Pediatric Venous Thromboembolism Research Articles

Hospital-associated venous thromboembolism in pediatrics: a systematic review and meta-analysis of risk factors and risk-assessment models.

Hospital-associated venous thromboembolism, including deep vein thrombosis and pulmonary embolism, is increasing in pediatric centers. The objective of this work was to systematically review literature on pediatric hospital-acquired venous thromboembolism risk factors and risk-assessment models, to inform future prevention research. We conducted a literature search on pediatric venous thromboembolism risk via PubMed (1946-2014) and Embase (1980-2014). Data on risk factors and risk-assessment models were extracted from case-control studies, while prevalence data on clinical characteristics were obtained from registries, large (n>40) retrospective case series, and cohort studies. Meta-analyses were conducted for risk factors or clinical characteristics reported in at least three studies. Heterogeneity among studies was assessed with the Cochran Q test and quantified by the I(2) statistic. From 394 initial articles, 60 met the final inclusion criteria (20 case-control studies and 40 registries/large case series/cohort studies). Significant risk factors among case-control studies were: intensive care unit stay (OR: 2.14, 95% CI: 1.97-2.32); central venous catheter (OR: 2.12, 95% CI: 2.00-2.25); mechanical ventilation (OR: 1.56, 95%CI: 1.42-1.72); and length of stay in hospital (per each additional day, OR: 1.03, 95% CI: 1.03-1.03). Three studies developed/applied risk-assessment models from a combination of these risk factors. Fourteen significant clinical characteristics were identified through non-case-control studies. This meta-analysis confirms central venous catheter, intensive care unit stay, mechanical ventilation, and length of stay as risk factors. A few pediatric hospital-acquired venous thromboembolism risk scores have emerged employing these factors. Prospective validation is necessary to inform risk-stratified prevention trials.

Pediatric thrombotic events: a single-center study.

Recent literature has reported an apparent increase in the incidence of pediatric venous thromboembolism over the last 10 years. In our study, data were collected from all children (ages 0 to 18 y) with a thrombotic event between January 2000 and May 2012, to determine whether an increased incidence of thromboembolism (TE) was evident and to investigate mitigating factors in the development of the TE. A total of 134 patients were entered into the study, 42% under the age of 1 year. There was no conclusive evidence of an increased incidence in our population over the period of the study. Within our population the peripheral venous system was the most common location for TE followed by cerebral vascular accidents. A thrombophilic risk factor was found in 84% of the patients. In our study 4.5% of the children had a second event.

New developments in pediatric venous thromboembolism and anticoagulation, including the target-specific oral anticoagulants.

Pediatric venous thromboembolism (VTE) can affect children of all ages, requiring considerable pharmacologic intervention and is often associated with significant morbidity. Current research efforts are directed toward the development of risk-stratified VTE prevention strategies employing pharmacologic thromboprophylaxis, the optimization of conventional anticoagulation, and the investigation of the safety and efficacy of target-specific oral anticoagulants (TSOACs) in children. Recent research has considerably improved the understanding of risk factors of hospital-acquired VTE and how these factors may be employed in risk-stratified paradigms for VTE prevention in children. Additional insight has been gained in the optimization of conventional anticoagulants in special populations such as neonates and children with inflammatory conditions, and in improving the overall safety and compliance with periprocedural anticoagulation and the use of home International Normalized Ratio monitoring. Furthermore, the use of TSOACs has been described in children and is the focus of numerous ongoing clinical trials that are evaluating the safety and efficacy of these agents in children with VTE. Identification of hospital-acquired VTE risk factors may inform pediatric VTE prevention strategies. Although initial use of TSOACs may be promising, investigation of safety and efficacy in children is still underway.

Development of a pediatric-specific clinical probability tool for diagnosis of venous thromboembolism: a feasibility study.

BackgroundPediatric venous thromboembolism (VTE) is an increasingly common, difficult to diagnose problem. Clinical probability tools (CPT) for adults estimate VTE likelihood, but are not available for children. We hypothesized that a pediatric-specific CPT is feasible.MethodsRadiology reports were utilized to identify children imaged for suspected VTE. Relevant signs, symptoms, and co-morbidity variables, identified from published literature, were extracted from corresponding medical records. Variables associated with pediatric VTE were incorporated into a multivariate logistic regression to create a pilot CPT which was confirmed on a separate cohort.Results389 subjects meeting inclusion criteria were identified: 91 with VTE and 298 without. Univariate analysis revealed male gender (OR 2.96; p<0.001), asymmetric extremity (OR 1.76; p=0.033), central venous catheter utilization and/or dysfunction (OR 2.51; p<0.001), and cancer (OR 2.35; p=0.014) as VTE predictive variables. Documentation of an alternate diagnosis was inversely related to VTE (OR 0.42; p=0.004). Receiver operating characteristic analysis of the derived CPT demonstrated reasonable ability to discriminate VTE probability in the training cohort (AUC 0.73; p<0.001) and moderate discrimination in a separate validation cohort of 149 children (AUC 0.64; p=0.011).ConclusionA pediatric-specific VTE CPT is feasible, would facilitate early diagnosis, and could lead to improved outcomes.

Healthcare burden of venous thromboembolism in childhood chronic renal diseases.

Chronic renal diseases (CRD) are associated with approximately 5% of pediatric venous thromboembolism (VTE) cases, but the epidemiology of VTE in CRD is ill-defined. Children (<18 years) with CRD were identified from MarketScan® Research databases. The VTE status of subjects with CRD who qualified for this study was ascertained during the 6 months following the initial diagnosis of CRD. Demographics, healthcare utilization, mortality, and co-morbid conditions were assessed. A total of 22,877 children with predefined CRD ICD-9-CM codes were identified between April 1, 2003 and June 30, 2012, among whom 0.55% had VTE. Our analysis revealed that in-hospital mortality was more likely in children with VTE than in those without VTE (11.9 vs. 0.9%, respectively; p < 0.0001). The usage of healthcare facilities, based on the number of inpatient admissions, length of stay, outpatient visits, and pharmaceutical claims, was also significantly higher in patients with VTE than in those without (p < 0.0001). Total mean healthcare expenditures for the 6-month follow-up period were 13-fold greater in the VTE group than in the group without VTE ($338,338 ± $544,045 vs. $25,171 ± $90,792; p < 0.0001). In a multivariate model, infection, hemodialysis, and trauma/surgery significantly increased the likelihood of VTE. Venous thromboembolism is rare in children with CRD, but it is associated with higher mortality and healthcare utilization when present. Among the children with CRD enrolled in our study, the likelihood of VTE was increased among those with co-morbid, non-renal chronic conditions.

Pilot/Feasibility Metrics, Real-Time Remote Monitoring, and Inter-Observer Agreement on Veno-Occlusion in a National Multicenter Randomized Controlled Trial of Pediatric Venous Thromboembolism: Findings from the Pilot/Feasibility Phase of the Kids-DOTT Trial

BACKGROUNDSuccessful completion of investigator-initiated pediatric venous thromboembolism (VTE) trials has been hampered when key assumptions in trial design have often not been met during trial execution. Unfortunately, pilot/feasibility (P/F) studies have rarely been conducted and reported prior to implementation of the definitive trials. METHODSThe Kids-DOTT trial is a multicenter, parallel-cohort randomized controlled trial (RCT) evaluating efficacy and safety of shortened (6 weeks) versus conventional (3 months) duration of anticoagulation in pediatric provoked VTE. The Kids-DOTT design included a pre-specified P/F phase consisting of the first 100 subjects enrolled. Quality assurance methods included real-time remote monitoring of patient eligibility criteria immediately prior to enrollment, as well as measurement of inter-observer agreement of mutually-blinded, central versus local radiologic assessments of complete thrombus veno-occlusion (yes/no) at 6 weeks post-diagnosis (a key randomization criterion in the trial). P/F metrics included: screened:enrolled ratio; radiologic inter-observer agreement (measured by percent agreement and kappa statistic); frequency of protocol violations pertaining to eligibility criteria and randomization procedures; proportion of the enrolled population comprising the non-randomized parallel cohorts; and rates of withdrawal/loss to follow-up. The blind was maintained for all P/F analyses. RESULTSScreened:enrolled ratio was approximately 6:1, of which 4% was due to declined consent. During the last 6 months of the P/F phase, with an average of 15 open centers, 24 subjects were enrolled. Protocol violations due to missed randomization occurred in 3% of subjects (3/92) who have reached the 6-week (randomization) visit. There were no eligibility violations and no improper randomizations. During the two most recent years of the trial, 14% of subjects were allocated to the observational, parallel cohorts on completely veno-occlusive thrombosis or persistent antiphospholipid antibody positivity; remaining subjects comprised the RCT population. Inter-observer agreement in the determination of complete veno-occlusion at 6-week imaging (n=71 adjudicated to date) was 97% (95% confidence interval, 89-100%) with Κ=0.79 (95% CI, 0.50-1.0), indicating “substantial agreement” (Landis-Koch criteria). Complete veno-occlusion, as defined by absence of flow throughout a venous segment (e.g. femoral vein; subclavian vein), was observed at 6 weeks in 6% of adjudicated patients (4/71). Rate of withdrawal/loss-to-follow-up prior to primary endpoint assessment was 10% (10/97). CONCLUSIONSThe P/F phase of the Kids-DOTT trial has provided novel multicenter feasibility data demonstrating substantial inter-observer agreement in radiologic determination of complete thrombus veno-occlusion, and a rate of completely veno-occlusive thrombosis of 6% at 6 weeks following diagnosis of provoked venous thrombosis. In addition, it has defined recruitment and retention rates on the trial that have facilitated determination of the required number of participating sites (40) to complete timely accrual. Kids-DOTT is now continuing toward completion of the definitive RCT, targeted for 2018. DisclosuresGoldenberg:Eisai Inc: Research Funding. Off Label Use: Anticoagulants for pediatric venous thrombosis, all of which are off-label for this (pediatric) indication despite their use in the pediatric standard of care. .

Daily Evaluation of Venous Thromboembolism (VTE) Risk Factors and Prophylaxis Safely Decreased Incidence of VTE in a Pediatric ICU

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

Proteomic and other mass spectrometry based "omics" biomarker discovery and validation in pediatric venous thromboembolism and arterial ischemic stroke: current state, unmet needs, and future directions.

Venous thromboembolism (VTE) and arterial ischemic stroke (AIS) are increasingly-recognized health conditions in children, with both acute and chronic sequelae. Risk factors for, and pathogenesis of, VTE are readily related to three principal factors, consisting of venous stasis, endothelial damage, and the hypercoagulable state (i.e. thrombophilia), termed the triad of Virchow. In children, greater than 90% of VTE are provoked by an overt clinical risk factor, the most common of which is a central venous catheter. Risk factors for childhood-onset (beyond the neonatal period) AIS include sickle cell disease, infection, cerebral arteriopathy, and congenital cardiac disease. In perinatal AIS, risk factors are less well-defined, and have been hypothesized to include maternal-fetal conditions. While some acquired and inherited thrombophilias have been associated with increased risk of incident and/or recurrent VTE and AIS, knowledge of other diagnostic and prognostic biomarkers of VTE/AIS in children remains quite limited. To date, very few published studies have employed plasma mass spectrometry-based "omics" approaches (proteomics, lipidomics or metabolomics). Ongoing and future research efforts involving multicenter prospective study-derived plasma biobanks in pediatric VTE (such as the Kids-DOTT trial) and AIS (including VIPS) along with new multi-omics-compatible sample processing methods offer fertile opportunities for discovery and validation of both novel risk factors and prognostic markers, with great potential to achieve improved prognostic stratification in these diseases.

Venous Thromboembolism at Uncommon Sites in Neonates and Children

We retrospectively analyzed the data of 24 children (whereof 11 neonates), with non-central venous line-related and nonmalignancy-related venous thromboembolism (VTE) at uncommon sites, referred to our Unit from January 1999 to January 2012. Thirty patients who also suffered deep vein thrombosis, but in upper/low extremities, were not included in the analysis. The location of rare site VTE was: portal (n=7), mesenteric (n=2) and left facial vein (n=1), spleen (n=3), lung (n=3), whereas 10 neonates developed renal venous thrombosis. The majority of patients (91.7%) had at least 1 risk factor for thrombosis. Identified thrombophilic factors were: antiphospholipid antibodies (n=2), FV Leiden heterozygosity (n=6), MTHFR C677T homozygosity (n=4), protein S deficiency (n=2), whereas all neonates had age-related low levels of protein C and protein S. All but 6 patients received low-molecular-weight heparin, followed by warfarin in 55% of cases, for 3 to 6 months. Prolonged anticoagulation was applied in selected cases. During a median follow-up period of 6 years, the clinical outcome was: full recovery in 15 patients, evolution to both chronic portal hypertension and esophageal varices in 2 children, and progression to renal failure in 7 of 10 neonates. Neonates are greatly vulnerable to complications after VTE at uncommon sites, particularly renal. Future multicentre long-term studies on neonatal and pediatric VTE at unusual sites are considered worthwhile.

Multicenter dose‐finding and efficacy and safety outcomes in neonates and children treated with dalteparin for acute venous thromboembolism

Low molecular weight heparins (LMWHs) constitute the mainstay of anticoagulant therapy for pediatric venous thromboembolism (VTE). The safety and effectiveness of dalteparin, an LMWH, has not been established in children, and pediatric data on dalteparin for VTE are limited to one single-center experience. To establish dose-finding (primary endpoint) and efficacy/safety outcomes (secondary endpoints) in children treated with dalteparin in a substudy of the Kids-DOTT trial. A prospective multicenter trial using dalteparin subcutaneously twice daily for acute VTE in children aged ≤ 21 years was conducted under an investigator-held Investigational New Drug application registered with the US Food and Drug Administration. Initial weight-based dosing per protocol was as follows: infants (< 12 months), 150 IU kg(-1) ; children (1-12 years), 125 IU kg(-1) ; and adolescents (13-18 years), 100 IU kg(-1) . Bleeding events were categorized according to ISTH criteria. Descriptive non-parametric statistics were employed for all analyses. Eighteen patients (67% male) were enrolled from January 2010 to October 2013 across four centers. No supratherapeutic levels were observed. Median (range) therapeutic doses by age group were as follows: infants (n = 3), 180 IU kg(-1) (146-181 IU kg(-1) ); children (n = 7), 125 IU kg(-1) (101-175 IU kg(-1) ); and adolescents (n = 8), 100 IU kg(-1) (91-163 IU kg(-1) ). The median duration of dalteparin use was 48 days (range: 2-169 days), and the median follow-up was 10.5 months (range: 2-35 months). There were no related serious adverse events, no clinically relevant bleeding events, and no symptomatic recurrent VTEs. Dalteparin successfully achieved targeted anti-factor Xa levels in 18 children and young adults with acute VTE with a standardized age-based dosing regimen, with a favorable safety and efficacy profile.

G245(P) Routine, structured assessment for venous thromboembolism risk in surgical admissions to a tertiary children’s hospital

AimsPrevalence of paediatric venous thromboembolism (VTE) is estimated at 5.3 per 10,000 hospital admissions.There is a bimodal distribution of incidences with peaks in the neonatal period and in adolescence. 90%...

Thrombophilia testing in children: A 7 year experience

Incidence of venous thromboembolism (VTE) in children is reported to be increasing. We examined thrombophilia testing results in children with VTE that presented in inpatient and outpatient settings to explore patterns of thrombophilia testing. Children, ages 0-20 years with VTE seen at our institution from Jan 2005 to Apr 2012 were studied retrospectively. All patients with VTE confirmed by imaging were eligible and the presence of significant risk factors was evaluated. Thrombophilia was diagnosed if >1 tests confirmed: persistently low protein C (PC), protein S (PS), and antithrombin (AT) following VTE resolution, persistent antiphospholipid antibodies (APA) positivity >12 weeks from first test, factor V Leiden (FVL) and prothrombin mutation (PTm) hetero- or homozygosity, elevated plasminogen activator inhibitor (PAI-1) levels with 4G/5G or 4G/4G polymorphisms, methylene tetrahydrofolate reductase (MTHFR) polymorphisms with elevated fasting homocysteine levels. Three hundred ninety-two patients met inclusion criteria. At least one test was ordered in 157/239 inpatients. All 153 outpatients had >1 test ordered. Thrombophilia rate differences between inpatients and outpatients did not reach statistical significance except for PC deficiency, which was significantly higher in outpatients. Of inpatients, central venous line (CVL) was significantly associated with not having tests done (P < 0.0022). This study of pediatric VTE demonstrated a low thrombophilia rate in both inpatient and outpatient populations. The role of testing in other pediatric patients should be further explored.

Risk of Thromboembolism in Hospitalized Children

Research Article| January 01 2013 Risk of Thromboembolism in Hospitalized Children AAP Grand Rounds (2013) 29 (1): 8. https://doi.org/10.1542/gr.29-1-8 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Risk of Thromboembolism in Hospitalized Children. AAP Grand Rounds January 2013; 29 (1): 8. https://doi.org/10.1542/gr.29-1-8 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: child, hospitalized, thromboembolism, venous thromboembolism, chronic disease Kerli BA, Setty BA, O'Brien SH. Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases. Pediatr Blood Cancer. 2012; 59(2): 258-264; doi: https://doi.org/10.1002/pbc.23388Google Scholar Investigators from Nationwide Children's Hospital in Columbus, Ohio conducted a retrospective cohort study using data from the 2006 Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) from the Agency for Healthcare Research and Quality (AHRQ) to identify risk factors for venous thromboembolism (VTE) in hospitalized pediatric patients. The KID 2006 includes inpatient data on children ≤20 years old hospitalized in 38 states. The investigators used the database to identify children ≤18 years old with in-hospital VTE (deep venous thrombosis and pulmonary embolism) based on the presence of thrombosis-specific ICD-9-CM diagnosis or procedure codes. ICD- 9-CM codes were also used to categorize patients as having either an acute or chronic condition. For the analyses, discharges were grouped by age of the child (<1, 1-4, 5-9, 10-14, and 15-18 years) and hospitals were classified as children's hospitals (tertiary) or community hospitals. The relative risks (RRs) of VTE in adolescents (15-18 years old) and infants (<1 year old) were compared to the reference age group (1-4 years old). Similarly, the RRs by hospital type and by underlying condition were assessed. There were 4,538 diagnoses of VTE among the 2,410,351 eligible patient discharges included in the analyses. Of the children with VTE, 67.6% were discharged from children's hospitals (RR = 5.09 compared to those hospitalized at community hospitals). Infants (23.1%) and adolescents (37.8%) accounted for most VTE discharges. However, when standardized for the number of discharges in each age category, infants were significantly less likely to suffer VTE than older patients (RR = 0.48; 95% CI, 0.43-0.52), while adolescents were at highest risk (RR = 1.89; 95% CI, 1.73-2.07). Most children (76%) with VTE had underlying chronic illness, with cardiovascular (18.4%), malignancy (15.7%), and neuromuscular disease (9.9%) being the most common chronic conditions. The most common etiologies for VTE in patients with acute illnesses were idiopathic (12.6%) or related to infection (9.5%) and trauma (9.1%). Pediatric patients with hospitalizations ending with death were more likely to suffer VTE than those who survived the hospitalization (RR = 6.16; 95% CI, 5.32-7.13). The investigators conclude that pediatric VTE is seen mostly in tertiary care centers, with adolescents and those patients whose hospitalizations end with death at greater risk of developing VTE. There is a growing body of literature regarding pediatric VTE, yet relatively little is known regarding its true incidence, implications, and best management strategies. Like other rare clinical problems in pediatrics, management of VTE has evolved based on adult data. Pediatric VTE is thought to be multifactorial and is seen mostly in children with underlying conditions and associated with predisposing risk factors, such as indwelling venous catheters, surgery, trauma, malignancy, inherited thrombophilia, and hospitalizations >5 days.1 Boulet et al analyzed hospital discharge data and found that the risk of pediatric... You do not currently have access to this content.

Recurrence Rate and Hazard Modeling for Recurrence in Children with a First Episode of Venous Thromboembolism

AbstractAbstract 3392 Background:Pediatric venous thromboembolism (VTE), although rare, is associated with significant morbidity and mortality. A more thorough understanding of the epidemiology of pediatric VTE is needed to advance the field. Published recurrence rates in this age group vary widely, ranging from 5.5% to 18.5%, and currently studies assessing contributing risk factors for recurrence are sparse. Objectives:To describe the recurrence rate of venous thromboembolism after a first time episode of VTE in a provincial cohort of children aged 0–17 (inclusive) and determine predictors of recurrence after incident VTE. Methods:A retrospective cohort of children (ages 0–17 inclusive) with a first time diagnosis of VTE in the province of Quebec over an eleven-year period was obtained from a comprehensive administrative hospital database (Med-Echo). The study period began on January 1st, 1994 and ended on December 31st, 2004 for inclusion of incident cases. Subjects were followed from the time of their admission into the cohort (at time of incident VTE), until their first recurrence, death, emigration from the province or end of the study period (December 31st, 2005), whichever came first. The following demographic and risk factor information were extracted for the cohort: age, age category, sex, type of VTE at initial presentation, prior major surgery, prior major infection, prior congenital heart disease, prior central line, prior trauma, cancer or recent bone marrow transplantation, and diagnosis of a chronic disease. Chronic diseases extracted included systemic lupus erythematosus, inflammatory bowel disease, cystic fibrosis, nephrotic syndrome and sickle cell disease. Recurrence rates were then calculated and univariate Cox-proportional hazard model and log rank testing were used to assess which risk factors would be incorporated into the final multivariate Cox-proportional hazard model evaluating risk of VTE recurrence. Results:In total, 518 incident cases of VTE in children 0–17 years of age were documented. Median follow up time in cohort was 4.4 years (range 1 day – 12 years). Overall the cohort had a recurrence rate of 2.77 per 1000 person-months (95% confidence interval (CI) 2.2–3.4) (recurrence risk of 16%). Multivariate Cox proportional hazard modeling showed a statistically significant increased risk of recurrence with the presence of a chronic disease (HR 2.40; 95% CI 1.26–4.56) and a diagnosis of portal vein thrombosis as the initial VTE presentation (HR 3.29; 95% CI 1.30–8.34). Overall all-cause mortality was 6.4% with 33 deaths in the cohort. Conclusions:The risk of recurrence is comparable to those prior studies that had shown higher recurrence risks. The rate of VTE recurrence is higher in those with a pre-existing chronic illness or with an initial diagnosis of portal vein thrombosis. Overall all-cause mortality was lower in our cohort than prior large studies of VTE in this age group. Our findings highlight the need for future studies to determine effective secondary prophylaxis strategies in children at high risk for VTE recurrence. Disclosures:No relevant conflicts of interest to declare.

Temporal Incidence Trends of Pediatric Venous Thromboembolism: A Population-Based Cohort Study

AbstractAbstract 1138 Background:Pediatric venous thromboembolism (VTE), although rare, is associated with significant morbidity and mortality. Published incidence rates in this age group vary from 0.07 to 0.49 VTE per 10 000 children/year and there is currently a paucity of studies evaluating temporal incidence trends. Objectives:To describe the age-adjusted incidence rates of pediatric VTE and its trend over time in a large pediatric cohort. Methods:A retrospective cohort of all children (ages 1–17 inclusive) with a first time diagnosis of VTE in the province of Quebec, Canada over an eleven-year period, from January 1st, 1994 to December 31st, 2004, was obtained from a comprehensive administrative hospital database (Med-Echo). Quebec census estimates were used to calculate age-standardized incidence rates (IR) of pediatric VTE. The incidence rate trend was then analyzed over the eleven-year study period using Poisson linear regression. Sex differences in incidence rates at the population level stratified by age group as a confounder as well as baseline characteristics of the cases were also evaluated. Results:In total, 487 incident cases of VTE in children 1–17 years of age were documented during the study period. Based on the estimated provincial census person-years during the study period, the age-standardized IR was 0.29 VTE per 10 000 person-years (95% confidence interval (CI) 0.26–0.31). Females overall had a statistically significant higher VTE incidence rate with an incidence rate ratio of 1.75 (95% CI 1.46–2.11) when controlled for age groups, as compared to males. When analyzed by age group, the age-standardized IRs were as follows: 1–5 year olds 0.04 VTE per 10 000 person-years (95% CI 0.03–0.05); 6–10 year olds 0.03 VTE per 10 000 person-years (95% CI 0.02–0.04); 11–14 year olds 0.06 VTE per 10 000 person-years (95% CI 0.05–0.07); 15–17 year olds 0.16 VTE per 10 000 person-years (95% CI 0.14–0.18).Trend analysis of the age-standardized IRs over the 11-year period showed no significant change in incidence rates whether using time as a continuous (yearly) or categorical variable (time-periods). Conclusions:Pediatric VTE is more frequent than previously described, however the rate is stable. As shown by others, children in their late-teen years have a higher risk of VTE than primary school-aged children. Unlike prior studies, females were more prone to VTE than males. Future studies that address sex differences in the incidence of pediatric VTE are needed to help determine effective primary thromboprophylaxis strategies in children at high risk for VTE. Disclosures:No relevant conflicts of interest to declare.

Pediatric venous thromboembolism following trauma: A review of the National Trauma Data Bank

Pediatric venous thromboembolism following trauma: A review of the National Trauma Data Bank

Inherited thrombophilia in children with venous thromboembolism and the familial risk of thromboembolism: an observational study

AbstractScreening for inherited thrombophilia (IT) is controversial; persons at high risk for venous thromboembolism (VTE) who benefit from screening need to be identified. We tested 533 first- and second-degree relatives of 206 pediatric VTE patients for IT (antithrombin, protein C, protein S, factor V G1691A, factor II G20210A) and determined the incidence of symptomatic VTE relative to their IT status. The risk for VTE was significantly increased among family members with, versus without, IT (hazard ratio = 7.6; 95% confidence interval [CI], 4.0-14.5; P < .001) and highest among carriers of antithrombin, protein C, or protein S deficiency (hazard ratio = 25.7; 95% CI, 12.2-54.2; P < .001). Annual incidences of VTE were 2.82% (95% CI, 1.63%-4.80%) among family members found to be carriers of antithrombin, protein C, or protein S deficiency, 0.42% (0.12%-0.53%) for factor II G202010A, 0.25% (0.12%-0.53%) for factor V G1691A, and 0.10% (0.06%-0.17%) in relatives with no IT. Given the high absolute risk of VTE in relatives with protein C, protein S, and antithrombin deficiency, we suggest screening for these forms of hereditary thrombophilia in children with VTE and their relatives. Interventional studies are required to assess whether thromboembolism can be prevented in this high-risk population.

The clinical development in pediatric venous thromboembotism

Pediatric venous thromboembolism is a life-threatening disease caused by many factors,of which the central venous catheter is the first high-risk factor,and the clinical presentation varies according to the position of obstruction.Color Doppler ultrasound,CT scan,MRI are the major diagnostic techniques.Low-molecular-weight heparin combines with oral anticoagulant agent are commonly used in therapy and prophylaxis.Early diagnosis and prevention are beneficial to the survival rate. Key words: Venous thromboembolism; Children

Early Recognition of Pediatric Venous Thromboembolism: A Risk-Assessment Tool

The incidence of venous thromboembolism in children has increased dramatically, with most cases occurring in children with cancer, surgery, trauma, congenital heart disease, and systemic lupus erythematosus. Early assessment of risk factors present in children would minimize morbidity and mortality from these events. To evaluate the reliability and validity of a tool for assessing risk for venous thromboembolism in children. The tool was developed after a review of the literature with assessment of content validity by a multidisciplinary team of experts. Patients' charts were reviewed retrospectively to establish reliability and validity of the tool. A P value less than .05 was considered statistically significant. Thirty-five charts were assessed for tool validity and were found to be statistically significant for all 3 risk score assessment categories. Logistic regression was used to assess 1001 patients' charts for internal consistency, which was found to be high (χ(2)(5)[n = 1001] = 100.6, P < .001). Results indicated that most patients at risk for venous thromboembolism were between the ages of 13 and 17 years, with females having more than 7 times greater risk than males. Descriptive statistics show that the assessment tool displays strong reliability and validity. Results validated a significant relationship between the risk score and the incidence of venous thromboembolism. Findings suggest that use of the assessment tool could significantly reduce adverse outcomes associated with venous thromboembolism in children.

Current and future management of pediatric venous thromboembolism

Venous thromboembolism (VTE) is an increasingly common complication encountered in tertiary care pediatric settings. The purpose of this review is to summarize the epidemiology, current and emerging pharmacotherapeutic options, and management of this disease. Over 70% of VTE occur in children with chronic diseases. Although they are seen in children of all ages, adolescents are at greatest risk. Pediatric VTE is associated with an increased risk of in-hospital mortality; recurrent VTE and post-thrombotic syndrome are commonly seen in survivors. In recent years, anticoagulation with low molecular weight heparin has emerged as the mainstay of therapy, but compliance is limited by its onerous subcutaneous administration route. New anticoagulants either already approved for use in adults or in the pipeline offer the possibility of improved dose stability and oral routes of administration. Current recommended anticoagulation course durations are derived from very limited case series and cohort data, or extrapolations from adult literature. However, the pathophysiologic underpinnings of pediatric VTE are dissimilar from those seen in adults and are often variable within groups of pediatric patients. Clinical studies and trials in pediatric VTE are underway which will hopefully improve the quality of evidence from which therapeutic guidelines are derived.