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Concise Critical Appraisal: Continued Rise of Venous Thromboembolism Across US Children’s Hospitals

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Daniel E. Sloniewsky, MD, FCCM
06/08/2022

Has the rate of venous thromboembolism (VTE) in children changed over time? A 2009 study reported a 70% increase in VTE in acutely and chronically ill children. The reasons for this increase were not clear but were postulated to be related to improved survival of critically ill children, increased use of central venous catheters, and increased prevalence of adolescent obesity. This Concise Critical Appraisal dives into a 2022 article that sought to determine whether the rate of VTE continued to increase between 2008 and 2019.
 
While the incidence of venous thromboembolism (VTE) in healthy children is rare, it is much higher in acutely and chronically ill children. In 2009, Raffini et al reported a 70% increase in VTE incidence between 2001 to 2007, primarily in this population.1 The reasons for this increase were not clear but were postulated to be related to improved survival of critically ill children, increased use of central venous catheters (CVCs), and increased prevalence of adolescent obesity. In a 2022 study, O’Brien et al sought to determine whether the rate of VTE continued to increase between 2008 and 2019.2
 
Similarly to the 2009 study, the authors of this work performed a retrospective multicenter study using the Pediatric Health Information System database, which collects data from nonprofit tertiary care children’s hospitals, representing about 25% of all pediatric centers in the United States. The authors searched for all admissions with an ICD-9 or ICD-10 diagnostic code for deep venous thrombosis or pulmonary embolism. They then recorded demographic data and VTE rates in different age groups and classified subjects according to their complex chronic conditions (CCCs), if any. They also looked at pharmacy data to determine anticoagulant use. Finally, they included an analysis of potential risk factors associated with VTE.
 
During the 12-year study period, there were 52,401 admissions with a diagnosis of VTE in 39,713 pediatric patients. Compared to the earlier Raffini study, the rate of VTE admissions increased by 130%, from 46/10,000 admissions to 106/10,000 admissions. As in the Raffini study, there was a bimodal age distribution; approximately one-third of the patients were younger than one year and another one-third were between ages 13 and 18 years. The relative risk of having a VTE on admission was highest in the adolescent population. In fact, the authors found that a VTE diagnosis was reported in more than 1 of every 100 inpatient admissions for 15- to 17-year-old patients.
 
The authors also cited some differences between patients admitted with VTE and those with other admitting diagnoses. Compared with the non-VTE admissions, patients with VTE were older (median 5.2 years vs. 3.8 years in the non-VTE group) and had longer hospital stays (median 30 days vs. 3 days in the non-VTE group). VTE patients were also more likely than non-VTE patients to have an underlying CCC. This number was higher than that in the earlier study (78% vs. 62%). The most commonly associated CCCs were cardiovascular, gastrointestinal, and neurologic conditions. Notably, the incidence of CCC was lower in the older adolescents with VTE than in those younger than 15 years.
 
The authors briefly discuss the risk factors associated with VTE in children—namely CVC placement, obesity, and CCC—although this study was not designed to explore these risk factors and does not report on the incidence of catheter placement or body mass index. Risk factors for VTE have been delineated in other studies. For example, Jaffray et al listed the risk factors for VTE, in decreasing order, as CVC, surgery, steroids, congenital heart disease, infection, and cancer.3
 
Finally, this study touches on the use of anticoagulants in the treatment of VTE. Enoxaparin use remained static during the study period, and the use of warfarin declined from 9% of VTE admissions in 2008 to 4% of VTE admissions in 2019. The authors noted that the use of direct anticoagulants was increasing in children since they were first noted in the data in 2014. While their use is still limited (3% of VTE admissions in 2019), it appears to be increasing.
 
This study has several limitations. The authors used ICD-9 and ICD-10 codes in their search, while only ICD-9 codes were available during the Raffini study, which could have affected the number of patients in the study. Also, the authors did not study risk factors other than CCCs, such as the number of CVCs used, which could have been useful. Finally, this study could not differentiate between hospital-acquired VTE and primary VTE, which would also help delineate risk factors.
 
Rates of VTE have been increasing in children, although the reason for this rise is not clear. This study supports the need for more research-driven VTE prevention and treatment strategies, which is important because hospital-acquired VTE is increasingly considered a patient safety issue.
 
References
  1. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children’s hospitals in the United States from 2001 to 2007. Pediatrics. 2009 Oct;124(4):1001-1008. https://pubmed.ncbi.nlm.nih.gov/19736261/
  2. O’Brien SH, Stanek JR, Witmer CM, Raffini L. The continued rise of venous thromboembolism across US children’s hospitals. Pediatrics. 2022 Mar 1;149(3):e2021054649. https://pubmed.ncbi.nlm.nih.gov/35156127/
  3. Jaffray, J, Mahajerin A, Young G, et al. A multi-institutional registry of pediatric hospital-acquired thrombosis cases: the children’s hospital-acquired thrombosis (CHAT) project. Thromb Res. 2018 Jan;161:67-72. https://pubmed.ncbi.nlm.nih.gov/29207321/
 

Daniel E. Sloniewsky, MD, FCCM
Author
Daniel E. Sloniewsky, MD, FCCM
Daniel E. Sloniewsky, MD, FCCM, is an associate professor in the Division of Pediatric Critical Care Medicine in the Department of Pediatrics at Stony Brook Long Island Children’s Hospital. Dr. Sloniewsky is an editor of Concise Critical Appraisal.
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