Pediatric Venous Thromboembolism Research Articles

The Risk of Venous Thromboembolism in Children With Inflammatory Bowel Disease.

Recent studies of children with inflammatory bowel disease (IBD) demonstrate an increased venous thromboembolism (VTE) risk. However, estimates of risk are variable and case numbers are limited. The aim of this study was to provide national estimates of the risk of VTE in children with IBD. Hospital Episode Statistics was used to identify patients diagnosed with either IBD or VTE before reaching 18 years of age between 2001 and 2019. Populations and subgroups are described, and the risks of developing VTE in the general and IBD populations were calculated. Children with VTE following a diagnosis of IBD or in the previous 6 months (n = 85) and with VTE without IBD (n = 4160) were studied. The absolute risk in children with IBD was 9.42 (95% confidence interval [CI], 7.4-11.4) per 10 000 patient-years, compared with 0.18 (95% CI, 18-0.19) in children without IBD. Between 6 months prior to and 1 year following IBD diagnosis was the highest absolute risk period for VTE (18.0; 95% CI, 13.7-22.4). The relative risk of VTE in children with IBD vs children without IBD was greatest in younger patient groups: the relative risk for the age band 0 to 8 years was 96.5 (95% CI, 51.8-179.9) and for 9 to 11 years was 153.1 (95% CI, 81.2-288.8) vs 14.3 (95% CI, 10.3-20.0) for 15 to 17 years. Cerebral venous sinus thrombosis represented 17.6% of pediatric VTE events in IBD patients compared with 4.2% in children without IBD (P = .001). This study confirms the increased risk of VTE in children with IBD compared with children without IBD. The time of greatest VTE risk was around diagnosis. Cerebral venous sinus thrombosis was significantly more common in children with IBD than other children.

Retrospective study evaluating safety, clinical effect, and dosing of dalteparin for the treatment of venous thromboembolism in term neonates.

There is an increased risk of venous thromboembolism (VTE) among neonates due to their unique hemostatic system. However, there is lack of approved treatment options for VTE in neonatal population. Importantly, dalteparin, a low molecular weight heparin approved for pediatric VTE in children ≥1month of age, has also been used for the treatment of neonatal VTE. Based on the request from the Food and Drug Administration, this retrospective study aimed to characterize the safety, clinical effects, and dosing of dalteparin for treatment of VTE among neonates. Data from electronic medical records for neonates (born ≥35weeks of gestation) treated with dalteparin for VTE between January 2010 and December 2021 were collected. The data assessed included bleeding and deterioration in hematological biomarkers among other adverse events, changes in relevant factor antifactor Xa (anti-Xa) levels and VTE status, and dosing of dalteparin and corresponding anti-Xa assay levels. Sixteen neonates from five participating sites in the United Kingdom were included. There were no bleeding events or deaths. Only one serious adverse event of hypoglycemic brain injury (unrelated to dalteparin) was documented in a patient with a history of hyperinsulinism. Median (range) daily dose of dalteparin at initiation was 309 (297-314)IU/kg. Eight of 16 neonates achieved therapeutic anti-Xa level, including two patients who did so after the first dose. Dalteparin treatment in neonates raised no major safety concerns. Larger cohort studies may help provide further insights on clinical effects of dalteparin for neonatal VTE.

Trends in the Diagnosis of Pediatric Venous Thromboembolism and Arterial Ischemic Stroke during the COVID-19 Pandemic: An Administrative Database Study

To investigate trends in the diagnosis of venous thromboembolism (VTE) and arterial ischemic stroke (AIS), and examine the use of pharmacological thromboprophylaxis during the COVID-19 pandemic. This retrospective cohort study used the Pediatric Health Information Systems database to investigate patients admitted to a participating hospital between January 1, 2018, and December 31, 2021. International Classification of Diseases, 10th edition codes were used to identify VTE, AIS, and COVID-19. Pharmacy billing codes were used to investigate pharmacological thromboprophylaxis use. 1 759 701 unique patients underwent 2 234 135 inpatient admissions. Rate of VTE increased from 84 cases per 10 000 admissions in 2018-2019 to 108 cases per 10 000 admissions in 2020-2021, representing a 28.6% increase (P<.001). In contrast, the rate of AIS remained stable through the study period. When compared with 2018-2019, children diagnosed with VTE during 2020-2021 had longer hospitalizations and were more likely to be admitted to the intensive care unit. When analysis was limited to 2020-2021, a diagnosis code of COVID-19 was associated with a 1.35-fold (95% CI: 1.24-1.45) increase in the odds of VTE diagnosis, but not AIS. Use of pharmacologic thromboprophylaxis increased from 1.5% of hospitalizations in 2018-2019 to 3.0% of hospitalizations in 2020-2021 (P<.001). When evaluating thromboprophylaxis during 2020-2021, a diagnosis code for COVID-19 was associated with an 11-fold (95% CI: 10.86-11.49; P<.001) increase in the utilization of pharmacological thromboprophylaxis. This study found an increase in the rate of VTE among hospitalized children during the pandemic. A diagnosis of COVID-19 was associated with a modest increase in odds of VTE diagnosis, which occurred despite increased use of pharmacological thromboprophylaxis.

Direct oral anticoagulant therapy in adolescent venous thromboembolism: A systematic review.

Adolescent venous thromboembolism (VTE) has unique challenges in management, complications, and compliance to anticoagulants. Direct oral anticoagulants (DOACs) have been approved for pediatric VTE management, with an increasing use especially in adolescents. Primary objective is to evaluate the safety and efficacy of DOAC therapy in adolescent VTE. Secondary objectives include adverse events, bleeding events, and overall mortality. A SR protocol was registered in PROSPERO 2022 (CRD42022363928). Databases were searched from inception to September 22, 2022. Studies with children aged 10-18years, VTE diagnosis, DOAC therapy, randomized control trials (RCTs), cohort, and relevant study types were included. Studies including prophylaxis, non-DOAC therapy, arterial thrombosis, age outliers, non-relevant study types were excluded. Findings are reported in accordance to PRISMA 2020. Nine reports from five studies, published between 2016 and 2022, were included. Rivaroxaban was the most common DOAC. VTE recurrence was 0.02% in the rivaroxaban phase III trial and one patient in the dabigatran phase IIb/III trial. Complete/partial thrombus resolution (CR/PR) was 76.6% in the rivaroxaban phase III trial, and 83.9% in the dabigatran phase IIb/III trial. CR/PR was found to be 68.4% in Dhaliwal etal. study and 83.3% in Hassan etal. study. Major bleeding occurred in one patient. Headache and gastrointestinal symptoms were commonly seen. All-cause mortality occurred in a patient due to cancer progression. DOAC therapy in adolescent VTE had CR/PR in two-thirds of the patients, with low incidence of VTE recurrence and major bleeding. As there are only two randomized controlled trial (RCTs), future adolescents' studies are required to validate our results.

Evaluation of the Safety and Efficacy of Enoxaparin Once-Daily Versus Twice-Daily Dosing for Prophylaxis in Pediatric Patients.

Enoxaparin for the prevention of venous thromboembolism (VTE) in pediatric patients is -typically dosed twice a day. The use of once-daily dosing like that used in adult patients is limited because of a lack of safety and efficacy data. The aim of this study was to evaluate the safety and efficacy of -once-daily versus twice-daily dosing of enoxaparin for pediatric VTE prophylaxis based on incidence of thrombotic and bleeding events. This was a 3-year retrospective chart review of enoxaparin received for VTE prophylaxis at -Cohen Children's Medical Center, New Hyde Park, NY. Exclusion criteria were age 18 years or older, and renal dysfunction. A total of 177 enoxaparin courses (81 in the once-daily and 96 in the twice-daily group) were included. The median dose in the once-daily group was 0.68 mg/kg/dose with dose capping at 40 mg/dose in 70% of patients. One patient in the once-daily group had a VTE, whereas no patients in the twice-daily group experienced a VTE. One major bleeding event occurred in the once-daily group (p = 0.46); however, minor bleeding events were comparable between the 2 groups (p = 0.69). Once-daily enoxaparin prophylaxis appears to be safe and effective based on minimal -differences in incidence of thrombotic and bleeding events when compared to twice-daily dosing. Based on this study, it may be reasonable to consider once-daily enoxaparin dosing for prophylaxis, especially in older children. A larger multicenter cohort study evaluating once-daily dosing for prophylaxis is warranted to validate the safety and efficacy specifically for risk-based dosing strategies.

Risk factors for venous thromboembolism in a single pediatric intensive care unit in China

BackgroundAnalyses of extensive, nationally representative databases indicate a rising prevalence of venous thromboembolism (VTE) among critically ill children. However, the majority of studies on childhood VTE have primarily concentrated on Caucasian populations in the United States and European countries. There is a lack of epidemiological studies on VTE in Chinese children.MethodsWe conducted a retrospective cohort study of data from the Pediatric Intensive Care (PIC) database. Data were obtained and extracted by using Structured Query Language (SQL) and the administrative platform pgAdmin4 for PostgreSQL. Bivariate analyses were conducted in which categorical variables were analyzed by a chi-square test and continuous variables were analyzed by a Student’s t-test. Separate multivariable logistic regressions were employed to investigate the associations between VTE and sociodemographic factors as well as clinical factors.ResultsOur study included 12,881 pediatric patients from the PIC database, spanning the years 2010 to 2018. The incidence rate of pediatric VTE was 0.19% (24/12,881). The venous thrombotic locations were deep venous thrombosis extremities (n = 18), superior vena cava (n = 1), cerebral sinovenous (n = 1), and other deep venous thrombosis (n = 4). Univariate analysis showed that age, weight, shock, sepsis, cancer and vasopressor receipt were statistically significant risk factors for pediatric VTE (all p ≤ 0.05). After multivariable logistic regression analysis, only shock (aOR: 6.77, 95%CI: 1.33–34.73, p = 0.019) and admission for sepsis (aOR: 6.09, 95%CI: 1.76–21.09, p = 0.004) were statistically significant associated with pediatric VTE.ConclusionsIn conclusion, data obtained from the Pediatric Intensive Care (PIC) database revealed a prevalence of VTE in pediatric patients of 0.19%. The most common location for venous thrombi was deep venous thrombosis (DVT) in the extremities. We identified that shock and sepsis were statistically significant factors associated with pediatric VTE.

Real-world experience of direct oral anticoagulant use in a single pediatric center.

Pediatric venous thromboembolism has increased by 130%-200%, specifically in hospitalized children, and direct oral anticoagulants (DOACs) offer several therapeutic advantages. This study aims to evaluate the real-world epidemiological and outcome data from a retrospective review of pediatric patients treated with DOACs from January 1, 2013 to December 31, 2022. In this single-center, IRB-approved study, 65 patients were identified and analyzed using SPSS statistical software, and a descriptive statistical analysis was conducted. Of the 65 patients, 37% were on apixaban, 61.5% were on rivaroxaban, and 1.5% were on dabigatran. Per the 2023 ISTH outcome definitions, one (2%) patient had a major bleeding episode, six (9%) had clinically relevant non-major bleeding, three (5%) patients had patient-important heavy menstrual bleeding (HMB), and one (1.5%) patient had minor bleeding. Seven (19%) of 37 postmenarchal patients had evidence of HMB. Six (9.2%) patients had recurrent venous thromboembolism while on a DOAC (one was on apixaban, and five were on rivaroxaban) and were transitioned to other forms of anticoagulation. Thus, bleeding rates after DOAC therapy are comparable to previous DOAC trials, as well as other anticoagulants in pediatrics. HMB is an important outcome measure and should continue to be investigated. This study reports a higher rate of recurrent thrombosis (9.2%) compared to other trials. However, this observation may be attributed to patients who had ongoing risk factors, as well as a longer duration of study follow-up. Additional multicentered outcome studies evaluating DOAC use in children are needed to determine long-term recurrence and HMB risks.

Abstract No. 62 Analysis of Pediatric Venous Thromboembolism Interventions

Abstract No. 62 Analysis of Pediatric Venous Thromboembolism Interventions

Venous Thromboembolism in Children: The Rivaroxaban Experience.

The incidence of venous thromboembolism (VTE) in the pediatric population has increased more than 10-fold in the last 20 years, as a consequence of the advancement of resuscitation and surgical techniques and the global increase in life expectancy of children suffering from chronic pathologies. Monitoring anticoagulant therapy to achieve outcomes within the target range in childhood VTE, parenteral administration of medications, and frequent blood tests in children are often cumbersome. Availability of safe and effective oral agents with pediatric data to support use would be of clear benefit. A physiologically based pharmacokinetic model was developed to estimate the appropriate dosing schedule for rivaroxaban in children. This incorporated growth/maturation and variability in anthropometrics (e.g., body height, weight, and body mass index), anatomy (e.g., organ weight), physiology (e.g., blood flow rates), metabolism and excretion. Rivaroxaban use in pediatric population underwent a complete investigational program, consisting mainly of one phase I pharmacokinetics/pharmacodynamics trial, three phase II trials, one phase III trial. The phase III trial enrolled 500 patients from birth to <18 years and documented the efficacy and safety of rivaroxaban regimens at dose equivalent to the adult 20 mg dose for the prevention of fatal or symptomatic nonfatal recurrent VTE and major bleeding versus heparin or vitamin K antagonists. Results were similar to those in rivaroxaban studies in adults. The efficacy and safety of rivaroxaban in children reported in the EINSTEIN JUNIOR trial provide further support to previous trials in adults (EINSTEIN Program), which demonstrate a favorable profile for the use of rivaroxaban for the management of VTE in challenging patient populations. Other clinical evidence contributing to the use of rivaroxaban among different risk groups in pediatric VTE population confirms the consistency with principal trial. Our review aims to describe the rationale for using rivaroxaban oral suspension in clinical practice and to summarize its multiple indications in each vascular bed (e.g., cerebral venous thrombosis, symptomatic or asymptomatic central venous catheter-associated thrombosis), etiology, and patients setting.

Pediatric Orthopaedic Venous Thromboembolism: A Systematic Review Investigating Incidence, Risk Factors, and Outcome.

There is growing evidence of increased venous thromboembolism (VTE) incidence in children with trauma or infection. The purpose of this study was to conduct a systematic review of existing literature related to VTE in the pediatric orthopaedic population, to estimate the overall incidence of VTE and identify risk factors associated with this condition. A systematic review of the available literature was performed to identify articles that described VTE in pediatric orthopaedic surgery or admission. Literature queries were performed to identify articles published from 1980 to 2021 that included patients ≤21 years of age. A stepwise search strategy of 5 electronic databases yielded 1,426 articles, which were filtered by 2 reviewers to identify 30 articles for full-text review. The primary aim was to determine the rate of VTE, and the secondary aim was to identify risk factors for VTE. The pooled incidence of VTE was estimated and reported in cases per 10,000. Studies were stratified by study size, by trauma versus elective surgery, and by orthopaedic subspecialty. The 30 articles reported 3,113 VTE events in 2,467,764 pediatric patients (including those with non-orthopaedic conditions), for a pooled VTE incidence of 20 events (95% confidence interval [CI] = 10.8 to 37.2) per 10,000. Four of the studies were excluded for incomplete data or high heterogeneity. The remaining 26 studies had 850,268 orthopaedic patients with 1,108 cases of VTE, for a pooled VTE incidence of 16.6 events (95% CI = 9.1 to 30.5) per 10,000. Studies with <10,000 patients and those involving a diagnosis of trauma had the highest VTE incidence when stratification was performed. The most frequently analyzed risk factors in 15 available studies included age, sex, obesity/body mass index, type of surgery, and use of a central venous catheter. This systematic review indicated that the risk of VTE associated with pediatric orthopaedic surgery or admission remains low, at <17 events per 10,000 cases. However, orthopaedic surgeons should be aware of the most common risk factors associated with pediatric orthopaedic VTE and should pay special attention to traumatic etiologies, as these yielded the highest incidence. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Direct Oral Anticoagulants for Treating Acute Venous Thromboembolism in Children: Meta-Analysis of Randomized Controlled Trials.

Acute venous thromboembolism (VTE) in children presents unique challenges due to the limitations of standard anticoagulation therapies. Herein, we aimed to systematically review randomized controlled trials (RCTs) evaluating the efficacy and safety of direct oral anticoagulants (DOACs) in pediatric patients with acute VTE. PubMed and Embase databases were searched for RCTs comparing DOACs to standard anticoagulation in pediatric VTE patients. Efficacy outcomes included VTE recurrence and all-cause mortality, while safety outcomes comprised major bleeding and other adverse events. Three RCTs with 790 participants were included. When compared with standard anticoagulation, DOACs demonstrated a reduced risk of VTE recurrence (risk difference[RD] = -3%, 95% confidence interval[CI]: -6% to 0%, P = 0.04) and an increased risk of any adverse event (RD = 8%, 95% CI: 1% to 14%, P = 0.02). No significant differences were found in all-cause mortality, major bleeding, clinically relevant non-major bleeding, or total bleeding between the DOAC and control groups. DOACs, primarily dabigatran and rivaroxaban, are non-inferior to standard anticoagulants in reducing VTE recurrence in pediatric patients, with comparable safety profiles. Further research is essential to confirm these findings.

Efficacy and Safety of Direct Oral Anticoagulants in Pediatric Venous Thromboembolism: A Systematic Review and Meta-Analysis.

To assess the efficacy and safety of direct oral anticoagulants (DOACs) in comparison to standard-of-care (SOC) anticoagulants in the management and prophylaxis of thromboembolic events in pediatric populations. A comprehensive search of electronic databases was conducted to identify relevant studies published between January 1, 2015, and December 18, 2022. A meta-analysis was undertaken to evaluate the effect of DOACs on clinically significant endpoints, employing trial-level data with harmonized endpoint definitions. The primary outcome was venous thromboembolism (VTE). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The study was registered with INPLASY (2022120065). Three studies encompassing 934 subjects were included. The incidence of VTE was reduced in patients administered DOACs compared to those on SOC anticoagulants (OR 0.41 [95% CI 0.19-0.93], I²=0%, P = 0.03). No significant differences were observed between the DOAC and SOC groups in all-cause mortality (OR 0.50 [95% CI 0.07-3.59], I²=0%, P = 0.35) or serious adverse events (OR 0.75 [95% CI 0.50-1.12], I²=0%, P = 0.16). The risk of major bleeding (OR 0.50 [95% CI 0.13-1.87], I²=44%, P = 0.30) and clinically relevant non-major bleeding (OR 1.23 [95% CI 0.50-3.00], I²=0%, P = 0.65) exhibited no significant differences between the groups. DOACs are associated with a reduced risk of VTE in pediatric patients without increasing the risk of bleeding, all-cause mortality, or serious adverse events when compared to SOC anticoagulants. DOACs may be an alternative for the treatment and prevention of thromboembolic events in the pediatrics.

Clinical Characteristics, Treatment, and Outcomes of Provoked Acute Cerebral Sinovenous Thrombosis in Patients

Background Cerebral sinus venous thrombosis (CSVT) is a rare pediatric condition with an estimated incidence of 0.7 per 100,000 children. However, amongst pediatric venous thromboembolism (VTE), the proportion of CSVT is high, at about 10% of all pediatric VTE. Key risk factors include perinatal stressors in cases of neonatal CSVT and acute infections, especially head and neck infections, in older children. To date, few multinational trials of pediatric VTE treatment have reported findings specifically among CSVT patients. Aims We sought to describe the clinical characteristics, treatment strategies, and outcomes of the patients with provoked acute CSVT enrolled in the Kids-DOTT trial and to compare these features to those of Kids-DOTT participants with non-CSVT VTE. Methods Kids-DOTT was an NIH-sponsored multinational randomized clinical trial (RCT) comparing 6 weeks vs. 3 months of anticoagulation for provoked acute VTE treatment in patients &amp;lt;21 years, with two non-randomized cohort arms run in parallel to the RCT for patients with persistent antiphospholipid antibodies or complete veno-occlusion at 6 weeks post-diagnosis of the index VTE. The primary RCT findings were recently published. In the present analysis, descriptive statistics were used to summarize patient and thrombus characteristics, treatments, and outcomes, and variables were compared between CSVT and non-CSVT VTE groups using Mann-Whitney U test for continuous variables and Chi-squared or Fisher's exact test, as appropriate, for categorical variables. All statistical analyses were performed using R Core Team, 2021. A P-value of &amp;lt;0.05 was considered statistically significant. Results Among 532 patients enrolled in the Kids-DOTT trial, the index VTE was a CSVT in 75 (14%). Age distribution differed significantly ( P=0.002) between CSVT and non-CSVT VTE patients, with the CSVT more likely to occur in neonates and children, compared to non-CSVT VTE more likely to occur in adolescents. CSVT was less likely to be CVC-related compared to non-CSVT VTE. The frequency of any infection (56.9% vs 26%, p&amp;lt;0.001) and specifically infection of the head/neck (35.4% vs 2%; P&amp;lt;0.001) as a provoking factor was significantly higher for CSVT vs. non-CSVT VTE. Non-head and neck infections were less likely to be associated with CSVT compared to non-CSVT VTE. One-third of CSVT patients received 6 weeks, while two-thirds received &amp;gt; 3 months, of anticoagulation (Table 2). No patients developed ISTH-defined symptomatic recurrent VTE or clinically relevant bleeding. Conclusions These multinational trial findings substantiate those of retrospective studies implicating head/neck infection as an important provoking factor for CSVT in young patients. The absence of recurrent VTE or clinically relevant bleeding among CSVT patients managed with anticoagulation in Kids-DOTT serve to augment recent RCT findings of CSVT treatment in children involving direct oral anticoagulants, demonstrating the safety and efficacy of therapeutic anticoagulation for pediatric CSVT.

High Rates of Pediatric Venous Thromboembolism After Elective Laparoscopic Splenectomy Suggest Need for Perioperative Prophylaxis

IntroductionIn adult populations, postoperative venous thromboembolism (VTE) is a reported complication of up to 8% of elective laparoscopic splenectomy (LS) cases. VTE is a rare event in the pediatric population, affecting less than 1% of all pediatric surgical patients. We hypothesized that pediatric patients are at a higher risk of postoperative VTE after undergoing elective LS relative to other laparoscopic procedures and may warrant prophylactic treatment. Materials and methodsWe queried the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database from 2012 to 2020. Patients were identified using the Current Procedural Terminology code 38120 and only elective cases were analyzed. ResultsThe incidence of VTE in all pediatric patients undergoing surgery in the American College of Surgeons NSQIP-P database was 0.13%. The incidence of VTE in pediatric patients undergoing elective laparoscopic abdominopelvic procedures was 0.17%. There were seven total cases of VTE (0.41%) in pediatric patients undergoing elective LS, more than twice the rate of the general population (P = 0.001). Eighty percent of pediatric patients undergoing elective LS had an underlying hematological disorder. ConclusionsBy analyzing the NSQIP-P database, we evaluated the largest cohort of pediatric patients undergoing elective LS to date. We identified a higher incidence of VTE following this procedure relative to the rate of VTE in the overall population in the NSQIP-P database, as well as those undergoing elective laparoscopic abdominopelvic operations. The relatively higher incidence of VTE after elective LS is likely due to the presence of underlying hematological conditions. Given the low incidence of complications associated with pharmacologic VTE prophylaxis, the results of this study suggest that further research is warranted to establish the efficacy of perioperative pharmacological VTE prophylaxis in pediatric patients undergoing elective LS.

Biomarkers in pediatric venous thromboembolism: a systematic review of the literature

BackgroundAccurate prediction of the individual risk of venous thromboembolism (VTE) remains suboptimal in children, and biomarkers are currently not used to stratify the risk of VTE in children. ObjectivesThis study aimed to assess which biological or radiological biomarkers may predict VTE or VTE complications in children. Patients/MethodsA literature search was performed for peer-reviewed publications (1990-2022). We included studies addressing the use of biomarkers for patients aged 29 days to 18 years to predict VTE or its complications, including but not limited to TE-related death, VTE recurrence, or postthrombotic syndrome. Given the heterogeneity of the study designs, populations, and outcomes, no quantitative data synthesis was performed. ResultsForty studies were included, totaling 10,987 participants (median age: 4.7 years). Reports were often lacking critical methodological data, including blood collection method (68% of studies) and timepoints, laboratory testing technique (41%), or primary outcome definition (20%). Forty-six individual biomarkers were assessed for VTE prediction (32 studies, 9525 participants), including d-dimers, fibrinogen, platelet count, white blood cell count, and factor VIII. Albumin, C-reactive protein, d-dimers, factor VIII, and thrombin-antithrombin levels showed promising results for VTE prediction. In 9 studies (1606 participants), no biomarker was consistently predictive of postthrombotic syndrome, VTE persistence, or VTE recurrence in children. ConclusionsSeveral candidate biomarkers were promising in the prediction of VTE in children. Still, discrepancies between different studies and the high risk of bias from the current literature prevent their widespread use in the clinical setting. Further prospective research in various pediatric subpopulations is required.

Impact of Institutional Prophylaxis Guidelines on Rates of Pediatric Venous Thromboembolism Following Trauma - a Multicenter Study from the Pediatric Trauma Society Research Committee.

A paucity of data exists with regard to the incidence, management, and outcomes of venous thromboembolism (VTE) in injured children. We sought to determine the impact of institutional chemoprophylaxis guidelines on VTE rates in a pediatric trauma population. A retrospective review of injured children (<15 years) admitted between 2009-2018 at ten pediatric trauma centers was performed. Data was gathered from institutional trauma registries and dedicated chart review. The institutions were surveyed as to whether they had chemoprophylaxis guidelines in place for high risk pediatric trauma patients, and outcomes were compared based on the presence of guidelines using chi-square analysis (p < 0.05). 45,202 patients were evaluated during the study period. Three institutions (28,359 patients, 63%) had established chemoprophylaxis policies during the study period ("Guidelines"); the other seven centers (16,843 patients, 37%) had no such guidelines ("Standard"). There were significantly lower rates of VTE in the Guidelines group, but these patients also had significantly fewer risk factors. Amongst critically injured children with similar clinical presentations, there was no difference in VTE rate. Specifically within the Guidelines group, 30 children developed VTE. The majority (17/30) were actually not indicated for chemoprophylaxis based on institutional guidelines. Still, despite protocols only one VTE patient in the Guidelines group who was indicated for intervention ended up receiving chemoprophylaxis prior to diagnosis. No consistent ultrasound screening protocol was in place at any institution during the study. The presence of an institutional policy to guide chemoprophylaxis for injured children is associated with a decreased overall frequency of VTE, but this disappears when controlling for patient factors. However, the overall efficacy is impacted by a combination of deficits in guideline compliance and structure. Further prospective data is needed to help determine the ideal role for chemoprophylaxis and protocols in pediatric trauma.Level IV, therapeutic/care management.

Just DOAC: Use of direct-acting oral anticoagulants in pediatrics.

The aim of this article is to provide an overview of the current literature for direct-acting oral anticoagulant (DOAC) use in pediatric patients and summarize ongoing trials. In treatment of venous thromboembolism (VTE) in pediatric patients, evidence supports use of both dabigatran and rivaroxaban. Dabigatran has been shown to be noninferior to standard of care (SOC) in terms of efficacy, with similar bleeding rates. Similarly, treatment with rivaroxaban in children with acute VTE resulted in a low recurrence risk and reduced thrombotic burden, without increased risk of bleeding, compared to SOC. Treatment of pediatric cerebral venous thrombosis as well as central venous catheter-related VTE with rivaroxaban appeared to be both safe and efficacious and similar to that with SOC. Dabigatran also has a favorable safety profile for prevention of VTE, and rivaroxaban has a favorable safety profile for VTE prevention in children with congenital heart disease. Many studies with several different DOACs are ongoing to evaluate both safety and efficacy in unique patient populations, as well as VTE prevention. The literature regarding pediatric VTE treatment and prophylaxis is growing, but the need for evidence-based pediatric guidelines remains. Additional long-term, postauthorization studies are warranted to further elucidate safety and efficacy in clinical scenarios excluded in clinical trials. Additional data on safety, efficacy, and dosing strategies for reversal agents are also necessary, especially as the use of DOACs becomes more common in the pediatric population.

Real world experience of efficacy and safety of rivaroxaban in paediatric venous thromboembolism

IntroductionPaediatric clinical practice for treatment of venous thromboembolism (VTE) is based on extrapolation from adult trials with minimal data on anticoagulation efficacy and safety in children. Based on EINSTEIN-Jr clinical trial data, rivaroxaban was approved to treat VTE and prevent its recurrence in children of all ages. AimTo report the safety and efficacy of rivaroxaban use in paediatric VTE and to present real-world data, specifically about very young children. MethodsWe conducted a retrospective observational study at Birmingham Children's Hospital. Data were collected from patients <16 years old who received rivaroxaban after its licensure in the period between March 2021 and June 2022. ResultsRivaroxaban was used for treatment of acute VTE in 64 patients. Thrombosis was CVC-related in 26 patients, unprovoked in 3, while the rest had one or more risk factors for VTE. Safety and efficacy of rivaroxaban were assessed in 52 patients after excluding patients who were on current rivaroxaban treatment and those who were lost to follow up or stopped rivaroxaban due to intolerance. No bleeding events were reported, and recurrence of thrombosis occurred in only 3.6 %. About 35 % had normalised re-imaging, 40.3 % improved, 9.6 % were unchanged and 11.5 % stopped rivaroxaban without re-imaging. Rivaroxaban was used for secondary VTE prophylaxis in 6 patients in our cohort with no recurrence of thrombosis or bleeding reports. ConclusionsOur real-world experience confirmed that rivaroxaban was well tolerated, effective and safe. Further real-world data and observational studies are essential to investigate the use of rivaroxaban among different risk groups.

Direct oral anticoagulants in pediatric venous thromboembolism: Experience in specialized pediatric hemostasis centers in the United States

BackgroundBefore the official US Food and Drug Administration approval in 2021, pediatric hematologists across the United States have used direct oral anticoagulants (DOACs) “off-label” and based on extrapolation from labeling for adults with venous thromboembolism (VTE) and interim results of pediatric-specific DOAC clinical studies. ObjectivesThe American Thrombosis and Hemostasis Network 15 (ATHN 15) study aimed to characterize the use of DOACs from 2015 to 2021 at 15 specialized pediatric hemostasis centers in the United States, with emphasis on safety and effectiveness. MethodsEligible participants were those aged 0 to 21 years who had a DOAC included as part of their anticoagulation regimen for the treatment of acute VTE or secondary prevention of VTE. Data were collected for up to 6 months after initiation of the DOAC. ResultsA total of 233 participants were enrolled, with a mean age of 16.5 years. Rivaroxaban was the most commonly prescribed DOAC (59.1%) followed by apixaban (38.8%). Thirty-one (13.8%) participants reported bleeding complications while on a DOAC. Major or clinically relevant nonmajor bleeding events occurred in 1 (0.4%) and 5 (2.2%) participants, respectively. Worsening menstrual bleeding was reported in 35.7% of females aged >12 years and occurred more frequently in those using rivaroxaban (45.6%) compared with apixaban (18.9%). The recurrent thrombosis rate was 4%. ConclusionPediatric hematologists at specialized hemostasis centers in the United States have been using DOACs for the treatment and prevention of VTEs, primarily in adolescents and young adults. Reported DOAC use showed adequate safety and effectiveness rates.

Real-World Experience of Direct Oral Anticoagulant Use in a Single Pediatric Center

Background: Pediatric venous thromboembolism (VTE), a disease comprising deep venous thrombosis and pulmonary embolism, has increased by 130-220%. Anticoagulation therapy is the mainstay of treatment, and direct oral anticoagulants (DOACs) offer several advantages. Recently, two DOACs (Dabigatran and Rivaroxaban) have been approved for use in children in the United States. Nonetheless, DOACs have been used "off-label” in children on an individualized basis, subject to approval from insurance plans. This study aims to evaluate real-world epidemiological and outcome data from a single-center cohort of pediatric patients treated with DOACs. Methods: In this single-center, IRB-approved study, 54 patients from the pediatric hematology oncology VTE database were identified and analyzed using SPSS statistical software, and a descriptive statistical analysis was conducted. Results: Epidemiological features: Of the 54 patients, 21 (39%) subjects were males, and 33 (61%) were females. Ages ranged from 4 to 22 years, with a mean age of 16.3 years. The majority of the subjects, 94%, were greater than 12 years old. Most (94%) of patients had venous thrombosis, 2% had an arterial thrombus, and 4 % had both arterial and venous. A breakdown of primary thromboembolism location highlights that the majority, 30%, had a pulmonary embolism on diagnosis, and the most common risk factors included obesity, catheterization, and infection (Tables 1 and 2). Of the 54 patients, 11% were started on DOACs as their initial anticoagulation treatment, 82% were switched to a DOAC on follow-up after initial treatment with heparin or low molecular weight heparin; four patients (7%) were started on DOACs after recurrent VTE on another anticoagulant. Twenty-one (39%) patients were on Apixaban, 32 (59%) were on Rivaroxaban, and 1 (2%) was on Dabigatran. One patient transitioned from Rivaroxaban to Apixaban due to an allergic reaction to the medication. Patients were on various durations of therapy ranging from 3 months to an extended duration depending on their clinical status and risk factors. Outcomes on DOACs: One (2%) patient had a major bleeding episode per ISTH definition. This was an episode of tonsillar artery bleeding status post tonsillectomy that required cauterization and surgical mesh placement in the operating room. Of the 33 females, two were premenarchal at the time of anticoagulation; therefore, 4 (13%) had evidence of heavy menstrual bleeding (HMB) that required medical intervention. HMB was identified by patients’ recall of menstrual bleeding; only one patient had a pictorial blood loss assessment chart (PBAC) score. Per ISTH definitions, 5 (9%) had clinically relevant non-major bleeding, including 4 patients with HMB and one additional patient with bloody diarrhea secondary to underlying ulcerative colitis that required medical intervention. One patient (2%) had minor bleeding with bloody secretions from a chest tube resulting in temporary holding of anticoagulantion. Five (9%) had recurrent VTE while on a DOAC (2 were on Apixaban, and 3 were on Rivaroxaban) and were transitioned to other forms of anticoagulation. Conclusion: The bleeding and recurrent VTE rates after DOACs appear comparable to other anticoagulants in pediatric VTE; heavy menstrual bleeding should be investigated in adolescent females. Given the recent approval of DOACs for pediatric patients, additional multi-centered outcome studies are needed to determine recurrence and bleeding risks. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal