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BACKGROUND: Children treated for cancer are at risk for adverse effects of iron due to transfusions administered during prolonged marrow suppression, which may increase exposure to toxic forms of iron, extrahepatic iron accumulation, and long-term organ damage. OBJECTIVE: This study aimed to characterize the severity and organ distribution of clinically significant, multisystem iron overload (IO) in an at-risk cohort of pediatric cancer patients. METHODS: This was a retrospective, cross-sectional study of childhood cancer patients who underwent a magnetic resonance imaging (MRI) due to clinical concern for IO. Data regarding cancer type and treatment, transfusion history, MRI and laboratory results, and treatment for IO were collected. Severity of IO was analyzed by non-parametric tests with respect to clinical characteristics. RESULTS: Of the 103 patients, 98% of whom had a Cancer Intensity Treatment Rating (ITR-3) of 3 or higher, 53% (54/102) had moderate or greater hepatic siderosis, 80% (77/96) had pancreatic siderosis, 4% (3/80) had cardiac siderosis, and 45% (13/29) had pituitary siderosis and/or volume loss. Pancreatic iron was associated with both cardiac (p = .0043) and pituitary iron (p = .0101). In the 73 off-therapy patients, ferritin levels were lower (p = .0008) with higher correlation with liver iron concentration (LIC) (p = .0016) than on-therapy patients. Fifty-eight subjects were treated for IO. CONCLUSION: In this heavily treated cohort of pediatric cancer patients, more than 80% had extrahepatic iron loading, which occurs with significant exposure to toxic forms of iron related to decreased marrow activity in setting of transfusions. Further studies should examine the effects of exposure to reactive iron on long-term outcomes and potential strategies for management.
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OBJECTIVES: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children. DESIGN: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry. SETTING: PICUs within U.S. CHAT Consortium participating centers. PATIENTS: Children younger than 21 years old admitted to a PICU receiving IMV for greater than or equal to 1 day duration from January 2012 to March 2022 were included for study. Cases with HA-VTE were matched 1:2 to controls without HA-VTE by patient age groups: younger than 1, 1-12, and older than 12 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was IMV duration in days. Descriptive data included demographics, anthropometrics, HA-VTE characteristics (i.e., type, location, and timing), central venous catheterization data, thromboprophylaxis practices, and Braden Q mobility scores. Descriptive, comparative, and associative (multivariate conditional logistic regression for HA-VTE) statistics were employed. A total of 152 cases were matched to 304 controls. Cases with HA-VTE were diagnosed at a median of 7 days (interquartile range [IQR], 3-16 d) after IMV. The HA-VTE were limb deep venous thromboses in 130 of 152 (85.5%) and frequently central venous catheterization-related (111/152, 73%). Cases with HA-VTE experienced a longer length of stay (median, 34 d [IQR, 18-62 d] vs. 11.5 d [IQR, 6-21 d]; p < 0.001) and IMV duration (median, 7 d [IQR, 4-15 d] vs. 4 d [IQR, 1-7 d]; p < 0.001) as compared with controls. In a multivariate logistic model, greater IMV duration (adjusted odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.023) was independently associated with HA-VTE. CONCLUSIONS: Among critically ill children undergoing IMV, HA-VTE was associated with greater IMV duration. If prospectively validated, IMV duration should be included as part of prothrombotic risk stratification and future pediatric thromboprophylaxis trials.
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Trombose , Tromboembolia Venosa , Criança , Humanos , Anticoagulantes , Estudos de Casos e Controles , Estado Terminal/terapia , Hospitais , Respiração Artificial/efeitos adversos , Fatores de Risco , Trombose/epidemiologia , Trombose/etiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Lactente , Pré-Escolar , AdolescenteRESUMO
[This corrects the article DOI: 10.1016/j.rpth.2023.102139.].
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Graphical representation of increasing percentage of female patients seen at HTCs, percentage of females by diagnosis, number of clinics in existence, and absolute number of female patients seen over a 10-year period (top left then clockwise).
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Hemofilia A , Humanos , Feminino , Hemofilia A/epidemiologia , Hemofilia A/terapiaRESUMO
BACKGROUND: Acutely ill and medically complex children frequently rely on central venous catheters (CVCs) to provide life-sustaining treatment. Unfortunately, catheter-related thrombosis (CRT) is a serious and common complication. Little is known why some with a CVC develop CRT and others develop venous thromboembolism unrelated to the CVC (non-CRT). OBJECTIVES: The aim of this study was to identify factors associated with CRT in children with hospital-acquired venous thromboembolism (HA-VTE). METHODS: This case-case study included participants in the Children's Hospital Acquired Thrombosis Registry with HA-VTE and CVC aged 0 to 21 years from 8 US children's hospitals. Participants were excluded if they developed HA-VTE prior to CVC insertion or if the CVC insertion date was unknown. Logistic regression models were used to assess associations between clinical factors and CRT status. RESULTS: There were 1144 participants with HA-VTE who had a CVC. CRT developed in 833 participants, and 311 developed non-CRT. Multivariable analysis showed increased odds of CRT (compared with non-CRT) in participants with peripherally inserted central catheters (odds ratio [OR], 3.80; 95% CI, 2.04-7.10; p < .001), CVCs inserted in the femoral vein (OR, 4.45; 95% CI, 1.70-11.65; p = .002), multiple CVCs (OR, 1.42; 95% CI, 1.18-1.71; p < .001), and CVC malfunction (OR, 3.30; 95% CI, 1.80-6.03; p < .001). CONCLUSION: The findings of this study provide new insights on risk factor differences between CRT and non-CRT. Prevention efforts should be directed at modifying the type of CVC, insertion location, and/or number of CVCs placed, if possible, to decrease the incidence of CRT.
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Cateterismo Venoso Central , Cateteres Venosos Centrais , Trombose , Tromboembolia Venosa , Humanos , Criança , Cateteres Venosos Centrais/efeitos adversos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Fatores de Risco , Trombose/etiologia , Hospitais , Cateterismo Venoso Central/efeitos adversosRESUMO
BACKGROUND: Excessive or abnormal mucocutaneous bleeding (MCB) may impact all aspects of the physical and psychosocial wellbeing of those who live with it (PWMCB). The evidence base for the optimal diagnosis and management of disorders such as inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD), Ehlers-Danlos syndromes (EDS), and von Willebrand disease (VWD) remains thin with enormous potential for targeted research. RESEARCH DESIGN AND METHODS: National Hemophilia Foundation and American Thrombosis and Hemostasis Network initiated the development of a National Research Blueprint for Inherited Bleeding Disorders with extensive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them. They recruited multidisciplinary expert working groups (WG) to distill community-identified priorities into concrete research questions and score their feasibility, impact, and risk. RESULTS: WG2 detailed 38 high priority research questions concerning the biology of MCB, VWD, inherited qualitative platelet function defects, HDS/EDS, HHT, bleeding disorder of unknown cause, novel therapeutics, and aging. CONCLUSIONS: Improving our understanding of the basic biology of MCB, large cohort longitudinal natural history studies, collaboration, and creative approaches to novel therapeutics will be important in maximizing the benefit of future research for the entire MCB community.
More people experience mucocutaneous bleeding (MCB), affecting tissues like skin and gums, than have hemophilia A or B. MCB is not understood as well as hemophilia. Common types of MCB include nosebleeds, bleeding gums, heavy menstrual bleeding, and digestive tract bleeding. Mucocutaneous inherited bleeding disorders include inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS), von Willebrand Disease (VWD), and others. Diagnosing and treating MCB is complicated and sometimes medical providers dismiss the bleeding that patients report when they cannot find a medical explanation for it. Many people with mucocutaneous bleeding (PWMCB) do not receive the care they need; for example, women with VWD live with symptoms for, on average, 16 years before they are diagnosed in the US. This struggle to obtain care has important negative impacts on patients' physical and psychological health and their quality-of-life. The National Hemophilia Foundation (NHF), a large US bleeding disorders patient advocacy organization, set out to develop a National Research Blueprint for Inherited Bleeding Disorders focused on community priorities. They brought together a group of patients, providers, and researchers with MCB expertise to identify the research that would most improve the lives of PWMCB through targeted and accessible diagnostics and therapies. We report in this paper that research is needed to better understand the biology of MCB and to define the mechanisms of disease in these disorders. We also describe high priority research questions for each of the main disorders, novel therapeutics, and aging.
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Transtornos Plaquetários , Hemofilia A , Doenças de von Willebrand , Humanos , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/genética , Doenças de von Willebrand/terapia , Transtornos Plaquetários/diagnóstico , Transtornos Plaquetários/genética , Transtornos Plaquetários/terapia , PesquisaRESUMO
Von Willebrand disease (VWD) is an inherited bleeding disorder caused by quantitative or qualitative deficiencies in von Willebrand factor (VWF). People with VWD may experience excessive, recurrent or prolonged bleeding, particularly during menstruation, childbirth, surgery or following trauma. However, many VWD patients are undiagnosed, and therefore inadequately treated. Reasons for the underdiagnosis of VWD include its relatively mild symptoms, complex diagnosis, lack of awareness among non-specialist healthcare providers and the general population, and a lack of prioritisation of disorders disproportionately affecting females. The vwdtest.com platform was launched as part of a global initiative to raise awareness and improve diagnosis of VWD. Besides providing VWD-specific educational resources, the website includes an online bleeding self-assessment tool and offers diagnostic support for individuals, and their providers, who have a score suggestive of a bleeding disorder. vwdtest.com helps to address these unmet needs, especially in regions with limited access to educational and diagnostic resources.
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Transtornos Hemorrágicos , Doenças de von Willebrand , Feminino , Humanos , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/terapia , Doenças de von Willebrand/complicações , Fator de von Willebrand , Hemorragia/diagnóstico , Hemorragia/etiologia , Hemorragia/terapiaRESUMO
INTRODUCTION: The incidence of pediatric hospital-acquired venous thromboembolism (HA-VTE) has increased over time. Congenital heart disease (CHD) as a co-morbidity has been demonstrated to significantly increase HA-VTE risk among hospitalized children. OBJECTIVE: To identify specific risks factors for the development of HA-VTE in hospitalized children with CHD. MATERIALS AND METHODS: This retrospective case-control study included hospitalized participants aged 0-21 years within the Children's Hospital Acquired Thrombosis (CHAT) Consortium Registry with a co-morbidity of CHD. Participants with HA-VTE and non-VTE controls with a past medical history of CHD were selected from the CHAT Registry and data regarding multiple clinical variables were extracted. These variables were then analyzed to assess their association with HA-VTE development. RESULTS: Three hundred and thirty-three participants with a co-morbidity of CHD were identified, comprising 275 HA-VTE cases and 58 controls. Median age for HA-VTE cases was 0.4 (IQR = 0-2.6) years compared to 3.4 (IQR = 0.7-6.5) for controls. Male participants were predominant in both groups (57.5 % HA-VTE cases vs 51.7 % controls). Multivariable analysis identified prior recent hospitalization (OR = 4.12, 95%CI = 1.66-10.24), intensive care unit (ICU) admission (OR = 3.29, 95 % CI = 1.15-9.40), and CVC placement (OR = 9.14, 95 % CI = 3.38-24.72) as significant risk factors for HA-VTE in subjects with CHD. CONCLUSIONS: ICU admission, CVC placement, and prior hospitalization were identified as statistically significant predictors associated with HA-VTE development in hospitalized children with history of CHD. Prospective studies are needed to validate these results and help develop strategies to mitigate HA-VTE development in these patients.
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Cardiopatias Congênitas , Trombose , Tromboembolia Venosa , Humanos , Masculino , Criança , Recém-Nascido , Lactente , Pré-Escolar , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Hospitais Pediátricos , Estudos de Casos e Controles , Estudos Retrospectivos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/epidemiologia , Fatores de RiscoRESUMO
Background: Surgery is a known risk factor for hospital-acquired venous thromboembolism (HA-VTE) in children. Objectives: To assess whether the odds of HA-VTE differs across six anatomic sites of noncardiac surgery and to identify risk factors for HA-VTE in these children. Methods: This was a multicenter, case-control study. Anatomic sites of surgery and risk factors for HA-VTE were collected on hospitalized pediatric patients who had undergone a single noncardiac surgery and developed HA-VTE (cases), and those who did not develop HA-VTE (controls), via the Children's Hospital-Acquired Thrombosis (CHAT) Registry. Logistic regression estimated the odds ratio (OR) and 95% confidence intervals (CIs) between six anatomic sites of surgery and 16 putative HA-VTE risk factors. Variables with a p value of 0.10 or less in unadjusted analyses were included in adjusted models for further evaluation. The final model used backward selection, with a significance level of 0.05. Results: From January 2012 to March 2020, 163 cases (median age, 5.7 years; interquartile range [IQR], 0.3-14.2) and 208 controls (median age of 7.5 years; IQR, 3.7-12.9) met our criteria. There was no statistically significant increased odds of VTE among the types of noncardiac surgery. In the final adjusted model, central venous catheter (CVC; OR, 14.69; 95% CI, 7.06-30.55), intensive care unit (ICU) stay (OR, 5.31; 95% CI, 2.53-11.16), and hospitalization in the month preceding surgery (OR, 2.75; 95% CI, 1.24-6.13) were each independently significant risk factors for HA-VTE. Conclusion: In children undergoing noncardiac surgery, placement of CVCs, admission/transfer to the ICU, or hospitalization in the month prior to surgery were positively associated with HA-VTE.
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Caring for children and adolescents with disorders of hemostasis and thrombosis (HAT) has become more specialized and requires a unique skill set that many providers are not able to obtain in standard pediatric hematology/oncology/bone marrow transplant fellowship training programs. The influx of numerous therapeutic advances and increasing medical complexity has expanded the need for experienced HAT providers and subspecialty collaboration in the inpatient setting due to the nuances in the management of patients with HAT complications and concerns. While there are data highlighting the benefits of an inpatient hemostasis, thrombosis, and anticoagulation management service in adult hospitals, there are limited pediatric data supporting such programs. In this article, we summarize the current practices of various pediatric institutions in the inpatient management of HAT patients and provide a consensus opinion for the development of a pediatric inpatient HAT service at tertiary care referral centers.
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Pacientes Internados , Trombose , Adolescente , Adulto , Criança , Comunicação , Consenso , Hemostasia , Hospitais Pediátricos , Humanos , Recém-Nascido , Encaminhamento e Consulta , Trombose/diagnóstico , Trombose/terapiaRESUMO
BACKGROUND: Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19, including primary respiratory infection and multisystem inflammatory syndrome in children (MISC). METHODS: We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg per dose; max: 60mg; target anti-Xa activity: 0.20-0.49IU/mL) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; enoxaparin dose-requirements; and cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by participant age (±12 years) and clinical presentation. RESULTS: Forty children were enrolled and 38 met analyses criteria. None experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P = .51) but was greater for participants with MISC (0.52 [0.5-0.61] mg/kg) as compared with primary COVID-19 (0.48 [0.39-0.51] mg/kg, P = .010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention. CONCLUSIONS: Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.
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COVID-19 , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , COVID-19/complicações , Criança , Enoxaparina/efeitos adversos , Hemorragia , Humanos , Estudos Prospectivos , Síndrome de Resposta Inflamatória Sistêmica , Resultado do Tratamento , Tromboembolia Venosa/prevenção & controleRESUMO
With the increasing incidence of thromboembolism in children and improvement in management for patients with medically complex diseases, expanded availability of safe and effective anticoagulant medications is needed. Traditionally, the most common anticoagulants used for the treatment or prevention of venous thromboembolism or embolic stroke in children were either unfractionated heparin or the low-molecular-weight heparins. These medications require either intravenous access or daily subcutaneous injections, in addition to multiple venepunctures to monitor drug concentrations. Direct oral anticoagulants provide an alternative, and potentially safer, choice for children, as they are available in oral formulations and do not require drug monitoring. With the approval of the direct factor Xa inhibitor, rivaroxaban (by the European Medicines Agency and Health Canada), and the direct thrombin inhibitor, dabigatran (by the European Medicines Agency and US Food and Drug Administration), the field of paediatric anticoagulation is changing. In this Review, we provide an overview of the four direct oral anticoagulants approved in adults for the treatment and prevention of thrombosis and the completed and ongoing paediatric trials.
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Ensaios Clínicos como Assunto , Dabigatrana/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Pediatria , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Tiazóis/uso terapêutico , Antitrombinas/uso terapêutico , Criança , HumanosRESUMO
BACKGROUND: Venous thromboembolism (VTE) is a known complication for children with acute lymphoblastic leukemia (ALL). The aim of this study was to identify laboratory biomarkers that predict which children with ALL are at risk for VTE during induction chemotherapy. MATERIALS AND METHODS: Newly diagnosed ALL patients admitted to Children's Hospital Los Angeles with a central venous catheter (CVC) were eligible to participate. Participants' blood samples (complete blood count [CBC], quantitative D-dimer, prothrombin fragment 1.2 [PTF 1.2], and thrombin-antithrombin complexes [TAT]) were collected at day 0 (baseline/prior to induction), day 7 (±2 days), day 14 (±2 days), day 21 (±2 days), and day 28 (±2 days) of induction chemotherapy or until participants presented with a symptomatic VTE. RESULTS: Seventy-five participants aged 1-21 years were enrolled and included in the final analysis. Twenty-six (35%) of the 75 participants were diagnosed with a CVC-associated VTE (22 asymptomatic and four symptomatic). There was a statistically significant difference between VTE and non-VTE participants for D-dimer (odds ratio [OR] 1.61, 95% confidence interval [CI]: 1.59-1.64), TAT (OR 1.34, 95% CI: 1.32-1.38), and PTF 1.2 (OR 1.31, 95% CI: 1.25-1.37) at all time points. Participants >10 years had a significantly higher risk of developing a VTE compared to participants <4 years (p = .007). CONCLUSION: Older children with ALL as well as those with an elevated TAT, PTF 1.2, or D-dimer showed an increased risk of VTE, which may hold potential for predicting VTE in future studies.
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Cateteres Venosos Centrais , Leucemia-Linfoma Linfoblástico de Células Precursoras , Trombofilia , Tromboembolia Venosa , Adolescente , Biomarcadores , Cateteres Venosos Centrais/efeitos adversos , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Fatores de Risco , Trombofilia/diagnóstico , Trombofilia/etiologia , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: Appropriate timing of central venous catheter (CVC) removal, in relation to start of anticoagulation, in children after the diagnosis of a CVC-related thrombosis (CRT) is not well established. OBJECTIVES: This retrospective cohort study evaluated the incidence of symptomatic pulmonary embolism (PE) after CVC removal using data from the multi-institutional Children's Hospital-Acquired Thrombosis (CHAT) Consortium Registry. PATIENTS/METHODS: The CHAT Registry consists of data from children aged 0-21 years with a hospital-acquired venous thromboembolism. Eligible subjects were those with CRT diagnosed <3 days after CVC removal. Subjects were excluded if the CRT was due to a failed CVC insertion. Subjects were divided into three groups: those with CVC removal without anticoagulation, those with CVC removal <48 h after starting anticoagulation, and those with CVC removal ≥48 h after starting anticoagulation. RESULTS: A total of 687 CRT events from 663 subjects were included. A majority of CRT events were in subjects with peripherally inserted central catheters (62.3%, n = 428). For the 611 CRT events in which the CVC was removed, there was only one case of symptomatic PE (0.16%), which occurred <48 h after initiation of anticoagulation. CONCLUSIONS: While current guidelines suggest anticoagulation before CVC removal in the setting of a CRT to prevent embolization, CVC removal is not associated with symptomatic PE regardless of duration of anticoagulation before CVC removal.
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Cateterismo Venoso Central , Cateteres Venosos Centrais , Embolia Pulmonar , Trombose , Adolescente , Adulto , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Embolia Pulmonar/complicações , Embolia Pulmonar/etiologia , Estudos Retrospectivos , Trombose/epidemiologia , Trombose/etiologia , Adulto JovemRESUMO
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.
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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.
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Trombose , Tromboembolia Venosa , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Estado Terminal , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Medição de Risco , Fatores de Risco , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Adulto JovemRESUMO
OBJECTIVES: Examine: (1) Prevalence of diagnosed venous thromboembolism (VTE) in infants <6 months discharged from U.S. NICUs; (2) Associations between sociodemographic and clinical factors and VTE; (3) Secondary outcomes related to VTE. STUDY DESIGN: Multivariable logistic regressions examined associations between VTE and sociodemographic and clinical factors among infants <6 months discharged from Pediatric Health Information System (PHIS) NICUs between 2016 and 2019. RESULTS: Of 201,033 infants, 2720 (1.35%) had diagnosed VTE. Birthweight 300-1000 g (aOR 3.14, 95% CI 2.54-3.88), 1000-1500 g (aOR 1.77, 95% CI 1.40-2.42) versus 2500-3999 g, and public (aOR 1.18, 95% CI 1.02-1.37) versus private insurance were associated with increased odds of VTE, as were CVC, TPN, mechanical ventilation, infection, ECMO, and surgery. All types of central lines (non-tunneled and tunneled CVCs, PICCs, and umbilical catheters) had higher odds of VTE than not having that type of line. CVCs in upper versus lower extremities had higher odds of VTE. CONCLUSION: Infants with risk factors may require monitoring for VTE. Results may inform VTE prevention.