ALBERT

Description: Key Points D1472H sequence variation is associated with a decreased VWF:RCo/VWF:Ag ratio in type 1 VWD subjects. D1472H sequence variation is not associated with an increase in bleeding as measured by bleeding score in type 1 VWD subjects.

Description: Abstract 189 Background: Growth Arrest Specific gene 6 (Gas6) signaling through platelet-surface Tyro3/Axl/Mer (TAM) receptors leads to platelet activation and thrombus stabilization. This occurs via activation of phosphatidylinositol-3-kinase (PI3K) and Akt, stimulating tyrosine phosphorylation of the β3 integrin. This process amplifies outside-in signaling via αIIbβ3, which is necessary for stable aggregate formation. iMer is a truncated form of the extracellular domain of the Mer receptor tyrosine kinase, produced by alternative splicing, that inhibits Gas6/TAM signaling, likely by acting as a decoy receptor for Gas6. Objectives: We hypothesized that inhibiting the Gas6/TAM pathway with a novel Gas6-sequestering protein would decrease platelet activation responses. We therefore evaluated iMer's inhibition of Gas6 signaling in human and murine platelets in vitro and in vivo. Methods: We measured the inhibitory effect of iMer on platelet activation using laboratory evaluations of platelet function and a murine carotid artery thrombosis model. In vitro studies included aggregometry, adhesion to collagen in a flow chamber, and platelet spreading. These platelet activation responses were tested in human platelets in the presence or absence of the inhibitor and also in wild type (WT) and Gas6/TAM −/− murine platelets. A ferric-chloride model of carotid artery injury was used to compare susceptibility to thrombosis between littermate C57BL/6 mice treated with either iMer or vehicle. Platelet aggregation data was evaluated by the Wilcoxon Signed Rank Test, and times to occlusion following carotid artery injury were compared using the Mann-Whitney Rank Sum Test. Results/Discussion: Western blot analysis demonstrated decreased β3 integrin phosphorylation in iMer-treated human platelets after addition of human Gas6 when compared to controls, consistent with decreased Mer signaling in the presence of iMer. iMer-treated human platelets exhibited significant decreases in ADP- and collagen-induced platelet aggregation. ADP-stimulated samples treated ex vivo with iMer showed an aggregation mean of 74% (SD= +/− 3%), compared to 86% aggregation (+/− 3%) in controls (p=0.016). Collagen-stimulated samples treated ex vivo with iMer exhibited a mean of 70% aggregation (+/− 8%), compared to 88% aggregation (+/−2%) in controls (p=0.004). Electron micrographs of adhered human platelets revealed that iMer delayed, but did not permanently abrogate, platelet spreading on fibrillar collagen (100 μg/mL). Flow cytometric analysis of human platelets showed reduced expression of platelet-surface activation markers (P-selectin and PAC-1) despite stimulation with fibrillar collagen (1 μg/mL). Microfluidic flow assay demonstrated that adhesion of untreated human platelets to collagen at a wall shear rate of 100s−1 resulted in 21.3% (SD=+/− 8%) mean surface area coverage, while ex vivo iMer-treated samples showed only 1.1% (+/− 0.9%) coverage. These results are consistent with those of WT mice compared to that of Gas6/TAM −/−mice in preliminary studies using the same system. Following ferric chloride injury to the carotid artery, 71% of vehicle-treated control mice (n=7) had initial occlusions that remained stable, and only 14% remained patent. In contrast, only 25% of the iMer-treated mice (n=8) formed initial occlusions that remained stable, while 50% remained patent. The iMer treated mice also had a significant decrease (p=0.02) in the duration of first occlusion time (i.e. length of time the initial occlusion lasted), suggesting decreased thrombus stability. Conclusions: iMer is a novel inhibitor of the Gas6/TAM pathway that decreases platelet activation responses and protects mice from arterial thrombosis by decreasing phosphorylation of β3 integrin, which has been shown to be necessary for thrombus stabilization. This compound may, therefore, have translational applications as a novel anti-platelet agent. Disclosures: No relevant conflicts of interest to declare.

Description: 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. Figure 1. Distribution of past medical history Figure 1. Distribution of past medical history Figure 2. Prevalence of acquired risk factors. *Some patients with more than 1 documented infection. ^Procedures included: dialysis, plasmapheresis, cardiac catheterization, stent placement, coiling procedure. Figure 2. Prevalence of acquired risk factors. *Some patients with more than 1 documented infection. ^Procedures included: dialysis, plasmapheresis, cardiac catheterization, stent placement, coiling procedure. Disclosures Young: Kedrion: Consultancy; Biogen Idec: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria; Bayer: Consultancy; Baxter: Consultancy.

Description: Background: Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is associated with significant morbidity and mortality. The incidence of VTE, particularly VTE acquired by hospitalized children, has increased dramatically over the last 15 years but may be preventable in some cases. Reducing the incidence of hospital-acquired VTE may not only improve patient care but also decrease healthcare costs associated with diagnosis and treatment. Methods: In conjunction with the Children’s Hospitals’ Solutions for Patient Safety, we have developed a risk-based intervention strategy for all non-neonatal hospitalized children. The 3-part care bundle includes (1) VTE risk assessment upon admission with daily reassessments thereafter, (2) consideration of VTE prophylaxis (mechanical and/or pharmacologic depending on risk of VTE versus bleeding), and (3) ongoing evaluation for complications and risk level changes. To facilitate risk assessments and risk-based interventions, we developed a clinical care guideline based on published pediatric VTE risk profiles. To most accurately track our outcome measure, number of VTE cases, we have augmented our prior ICD-9-based method of identifying VTE cases to include a radiographic dictation trigger, anticoagulant medications, and nursing report of clot treatment. This new approach has led to improved specificity and sensitivity of VTE identification. Outcome and Process Measures: This risk-based intervention approach was implemented as a pilot program in our pediatric ICU and has been associated with a 52% decrease in validated VTE cases over a 12-month period, coincident with an increase in documented care bundle compliance from 40% to 93%. During this pilot program, 134 of 2190 pediatric ICU patients (6.1%) were initially classified as high risk, with 5.2% of those developing VTE, and 952 patients (43%) were initially classified as moderate risk, with 2.3% of those developing VTE. Ninety-five patients received pharmacologic prophylaxis at some point during admission, with 13.6% developing VTE; 428 received mechanical prophylaxis, with 3.7% developing VTEs; and 61 received both pharmacologic and mechanical prophylaxis, with 13.1% developing VTEs. Balancing Measures: We are also tracking adverse events related to mechanical or pharmacologic prophylaxis. No patients had significant bleeding while on pharmacologic prophylaxis, and one patient developed pressure ulcers associated with sequential compression devices. Conclusion: Implementation of our 3-part VTE prevention care bundle was associated with a decrease in VTE cases without a notable increase in bleeding or pressure ulcers. Future Directions: Ongoing work includes refining our clinical care guideline to incorporate recent risk factor data, expanding the 3-part care bundle outside of the ICU to include the entire hospital, continuing to improve sensitivity and specificity of VTE case identification methods, and continuing to monitor balancing measures of bleeding and pressure ulcers. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: High-density lipoprotein (HDL) protects against thromboembolic coronary disease via reverse cholesterol transport mediated by HDL's primary lipoprotein subunit, apolipoprotein A-I (apoA-I), binding to scavenger receptor BI (SR-BI). Absence of SR-BI increases platelet aggregation and venous/arterial thrombosis in mice, consistent with an antithrombotic role of this signaling axis. To date, the effects of the isolated apoA-I subunit on platelet activation remain unknown. We hypothesize that the antithrombotic effect is mediated by apoA-I signaling through platelet-specific SR-BI. Methods: Platelet function assays were performed on samples from healthy human volunteers (n=3). ApoA-I levels were determined using an ELISA kit. Microfluidic analysis of platelet aggregate formation on collagen under physiologic flow conditions (650 sec-1) was carried out in whole blood samples. Light transmission platelet aggregation in response to collagen and ristocetin was conducted using both platelet rich plasma (PRP) and washed platelets (WP). Venous and arterial thromboses were induced in wild type C57Bl/6 mice in a collagen (0.3 mg/kg)/epinephrine (0.03 mg/kg)-induced pulmonary embolism model and a 6% ferric chloride (FeCl3)-induced carotid artery thrombosis model, respectively. Recombinant human apoA-I was used with a final concentration of 300 µg/mL. Results/Discussion: ApoA-I plasma levels in the subjects studied fell within previously published ranges. Microfluidic analysis of platelet aggregate formation on collagen under shear stress did not demonstrate significant difference in total surface area coverage (n=3 in quadruplicate), but apoA1-treated samples demonstrated a significantly greater proportion of small aggregates (3-10 platelets/aggregate, 40.2% vs 31.8%, p

Description: 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. Disclosures Young: Novo Nordisk: Consultancy, Speakers Bureau; Kedrion: Consultancy; Baxter: Consultancy; Biogen: Consultancy, Speakers Bureau.

Description: Background - Hospital-acquired venous thromboembolism (HA-VTE), comprised of deep vein thrombosis and pulmonary embolism, is associated with significant mortality and morbidity and the overall incidence is rising, leading to its recognition as a leading quality and patient safety concern in pediatric hospitals. Risk-based prophylactic strategies are used in adults but a paucity of high quality evidence exists regarding the safety and efficacy of these interventions in the pediatric population. Defining an objective assessment of VTE risk to guide standard approaches to the use of mechanical and/or pharmacologic prophylaxis (in the absence of contraindications) is a desirable strategy to decrease HA-VTE incidence while minimizing potential risks associated with prophylaxis. Methods- With Institutional Review Board approval, we retrospectively evaluated electronic health record data from 39 patients age 0-21 years (inclusive) who developed VTE more than 48 hours after admission to Children's Hospital Colorado (Aurora, CO, USA) from January 1, 2014 - December 31, 2014. We identified purported HA-VTE cases via ICD-9 discharge diagnosis codes, then two different reviewers cross-referenced and validated with pharmacy and radiology records. We evaluated the HA-VTE patient's VTE risk scores (high, moderate, or low) using our institutional VTE prevention clinical care guideline (CCG) at discrete time points prior to clot diagnosis, as well as whether the patient received mechanical and/or pharmacologic thromboprophylaxis. Objectives: We sought to determine the ability of our CCG to accurately assess HA-VTE risk prior to clot development and to assess the utilization and timing of thromboprophylaxis. Results: Of the 39 patients who developed a HA-VTE during the study period, CCG-based risk assessment on the day before the event had identified four (10.3%) patients as low risk, two (5.1%) as moderate risk, and 33 (84.6%) as high risk, as seen in Table 1. This distribution represents an overall increase in risk score compared to those determined on admission when 13 (33.3%) were low risk, 4 (10.3%) were moderate risk, and 22 (56.4%) were high risk. Admission risk scores tended to hold steady or increase during the hospitalization (Figure 1) and only one patient experienced a decrease in risk level prior to HA-VTE diagnosis. HA-VTE patients often had high risk scores as early as seven or even 14 days prior to the event, and 20 (51%) of the patients who developed HA-VTE were high risk during the entire admission. Of the HA-VTE patients, 19 (48.7%) were receiving thromboprophylaxis on the day prior to the event. 4 (21.1%) received pharmaceutical type only, 12 (63.2%) received mechanical type only, and 3 (15.8%) received both types. Conclusion: Institutional CCGs can be used to determine HA-VTE risk stratification in hospitalized children, thereby informing decisions regarding initiation of thromboprophylaxis as a preventative strategy in the absence of contraindications. Comparison to a group of age group- and risk level-matched control patients who did not develop HA-VTE is underway and will give appropriate context to the high risk designation as it pertains to HA-VTE incidence and the impact of thromboprophylaxis strategies. Table 1. Risk scores prior to HA-VTE diagnosis: Risk scores at various time points during hospitalization Risk Level Risk Score on Admission Risk Score 14 Days Prior Risk Score 7 Days Prior Risk Score 1 Day Prior Risk Score Day of VTE Low 13 (33.3%) 0 (0%) 2 (10.5%) 4 (10.3%) 4 (10.3%) Moderate 4 (10.3%) 1 (9.1%) 1 (5.3%) 2 (5.1%) 2 (5.1%) High 22 (56.4%) 10 (90.9%) 16 (84.2%) 33 (84.6%) 33 (84.6%) Total 39 11 19 39 39 Figure 1. Patient-level risk score tracking: Each colored line represents a unique HA-VTE patient's risk score trajectory during hospitalization. Risk scores upon admission correspond to days represented by negative numbers denoting various days prior to event (Day 0), and all patients have evaluations from 14, 7, and 1 day prior to the event, if applicable. Figure 1. Patient-level risk score tracking: Each colored line represents a unique HA-VTE patient's risk score trajectory during hospitalization. Risk scores upon admission correspond to days represented by negative numbers denoting various days prior to event (Day 0), and all patients have evaluations from 14, 7, and 1 day prior to the event, if applicable. Disclosures Off Label Use: We may discuss use of heparin (unfractionated or low molecular forms) for VTE thromboprophylaxis in children.

Description: Background: Pediatric venous thromboembolism (VTE) is a rare but serious medical condition resulting in significant morbidity, mortality and healthcare costs. In the recent decade, the rate of general pediatric VTE has dramatically increased across all age ranges, from neonates to adolescents. This increase is likely multi-factorial, including more aggressive management of critically ill patients, improved survival of children with chronic disease and the increased use of central venous catheters (CVCs). Cystic fibrosis (CF) is a chronic, inflammatory disease process often managed with courses of intravenous antibiotics administered through CVCs, both peripherally inserted central catheters (PICC) and implantable venous ports. There are limited data documenting an increased risk of VTE in CF patients with ports. However, there are no published data on PICC line-associated VTE or overall VTE incidence specifically in the pediatric CF population. Methods: A retrospective cohort study was conducted in CF patients, ages 0 to 21 years, followed at the CF Care Center at Children's Hospital Colorado between 2003 and 2016, who were enrolled in the national CF Foundation Patient Registry. VTE cases were identified by informatics, including anticoagulation administration, documentation of VTE in radiographic reports and nursing flowsheets, and use of VTE ICD-9 and ICD-10 codes. All identified cases were confirmed by manual chart review and data including personal and family history of VTE, use of prophylaxis and VTE type, diagnosis date, diagnostic modality and line-association were entered into a secured REDCap longitudinal database. Data including CF mutation, CF co-morbidities, microbiology history, pulmonary function testing, disease modifying medications, thrombophilia testing and central line specifications and duration were collected for every admission on all study participants to allow for future risk factor analysis. Results: The cohort consisted of 488 participants with a total of 2,590 admissions (mean 5.34 per participant, range 1-56). Two hundred and forty-nine individuals were male (51%) and the majority were Caucasian (463, 95.3%) with a normal BMI (average 19.7, range 14.8-25.4). A total of 1,157 CVCs were placed over the study period including 981 PICCs (84.8%), 93 ports (8%) and 83 unspecified (7.2%). Thirty-one VTEs were diagnosed in 23 participants (4.3%) on 29 admissions (1.12%). Twelve of the 23 participants with VTE were male (52%) and the average age of those with VTE was 15.3 years (range 4-21). Twenty-two of the VTEs were deep vein thromboses, including 4 pulmonary emboli, and 9 were in superficial veins. The average day of VTE diagnosis was hospital day 4.9 (range 0-14). At the time of diagnosis, 11 had ports, 15 had PICCs and 5 had no CVC. The majority of VTEs were associated with the CVC (19, 61.3%) and of those CVC-associated VTEs, the majority were seen with PICCs (14, 73.7%). On average, PICC-associated VTE occurred on line day 5.2 (range 2-14) and port-associated VTE occurred on line day 897.5 (range 37-1496). Of the 23 participants with VTE, 14 were tested for Factor V Leiden mutation and 2 were heterozygous. Similarly, for the prothrombin mutation, 13 were tested and two were heterozygous. While the majority of participants had minimal to no thrombophilia evaluation, notably, an elevated factor VIII was associated with 11 of 12 VTE diagnoses (91.7%, average 215.47, range 61-341.3). Conclusion: In this large pediatric cohort of patients with CF, there was an increased number of VTE when compared to previously published general pediatric populations. Consistent with known risk factors, the average participant with VTE was in their teenage years and had a CVC, although 16% occurred without a line in place. Gender and obesity did not appear to contribute dramatically as the male/female distribution was roughly equal and the average BMI was within normal range. If a CVC was placed, the vast majority of CF patients received PICCs. PICCs also made up the majority of CVC-associated VTE with the average thrombosis occurring on day 5 following line placement. Few participants with VTE had complete thrombophilia evaluations but of those that did, factor VIII was elevated in all but one individual. Disclosures Wang: HEMA Biologics: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees; LFB: Membership on an entity's Board of Directors or advisory committees; Biogen: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees.

Description: Introduction Incidence of hospital-acquired venous thromboembolism (HA-VTE) in children has been increasing in the absence of proven effective preventative interventions. To decrease the incidence of HA-VTE, we must first identify children at the highest risk by creating a risk assessment model (RAM). Critically ill children, especially those with a central venous catheter (CVC), inflammatory condition and/or prolonged hospital stay have been identified as high-risk. To date, studies of HA-VTE in critically ill children have only been at single-center and have not been well-validated in diverse populations. The Children's Hospital-Acquired Thrombosis (CHAT) consortium established a large multicenter Registry to develop and validate pediatric RAMs for HA-VTE. This multicenter study aimed to derive a RAM for HA-VTE among critically ill children (RAM-ICU) performed upon admission/transfer to a pediatric intensive care unit (PICU). The CHAT Registry consists of retrospectively-identified, imaging confirmed cases of symptomatic HA-VTE and hospitalized controls (without HA-VTE) aged 0-21 years from eight U.S. centers. Controls were frequency-matched by year of admission and center. Details on demographics, medical history and hospital course were extracted from the medical record. For the RAM-ICU, only HA-VTE subjects and controls admitted/transferred into an ICU were included. Subjects who had a cardiac surgery up to 2 weeks prior to ICU admission were excluded. Fourteen variables that were present at or within 24 hours of ICU admission/transfer were evaluated by univariate logistic regression. These included demographics, medications, medical history, recent surgeries, mechanical ventilation, patient mobility and presence of a CVC. Those variables with p-values of