critically-ill children older than 1 year of age with short-term central lines.
• The guidelines also encourage hospitals to develop protocols to manage interruptions to therapy, particularly for patients undergoing lumbar puncture or spinal anesthesia procedures.
• The panel also emphasized the need for further research to develop VTE risk assessment models for the pediatric patient population, and to evaluate the safety and efficacy of preventive measures across different pediatric patient subgroups.

Betensky says her team at All Children’s was already ahead of the curve, utilizing their own electronic medical record-based screening tools for VTE prophylaxis. Does the patient have a central line? Does the patient have a history of clots? These questions and more about risk factors provide a score to help clinicians decide on whether to provide prophylaxis, and whether pharmacological or mechanical measures are called for.

Now, the new guidelines will allow them to refine their screening tools and develop a better understanding of how to use VTE prophylaxis across various patient subgroups and make even better decisions alongside the patients and their families. “At the end of the day,” Betensky adds, “we’re hoping we will be able to prevent these events in children.”

For more information on pediatric VTE, please see “Blood Clots in Children,” from the National Blood Clot Alliance.