Enoxaparin treatment dosing for venous thromboembolism in pediatric patients with obesity.

BACKGROUND: The optimal enoxaparin dosing for treatment of venous thromboembolism (VTE) in pediatric patients with obesity remains uncertain. We described the mean enoxaparin dose required to attain anti-factor Xa (anti-Xa) levels of 0.5-1 unit/mL in pediatric patients with obesity. METHODS: Pediatric patients with obesity (body mass index [BMI] ≥95th percentile) who received treatment dose of enoxaparin from 2013 to 2022 and had at least one appropriately timed anti-Xa level were retrospectively evaluated. Daily enoxaparin dose required to achieve an anti-Xa level of 0.5-1 unit/mL was reviewed and compared by the severity of obesity. The correlation coefficients between enoxaparin dose requirement and BMI, BMI percentile, and weight were measured by Spearman's rank correlation coefficient. RESULTS: Pediatric patients with obesity (n = 89) required a mean enoxaparin dose of 0.8 ± 0.18 mg/kg twice daily to attain a therapeutic anti-Xa level. Children with BMI 95th-99th percentile and weight ≤100 kg achieved the target level on a significantly higher weight-based enoxaparin dose compared to BMI greater than 99th percentile (0.95 ± 0.15 vs. 0.75 ± 0.15 mg/kg twice daily; p < .001) and weight greater than 100 kg (0.95 ± 0.14 vs. 0.7 ± 0.12 mg/kg twice daily; p < .001). BMI, BMI percentile, and weight showed a moderate to strong negative correlation with enoxaparin dose requirement. CONCLUSIONS: Pediatric patients with obesity required a lower weight-based dose of enoxaparin to achieve a therapeutic anti-Xa than the recommended starting dose of 1 mg/kg twice daily for treatment of VTE. Among obesity indices, weight showed the strongest negative correlation with total daily enoxaparin requirement.

Enoxaparin thromboprophylaxis in hospitalized obese pediatric patients.

BACKGROUND: Enoxaparin is an anticoagulant used for pharmacologic thromboprophylaxis in pediatrics. Enoxaparin pharmacokinetics can be altered in the setting of obesity. Optimal enoxaparin dosing for thromboprophylaxis in children with obesity remains unclear. PROCEDURE: A retrospective review was conducted of pediatric patients who weighed ≥60 kg with BMI ≥ 95th percentile, received enoxaparin for thromboprophylaxis, and had at least one appropriately drawn anti-factor Xa (anti-Xa) from 2013 to 2022. Anti-Xa levels were reviewed for patients initially treated with enoxaparin 30 mg every 12 h. The average daily enoxaparin dose required to achieve an anti-Xa of 0.2-0.4 unit/mL, which was stratified by BMI percentile and weight, was calculated. RESULTS: Of 116 patients (median age 15.8 years) included for analysis, 106 patients were initially treated with enoxaparin 30 mg every 12 h. Anti-Xa levels were <0.2 unit/mL in 53% of patients with BMI > 99th percentile and 54% of patients >100 kg. Ninety-one patients had at least one anti-Xa 0.2-0.4 unit/mL with an average daily enoxaparin dosing of 66 mg. When stratified by severity of obesity, higher doses were required to attain an anti-Xa 0.2-0.4 unit/mL in patients with BMI > 99th percentile compared with those with 95th-99th percentile (67.8 ± 15.7 vs. 62 ± 5.6 mg/day, p = .01). Patients > 100 kg required significantly higher dose than those ≤100 kg (69.1 ± 15.5 vs 61.2 ± 7.3 mg/day, p = .002). CONCLUSIONS: Increased initial dosing and/or anti-Xa level monitoring should be considered in adolescents with severe obesity receiving enoxaparin thromboprophylaxis.

Technical Feasibility and Clinical Efficacy of Iliac Vein Stent Placement in Adolescents and Young Adults with May-Thurner Syndrome.

PURPOSE: To report technical feasibility and clinical efficacy of iliac vein stent placement in adolescent patients with May-Thurner Syndrome (MTS). MATERIALS AND METHODS: Single-institution retrospective review of the medical record between 2014 and 2021 found 63 symptomatic patients (F = 40/63; mean age 16.1 years, 12-20 years) who underwent left common iliac vein (LCIV) stent placement for treatment of LCIV compression from an overriding right common iliac artery, or equivalent (n = 1, left IVC). 32/63 (50.7%) patients presented with non-thrombotic iliac vein lesions (NIVL). 31/63 (49.2%) patients presented with deep vein thrombosis of the lower extremity and required catheter-directed thrombolysis after stent placement (tMTS). Outcomes include technically successful stent placement with resolution of anatomic compression and symptom improvement. Stent patency was monitored with Kaplan-Meier analysis at 3, 6, 12, 24, and 36 months. Anticoagulation and antiplatelet (AC/AP) regimens were reported. RESULTS: Technical success rate was 98.4%. 74 bare-metal self-expanding stents were placed in 63 patients. Primary patency at 12, and 24-months was 93.5%, and 88.9% for the NIVL group and 84.4% and 84.4% for the tMTS group for the same period. Overall patency for the same time intervals was 100%, and 95.4% for the NIVL group and 96.9%, and 96.9% for the tMTS group. Procedural complication rate was 3.2% (2/63) with no thrombolysis-related bleeding complications. Clinical success was achieved in 30/32 (93.8%) and 29/31 (93.5%) patients with tMTS and NIVL groups, respectively. CONCLUSION: CIV stent placement in the setting of tMTS and NIVL is technically feasible and clinically efficacious in young patients with excellent patency rates and a favorable safety profile.

Novel Dosing and Monitoring of Aspirin in Infants With Systemic-to-Pulmonary Artery Shunt Physiology: the SOPRANO Study.

OBJECTIVES: Provision of pulmonary blood flow with a systemic-to-pulmonary artery shunt is essential in some patients with cyanotic congenital heart disease. Traditionally, aspirin (ASA) has been used to prevent thrombosis. We evaluated ASA dosing with 2 separate antiplatelet monitoring tests for accuracy and reliability. METHODS: This is a retrospective, pre-post intervention single center study. Two cohorts were evaluated; the pre-intervention group used thromboelastography platelet mapping (TPM) and post-intervention used VerifyNow aspirin reactivity unit (ARU) monitoring. The primary endpoint was to compare therapeutic effect of TPM and ARU with regard to platelet inhibition. Inadequate platelet inhibition was defined as TPM <50% inhibition and ARU >550. RESULTS: Data from 49 patients were analyzed: 25 in the TPM group and 24 in the ARU group. Baseline characteristics were similar amongst the cohorts. The TPM group had significantly more patients with inadequate platelet inhibition (14 [56%] vs 2 [8%]; p = 0.0006) and required escalation with additional thromboprophylaxis (15 [60%] vs 5 [21%]). There was no difference in shunt thrombosis (1 [2%] vs 0 [0%]; p = 0.32), cyanosis requiring early re-intervention (9 [36%] vs 14 [58%]; p = 0.11), or bleeding (15 [60%] vs 14 [58%]; p = 0.66). CONCLUSION: With similar cohorts and the same ASA-dosing nomogram, ARU monitoring resulted in a reduced need for escalation of care and concomitant thromboprophylaxis with no difference in adverse outcomes. Our study suggests ARU monitoring compared with TPM may be a more reliable therapeutic platelet inhibition test for determining ASA sensitivity in children with congenital heart disease requiring systemic-to-pulmonary artery shunt.

Successful Medical-Surgical Management of Intracardiac Thrombosis and Pulmonary Pseudoaneurysms in an Adolescent With Hughes-Stovin Syndrome.

We present an adolescent male with a single intracardiac mass and pulmonary emboli, complicated by peripheral venous thrombosis and subsequent development of pulmonary pseudoaneurysms, leading to diagnosis of Hughes-Stovin syndrome. Remission was achieved with cyclophosphamide, corticosteroids, and pseudoaneurysm resection and maintained with infliximab and methotrexate.

Practical considerations and consensus opinion for children's hospital-based inpatient hemostasis and thrombosis (HAT) consultative services: Communication from the ISTH SSC Subcommittee on Pediatric/Neonatal Thrombosis and Hemostasis.

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.

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.

Successful Perioperative Management of Orthotopic Cardiac Transplantation in a Pediatric Patient With Concurrent Congenital von Willebrand Disease and Acquired von Willebrand Syndrome Using Recombinant von Willebrand Factor.

Von Willebrand disease (VWD) is the most common bleeding disorder and reportedly affects 1:1,000 of the world's population. There are three subtypes of VWD characterized by a quantitative defect (types 1 and 3 VWD) or a qualitative defect (type 2 VWD). Type 1 VWD results in a partial deficiency of von Willebrand factor (VWF) and affects approximately 75% of individuals with VWD, whereas type 3 VWD results in a severe or complete deficiency of VWF. Individuals with type 2 VWD subtypes (types 2A, 2B, 2M, and 2N VWD) express a dysfunctional VWF protein that has impaired interactions with platelets or factor VIII. The majority of individuals with VWD have mild type 1 VWD and occasionally require bolus infusions of VWF for severe bleeding or major surgery. A subset of patients, especially those with type 2A or 3 VWD, may require more frequent VWF replacement or prophylaxis for refractory bleeding or bleeding prevention, respectively. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that primarily occurs as a result of an underlying disease or other pathologic mechanism. Cases of AVWS associated with heart valve defects, left ventricular assist devices, or congenital cardiac disease result from high shear stress in the circulation that induces VWF unfolding and subsequent proteolysis of high-molecular-weight multimers by ADAMTS-13. In rare instances, plasma-derived factor VIII-containing VWF concentrates have been administered to individuals with AVWS for persistent or challenging bleeding events. In this case report, the hemostatic challenges and the perioperative management of cardiac transplantation surgery using a novel recombinant VWF product in a pediatric patient diagnosed with AVWS concomitant with congenital type 1 VWD are described. Written informed consent was obtained from the patient's mother for this case report. The diagnosis of congenital VWD remains a challenge because of multiple potential modifiers that can alter VWF laboratory results. Concurrent conditions, such as congenital heart disease and the rare secondary condition of AVWS, in addition to congenital VWD, can further affect interpretation of coagulation studies. This can result in delays in diagnosis, increase severity of the bleeding phenotype, and complicate hemostatic management in individuals at risk for bleeding and thrombosis. A multidisciplinary approach, including anesthesiologists, cardiologists, cardiovascular surgeons, hematologists, and pharmacists, is critical to achieving optimal patient outcomes, as highlighted in this case report. As diagnostic capabilities and understanding of VWD broaden, future studies evaluating alternative treatment approaches for individuals with various types of VWD would be of great benefit to the medical community.

Mental health difficulties among professional jockeys: a narrative review.

INTRODUCTION: Emerging academic literature and high-profile disclosures of mental health difficulties and mental illness from current and former professional jockeys suggest that further exploration of the mental health of jockeys is required. To date, a comprehensive review of jockeys' mental health has yet to be conducted. OBJECTIVES: To examine the existing literature related to jockeys' mental health, including the prevalence of symptoms associated with mental health difficulties and help-seeking. DESIGN: A narrative review of the literature was conducted with articles screened from inception until January 2021. RESULTS: Sixteen studies were included in the narrative review. Studies covered a range of mental health difficulties which included mood (depression), anxiety, distress, disordered eating and substance misuse. Rates of help-seeking among jockeys were also explored. Results indicated that jockeys reported higher levels of depressive and anxiety symptoms compared with other elite athletes. Substance misuse, in particular adverse alcohol use, also appears greater among jockeys than other elite athletes. Distress symptoms appear comparable with other elite athletes. Risk factors for mental health difficulties included injury, perceived stress, athlete burnout, career dissatisfaction and the contemplation of retirement. Weight-making negatively impacts jockeys' mood and attitudes towards eating, with lower competitive riding weights associated with more disordered eating attitudes. Moreover, help-seeking from mental health professionals appears low. CONCLUSION: The review identifies a high prevalence of symptoms of mental health difficulties among professional jockeys. Applied recommendations and future research considerations are proposed throughout the review article.

Thrombolysis in Children: A Case Report and Review of the Literature.

Thromboembolism (TE), including venous thromboembolism (VTE), arterial TE, arterial ischemic stroke (AIS), and myocardial infarction (MI), is considered a relatively rare complication in the pediatric population. Yet, the incidence is rising, especially in hospitalized children. The vast majority of pediatric TE occurs in the setting of at least one identifiable risk factor. Most recently, acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) have demonstrated an increased risk for TE development. The mainstay for the management pediatric TE has been anticoagulation. Thrombolytic therapy is employed more frequently in adult patients with ample data supporting its use. The data for thrombolysis in pediatric patients is more limited, but the utilization of this therapy is becoming more commonplace in tertiary care pediatric hospitals. Understanding the data on thrombolysis use in pediatric TE and the involved risks is critical before initiating one of these therapies. In this paper, we present the case of an adolescent male with acute fulminant myocarditis and cardiogenic shock likely secondary to MIS-C requiring extracorporeal life support (ECLS) who developed an extensive thrombus burden that was successfully resolved utilizing four simultaneous catheter-directed thrombolysis (CDT) infusions in addition to a review of the literature on the use of thrombolytic therapy in children.

Venous thromboembolism in chronic pediatric heart disease is associated with substantial health care burden and expenditures.

ABSTRACT: Background: Venous thromboembolism (VTE) is a complication in children with chronic pediatric heart disease (CPHD). The influence of acute VTE risk factors and the health care burden associated with VTE in CPHD is unknown.Methods: Children <18 years of age with a CPHD diagnostic code were identified from the 2003-2013 MarketScan Commercial Databases. VTE diagnoses were identified either concomitantly with initial CPHD diagnoses or during a 6-month follow-up. The associations between demographic and clinical characteristics and VTE among children with CPHD, stratified by recent cardiac surgery, were assessed by multivariable logistic regression models. Estimates of health care utilization were compared using Wilcoxon rank-sum tests.Results: VTE events occurred in 957 of 120 884 children with CPHD (0.8%). In-hospital mortality was significantly higher in children with VTE. Single-ventricle physiology had the highest VTE rate (2.3%). All comorbid conditions were significantly associated with VTE, but the prevalence was highest in children with recent cardiac (11.1%) or noncardiac surgery (7.8%). The magnitude of association between noncardiac comorbidities and acquired acute cardiovascular conditions and VTE were larger for children without a recent cardiac surgery. Children with VTE had significantly higher health care utilization.Conclusions: VTE in CPHD is associated with significantly increased health care resource utilization and in-hospital mortality. All of the comorbid conditions examined were significantly associated with VTE, but a recent surgical procedure, especially cardiac surgery, conferred the highest VTE risk. Although confounding inherently limits observational studies, these findings provide practical information about the health care costs among patients with CPHD and VTE.

Variation in Platelet Delta Granules Over Time in Young Women Undergoing Evaluation for Heavy Menstrual Bleeding.

Delta-granule platelet storage pool deficiency (δ-PSPD) is a qualitative platelet function defect associated with variable bleeding phenotypes. Platelet electron microscopy (EM) is commonly utilized to evaluate for δ-PSPD, but intrapatient variability in platelet δ-granule numbers by EM is currently unknown. Fifteen young women aged 11 to 17 years presenting to a young women's hematology clinic for the evaluation of heavy menstrual bleeding underwent platelet EM testing at their initial hematology clinic visit and at 1 and 3 months later. Platelet aggregation of platelet-rich plasma by light transmission was also performed on all patients at their initial visit. Eight patients had average δ-granules per platelet consistently ≥2. Three patients were found to have average δ-granules per platelet <2 on initial testing, 2 of which reverted to ≥2 on subsequent testing. When initial average δ-granules per platelet was ≥2, initial repeat testing remained so in 83% (95% confidence interval [CI], 52%-98%) of cases and subsequent repeat testing remained so in 75% (95% CI, 43%-95%) of the cases. Platelet aggregation testing was abnormal in 53% of patients, and there was no apparent correlation between platelet EM findings and platelet aggregation testing. In this small group of young women presenting for the evaluation of bleeding symptoms, we found that almost half of the patients had substantial variability in platelet EM results. Given other identified limitations in platelet EM testing, and the intrapatient variability identified in this study, providers should use caution in utilizing EM in isolation to diagnose δ-PSPD.

Impact of erythrocytapheresis on natural anticoagulant levels in children with sickle cell disease: A pilot study.

Venous thromboembolism (VTE) is being increasingly recognized in children with sickle cell disease (SCD). In a retrospective cohort study, we identified bilateral central venous catheter (CVC) placement as an independent risk factor for VTE. At our institution, the only indication for bilateral CVC placement in children with SCD is erythrocytapheresis. To investigate the impact of erythrocytapheresis on coagulation, we measured levels of natural anticoagulants in 11 patients with SCD on chronic erythrocytapheresis, immediately before and after apheresis. We demonstrated a statistically significant reduction in most parameters. Additional studies are needed to further investigate the exact etiology and clinical impact of this acute decrease.

Venous Thromboembolism in Children with Sickle Cell Disease: A Retrospective Cohort Study.

OBJECTIVES: To describe the cumulative incidence of venous thromboembolism (VTE) in children with sickle cell disease (SCD) followed at a single institution and report on the risk factors associated with VTE development. STUDY DESIGN: Charts for all patients with SCD, aged 0-21 years, followed at Nationwide Children's Hospital over a 6-year period (January 1, 2009, to January 31, 2015) were reviewed. Data on VTE diagnosis, sex, body mass index/weight-for-length, SCD genotype, SCD clinical complications, central venous catheter (CVC) placement, and thrombophilia testing were collected. RESULTS: Cumulative incidence of VTE in children with SCD followed at a single tertiary care institution was found to be 2.9% (12/414). Nine of the 12 VTE were CVC-associated. On univariate analysis, hemoglobin SS genotype (OR 10.7, 95% CI 1.4-83.5), CVC presence (OR 34.4, 95% CI 8.9-134.6), central nervous system vasculopathy (OR 19.4, 95% CI 5.6-63.4), chronic transfusion therapy (OR 30.6, 95% CI 8.9-122.2), and older age (P = .03) were associated with VTE. However, presence of CVC was the only independent risk factor identified on multivariable logistic regression analysis (OR 33.8, 95% CI 8.7-130.9). CONCLUSION: In our institution, nearly 3% of children with SCD had a history of VTE. CVC is an independent predictor of VTE in children with SCD.

Pediatric Oral/Maxillofacial Soft Tissue Sarcomas: A Clinicopathologic Report of Four Cases.

Pediatric soft tissue sarcomas of the oral/maxillofacial region are rare neoplasms that present significant difficulty with respect to treatment and local control measures. We report four cases of pediatric oral/maxillofacial soft tissue sarcomas from our tertiary care pediatric hospital and emphasize the rarity of these malignancies and the challenges encountered in treating these lesions, and suggest areas for further research. We conclude that multimodal therapy and interdisciplinary cooperation are paramount to successful management of these lesions.

A Review of Hormonal Contraception and Venous Thromboembolism in Adolescents.

BACKGROUND: The number of adolescents who are prescribed hormonal contraception (HC) for contraceptive and noncontraceptive indications is increasing. Approximately 1 of 4 female adolescents will use some form of HC by age 19 years. Venous thromboembolism (VTE) is a rare, but life-threatening complication associated with HC use. Although adolescents aged 15 to 19 years have the lowest absolute HC-associated VTE risk, they still account for 5.9% of HC-associated VTE. The absolute HC-associated VTE risk for those younger than 15 years of age is not well described. OBJECTIVE: The objectives of this report are to describe the current literature regarding HC-associated VTE in adolescents, to review the coagulation cascade and in vivo coagulation, to highlight differences between the adolescent and adult coagulation profiles, to discuss coagulation profile changes related to HC use, and to identify knowledge deficits for future study. CONCLUSION: The mechanisms and confounding variables that lead to HC-associated VTE in all adolescents are not well understood because many large HC studies exclude female adolescents younger than 18 years of age. Because of the paucity of data in this age group, observational studies and randomized controlled trials of VTE risk in adolescents on varying forms of HC are needed. Studies should include female adolescents across the entire adolescent age span (12-21 years) to better understand HC-associated VTE risk in this population.