To create a risk model for hospital-acquired venous thromboembolism in critically ill children upon admission to an ICU.
DESIGN:Case-control study.
SETTING:ICUs from eight children's hospitals throughout the United States.
SUBJECTS:Critically ill children with hospital-acquired venous thromboembolism (cases) 0-21 years old and similar children without hospital-acquired venous thromboembolism (controls) from January 2012 to December 2016. Children with a recent cardiac surgery, asymptomatic venous thromboembolism, or a venous thromboembolism diagnosed before ICU admission were excluded.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS:The multi-institutional Children's Hospital-Acquired Thrombosis registry was used to identify cases and controls. Multivariable logistic regression was used to determine the association between hospital-acquired venous thromboembolism and putative risk factors present at or within 24 hours of ICU admission to develop the final model. A total of 548 hospital-acquired venous thromboembolism cases (median age, 0.8 yr; interquartile range, 0.1-10.2) and 187 controls (median age, 2.4 yr; interquartile range, 0.2-8.3) were analyzed. In the multivariable model, recent central venous catheter placement (odds ratio, 4.4; 95% CI, 2.7-7.1), immobility (odds ratio 3.6, 95% CI, 2.1-6.2), congenital heart disease (odds ratio 2.9, 95% CI, 1.7-4.7), length of hospital stay prior to ICU admission greater than or equal to 3 days (odds ratio, 2.5; 95% CI, 1.1-5.6), and history of autoimmune/inflammatory condition or current infection (odds ratio, 2.1; 95% CI, 1.2-3.4) were each independently associated with hospital-acquired venous thromboembolism. The risk model had an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.73-0.84).
CONCLUSIONS:Using the multicenter Children's Hospital-Acquired Thrombosis registry, we identified five independent risk factors for hospitalacquired venous thromboembolism in critically ill children, deriving a new hospital-acquired venous thromboembolism risk assessment model. A prospective validation study is underway to define a high-risk group for risk-stratified interventional trials investigating the efficacy and safety of prophylactic anticoagulation in critically ill children.
Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off‐site laboratory processing, instead of a coagulation facility with onsite processing. Off‐site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off‐site and onsite specimen processing for VWD in this multicenter, retrospective study. We enrolled females aged 12 to 50 years who had off‐site specimen processing for VWF assays, and repeat testing performed at a consulting institution with onsite coagulation phlebotomy and processing. A total of 263 females from 17 institutions were included in the analysis. There were 251 subjects with both off‐site and onsite VWF antigen (VWF:Ag) processing with 96 (38%) being low off‐site and 56 (22%) low onsite; 223 subjects had VWF ristocetin co‐factor (VWF:RCo), 122 (55%) were low off‐site and 71 (32%) were low onsite. Similarly, 229 subjects had a Factor VIII (FVIII) assay, and 67 (29%) were low off‐site with less than half, 29 (13%) confirmed low with onsite processing. Higher proportions of patients demonstrated low VWF:Ag, VWF:RCo, and/or FVIII with off‐site processing compared to onsite (McNemarʼs test P‐value <.0005, for all assays). These results emphasize the need to decrease delays from sample procurement to processing for VWF assays. The VWF assays should ideally be collected and processed at the same site under the guidance of a hematologist.
Background
Risk assessment models (RAMs) have been developed to identify children at high risk of hospital‐acquired venous thromboembolism (HA‐VTE). None have been externally validated nor compared.
Objectives
The objective was to compare performance of these RAMs by externally validating them using the Children's Hospital‐Acquired Thrombosis (CHAT) Registry, ie, a multicenter database of children with radiographic‐confirmed HA‐VTE and corresponding controls.
Patients/Methods
Risk assessment models were included if the full logistic regression equation was available and all RAM variables were collected in the CHAT Registry. A random sample of 200 cases and 200 controls was selected. The performance of the RAMs was assessed for discrimination using area under the receiver operating characteristic curves (AUROC), and calibration using plots, slopes, and intercepts, and the Hosmer‐Lemeshow test.
Results
Three RAMs were included. Each had excellent discrimination with AUROC ≥ 0.85. However, calibration was generally poor, with calibration slopes significantly different from 1 (0.71, P < .001; 1.44, P = .002; 0.68, P < .001), intercepts significantly different from 0 (−1.64, P < .001; −0.62, P < .001; 0.78, P < .001), and Hosmer‐Lemeshow test P < .001 for each. Exceptions included the Arlikar et al and Atchison et al RAMs for pediatric HA‐VTE in non‐intensive care unit (ICU) patients and ICU patients, respectively, despite derivation from ICU and non‐ICU patients, respectively. In these subpopulations, both showed excellent discrimination and good calibration.
Conclusion
Given the lack of adequate calibration for evaluated RAMs, further investigation and refinement of RAMs for pediatric HA‐VTE is needed prior to application of a RAM in a clinical setting or risk‐stratified clinical trial of primary thromboprophylaxis against HA‐VTE in children.
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