Moderate-intensity aerobic exercise vs desmopressin in adolescent males with mild hemophilia A: a randomized trial.

Persons with mild hemophilia A (HA) may use intranasal desmopressin prior to sports participation. Desmopressin is expensive and can cause vomiting, headache, palpitation, and occasionally seizures. Our group has previously documented a 2.3-fold increase in factor VIII activity (FVIII:C) in adolescents with mild HA after moderate-intensity aerobic exercise. Herein, we report principal findings of a randomized trial of intranasal desmopressin vs a standardized, moderate-intensity aerobic exercise regimen in adolescents with mild HA. Our primary objective was to compare the change in FVIII:C associated with these 2 interventions. We also examined changes in hemostatic parameters arising from their sequential administration. The study was conducted simultaneously at the Hospital for Sick Children, Canada, and Nationwide Children's Hospital, USA. Thirty-two eligible male adolescents (mean age ± standard deviation: 16.1 ± 2.6 years) with mild HA (mean baseline FVIII:C: 27.9% ± 18.4%) were randomized to 1 of 4 study arms (desmopressin followed by exercise, desmopressin alone, exercise followed by desmopressin, and exercise alone). Blood work was obtained at baseline and at 3 subsequent time-points. Participants randomized to exercise cycled on an ergometer for approximately 12 minutes, with the final 3 minutes at 85% of their predicted maximum heart rate. Standard weight-based dosing of desmopressin was used. Mean immediate increase in FVIII:C was 1.7-fold with exercise compared with 1.9-fold with desmopressin (noninferiority, P = .04). Exercise-induced improvement in hemostatic parameters including FVIII:C was brief compared with more sustained improvements seen with desmopressin. More than 60% of participants randomized to receive both exercise and desmopressin achieved normal (>50%) FVIII:C, 75 and 135 minutes into the study protocol.

Clinical decision support to enhance venous thromboembolism pharmacoprophylaxis prescribing for pediatric inpatients with COVID-19.

OBJECTIVE: To design and evaluate a clinical decision support (CDS) module to improve guideline concordant venous thromboembolism (VTE) pharmacoprophylaxis prescribing for pediatric inpatients with COVID-19. MATERIALS AND METHODS: The proportion of patients who met our institutional clinical practice guideline's (CPG) criteria for VTE prophylaxis was compared to those who triggered a CDS alert, indicating the patient needed VTE prophylaxis, and to those who were prescribed prophylaxis pre and post the launch of a new VTE CDS module to support VTE pharmacoprophylaxis prescribing. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, F1-score and accuracy of the tool were calculated for the pre- and post-intervention periods using the CPG recommendation as the gold standard. Accuracy was defined as the sum of the true positives and true negatives over the sum of the true positives, false positives, true negatives, and false negatives. Logistic regression was used to identify variables associated with correct thromboprophylaxis prescribing. RESULTS: A significant increase in the proportion of patients triggering a CDS alert occurred in the post-intervention period (44.3% vs. 6.9%, p < .001); however, no reciprocal increase in VTE prophylaxis prescribing was achieved (36.6% vs. 40.9%, p = .53). The updated CDS module had an improved sensitivity (55.0% vs. 13.3%), NPV (44.9% vs. 36.3%), F1-score (66.7% vs. 23.5%), and accuracy (62.5% vs. 42.0%), but an inferior specificity (78.6% vs. 100%) and PPV (84.6% vs. 100%). DISCUSSION: The updated CDS model had an improved accuracy and overall performance in correctly identifying patients requiring VTE prophylaxis. Despite an increase in correct patient identification by the CDS module, the proportion of patients receiving appropriate pharmacologic prophylaxis did not change. CONCLUSION: CDS tools to support correct VTE prophylaxis prescribing need ongoing refinement and validation to maximize clinical utility.

High Rate of Venous Thromboembolism in Severe Pediatric Intestinal Failure.

OBJECTIVE: To quantify the rate of venous thromboembolism (VTE) in patients with pediatric intestinal failure and identify associated risk factors. STUDY DESIGN: We performed a retrospective cohort study in pediatric patients (<21 years old) with severe pediatric intestinal failure (≥90 consecutive days of parenteral nutrition) secondary to short bowel syndrome who were treated from 2014 to 2021 at an interdisciplinary intestinal rehabilitation program. The primary outcome was the incidence of VTE. Multivariable regression was performed to identify independent clinical predictors of VTE. RESULTS: A total of 263 patients (59.7% male) met the criteria for inclusion. The cumulative incidence of VTE was 28.1%, with a rate of 0.32 VTEs per 1000 catheter-days. On univariate analysis, the number of catheter days, number of catheters, and history of central line-associated blood stream infection were associated with VTE. On multivariable logistic regression, a higher number of catheters was an independent risk factor for VTE (aOR, 1.17; 95% CI, 1.06-1.29). Additionally, earlier gestational age was a risk factor for VTE such that every week decrease in gestational age conferred a 9% increased risk of VTE (aOR, 1.09; 95% CI, 1.02-1.16). CONCLUSIONS: In this retrospective study, 28.1% of patients with severe pediatric intestinal failure developed VTE; the number of catheters and early gestational age were noted to be independent risk factors for VTE. This high incidence of VTE highlights the need to investigate VTE in pediatric intestinal failure prospectively, including the potential benefit of prophylactic anticoagulation.

Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombotic complications in adults, but the incidence of COVID-19-related thrombosis in children and adolescents is unclear. Most children with acute COVID-19 have mild disease, but coagulopathy has been associated with multisystem inflammatory syndrome in children (MIS-C), a postinfectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and evaluate associated risk factors. We classified patients into 1 of 3 groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (COVID-19, n = 426; MIS-C, n = 138; and asymptomatic SARS-CoV-2, n = 289) in 814 patients, there were 20 patients with thrombotic events (TEs; including 1 stroke). Patients with MIS-C had the highest incidence (9 [6.5%] of 138) vs COVID-19 (9 [2.1%] of 426) or asymptomatic SARS-CoV-2 (2 [0.7%] of 289). In patients with COVID-19 or MIS-C, a majority of TEs (89%) occurred in patients age ≥12 years. Patients age ≥12 years with MIS-C had the highest rate of thrombosis at 19% (9 of 48). Notably, 71% of TEs that were not present on admission occurred despite thromboprophylaxis. Multivariable analysis identified the following as significantly associated with thrombosis: age ≥12 years, cancer, presence of a central venous catheter, and MIS-C. In patients with COVID-19 or MIS-C, hospital mortality was 2.3% (13 of 564), but it was 28% (5 of 18) in patients with TEs. Our findings may help inform pediatric thromboprophylaxis strategies.

Improving guideline-concordant thromboprophylaxis prescribing for children admitted to hospital with COVID-19.

BACKGROUND: The incidence of venous thrombo-embolism (VTE) in hospitalized children has increased by 130%-200% over the last two decades. Given this increase, many centers utilize electronic clinical decision support (CDS) to prognosticate VTE risk and recommend prophylaxis. SARS-CoV-2 infection (COVID-19) is a risk factor for VTE; however, CDS developed before the COVID-19 pandemic may not accurately prognosticate VTE risk in children with COVID-19. This study's objective was to identify areas to improve thromboprophylaxis recommendations for children with COVID-19. METHODS: Inpatients with a positive COVID-19 test at admission were identified at a quaternary-care pediatric center between March 1, 2020 and January 20, 2022. The results of the institution's automated CDS thromboprophylaxis recommendations were compared to institutional COVID-19 thromboprophylaxis guidelines and to the actual thromboprophylaxis received. CDS optimization was performed to improve adherence to COVID-19 thromboprophylaxis recommendations. RESULTS: Of the 329 patients included in this study, 106 (28.2%) were prescribed pharmaco-prophylaxis, 167 (50.8%) were identified by the institutional COVID-19 guidelines as requiring pharmaco-prophylaxis, and 45 (13.2%) were identified by the CDS as needing pharmaco-prophylaxis. On univariate analysis, only age 12 years or more was associated with recipient of appropriate prophylaxis (OR 1.78, 95% CI: 1.13-2.82, p = .013). Five patients developed VTEs; three had symptoms at presentation, two were identified as high risk for VTE by both the automated and best practice assessments but were not prescribed pharmaco-prophylaxis. CONCLUSION: Automated thromboprophylaxis recommendations developed prior to the COVID-19 pandemic may not identify all COVID-19 patients needing pharmaco-prophylaxis. Existing CDS tools need to be updated to reflect COVID-19-specific risk factors for VTEs.

Appendix to the Society of Interventional Radiology Consensus Guidelines for the Periprocedural Management of Thrombotic and Bleeding Risk in Patients Undergoing Percutaneous Image-Guided Interventions: Pediatric Considerations.

PURPOSE: To provide guidance on the use of anticoagulant and antithrombotic agents in pediatric patients undergoing interventional radiology procedures. MATERIALS AND METHODS: A multidisciplinary writing group conducted a comprehensive literature search to identify studies on the topic of interest. Recommendations were developed for procedural risk and medication dosage and withholding. A modified Delphi technique was used to achieve consensus agreement on the recommendations. RESULTS: A total of 24 studies, including systematic reviews and meta-analyses, randomized controlled trials, and prospective and retrospective cohort studies, were identified as relevant. The expert writing group agreed on procedural risk categorization, laboratory testing thresholds, and medication dosage and withholding recommendations specific to pediatric practice. They additionally described the nuances of anticoagulation in clinical conditions specific to pediatrics. CONCLUSIONS: The Society of Interventional Radiology recommends following the guidance provided in the document when developing multidisciplinary management protocols for anticoagulation and antithrombotic treatment in pediatric patients undergoing interventional radiology procedures.

Bleeding Severity and Phenotype in 22q11.2 Deletion Syndrome-A Cross-Sectional Investigation.

OBJECTIVES: To prospectively quantify bleeding severity and elaborate hemorrhagic symptoms in children with 22q11.2 deletion syndrome (22q11DS) using 2 validated bleeding assessment tools (BATs), namely the Pediatric Bleeding Questionnaire and the International Society on Thrombosis and Hemostasis BAT (ISTH-BAT). We also sought to compare subjects' bleeding scores to unaffected first-degree family members. STUDY DESIGN: Children with 22q11DS and unaffected first-degree family members were recruited for the study. Two validated BATs were administered by a pediatric hematologist. Additional clinical and laboratory data were abstracted from patient medical records. Standard descriptive and nonparametric statistical methods were used. RESULTS: In total, 29 eligible subjects and controls were assessed. Median age (range) of subjects and controls was 8 (5-17) years and 38 (9-56) years, respectively. In total, 17 of 29 subjects had a positive bleeding score on ISTH-BAT compared with 1 of 29 control patients (P < .0001). Median ISTH-BAT score in subjects was 3 (0-12), compared with 2 (0-6) in control patients (P = .022). Median Pediatric Bleeding Questionnaire score in subjects was 2 (-1 to 12). The most frequent bleeding symptoms reported in subjects with 22q11DS were epistaxis (69%) and bruising (52%). Eighteen subjects had been surgically challenged, and 6 were noted to have increased perioperative hemorrhage. CONCLUSIONS: Children with 22q11DS have increased bleeding scores compared with their first-degree unaffected relatives. The majority of the bleeding symptoms described were mucocutaneous.

Unfractionated heparin using actual body weight without dose capping in obese pediatric patients-Subgroup analysis from an observational cohort study.

To evaluate the correlation between an uncapped, actual body weight-based unfractionated heparin dosing strategy, we performed a body mass index-based subanalysis of a previously reported pediatric cohort. Nearly half (45%) of obese patients were supra-therapeutic on initial anti-FXa assessment. Obese patients achieved therapeutic anti-FXa significantly faster than nonobese patients (median 4 vs 12 hours, P = .0192) and were more likely to have any supra-therapeutic anti-FXa levels (77% vs 35%; P = .0021). There was no statistically significant difference in major or clinically relevant nonmajor bleeding rates between weight categories (P = .69). Prospective pediatric studies are warranted to confirm our findings.

Venous thromboembolism in children with central nervous system tumors: Comparison of an institutional cohort to a national administrative database.

BACKGROUND: Central nervous system (CNS) tumors are the second most common malignancy of childhood, and published data on venous thromboembolism (VTE) rate and risk factors for these patients are outdated or incomplete. Here, we determine the cumulative incidence and risk factors for VTE in this population. PROCEDURE: VTE diagnosis and associated clinical risk factors were abstracted and analyzed for two cohorts of children (0-21 years) diagnosed with CNS tumors between January 1, 2010 to September 30, 2018. The first study was a retrospective single institution cohort study. The initial observations were confirmed across multiple pediatric hospitals using the Pediatric Health Information System (PHIS) administrative database. RESULTS: The single-institution cohort included 338 patients aged 3 days to 20.9 years (median age, 8.6 years); VTE developed in eight (2.4%) patients. The PHIS cohort included 17 634 patients aged from 0 to 21.9 years (median: 9.5 years); VTE developed in 354 (2.0%) patients. Univariate analysis for the single-institution cohort identified central venous catheter (CVC) placement as a risk factor for VTE (odds ratio [OR] 8.40, 95% confidence interval [CI] 1.43-49.41, P = .0186). Multivariable analysis of the PHIS dataset identified CVC placement (OR 1.97, 95% CI 1.57-2.46; P < .0001), obesity (OR 2.96, 95% CI 1.21-7.26; P = .0177), and more than one hospital admission (OR 3.54, 95% CI 2.69-4.64; P < .0001) as significant predictors of VTE. VTE diagnosis was not associated with increased mortality in either cohort. CONCLUSIONS: The VTE rate in children with CNS tumors is low (2%). CVC placement was identified as a modifiable risk factor in both cohorts.

Catheter-directed thrombolysis for submassive pulmonary embolism in children: A case series.

Incidence of venous thromboembolism, including pulmonary embolism (PE), continues to rise in children. Optimum management of submassive PE is unclear. The principal objective of this retrospective study was to investigate the radiological and clinical outcomes in children with submassive PE treated with catheter-directed thrombolysis (CDT). Five patients underwent six episodes of CDT. No patient developed major/clinically relevant non-major bleeding. Most patients had complete radiological thrombus resolution and no patient had evidence of chronic thromboembolic pulmonary hypertension. There is an urgent need for larger prospective cohort studies/randomized controlled trials to investigate the role of CDT in pediatric PE.

Anti-Factor Xa-Based Monitoring of Unfractionated Heparin: Clinical Outcomes in a Pediatric Cohort.

OBJECTIVES: To assess clinical outcomes in children treated with unfractionated heparin and monitored using an anti-factor Xa (Anti-FXa)-based nomogram. We also sought to assess the correlation between activated partial thromboplastin time (APTT) and Anti-FXa. STUDY DESIGN: This was a single-center, observational cohort study conducted over a 20-month period that included all pediatric patients (<21 years) who received therapeutic unfractionated heparin and were monitored using an anti-FXa-based nomogram. RESULTS: In total, 95 patients met prespecified inclusion criteria, and 1098 pairs of APTT and Anti-FXa measurements were performed. The median unfractionated heparin dose required to reach therapeutic Anti-FXa goal was significantly greater in infants compared with older children (P <.0001). The median time to achieve therapeutic Anti-FXa was 10 hours (range 2-96 hours) and was significantly shorter in patients who received a bolus compared with those who did not (P = .03). Five (5.3%) major bleeding events were noted. Age, peak Anti-FXa, peak APTT, lowest platelet count, and fibrinogen were not predictive of major and clinically relevant nonmajor bleeds. Moderate correlation between the APTT and Anti-FXa (r = 0.75; 95% CI 0.72-0.77) assays was appreciated. CONCLUSIONS: Using an anti-FXa-based nomogram to monitor unfractionated heparin in children is feasible. Although moderate correlation was observed between the APTT and Anti-FXa assays, the APTT frequently overestimated heparin activity. Safety and efficacy of an Anti-FXa nomogram needs further validation.

Treatment-Related Outcomes in Paget-Schroetter Syndrome-A Cross-Sectional Investigation.

OBJECTIVE: To investigate treatment-related outcomes, namely radiological clot resolution, post-thrombotic syndrome (PTS), and health related quality-of-life (HRQoL) scores, in children with Paget-Schroetter syndrome (PSS) undergoing multidisciplinary management, including anticoagulation and decompressive rib-resection surgery, with or without thrombolytic therapy. STUDY DESIGN: We identified all patients treated for PSS at our institution between the years 2010 and 2017. Baseline clinical and radiologic data were abstracted from medical records. Two validated survey instruments to quantify PTS and HRQoL were mailed to eligible patients. Standard statistical methods were used to summarize these measures. RESULTS: In total, 22 eligible patients were identified; 10 were treated with thrombolysis followed by anticoagulation and rib resection, and 12 were treated with anticoagulation and rib resection alone. Nineteen patients responded to the survey instruments. Median age at deep vein thrombosis diagnosis and survey completion were 16.3 and 20.4 years, respectively. Nineteen of 22 patients had thrombus resolution on radiologic follow-up. Fourteen of 19 survey respondents reported signs/symptoms of PTS of which the majority (12/14) reported mild PTS. Aggregate total, physical, and psychosocial HRQoL scores reported were 90.6, 96.7, and 93.3, respectively. Thrombolytic therapy was not associated with a significant improvement in radiologic, clinical or HRQoL outcomes. CONCLUSIONS: Most patients with PSS had complete thrombus resolution on imaging. Only 11% of survey respondents reported moderate PTS. The entire cohort reported excellent HRQoL scores. The role for thrombolytic therapy in the management of childhood PSS remains incompletely elucidated.

Fibrinogen Columbus II: A novel c.1075G>T mutation in the FGG gene causing hypodysfibrinogenemia and thrombosis in an adolescent male.

Hypodysfibrinogenemia, the least frequently reported congenital fibrinogen disorder is characterized by low circulating levels of a dysfunctional protein, and is associated with phenotypic features of both hypo- and dysfibrinogenemia. Herein, we report an adolescent male with unprovoked venous thromboembolism and hypodysfibrinogenemia. Patient had recurrent, progressive thrombosis despite therapeutic anticoagulation with both low molecular weight heparin and warfarin. He had clinical and radiological improvement after transition to a direct thrombin inhibitor. Sequencing of the FGG gene identified a novel heterozygous mutation, c.1075G>T. Structural visualization of the identified variant was pursued and suggested that the mutation likely destabilizes the Ca2+ -binding site of fibrinogen resulting in pathogenicity.

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 Pediatric Hematopoietic Cell Transplant: A Multicenter Cohort Study.

Hematopoietic cell transplant (HCT) is associated with a proinflammatory, procoagulant environment that places recipients at increased risk of venous thromboembolism (VTE). Although the incidence of VTE in adult HCT recipients has been extensively studied, similar data for children are lacking. We conducted a multicenter retrospective study to analyze the prevalence of VTE and associated risk factors in a large cohort of patients who underwent HCT at tertiary care US children's hospitals. The Pediatric Health Information System database, a large administrative database that contains clinical and resource utilization data from 49 freestanding children's hospitals in the United States, was used to extract data. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HCT recipients, VTE events, post-HCT complications, and associated risk factors up to 1 year post-transplant. Data on patients who received HCT from January 2010 through September 2014 were collected. A total of 4158 unique patients mean ± standard deviation age at transplant admit, 8.8 ± 6.5 years; range, birth to 33.4 years) were identified. After HCT 290 subjects (6.9%) developed VTE. VTE prevalence was greater in patients aged ≥ 13 versus <13 years (8.54% versus 6.33%; P = .01) and in recipients of allogeneic versus autologous grafts (7.7% versus 5%; P ≤ .01). VTE was associated with prolonged median duration of hospitalization (81 versus 54 days; P ≤.01) and increased 1-year mortality (13.9% versus 5.9%; P ≤ .01). Infections and presence of any graft-versus-host disease (GVHD) were significantly associated with VTE occurrence in recipients of allogenic grafts. Prevalence of VTE in patients who underwent HCT at pediatric tertiary care hospitals is about 7%. Age ≥ 13 years and allogeneic grafts were significant pre-HCT VTE risk factors, with GVHD and infections seen more frequently in patients with VTE.

Risk Factors for Neonatal Venous and Arterial Thromboembolism in the Neonatal Intensive Care Unit-A Case Control Study.

OBJECTIVE: To identify risk factors associated with venous and arterial thrombosis in sick neonates admitted to the neonatal intensive care unit. STUDY DESIGN: A case-control study was conducted at 2 centers between January 2010 and March 2014 using the Children's Hospital Neonatal Database dataset. Cases were neonates diagnosed with either arterial or venous thrombosis during their neonatal intensive care unit stay; controls were matched in a 1:4 ratio by gestational age and presence or absence of central access devices. Bivariable and conditional logistic regression analyses for venous and arterial thrombosis were performed separately. RESULTS: The overall incidence of neonatal thrombosis was 15.0 per 1000 admissions. A higher proportion of neonates with thrombosis had presence of central vascular access devices (75% vs 49%; P < .01) were of extremely preterm gestational age (22-27 weeks; 26% vs 15.0%; P <.05) and stayed ≥31 days in the neonatal intensive care unit (53% vs 32.9%; P <.01), when compared with neonates without thrombosis. A final group of 64 eligible patients with thrombosis and 4623 controls were analyzed. In a conditional multivariable logistic regression model, venous thrombosis was significantly associated with male sex (AOR, 2.12; 95% CI, 1.03-4.35; P = .04) and blood stream infection (AOR, 3.47; 95% CI, 1.30-9.24; P = .01). CONCLUSIONS: The incidence of thrombosis was higher in our neonatal population than in previous reports. After matching for central vascular access device and gestational age, male sex and blood stream infection represent independent risk factors of neonatal venous thrombosis. A larger cohort gleaned from multicenter data should be used to confirm the study results and to develop thrombosis prevention strategies.

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.

Inferior vena cava atresia predisposing to acute lower extremity deep vein thrombosis in children: A descriptive dual-center study.

PURPOSE: Thrombosis in the healthy pediatric population is a rare occurrence. Little is known about the optimal treatment or outcomes of children with unprovoked acute lower extremity (LE) deep vein thrombosis (DVT) associated with atresia of the inferior vena cava (IVC). METHODS: We retrospectively analyzed the records of patients with acute LE DVT subsequently found to have IVC atresia who presented to two tertiary pediatric institutions between 2008 and 2016. Data were reviewed for thrombophilia risk factors, treatment, and outcomes. RESULTS: Eighteen patients, aged 13-18 years (median: 16 years), presenting with acute LE DVT were found to have IVC atresia. Three patients also presented with pulmonary embolism. Fourteen patients underwent site-directed thrombolysis in addition to anticoagulation. Five patients (28%) had confirmed or suspected recurrent thrombosis. Thirteen patients (72%) had no identified provocation for DVT. Ten patients (56%) had post-thrombotic syndrome, and 17 of 18 patients remain on indefinite anticoagulation. CONCLUSION: This study suggests that IVC atresia is a risk factor for LE DVT and pulmonary embolism in otherwise healthy children and highlights the importance of dedicated imaging of the IVC in young patients with unprovoked LE DVT. Indefinite anticoagulation may be considered in pediatric patients presenting with unprovoked thrombosis secondary to an atretic IVC.

Changing Paradigm of Hemophilia Management: Extended Half-Life Factor Concentrates and Gene Therapy.

Management of hemophilia has evolved significantly in the last century-from recognition of the causative mechanism in the 1950s to commercially available clotting factor concentrates in the 1960s. Availability of lyophilized concentrates in the 1970s set the stage for home-based therapy, followed by introduction of virally attenuated plasma-derived, and then recombinant factor concentrates in the 1980s and 1990s, respectively. The subsequent years saw a paradigm shift in treatment goals from on-demand therapy to prophylactic factor replacement starting at an early age, to prevent hemarthrosis becoming the standard of care for patients with severe hemophilia. In the developed world, the increasing use of home-based prophylactic regimens has significantly improved the quality of life, and life expectancy of patients with severe hemophilia. Seminal developments in the past 5 years, including the commercial availability of extended half-life factor concentrates and the publication of successful results of gene therapy for patients with hemophilia B, promise to further revolutionize hemophilia care over the next few decades. In this review, we summarize the evolution of management for hemophilia, with a focus on extended half-life factor concentrates and gene therapy.