Long-term follow-up of patients with congenital thrombotic thrombocytopenia purpura receiving a plasma-derived factor VIII (Koate) that contains ADAMTS13.

BACKGROUND: Hereditary thrombotic thrombocytopenia purpura (hTTP) is an ultra-rare disorder resulting from an inherited deficiency of ADAMTS13, a von Willebrand factor (VWF)-cleaving metalloprotease. The plasma-derived factor VIII/VWF Koate (FVIII/VWFKoate ) has been shown to contain ADAMTS13, allowing for its use to treat hTTP at home by the patient/caregiver. AIM: Based on prior demonstration of safe and effective use of FVIII/VWFKoate in eight patients with hTTP, we conducted a retrospective study to gather additional data regarding the use of FVIII/VWFKoate for hTTP. METHODS: This was a multicentre, retrospective, noninterventional chart review of patients who had received FVIII/VWFKoate for the management of hTTP. Data collected included demographics, medical history, relevant family history, past use and tolerability of fresh frozen plasma, and details regarding FVIII/VWFKoate therapy. RESULTS: The cohort included 11 patients (seven males, four females) with hTTP, ranging in age at study entry from 2 to 28 years. The average duration of FVIII/VWFKoate therapy was 4.8 years (range, 0.5-6.5 years). Among nine patients using FVIII/VWFKoate as prophylaxis, the normalized annual rate of breakthrough TTP episodes ranged from 0.2 to 1.1 episodes/year. All nine patients who received FVIII/VWFKoate prophylaxis had thrombocytopenia recorded at baseline, while eight (88.9%) did not have thrombocytopenia after using FVIII/VWFKoate . There was one AE (unspecified) attributed to FVIII/VWFKoate . CONCLUSION: These data suggest that FVIII/VWFKoate is a safe and well-tolerated source of the missing ADAMTS13 enzyme in patients with hTTP, producing a marked reduction in thrombocytopenia prevalence, low frequency of TTP episodes, and with the added benefit of self- or caregiver-administration.

Use of Pharmacologic Prophylaxis Against Venous Thromboembolism in Hospitalized Injured Children.

Despite a practice management guideline and risk prediction model for venous thromboembolism (VTE), pediatric-specific evidence on pharmacologic prophylaxis is lacking. In a retrospective study, we characterized receipt of prophylaxis and explored its effectiveness in hospitalized injured patients below 18 years old using data from the Trauma Quality Improvement Program. Concordance of receipt of prophylaxis with guideline and predicted risk of VTE was estimated using κ statistic. Effectiveness was explored using cohorts matched based on the risk prediction model. A total of 11,165 (6.2%) of 180,932 patients received prophylaxis. Those who received prophylaxis were more commonly post-pubertal and more severely injured. Receipt of prophylaxis was fairly concordant with the guideline (κ=0.32) and predicted risk of VTE (κ=0.29). Receipt of prophylaxis was associated with higher rates of VTE likely due to confounding by indication. Low molecular weight heparin seemed more effective against VTE than unfractionated heparin (incidence rate ratio: 0.52; 95% confidence interval: 0.36, 0.75), but less effective when received ≥72 hours after admission to the hospital. We showed that hospitalized injured children did not commonly receive prophylaxis. We also showed that prophylaxis may be effective in hospitalized injured children, but it needs to be proven definitively in a randomized clinical trial.

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.

Recurrent Stroke in a Child With Atlantoaxial Instability Following Chiropractic Manipulation.

Pediatric stroke presents with a variety of signs and symptoms. Correct modality of imaging is essential in decreasing the time from symptom onset to appropriate management. Evaluation of pediatric stroke should include both blood work as well as imaging in a parallel rather than a sequential matter. We report a case of a child with a bow hunter's stroke that was challenging to diagnose. This type of stroke happens when the vertebral artery is occluded at the atlantoaxial or subaxial level during neck rotation. This case demonstrates that workup of stroke should be comprehensive to include all mechanical and anatomic possibilities before investigating rarer hypercoagulable disorders.

Impact of the Hemostasis and Thrombosis Research Society trainee workshop in recruiting the next generation of nonmalignant hematologists.

The United States is facing a shortage of physicians dedicated to nonmalignant hematology to meet future needs. The Hemostasis and Thrombosis Research Society (HTRS) developed a medical education program for trainees, "HTRS Trainee Workshops: Building a Career in Hemostasis and Thrombosis" in 2016. The aim of this study is to evaluate the impact of the workshop in recruiting the next generation of nonmalignant hematologists. Two surveys (post-workshop survey and alumni survey) were conducted. The post-workshop survey occurred within 30 days of each workshop and was completed by 81.9% (n = 185) of participants. Majority of respondents reported that the workshop had a positive impact to their practice and/or research (93.0%, n = 174) and career development (87.7%, n = 164). For the alumni survey which was conducted in 2018, 73 participants responded to the survey (38.2% response rate). Of the 38 respondents who had graduated from fellowship at the time of the survey, almost all chose a career in academic medicine. 41.7% (n = 15) reported their specialty as adult nonmalignant hematology and 25.0% (n = 9) as pediatric hematology/oncology with a nonmalignant hematology focus. 41.1% (n = 30) developed collaborative professional relationships, and 78.1% (n = 57) reported that the workshop had a positive influence in their choice to pursue nonmalignant hematology as a career. 67.1% (n = 49) were actively involved in research in nonmalignant hematology, with the most common being clinical research. This survey suggests that the HTRS Trainee Workshop is meeting its goals to recruit, train, and mentor the next generation of nonmalignant hematologists.

Promising biomarkers for the prediction of catheter-related venous thromboembolism in hospitalized children: An exploratory study.

BACKGROUND: Pediatric venous thromboembolism (VTE) has increased over the past 10 years, with central venous catheters (CVC) being the strongest risk factor. Current tools are not sufficient to predict VTE risk. The utility of biomarkers in predicting CVC-related VTE has been minimally explored. Our objective is to determine the utility of microparticles (MPs), factor VIII (FVIII) activity, and thrombin generation (TG) in prospectively predicting VTE occurrence in hospitalized children with CVCs. PROCEDURE: In this nested case-control pilot study, consecutive hospitalized children needing CVC placement (1 month to 21 years) were enrolled. Venous samples were collected prior to or within 24 h of CVC placement. MPs were measured using factor Xa initiated clot-based assay. FVIII was measured using a one-stage clot-based assay. TG was measured using calibrated automated thrombogram. RESULTS: There were three CVC-related VTE events (7%) in our cohort of 42 subjects. Xa clotting time (XaCT) ratio was lower (0.68 ± 0.07 vs 0.95 ± 0.21, P = .4), while FVIII (461 ± 120 vs 267 ± 130, P = .02), peak thrombin (418 ± 89 vs 211 ± 101, P = .001), endogenous thrombin potential (ETP) (1828 ± 485 vs 1282 ± 394, P = .03), and velocity index (VI) (182 ± 28 vs 75 ± 53, P = .001) were higher in subjects with CVC-related VTE compared to those without CVC-related VTE. Sensitivity/specificity analysis revealed optimal cutoff values for XaCT ratio (0.75), FVIII (370), ETP (1680), peak (315), and VI (130), with receiver operating characteristic area under the curve values >0.9. CONCLUSION: MPs, FVIII, and TG can potentially predict pediatric CVC-related VTE in a prospective fashion. Stratification according to VTE risk may aid in guiding preventative efforts in future studies.

Pediatric superior vena cava syndrome: An evidence-based systematic review of the literature.

Superior vena cava syndrome (SVCS) results in vascular, respiratory, and neurologic compromise. A systematic search was conducted to determine the prevalence of pediatric SVCS subtypes and identify clinical characteristics/treatment strategies that may influence overall outcomes. Data from 101 case reports/case series (142 patients) were analyzed. Morbidity (30%), mortality (18%), and acute complications (55%) were assessed as outcomes. Thrombosis was present in 36%, with multi-modal anticoagulation showing improved outcome by >50% (P = 0.004). Infant age (P = 0.04), lack of collaterals (P = 0.007), acute complications (P = 0.005), and clinical presentation may have prognostic utility that could influence clinical decisions and surveillance practices in pediatric SVCS.

Lupus anticoagulant hypoprothrombinemia syndrome associated with severe thrombocytopenia in a child.

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) comprises lupus anticoagulant, acquired hypoprothrombinemia, and often mild thrombocytopenia or normal platelets. It is usually associated with autoimmunity or postviral illness. We describe a case of a 10-year-old boy with oral bleeding and severe thrombocytopenia initially suggestive of immune thrombocytopenia. Secondary to bleeding, evaluation demonstrated prolonged coagulation tests and subsequently revealed the presence of lupus anticoagulant and hypoprothrombinemia, along with marked autoimmunity, suggestive of LAHPS. He was treated with intravenous immunoglobulin and hydroxychloroquine. This case report and discussion highlight the diagnostic and therapeutic challenges associated with LAHPS and coincident severe thrombocytopenia.

Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency.

The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency.

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.

Successful treatment of secondary graft failure following unrelated cord blood transplant with hematopoietic growth factors in a pediatric patient with Fanconi anemia.

Graft failure following allogeneic HCT in Fanconi anemia is associated with significant mortality. Retransplantation may be considered; however, the limited toxicity profile of HGFs also makes them an option for the treatment of graft failure. We describe a five-yr-old female diagnosed with Fanconi anemia and marrow failure treated with HCT. The course was complicated by secondary graft failure treated successfully with HGFs including G-CSF, EPO, and romiplostim. The outcome could be related to the intervention, but could also be the natural course of recovery, including recovering from a recent CMV infection treated with ganciclovir. We found the use of HGFs to be an effective and safe alternative to the potential complications as well as morbidity and mortality associated with the use of retransplantation.

Clinical and treatment characteristics of infants and toddlers less than 2 years of age with hemophilia.

ABSTRACT: Infants and toddlers (ITs) with hemophilia have unique bleeding features. Factor prophylaxis has been shown to decrease the risk of intracranial hemorrhage (ICH), which supports recommendations to begin at a young age. Clinical and demographic characteristics were analyzed for 883 ITs ≤2 years old with hemophilia A and B, seen at US Hemophilia Treatment Centers and enrolled in the Community Counts Registry, a surveillance program of the Centers for Disease Control and Prevention. ICH in the first 2 years of life was seen in 68 of 883 (7.7%) ITs, of whom 8 of 68 (11.8%) were on continuous prophylaxis at the time of ICH. ITs in this study usually started prophylaxis within the first year of life (mean, 10.3 months), with earlier ages of prophylaxis initiation in later birth cohorts in ITs with hemophilia A. Compared with those without a family history (FH) of hemophilia, known positive FH of hemophilia was associated with earlier age of diagnosis (P ≤ .0001) and decreased rates of vaginal delivery (P = .0006). The use of factor VIII mimetics and extended half-life clotting factor prophylaxis increased with later birth cohorts for ITs with hemophilia A and B. The study highlights that ICH rates in ITs with hemophilia remains substantial and underscores the need for further research to identify modifiable risk factors to prevent ICH by earlier diagnosis and initiating prophylaxis early, even within the first month of life.

Antithrombin Therapy: Current State and Future Outlook.

Antithrombin (AT) is a natural anticoagulant pivotal in inactivating serine protease enzymes in the coagulation cascade, making it a potent inhibitor of blood clot formation. AT also possesses anti-inflammatory properties by influencing anticoagulation and directly interacting with endothelial cells. Hereditary AT deficiency is one of the most severe inherited thrombophilias, with up to 85% lifetime risk of venous thromboembolism. Acquired AT deficiency arises during heparin therapy or states of hypercoagulability like sepsis and premature infancy. Optimization of AT levels in individuals with AT deficiency is an important treatment consideration, particularly during high-risk situations such as surgery, trauma, pregnancy, and postpartum. Here, we integrate the existing evidence surrounding the approved uses of AT therapy, as well as potential additional patient populations where AT therapy has been considered by the medical community, including any available consensus statements and guidelines. We also describe current knowledge regarding cost-effectiveness of AT concentrate in different contexts. Future work should seek to identify specific patient populations for whom targeted AT therapy is likely to provide the strongest clinical benefit.

Atypical Hemolytic Uremic Syndrome Treated With Ravulizumab or Eculizumab: A Claims-Based Evaluation of Health Care Resource Utilization and Clinical Outcomes in the United States.

Rationale and Objective: Ravulizumab and eculizumab have shown efficacy for the treatment of atypical hemolytic uremic syndrome (aHUS), but real-world evidence for ravulizumab is limited owing to its more recent approval. This real-world database study examined outcomes for adult patients switching to ravulizumab from eculizumab and patients treated with individual treatments. Study Design: A retrospective, observational study using the Clarivate Real World Database. Setting and Population: US health-insurance billing data (January 2012 to March 2021) of patients aged 18 years or older with ≥1 diagnosis relevant to aHUS, ≥1 claim for treatment with eculizumab or ravulizumab, and no evidence of other indicated conditions. Exposures: Treatment-switch (to ravulizumab after eculizumab), ravulizumab-only, and eculizumab-only cohorts were examined. Outcomes: Clinical procedures, facility visits, health care costs, and clinical manifestations. Analytical Approach: Paired-sample statistical testing compared the mean numbers of claims for each group 0-3 months before (preindex period) and 0-3 months and 3-6 months after (postindex period) the index date (point of initiation with a single treatment or treatment switch). Results: In total, 322 patients met the eligibility criteria at 3-6 months postindex in the treatment-switch (n=65), ravulizumab-only (n=9), and eculizumab-only (n=248) cohorts. The proportions of patients with claims for key clinical procedures continued to be small after treatment switch and were small (0%-11%) across all cohorts at 3-6 months postindex. Inpatient visits were reduced in the postindex period across all cohorts. At 3-6 months after treatment switch, patients reported fewer claims for outpatient, private practice, and home visits and lower median health care costs. The proportions of patients with claims for clinical manifestations of aHUS were generally reduced in the postindex period compared with those of the preindex period. Limitations: Low patient numbers receiving ravulizumab only. Conclusions: The health-insurance claims data showed a reduced health care burden for US adult patients after treatment with ravulizumab or eculizumab for treatment of aHUS.

Channeling effects in the prescription of new therapies: the case of emicizumab for hemophilia A.

Aim: To determine if emicizumab was channeled to clinically complex people with hemophilia A upon approval. Methods: Claims data (16 November 2017, through 31 December 2019) from US-based insurance databases were analyzed to compare the clinical complexity of people with hemophilia A initiating emicizumab with matched individuals receiving factor VIII (FVIII) episodically or prophylactically. People with hemophilia A with evidence of previous bypassing agent use (indicating FVIII inhibitors) were excluded. Outcomes included bleeding events, arthropathy, pain, comorbidities and healthcare costs. Results: A larger proportion of emicizumab users had bleeding events, comorbidities and arthropathy and greater healthcare costs in the year prior to starting emicizumab compared with FVIII users. Conclusion: Claims-based data limitations prevent an absolute conclusion. Nevertheless, emicizumab users appear more clinically complex than FVIII users, suggesting post-approval channeling.

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.

Risks of venous thrombosis and bleeding in critically ill adolescents after trauma or major surgery.

BACKGROUND: The risks of venous thromboembolism (VTE) and bleeding in critically ill adolescents based on interventions received and anatomic site of trauma or major surgery may identify a cohort eligible for enrollment in a trial of pharmacologic prophylaxis. METHODS: This retrospective cohort study using the Virtual Pediatric Systems database included adolescents admitted to pediatric intensive care units after trauma or major surgery between 2013 and 2017. Mixed effects logistic regression was used to determine the adjusted risks of VTE and bleeding with central venous catheterization (CVC), mechanical ventilation (MV) and anatomic site of trauma or major surgery. The adjusted risks were used to identify the cohort eligible for enrollment. MEASUREMENTS AND MAIN RESULTS: VTE developed in 212 (0.8%) of 27,647 adolescents. The adjusted risk of VTE was >2% with CVC and 2 or more of MV and trauma or major surgery to the brain or abdomen. Excluding those with bleeds present on admission or at high risk of bleeding, 375 (1.4%) adolescents would be eligible for enrollment. CONCLUSIONS: VTE is generally uncommon in adolescents after trauma or major surgery. The small proportion of adolescents who are at high risk of VTE and at low risk of bleeding impacts the feasibility of a trial. LEVEL OF EVIDENCE: Prognostic Study Level II.

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.