Pediatric Hospital-acquired Venous Thromboembolism Research Articles

Reducing Pediatric Hospital-Acquired Venous Thromboembolism—Overcoming Challenges Using Quality Improvement

Reducing Pediatric Hospital-Acquired Venous Thromboembolism—Overcoming Challenges Using Quality Improvement

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

IntroductionThe 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. ObjectiveTo identify specific risks factors for the development of HA-VTE in hospitalized children with CHD. Materials and methodsThis 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. ResultsThree 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. ConclusionsICU 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.

The Children's Hospital-Acquired Thrombosis (CHAT) Consortium Admission Risk-Assessment Models from Traditional Biostatistics and Machine Learning

Introduction Incidence of pediatric hospital-acquired venous thromboembolism (HA-VTE) is increasing raising concern for acute and chronic sequelae and impact on the health care system. This has prompted many pediatric centers to implement prophylaxis programs despite the lack of a validated risk-assessment model (RAM) or evidence of a favorable risk/benefit ratio for pharmacologic prophylaxis. The multi-center Children's Hospital-Acquired Thrombosis (CHAT) Consortium was created in 2014 to derive RAMs with subsequent prospective validation (i.e. CHAT 1901, the second study from the CHAT Consortium). We present the CHAT RAMs using traditional biostatistical (CHAT-TB) and machine learning (CHAT-ML) methods. Methods The first project of the CHAT Consortium was an eight-center, retrospective, case-control study of subjects aged 0-21 years diagnosed with a radiographic-confirmed, symptomatic HA-VTE and frequency-matched controls (by year and hospital) from January 1, 2012 through December 31, 2016. Controls were randomly sampled from the complete list of children without HA-VTE hospitalized and the sampling proportion of controls with hospital stay < 48 hours was 20%. CHAT-TB: Weighted logistic regression examined univariate effects of variables known at baseline (prior to and on day of admission) on incidence of symptomatic HA-VTE. Key predictors with sufficient frequency and significance in univariate analyses progressed as candidates in the multivariable RAM developed via the Lasso method. Clinically important interaction effects were tested separately and considered a candidate predictor when the p-value of the interaction term was < 0.10. Five approximately equal-sized samples were used for internal validation. The RAM was built independently in each sub-sample and the model fit was tested in the n - sub-sample cohort. Receiver operating characteristic (ROC) curves were used to assess performance in both a model re-substitution and average of the 5-sample internal validation subsets. CHAT-ML: We developed and evaluated four machine learning (ML) models (adaptive boosting, random forest, gradient boosting, and logistic regression), and the most accurate RAM was selected by comparing the relationship of model specificity and sensitivity in ROC curves. ML modelling consists of: pre-processing and feature extraction, data profiling and exploration, model selection, training, and testing, model re-calibration in partnership with subject-matter experts. With more than 250 variables for each patient, lasso regression was utilized to reduce the number of features to have only those with non-zero weight in the regression. We then divided the dataset into training (n=1250) and test (n=540) groups and report the F1 score, i.e. the harmonic mean of precision (i.e. positive predictive value) and recall (i.e. sensitivity) which is used to measure accuracy of a ML classifier. Results Demographics are summarized in Table 1. CHAT-TB: Significant predictors from the weighted logistic regression model are shown in Table 2 and ROC curves from the model re-substitution and 5-sample internal validation demonstrate precision with AUC of 79.9% (CI: 77.7-82.1%) and 77.9% (75.6-80.2%), respectively. CHAT-ML: Significant clinical variables included: change in mobility as assessed by BradenQ scoring, CVC, congenital heart disease, presence of a complex chronic condition (Feudtner 2014), contraindication to VTE prophylaxis (Table 3), ICU admission, infection, and change in platelet count. Figure 1 shows that gradient boosting outperformed other models via area under the ROC curve (AUC=0.95) and F1-score (0.89). Adaptive boosting also performed well with AUC=0.93 and F1-score (0.87). Discussion We present two novel RAMs from the CHAT Consortium. The CHAT RAM-TB and RAM-ML demonstrate sufficient performance for prospective validation and RAM-ML shows a stronger AUC. CHAT 1901 is designed to validate the RAMs, assess performance individually and comparatively, and develop risk-assessment calculators for clinical use and/or integration into the electronic health record (specific to the CHAT-ML, a visual analytics application will provide an interface for clinicians to enter information on significant predictors and receive a calculated risk score). Disclosures Mahajerin: Spark: Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Kedrion: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau. Jaffray:CSL Behring: Research Funding. Croteau:Bayer: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria, Research Funding; Spark Therapeutics: Research Funding; Pfizer: Research Funding; Genentech: Consultancy, Honoraria; Octapharma: Honoraria; Genentech: Consultancy, Honoraria; Octapharma: Honoraria. Silvey:Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees. Goldenberg:NIH: Other: research support and salary support. Young:Kedrion: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria; Spark: Consultancy, Honoraria; Shire/Takeda: Consultancy, Honoraria; Uniqure: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria; Freeline: Consultancy, Honoraria; Genentech/Roche: Consultancy, Honoraria, Research Funding; Bioverativ/Sanofi: Consultancy, Honoraria; Grifols: Consultancy, Honoraria.

Quality Initiative to Introduce Pediatric Venous Thromboembolism Risk Assessment for Orthopedic and Surgery Patients.

Pediatric hospital-acquired venous thromboembolism (VTE) is costly, has high morbidity, and is often preventable. The objective of this quality-improvement effort was to increase the percentage of general surgery and orthopedic patients ≥10 years of age screened for VTE risk from 0% to 80%. At a freestanding children's hospital, 2 teams worked to implement VTE risk screening for postoperative inpatients. The general surgery team used residents and nurse practitioners to perform screening whereas the orthopedic team initially used bedside nursing staff. Both groups employed multiple small tests of change. Shared key interventions included refinement of a screening tool, provider education, mitigation of failures, and embedding the risk assessment task into staff workflow. The primary outcome measure, the percentage of eligible patients with a completed VTE risk assessment, was plotted on run charts. Secondary outcome measures for screened patients included the level of risk, the use of appropriate prophylaxis, and VTE events. Median weekly percentage of general surgery patients screened for VTE risk increased from 0% to 86% within 12 months, and median weekly percentage of orthopedic patients screened for VTE risk increased from 0% to 46% within 8 months. Among screened patients, the majority were at low or moderate risk for VTE and received prophylaxis in accordance with or beyond guideline recommendations. No screened patients developed VTE. Quality-improvement methods were used to implement a VTE risk screening process for postoperative patients. Using providers as screeners, as opposed to bedside nurses, led to a greater percentage of patients screened.

Development of a Surveillance System for Pediatric Hospital-Acquired Venous Thromboembolism.

Pediatric hospital-acquired (HA) venous thromboembolism (VTE) is a vexing problem with improvement efforts hampered by lack of robust surveillance methods to establish accurate rates of HA-VTE. At a freestanding children's hospital, a multidisciplinary team worked to develop a comprehensive surveillance strategy for HA-VTE. Starting with diagnosis codes, we implemented complementary detection methods, including clinical and radiology data, to develop a robust surveillance system. HA-VTE events were tracked by using descriptive statistics and a statistical process control chart. Detection methods were evaluated via retrospective application of each method to every identified HA-VTE. Initial detection method was tracked. A total of 68 HA-VTE events were identified and the median number of events per 1000 patient days increased from 0.18 to 0.34. No single detection method would have identified all events. Each detection method initially identified HA-VTE events. Implementation of multiple detection methods has optimized timely detection of HA-VTE. This allows the establishment of a reliable baseline rate, enabling quality improvement efforts to address HA-VTE.

Pediatric Hospital Acquired Venous Thromboembolism.

Pediatric hospital acquired venous thromboembolism (HA-VTE) is an increasing problem with an estimated increase from 5.3 events per 10,000 pediatric hospital admissions in the early 1990s to a current estimate of 30–58 events per 10,000 pediatric hospital admissions. Pediatric HA-VTE is associated with significant morbidity and mortality. The etiology is multifactorial but central venous catheters remain the predominant risk factor. Additional HA-VTE risk factors include both acquired (recent surgery, immobility, inflammation, and critical illness) and inherited risk factors. Questions remain regarding the most effective method to assess for HA-VTE risk in hospitalized pediatric patients and what preventative strategies should be implemented. While several risk-assessment models have been published in pediatric patients, these studies have limited power due to small sample size and require prospective validation. Potential thromboprophylactic measures include mechanical and pharmacologic methods both of which have associated harms, the most significant of which is bleeding from anticoagulation. Standard anticoagulation options in pediatric patients currently include unfractionated heparin, low molecular weight heparin, or warfarin all of which pose a monitoring burden. Ongoing pediatric studies with direct oral anticoagulants could potentially revolutionize the prevention and treatment of pediatric thrombosis with the possibility of a convenient route of administration and no requirement for monitoring. Further studies assessing clinical outcomes of venous thromboembolism (VTE) prevention strategies are critical to evaluate the effectiveness and harm of prophylactic interventions in children. Despite HA-VTE prevention efforts, thrombotic events can still occur, and it is important that clinicians have a high clinical suspicion to ensure prompt diagnosis and treatment to prevent further associated harms.

Thrombin Generation and Microparticles As Promising Biomarkers for Venous Thromboembolism in Children with Central Venous Lines

Background: Pediatric hospital-acquired venous thromboembolism (HA-VTE) has increased over the past ten years (Raffini et al. Pediatrics 2009; 124; 1001-1008), with an associated increase in both VTE-associated complications and treatment-related adverse events. Children with VTE have a four-fold increase in length of admission compared to children without VTE. There are many known clinical risk factors but the presence of central venous lines (CVLs) has been shown to be among the strongest risk factors in children (Mahajerin et al. Haematologica 2015 Aug; 100(8): 1045-50). Current tools, including clinical risk-prediction scoring systems as well as genetic risk factors, are not sufficient to predict VTE risk at this time. Identification of dependable, rapid and cost-effective biomarkers for the prediction of VTE in children with CVLs is essential in guiding anti-coagulation prophylaxis, thus reducing VTE occurrence among hospitalized children with CVLs.Objectives: Determine the ability of thrombin generation (TG) and microparticle-based phospholipid-dependent procoagulant potential (MP-PPL) to predict VTE occurrence in hospitalized children with CVLs.Methods: Plasma sample were collected from 34 hospitalized acutely ill children between the age of 1 month and 21 years, who are at risk for VTE due to multiple known clinical risk factors, including a newly placed non-tunneled CVL. Children that had undergone a recent cardiac catheterization or on dialysis, plasmapheresis or ECMO were excluded. Samples from 16 age matched healthy controls were also collected. Venous samples were collected prior to CVL placement. Platelet poor plasma (PPP) was obtained according to a strict protocol to minimize pre-analytical variable. All pertinent clinical and laboratory information was extracted, including CVL-related variables and details of VTE in affected subjects. TG was measured by means of the calibrated automated thrombogram (CAT). MP-PPL was measured using two methods: 1) Functional assay that detects the ability of circulating MPs to indirectly facilitate thrombin generation (Zymuphen MP-Activity kit, Hyphen BioMed, France), 2) Clot-based assay that measures phospholipid-dependent, factor Xa initiated clotting time in relation to normal controls (STA-Procoag-PPL, Diagnostica Stago).Results: The median age of our cohort was 10 yrs (IQR 12, range 0 - 19), with a slight male predominance (53%) and increased representation of adolescents (41%). CVLs were placed in an intensive care setting in 38% of subjects and 39% of subjects had an underlying condition associated with chronic inflammation. The median duration of CVL placement from admission was 2 days (IQR 5, range 1 - 19) and the median total duration of CVLs were 14 days (IQR 20, range 5 - 84). Line-associated VTE occurred in 9% (3/34) of children with CVL and one subject had a VTE unrelated to CVL. There was no observed significant difference between children with or without line-related VTE in terms of age, gender, lag of CVL placement from admission, duration of CVLs, caliber of initial vessel of insertion, number of lumens, size of CVL and internal length of the CVL. However, all subjects with line-associated VTE were admitted for acute infection to an intensive care setting, with the majority of VTE occurring within 48 hours from line placement (2/3). Correlation analysis of the two MP-PPL assays was significant (r = -0.659). Even though the MP-PPL functional assay did not show a significant difference between subjects with and without line-associated VTE (p-value 0.189), the MP-PPL clot-based assay showed measurable difference between the two groups, both as an absolute value and as a ratio (p-value: 0.04 and 0.038 respectively, Table 1). Peak thrombin generation (p-value 0.001), estimated thrombin potential (ETP) - (p-value 0.02) and velocity index (p-value 0.001) were significantly higher in subjects with line-associated VTE (see Figure 1). Subject recruitment and sample analyses, involving these assays and other potential biomarker candidates, are ongoing.Conclusion: Given the rising incidence of pediatric VTE, the ability to use biomarkers to stratify patients according to their VTE risk will provide a vital tool to guide preventative efforts, and minimizing unnecessary expense and toxicities. TGA and MP-PPL have shown great potential for differentiating children with CVLs that may develop a line-related VTE as a HA-VTE. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Children's Hospital-Acquired Thrombosis (CHAT) Registry: A Multi-Institutional Registry for Prospective Identification of Independent Risk Factors

Background: Pediatric hospital-acquired venous thromboembolism (HA-VTE) incidence is rising and many centers are instituting pediatric-specific prophylaxis programs despite a lack of evidence-based risk stratification to reduce unnecessary thromboprophylaxis exposure.Objectives: The multi-institutional Children's Hospital-Acquired Thrombosis (CHAT) Registry via Research Electronic Data Capture (REDCap) can identify independent HA-VTE risk factors for prospective validation and creation of a risk-assessment scoring system.Methods: This IRB-approved, retrospective registry reveals HA-VTE risk factors from subjects aged 0-21 years with radiographically-validated VTE ≥ 48 hours after hospital admission, or after central venous line placement, at 5 pediatric hospitals from January 2012 - June 2015. Descriptive statistics summarize demographics, medical comorbidities, characteristics of the VTEs themselves and associated laboratory testing for 555 subjects. Further analyses are currently utilizing matched controls and logistic regression to identify specific odds ratios for independent risk factors.Results: The median time to VTE diagnosis was 9 days with interquartile range (IQR) of 5-18.5 days, 34% of VTE occurred in a critical care unit, and 36.8% of subjects had been hospitalized in the 30 days prior to the index hospitalization. 22.7% of VTE events were incidentally found. VTE distribution was: deep vein thromboses of arms/legs (79.6%), cerebral sinus venous thrombosis (7%), abdominal VTE (5%), pulmonary embolism (4.3%), and other (intra-cardiac and superior vena cava/right atrial junction - 5.5%) with overlap due to some subjects with multiple, separate, concurrent VTE events. Demographic characteristics revealed median age of 3.6 years (IQR: 0.4 - 13.6 years) at VTE diagnosis and slight male predominance (55%). 66.1% of subjects had significant past medical history (Table 1) and 7.2% were immobile at baseline.Evaluation of hospital course revealed a multitude of acquired putative risk factors for HA-VTE (Table 2). 70.8% of VTE were associated with a central venous catheter (CVC). Of CVC-related VTE, 70.5% were in the same vein as CVC, 20.1% were in a vein which previously held a CVC, 10.7% surrounded the CVC tip, 2.5% occurred in a vein where CVC placement was attempted but unsuccessful. 55% of subjects had at least one documented infection during hospitalization, 42% of subjects had surgery, 20.7% had a procedure involving intravascular instrumentation (defined as dialysis, plasmapheresis, cardiac catheterization, stent placement/removal, or coiling procedure), 5% of subjects underwent trauma prior to admission with 82% of trauma classified as "major", and 59.5% of subjects were intubated at some point during their admission. Regarding medications, 31.9% of subjects were on steroids at VTE diagnosis and an additional 13.2% of subjects received steroids in the 30 days prior to VTE diagnosis, 2.2% of subjects were on estrogen with all of these subjects having started estrogen within 6 months prior to VTE diagnosis, 4.1% of subjects received asparaginase prior to VTE, 1.6% of subjects received recombinant factor VIIa prior to VTE, and 0.4% of subjects received prothrombin complex concentrates prior to VTE.Laboratory testing of hospitalized patients revealed 43.2% of patients had a d-dimer level obtained at time of VTE and 96.5% of those patients had an elevated level. 48.3% of patients had at least one thrombophilia lab test ordered. 17.8% of subjects received VTE prophylaxis - 55% of which was pharmacologic anticoagulation.Conclusions: The CHAT registry results demonstrate a slight male predisposition and multiple associated chronic medical illnesses and acquired hospital course co-morbidities, particularly CVCs which were involved in the majority of events. Ongoing work includes incorporating additional institutions to reach a goal of 1000 cases and 2000 controls to identify independent risk factors for the development of a risk-assessment scoring system. Long-term goals include prospective validation of the scoring system to serve as the basis of identifying subjects for a future randomized clinical trial of risk-based prevention strategies. Such a trial would evaluate efficacy, safety, and cost-benefit of thromboprophylaxis in hospitalized children and help inform best practices. [Display omitted] [Display omitted] DisclosuresYoung:Novo Nordisk: Consultancy, Speakers Bureau; Kedrion: Consultancy; Baxter: Consultancy; Biogen: Consultancy, Speakers Bureau.

Abstract 128: Risk Factors for Hospital-associated Venous Thromboembolism in Critically-ill Children with Cardiac Disease Undergoing Cardiothoracic Surgery or Cardiac Catheter-based Therapeutic Intervention

Background: Pediatric hospital-acquired venous thromboembolism (HA-VTE) has dramatically risen in recent years. Children with congenital or acquired heart disease are at particular risk and have not been addressed by recent, novel retrospectively-derived risk scores. Aims: We sought to develop a risk model for HA-VTE in critically-ill children with cardiac disease. Methods: We conducted a retrospective, case-control study of children admitted to the CVICU at All Children's Hospital Johns Hopkins Medicine (St. Petersburg, FL, USA) from January 2006 - April 2013. We identified cases via ICD-9 codes, and employed case validation via review of radiologic records. Two controls were randomly selected for each case. Associations between putative risk factors and HA-VTE were estimated using odds ratios (ORs) and ninety-five percent confidence intervals (95%CIs) from univariate and multivariate logistic regression analyses. Variables with P-values < 0.1 in univariate analyses were included in the multivariate model. A HA-VTE risk score was developed with weighting based on the relative magnitudes of the individual ORs from the multivariate model. Results: After adjustment in a multiple logistic regression, length of stay (LOS) >30 days, cardiac catheterization, and major infection were found to be statistically-significant independent risk factors for HA-VTE in these children. An 8-point risk score was developed in which scores of 0-1, 2-6, and 7-8 yielded HA-VTE risks of < 1%, 1-< 2%, and ≥2%, corresponding to conventional thresholds for instituting no prophylaxis, mechanical prophylaxis, and pharmacological prophylaxis (respectively) in hospitalized adults. Conclusions: LOS >30 days, cardiac catheterization, and major infection are significant independent risk factors for HA-VTE in critically-ill children with cardiac disease leading to the development of a novel HA-VTE risk score in this population. If prospectively validated, this risk score will inform the design of risk-stratified clinical trials of HA-VTE prevention.

Children's Hospital-Acquired Thrombosis Database (CHAT): A Multi-Institutional Database for Prospective Identification of Independent Risk Factors

Background: Pediatric hospital-acquired venous thromboembolism (HA-VTE) incidence is rising but remains relatively low overall, requiring risk stratification to reduce unnecessary thromboprophylaxis exposure. Large sample sizes are needed for prospective epidemiologic risk factor studies, necessitating collaboration.Objectives: We formed the multi-institutional Children's Hospital-Acquired Thrombosis (CHAT) web-based registry via Research Electronic Data Capture (REDCap) to identify independent HA-VTE risk factors for future clinical risk score development.Methods: This IRB-approved, retrospective chart review reveals HA-VTE risk factors from patients aged 0-21 years who developed diagnostically-validated VTE more than 48 hours after hospital admission, or after central venous line placement, at 3 pediatric hospitals from January 2012 - December 2014. We used descriptive statistics to summarize demographics, medical comorbidities and types of any applicable central lines for the initial 373 patients entered into the database, as well as characteristics of the VTEs themselves and associated laboratory testing. Further analysis is currently underway utilizing matched controls and logistic regression to identify specific odds ratios for independent risk factors.Results: The median length of time to VTE diagnosis was 9 with interquartile range (IQR) of day 4-18, 35.3% of VTE occurred in a critical care unit, and 21% were incidentally found. The distribution of VTE included deep vein thromboses (DVT) of the arms/legs (81.1%) followed by cerebral sinus venous thrombosis (7.3%), pulmonary embolism (5.4%), DVT of the abdomen (4%), and intracardiac DVT (4%) with some overlap due to patients with multiple, separate, concurrent VTE events. Demographic characteristics of the initial 373 subjects revealed median age of 3.7 years (IQR of 0.4 years to 13.8 years) at VTE diagnosis and a slight male predominance (57.4%). 62.6% of patients had significant past medical history (Figure 1) and 8% were immobile at baseline.Evaluation of hospital course revealed a multitude of acquired putative risk factors for HA-VTE (Figure 2). 75.7% of VTE were associated with a central venous catheter (CVC). Of CVC-related VTE, 72% were in the same vein as CVC, 20% were in a vein which previously held a CVC, 3.6% surrounded the CVC tip, 2.9% occurred in a vein where CVC placement was attempted but unsuccessful. 59% of patients had at least one documented infection during hospitalization, 48% of patients had surgery, 5.5% of patients underwent trauma prior to admission, and 59.7% (n=221) of patients were intubated at some point during their admission with 86.9% (n=192) of those patients developing VTE after a minimum of 24 hours of mechanical ventilation. Laboratory testing of hospitalized patients revealed 51.2% of patients had a d-dimer level obtained at time of VTE and 97.8% of those patients had an elevated level. 44% of patients had at least one thrombophilia lab test ordered.Conclusions: The initial CHAT database results demonstrate a slight male predisposition and multiple associated chronic medical illnesses and acquired hospital course co-morbidities, particularly CVCs which were involved in three-fourths of VTE events. Ongoing work includes incorporating additional institutions and utilizing control subjects to identify independent risk factors for the development of a risk score model. Long-term goals include prospective validation of the scoring system in a cohort of patients from pediatric centers not involved in development of the risk score with the ultimate plan of using the scoring system to stratify patients for future randomized clinical trials of risk-based prevention strategies to evaluate the safety and efficacy of this approach for reduction of pediatric HA-VTE incidence without unnecessary thromboprophylaxis exposure. [Display omitted] [Display omitted] DisclosuresYoung:Kedrion: Consultancy; Biogen Idec: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria; Bayer: Consultancy; Baxter: Consultancy.

Hospital-associated venous thromboembolism in pediatrics: a systematic review and meta-analysis of risk factors and risk-assessment models.

Hospital-associated venous thromboembolism, including deep vein thrombosis and pulmonary embolism, is increasing in pediatric centers. The objective of this work was to systematically review literature on pediatric hospital-acquired venous thromboembolism risk factors and risk-assessment models, to inform future prevention research. We conducted a literature search on pediatric venous thromboembolism risk via PubMed (1946-2014) and Embase (1980-2014). Data on risk factors and risk-assessment models were extracted from case-control studies, while prevalence data on clinical characteristics were obtained from registries, large (n>40) retrospective case series, and cohort studies. Meta-analyses were conducted for risk factors or clinical characteristics reported in at least three studies. Heterogeneity among studies was assessed with the Cochran Q test and quantified by the I(2) statistic. From 394 initial articles, 60 met the final inclusion criteria (20 case-control studies and 40 registries/large case series/cohort studies). Significant risk factors among case-control studies were: intensive care unit stay (OR: 2.14, 95% CI: 1.97-2.32); central venous catheter (OR: 2.12, 95% CI: 2.00-2.25); mechanical ventilation (OR: 1.56, 95%CI: 1.42-1.72); and length of stay in hospital (per each additional day, OR: 1.03, 95% CI: 1.03-1.03). Three studies developed/applied risk-assessment models from a combination of these risk factors. Fourteen significant clinical characteristics were identified through non-case-control studies. This meta-analysis confirms central venous catheter, intensive care unit stay, mechanical ventilation, and length of stay as risk factors. A few pediatric hospital-acquired venous thromboembolism risk scores have emerged employing these factors. Prospective validation is necessary to inform risk-stratified prevention trials.

Venous thromboembolism in hospitalized adolescents: an approach to risk assessment and prophylaxis.

Pediatric hospital-acquired venous thromboembolism (VTE) is an increasingly prevalent and morbid disease. A multidisciplinary team at a tertiary children's hospital sought to answer the following clinical question: "Among hospitalized adolescents, does risk assessment and stratified VTE prophylaxis compared with no prophylaxis reduce VTE occurrence without an increase in significant adverse effects?" Serial literature searches using key terms were performed in the following databases: Medline, Cochrane Database, CINAHL (Cumulative Index to Nursing and Allied Health), Scopus, EBMR (Evidence Based Medicine Reviews). Pediatric studies were sought preferentially; when pediatric evidence was sparse, adult studies were included. Abstracts and titles were screened, and relevant full articles were reviewed. Studies were rated for quality using a standard rating system. Moderate evidence exists to support VTE risk assessment in adolescents. This evidence comes from pediatric studies that are primarily retrospective in design. The results of the studies are consistent and cite prominent factors such as immobilization and central venous access. There is insufficient evidence to support specific prophylactic strategies in pediatric patients because available pediatric evidence for thromboprophylaxis efficacy and safety is minimal. There is, however, high-quality, consistent evidence demonstrating efficacy and safety of thromboprophylaxis in adults. On the basis of the best available evidence, we propose a strategy for risk assessment and stratified VTE prophylaxis for hospitalized adolescents. This strategy involves assessing risk factors and considering prophylactic measures based on level of risk. We believe this strategy may reduce risk of VTE and appropriately balances the adverse effect profile of mechanical and pharmacologic prophylactic methods.