Corrigendum to ' Recurrent venous thromboembolism in hospitalized children with a history of prior venous thromboembolism: a report from the Children's Hospital-Acquired Thrombosis Consortium' [Research and Practice in Thrombosis and Haemostasis Volume 7, Issue 5, July 2023, 102139].

[This corrects the article DOI: 10.1016/j.rpth.2023.102139.].

Evaluation of venous thromboembolism risk factors reveals subtype heterogenicity in children with central venous catheters: a multicenter study from the Children's Hospital Acquired Thrombosis consortium.

BACKGROUND: Acutely ill and medically complex children frequently rely on central venous catheters (CVCs) to provide life-sustaining treatment. Unfortunately, catheter-related thrombosis (CRT) is a serious and common complication. Little is known why some with a CVC develop CRT and others develop venous thromboembolism unrelated to the CVC (non-CRT). OBJECTIVES: The aim of this study was to identify factors associated with CRT in children with hospital-acquired venous thromboembolism (HA-VTE). METHODS: This case-case study included participants in the Children's Hospital Acquired Thrombosis Registry with HA-VTE and CVC aged 0 to 21 years from 8 US children's hospitals. Participants were excluded if they developed HA-VTE prior to CVC insertion or if the CVC insertion date was unknown. Logistic regression models were used to assess associations between clinical factors and CRT status. RESULTS: There were 1144 participants with HA-VTE who had a CVC. CRT developed in 833 participants, and 311 developed non-CRT. Multivariable analysis showed increased odds of CRT (compared with non-CRT) in participants with peripherally inserted central catheters (odds ratio [OR], 3.80; 95% CI, 2.04-7.10; p < .001), CVCs inserted in the femoral vein (OR, 4.45; 95% CI, 1.70-11.65; p = .002), multiple CVCs (OR, 1.42; 95% CI, 1.18-1.71; p < .001), and CVC malfunction (OR, 3.30; 95% CI, 1.80-6.03; p < .001). CONCLUSION: The findings of this study provide new insights on risk factor differences between CRT and non-CRT. Prevention efforts should be directed at modifying the type of CVC, insertion location, and/or number of CVCs placed, if possible, to decrease the incidence of CRT.

Risk factors for hospital acquired venous thromboembolism in congenital heart disease patients: A report from the children's hospital acquired thrombosis (CHAT) consortium.

INTRODUCTION: The incidence of pediatric hospital-acquired venous thromboembolism (HA-VTE) has increased over time. Congenital heart disease (CHD) as a co-morbidity has been demonstrated to significantly increase HA-VTE risk among hospitalized children. OBJECTIVE: To identify specific risks factors for the development of HA-VTE in hospitalized children with CHD. MATERIALS AND METHODS: This retrospective case-control study included hospitalized participants aged 0-21 years within the Children's Hospital Acquired Thrombosis (CHAT) Consortium Registry with a co-morbidity of CHD. Participants with HA-VTE and non-VTE controls with a past medical history of CHD were selected from the CHAT Registry and data regarding multiple clinical variables were extracted. These variables were then analyzed to assess their association with HA-VTE development. RESULTS: Three hundred and thirty-three participants with a co-morbidity of CHD were identified, comprising 275 HA-VTE cases and 58 controls. Median age for HA-VTE cases was 0.4 (IQR = 0-2.6) years compared to 3.4 (IQR = 0.7-6.5) for controls. Male participants were predominant in both groups (57.5 % HA-VTE cases vs 51.7 % controls). Multivariable analysis identified prior recent hospitalization (OR = 4.12, 95%CI = 1.66-10.24), intensive care unit (ICU) admission (OR = 3.29, 95 % CI = 1.15-9.40), and CVC placement (OR = 9.14, 95 % CI = 3.38-24.72) as significant risk factors for HA-VTE in subjects with CHD. CONCLUSIONS: ICU admission, CVC placement, and prior hospitalization were identified as statistically significant predictors associated with HA-VTE development in hospitalized children with history of CHD. Prospective studies are needed to validate these results and help develop strategies to mitigate HA-VTE development in these patients.

Risk of venous thromboembolism in pediatric hospitalized patients undergoing noncardiac surgery: A report from the Children's Hospital-Acquired Thrombosis consortium.

Background: Surgery is a known risk factor for hospital-acquired venous thromboembolism (HA-VTE) in children. Objectives: To assess whether the odds of HA-VTE differs across six anatomic sites of noncardiac surgery and to identify risk factors for HA-VTE in these children. Methods: This was a multicenter, case-control study. Anatomic sites of surgery and risk factors for HA-VTE were collected on hospitalized pediatric patients who had undergone a single noncardiac surgery and developed HA-VTE (cases), and those who did not develop HA-VTE (controls), via the Children's Hospital-Acquired Thrombosis (CHAT) Registry. Logistic regression estimated the odds ratio (OR) and 95% confidence intervals (CIs) between six anatomic sites of surgery and 16 putative HA-VTE risk factors. Variables with a p value of 0.10 or less in unadjusted analyses were included in adjusted models for further evaluation. The final model used backward selection, with a significance level of 0.05. Results: From January 2012 to March 2020, 163 cases (median age, 5.7 years; interquartile range [IQR], 0.3-14.2) and 208 controls (median age of 7.5 years; IQR, 3.7-12.9) met our criteria. There was no statistically significant increased odds of VTE among the types of noncardiac surgery. In the final adjusted model, central venous catheter (CVC; OR, 14.69; 95% CI, 7.06-30.55), intensive care unit (ICU) stay (OR, 5.31; 95% CI, 2.53-11.16), and hospitalization in the month preceding surgery (OR, 2.75; 95% CI, 1.24-6.13) were each independently significant risk factors for HA-VTE. Conclusion: In children undergoing noncardiac surgery, placement of CVCs, admission/transfer to the ICU, or hospitalization in the month prior to surgery were positively associated with HA-VTE.

Current practices in pediatric hospital-acquired thromboembolism: Survey of the Children's Hospital Acquired Thrombosis (CHAT) Consortium.

Background: A rise in hospital-acquired venous thromboembolism (HA-VTE) in children has led to increased awareness regarding VTE prophylaxis and risk assessment. Despite no consensus exists regarding these practices in pediatrics. Objective: To describe common practices in VTE prophylaxis, VTE risk assessment models, and anticoagulation dosing strategies in pediatric hospitals that are members of the Children's Hospital Acquired Thrombosis (CHAT) Consortium. Methods: An electronic survey of 44 questions evaluating practices surrounding pediatric HA-VTE risk assessment and prevention was distributed between August 9, 2021, and August 30, 2021, to the primary investigators from the 32 institutions within the CHAT Consortium. Results: The survey response rate was 100% (n = 32). In total, 85% (n = 27) of the institutions assess HA-VTE, but only 63% (n = 20) have formal hospital guidelines. Within the institutions with formal guidelines, 100% (n = 20) include acute systemic inflammation or infection and presence of a central venous catheter (CVC) as risk factors for VTE. Pharmacologic prophylaxis is prescribed at 87% (28) of institutions, with enoxaparin being the most frequent (96%, n = 27). Variability in responses persisted regarding risk factors, risk assessment, thromboprophylaxis, dosing of prophylactic anticoagulation or anticoagulant drug monitoring. A majority of providers were comfortable providing thromboprophylaxis across all age groups. In addition, the global coronavirus disease 2019 increased the providers' use of prophylactic anticoagulation 78% (n = 25). Conclusion: Practices among institutions are variable in regard to use of HA-VTE prophylaxis, risk assessment, or guideline implementation, highlighting the need for further research and a validated risk assessment model through groups like the CHAT Consortium.

Symptomatic pulmonary embolus after catheter removal in children with catheter related thrombosis: A report from the CHAT Consortium.

BACKGROUND: Appropriate timing of central venous catheter (CVC) removal, in relation to start of anticoagulation, in children after the diagnosis of a CVC-related thrombosis (CRT) is not well established. OBJECTIVES: This retrospective cohort study evaluated the incidence of symptomatic pulmonary embolism (PE) after CVC removal using data from the multi-institutional Children's Hospital-Acquired Thrombosis (CHAT) Consortium Registry. PATIENTS/METHODS: The CHAT Registry consists of data from children aged 0-21 years with a hospital-acquired venous thromboembolism. Eligible subjects were those with CRT diagnosed <3 days after CVC removal. Subjects were excluded if the CRT was due to a failed CVC insertion. Subjects were divided into three groups: those with CVC removal without anticoagulation, those with CVC removal <48 h after starting anticoagulation, and those with CVC removal ≥48 h after starting anticoagulation. RESULTS: A total of 687 CRT events from 663 subjects were included. A majority of CRT events were in subjects with peripherally inserted central catheters (62.3%, n = 428). For the 611 CRT events in which the CVC was removed, there was only one case of symptomatic PE (0.16%), which occurred <48 h after initiation of anticoagulation. CONCLUSIONS: While current guidelines suggest anticoagulation before CVC removal in the setting of a CRT to prevent embolization, CVC removal is not associated with symptomatic PE regardless of duration of anticoagulation before CVC removal.

A New Risk Assessment Model for Hospital-Acquired Venous Thromboembolism in Critically Ill Children: A Report From the Children's Hospital-Acquired Thrombosis Consortium.

OBJECTIVES: 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 hospital-acquired 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.

Development of a Risk Model for Pediatric Hospital-Acquired Thrombosis: A Report from the Children's Hospital-Acquired Thrombosis Consortium.

OBJECTIVE: To identify pertinent clinical variables discernible on the day of hospital admission that can be used to assess risk for hospital-acquired venous thromboembolism (HA-VTE) in children. STUDY DESIGN: The Children's Hospital-Acquired Thrombosis Registry is a multi-institutional registry for all hospitalized participants aged 0-21 years diagnosed with a HA-VTE and non-VTE controls. A risk assessment model (RAM) for the development of HA-VTE using demographic and clinical VTE risk factors present at hospital admission was derived using weighted logistic regression and the least absolute shrinkage and selection (Lasso) procedure. The models were internally validated using 5-fold cross-validation. Discrimination and calibration were assessed using area under the receiver operating characteristic curve and Hosmer-Lemeshow goodness of fit, respectively. RESULTS: Clinical data from 728 cases with HA-VTE and 839 non-VTE controls, admitted between January 2012 and December 2016, were abstracted. Statistically significant RAM elements included age <1 year and 10-22 years, cancer, congenital heart disease, other high-risk conditions (inflammatory/autoimmune disease, blood-related disorder, protein-losing state, total parental nutrition dependence, thrombophilia/personal history of VTE), recent hospitalization, immobility, platelet count >350 K/µL, central venous catheter, recent surgery, steroids, and mechanical ventilation. The area under the receiver operating characteristic curve was 0.78 (95% CI 0.76-0.80). CONCLUSIONS: Once externally validated, this RAM will identify those who are at low-risk as well as the greatest-risk groups of hospitalized children for investigation of prophylactic strategies in future clinical trials.

Laboratory misdiagnosis of von Willebrand disease in post-menarchal females: A multi-center study.

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 (McNemar's 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.

Comparative validation study of risk assessment models for pediatric hospital-acquired venous thromboembolism.

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.

A multi-institutional registry of pediatric hospital-acquired thrombosis cases: The Children's Hospital-Acquired Thrombosis (CHAT) project.

BACKGROUND: Pediatric hospital-acquired venous thromboembolism (HA-VTE) rates have increased dramatically. To achieve generalizable knowledge in the derivation and validation of HA-VTE risk factors and risk prediction models and inform future risk-stratified prevention strategies, multi-institutional studies are needed. OBJECTIVES: This paper presents an investigator-initiated, multicenter pediatric case-cohort study designed to identify risk factors for HA-VTE to create a HA-VTE risk prediction model. METHODS: A registry, which houses pertinent variables from HA-VTE subjects and non-HA-VTE controls, was created for the Children's Hospital-Acquired Thrombosis (CHAT) study. Specific variables from the registry associated with HA-VTE risk will be identified using multivariable regression to create a pediatric HA-VTE risk prediction model to be prospectively validated. RESULTS: Seven large pediatric institutions have entered over 600 HA-VTE subjects aged 0-21years of age into the registry. Subjects showed a male predominance (57%), a median age of three years (IQR 0.3-13) and were most likely admitted to an intensive care unit (57%) at VTE diagnosis. Median time to HA-VTE was 10days after admission. The most prevalent risk factors include central venous catheters (80%), surgery (43%), systemic steroids (31%), congenital heart disease (27%), infection (14%) and cancer (13%). CONCLUSIONS: CHAT, with its creation of a risk prediction model with prospective validation using the CHAT registry, is a novel study design and will be the first step in identifying safe and effective strategies to decrease HA-VTE in children by helping define the highest risk population for initial, or more aggressive, thromboprophylaxis efforts.