Publications by authors named "Riten Kumar"

47 Publications

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

J Pediatr 2021 Apr 6. Epub 2021 Apr 6.

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA. Electronic address:

Objectives: To prospectively quantify bleeding severity and elaborate hemorrhagic symptoms in children with 22q11.2 deletion syndrome (22q11DS) using two validated bleeding-assessment-tools (BATs), namely the pediatric bleeding questionnaire (PBQ) and the International Society on Thrombosis and Hemostasis BAT (ISTH-BAT). We additionally 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: 29 eligible subjects and controls were assessed. Median age (range) of subjects and controls were 8 (5-17) and 38 (9-56) years, respectively. 17/29 subjects had a positive bleeding score on ISTH-BAT compared with 1/29 control (p<0.0001). Median ISTH-BAT score in subjects was 3 (0 - 12), compared with 2 (0 - 6) in controls (P = .022). Median Pediatric Bleeding Questionnaire score in subjects was 2 (-1 - 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 peri-operative hemorrhage.

Conclusion: Children with 22q11DS have increased bleeding scores compared with their first-degree unaffected relatives. The majority of the bleeding symptoms described were muco-cutaneous.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2021.03.071DOI Listing
April 2021

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

Pediatr Blood Cancer 2021 Mar 5;68(3):e28872. Epub 2021 Jan 5.

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28872DOI Listing
March 2021

Safety and efficacy of rivaroxaban in pediatric cerebral venous thrombosis (EINSTEIN-Jr CVT).

Blood Adv 2020 12;4(24):6250-6258

Department of Neurology, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, The Netherlands.

Anticoagulant treatment of pediatric cerebral venous thrombosis has not been evaluated in randomized trials. We evaluated the safety and efficacy of rivaroxaban and standard anticoagulants in the predefined subgroup of children with cerebral venous thrombosis (CVT) who participated in the EINSTEIN-Jr trial. Children with CVT were randomized (2:1), after initial heparinization, to treatment with rivaroxaban or standard anticoagulants (continued on heparin or switched to vitamin K antagonist). The main treatment period was 3 months. The primary efficacy outcome, symptomatic recurrent venous thromboembolism (VTE), and principal safety outcome, major or clinically relevant nonmajor bleeding,were centrally evaluated by blinded investigators. Sinus recanalization on repeat brain imaging was a secondary outcome. Statistical analyses were exploratory. In total, 114 children with confirmed CVT were randomized. All children completed the follow-up. None of the 73 rivaroxaban recipients and 1 (2.4%; CVT) of the 41 standard anticoagulant recipients had symptomatic, recurrent VTE after 3 months (absolute difference, 2.4%; 95% confidence interval [CI], -2.6% to 13.5%). Clinically relevant bleeding occurred in 5 (6.8%; all nonmajor and noncerebral) rivaroxaban recipients and in 1 (2.5%; major [subdural] bleeding) standard anticoagulant recipient (absolute difference, 4.4%; 95% CI, -6.7% to 13.4%). Complete or partial sinus recanalization occurred in 18 (25%) and 39 (53%) rivaroxaban recipients and in 6 (15%) and 24 (59%) standard anticoagulant recipients, respectively. In summary, in this substudy of a randomized trial with a limited sample size, children with CVT treated with rivaroxaban or standard anticoagulation had a low risk of recurrent VTE and clinically relevant bleeding. This trial was registered at clinicaltrials.gov as #NCT02234843.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020003244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756994PMC
December 2020

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

Pediatr Blood Cancer 2021 Mar 19;68(3):e28846. Epub 2020 Dec 19.

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28846DOI Listing
March 2021

Fibrinogen Columbus III: A novel c.963del frameshift mutation in the FGG gene resulting in hypofibrinogenemia with a bleeding phenotype.

Pediatr Blood Cancer 2021 Mar 15;68(3):e28713. Epub 2020 Oct 15.

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28713DOI Listing
March 2021

Rivaroxaban for treatment of pediatric venous thromboembolism. An Einstein-Jr phase 3 dose-exposure-response evaluation.

J Thromb Haemost 2020 07 4;18(7):1672-1685. Epub 2020 Jun 4.

Bayer AG, Wuppertal, Germany.

Background: Recently, the randomized EINSTEIN-Jr study showed similar efficacy and safety for rivaroxaban and standard anticoagulation for treatment of pediatric venous thromboembolism (VTE). The rivaroxaban dosing strategy was established based on phase 1 and 2 data in children and through pharmacokinetic (PK) modeling.

Methods: Rivaroxaban treatment with tablets or the newly developed granules-for-oral suspension formulation was bodyweight-adjusted and administered once-daily, twice-daily, or thrice-daily for children with bodyweights of ≥30, ≥12 to <30, and <12 kg, respectively. Previously, these regimens were confirmed for children weighing ≥20 kg but only predicted in those <20 kg. Based on sparse blood sampling, the daily area under the plasma concentration-time curve [AUC ] and trough [C ] and maximum [C ] steady-state plasma concentrations were derived using population PK modeling. Exposure-response graphs were generated to evaluate the potential relationship of individual PK parameters with recurrent VTE, repeat imaging outcomes, and bleeding or adverse events. A taste-and-texture questionnaire was collected for suspension-recipients.

Results: Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable.

Discussion: Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.14813DOI Listing
July 2020

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

Pediatr Blood Cancer 2020 04 25;67(4):e28144. Epub 2019 Dec 25.

Nationwide Children's Hospital, Columbus, Ohio.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28144DOI Listing
April 2020

Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.

Lancet Haematol 2020 Jan 5;7(1):e18-e27. Epub 2019 Nov 5.

Department of Clinical Haematology, Royal Children's Hospital, Haematology Research Murdoch Children's Research Institute, Department of Paediatrics, University of Melbourne, VIC, Australia.

Background: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism.

Methods: In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed.

Findings: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11-1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51-6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths.

Interpretation: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants.

Funding: Bayer AG and Janssen Research & Development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3026(19)30219-4DOI Listing
January 2020

Popliteal Artery Entrapment Syndrome Presenting with Critical Limb Ischemia in an Adolescent.

J Pediatr 2020 02 9;217:215-215.e1. Epub 2019 Oct 9.

Department of Vascular Surgery, Fairfield Medical Center, Lancaster, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2019.09.004DOI Listing
February 2020

Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies.

Lancet Haematol 2019 Oct 13;6(10):e500-e509. Epub 2019 Aug 13.

Bayer AG, Wuppertal, Germany.

Background: Rivaroxaban has been shown to be efficacious for treatment of venous thromboembolism in adults, and has a reduced risk of bleeding compared with standard anticoagulants. We aimed to develop paediatric rivaroxaban regimens for the treatment of venous thromboembolism in children and adolescents.

Methods: In this phase 2 programme, we did three studies to evaluate rivaroxaban treatment in children younger than 6 months, aged 6 months to 5 years, and aged 6-17 years. Our studies used a multicentre, single-arm design at 54 sites in Australia, Europe, Israel, Japan, and north America. We included children with objectively confirmed venous thromboembolism previously treated with low-molecular weight heparin, fondaparinux, or a vitamin K antagonist for at least 2 months or, in children who had catheter-related venous thromboembolism for at least 6 weeks. We administered rivaroxaban orally in a bodyweight-adjusted 20 mg-equivalent dose, based on physiologically-based pharmacokinetic modelling predictions and EINSTEIN-Jr phase 1 data in young adults, in either a once-daily (tablets; for those aged 6-17 years), twice-daily (in suspension; for those aged 6 months to 11 years), or three times-daily (in suspension; for those younger than 6 months) dosing regimen for 30 days (or 7 days for those younger than 6 months). The primary aim was to define rivaroxaban treatment regimens that match the target adult exposure range. The principal safety outcome was major bleeding and clinically relevant non-major bleeding. Analyses were per-protocol. The predefined efficacy outcomes were symptomatic recurrent venous thromboembolism, asymptomatic deterioration on repeat imaging at the end of the study treatment period. These trials are registered at ClinicalTrials.gov, numbers NCT02564718, NCT02309411, and NCT02234843.

Findings: Between Feb 11, 2013, and Dec 20, 2017, we enrolled 93 children (ten children younger than 6 months; 15 children aged 6 months to 1 year; 25 children aged 2-5 years; 32 children aged 6-11 years; and 11 children aged 12-17 years) into our study. 89 (96%) children completed study treatment (30 days of treatment, or 7 days in those younger than 6 months), and 93 (100%) children received at least one dose of study treatment and were evaluable for the primary endpoints. None of the children had a major bleed, and four (4%, 95% CI 1·2-10·6) of these children had a clinically relevant non-major bleed (three children aged 12-17 years with menorrhagia and one child aged 6-11 years with gingival bleeding). We found no symptomatic recurrent venous thromboembolism in any patients (0%, 0·0-3·9). 24 (32%) of 75 patients with repeat imaging had their thrombotic burden resolved, 43 (57%) patients improved, and eight (11%) patients were unchanged. No patient deteriorated. We confirmed therapeutic rivaroxaban exposures with once-daily dosing in children with bodyweights of at least 30 kg and with twice-daily dosing in children with bodyweights of at least 20 kg and less than 30 kg. Children with low bodyweights (<20 kg, particularly <12 kg) showed low exposures so, for future studies, rivaroxaban dosages were revised for these weight categories, to match the target adult exposure range. 61 (66%) of 93 children had adverse events during the study. Pyrexia was the most common adverse event (ten [11%] events), and anaemia and neutropenia or febrile neutropenia were the most frequent grade 3 or worse events (four [4%] events each). No children died or were discontinued from rivaroxaban because of adverse events.

Interpretation: Treatment with bodyweight-adjusted rivaroxaban appears to be safe in children. The treatment regimens that we confirmed in children with bodyweights of at least 20 kg and the revised treatment regimens that we predicted in those with bodyweights less than 20 kg will be evaluated in the EINSTEIN-Jr phase 3 trial in children with acute venous thromboembolism.

Funding: Bayer AG, Janssen Research and Development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3026(19)30161-9DOI Listing
October 2019

Valproic Acid-Induced Coagulopathy.

Pediatr Neurol 2019 09 2;98:25-30. Epub 2019 May 2.

Department of Pediatrics, The Ohio State University, Columbus, Ohio; Division of Pediatric Neurology, Nationwide Children's Hospital, Columbus, Ohio. Electronic address:

Background: Valproic acid is one of the most commonly used antiseizure medications. Multiple hematologic abnormalities have been reported with the use of valproic acid, which may be particularly relevant in the perioperative surgical setting. The incidence of these abnormalities and prevalence of periprocedural hemorrhage vary significantly in the published literature. In this article we analyze the prevalence and possible etiology of coagulopathy and hemorrhage in patients receiving valproic acid.

Methods: A literature search was completed using "VPA," "coagulopathy," and "surgery." The available published data from case reports to large case series were reviewed.

Results: Thrombocytopenia was noted to be the most common laboratory abnormality associated with valproic acid. An association between valproic acid and acquired von Willebrand disease has also been suggested. There are case reports describing bleeding in the setting of hypofibrinogenemia and factor XIII deficiency. Perioperative hemorrhage was reported in pediatric studies of orthopedic procedures, but not in adult cohorts undergoing neurosurgical interventions.

Conclusions: VPA use can cause thrombocytopenia and other coagulation abnormalities. Rigorous, prospective trials are needed to better assess the association between valproic acid and clinically significant coagulopathy. Until such data are available, physicians need to be aware of the potential risk of bleeding in patients receiving valproic acid. A hemostatic evaluation should be considered in symptomatic patients, and may be considered for patients taking VPA who are scheduled for surgery. If an abnormality is detected, hematologists should be involved to make recommendation on perioperative hemostatic strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2019.04.019DOI Listing
September 2019

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

Pediatr Blood Cancer 2019 09 27;66(9):e27832. Epub 2019 May 27.

Division of Pediatric Hematology/Oncology/BMT, Nationwide Children's Hospital, Columbus, Ohio.

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 Ca -binding site of fibrinogen resulting in pathogenicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.27832DOI Listing
September 2019

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

J Pediatr 2019 06 5;209:212-219.e1. Epub 2019 Apr 5.

Division of Pediatric Hematology/Oncology/BMT, Nationwide Children's Hospital, Columbus, OH; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2019.02.015DOI Listing
June 2019

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

Pediatr Blood Cancer 2019 04 13;66(4):e27588. Epub 2018 Dec 13.

Department of Pediatrics, The Ohio State University, Division of Hematology/Oncology, Nationwide Children's Hospital, Columbus, Ohio.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.27588DOI Listing
April 2019

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

J Pediatr 2019 04 7;207:226-232.e1. Epub 2018 Dec 7.

Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital, Columbus, OH; Department of Pediatrics, The Ohio State University, Columbus, OH.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2018.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556226PMC
April 2019

Klinefelter syndrome as a risk factor for recurrent deep vein thrombosis in an adolescent male: Significance of a thorough physical examination.

Pediatr Blood Cancer 2018 08 10;65(8):e27080. Epub 2018 Apr 10.

Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.27080DOI Listing
August 2018

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

J Pediatr 2018 06 28;197:186-190.e1. Epub 2018 Mar 28.

Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital, Columbus, OH; Department of Pediatrics, The Ohio State University, Columbus, OH. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2018.01.073DOI Listing
June 2018

Prevalence and risk factors for venous thromboembolism in children with sickle cell disease: an administrative database study.

Blood Adv 2018 02;2(3):285-291

Division of Hematology/Oncology, Department of Pediatrics, The Ohio State University, Nationwide Children's Hospital, Columbus, OH; and.

A hypercoagulable state resulting in increased venous thromboembolism (VTE) has been described in adults with sickle cell disease (SCD), but similar data for children are lacking. The objective of this retrospective cohort study was to describe the rate of VTE and risk factors associated with VTE in children with SCD across tertiary-care children's hospitals in the United States between the years 2009 and 2015. We used the Pediatric Health Information System database to investigate all pediatric patients with SCD admitted to 1 of 48 participating institutions between 1 January 2009 and 30 September 2015. International Classification of Disease, Ninth Edition, Clinical Modification codes were used to identify index thromboembolic events and chronic medical conditions known to be associated with VTE. Billing codes were used to identify central venous line (CVL) placement and pharmaceutical billing codes to identify estrogen containing oral-contraceptive use. Logistic regression analysis was used to study the association among unique patient characteristics, VTE, and death. 10 454 eligible subjects with SCD were identified. Median age (±interquartile range) of study cohort was 10 (±11) years. 181 subjects (1.7%) developed an index venous thromboembolic event during the study period. Median age at VTE diagnosis was 15.9 (±7.4) years. On multivariable logistic regression analysis, CVL placement, chronic renal disease, history of stroke, female sex, length of hospitalization, intensive care unit utilization, and older age were associated with VTE. After adjusting for other variables, VTE was independently associated with death. In summary, VTE can occur in pediatric patients with SCD. CVL placement is a modifiable risk factor for VTE development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2017012336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812330PMC
February 2018

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

J Pediatr 2018 04 2;195:28-32. Epub 2018 Feb 2.

Division of Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2017.12.015DOI Listing
April 2018

Mesoaortic compression of a left-sided inferior vena-cava presenting as recurrent pulmonary embolism in a child-a novel anatomic thrombophilia?

Pediatr Blood Cancer 2018 06 19;65(6):e26986. Epub 2018 Jan 19.

Department of Pediatrics, Division of Pediatric Hematology/Oncology, The Ohio State University, Nationwide Children's Hospital, Columbus, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.26986DOI Listing
June 2018

Venous Thromboembolism in Pediatric Hematopoietic Cell Transplant: A Multicenter Cohort Study.

Biol Blood Marrow Transplant 2018 02 8;24(2):337-342. Epub 2017 Nov 8.

Division of Pediatric Hematology, Oncology and Bone Marrow Transplant, Nationwide Children's Hospital, Columbus, Ohio; Department of Pediatrics, The Ohio State University, Columbus, Ohio.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2017.10.038DOI Listing
February 2018

Thrombosis of the Abdominal Veins in Childhood.

Front Pediatr 2017 5;5:188. Epub 2017 Sep 5.

Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.

Abdominal venous thrombosis is a rare form of venous thromboembolic disease in children. While mortality rates are low, a significant proportion of affected children may suffer long-term morbidity. Additionally, given the infrequency of these thrombi, there is lack of stringent research data and evidence-based treatment guidelines. Nonetheless, pediatric hematologists and other subspecialists are likely to encounter these problems in practice. This review is therefore intended to provide a useful guide on the clinical diagnosis and management of children with these rare forms of venous thromboembolic disease. Herein, we will thus appraise the current knowledge regarding major forms of abdominal venous thrombosis in children. The discussion will focus on the epidemiology, presentation, diagnosis, management, and outcomes of (1) inferior vena cava, (2) portal, (3) mesenteric, (4) hepatic, and (5) renal vein thrombosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2017.00188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591784PMC
September 2017

Activated Partial Thromboplastin Time versus Anti-Factor Xa Levels for Monitoring Unfractionated Heparin Therapy in Children: An Institutional Experience.

J Pediatr Hematol Oncol 2017 10;39(7):576-577

*Department of Pediatrics, Eastern Virginia Medical School, Division of Hematology/Oncology, Children's Hospital of the King's Daughters, Norfolk, VA †Department of Pediatrics, Division of Hematology/Oncology §Department of Pediatrics, Division of Cardiology, The Ohio State University ‡Quality Improvement Services, Nationwide Children's Hospital, Columbus, OH.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPH.0000000000000966DOI Listing
October 2017

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

Pediatr Blood Cancer 2018 Feb 29;65(2). Epub 2017 Aug 29.

Division of Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.26785DOI Listing
February 2018

Arterial Ischemic Stroke in Children and Young Adults.

Continuum (Minneap Minn) 2017 02;23(1, Cerebrovascular Disease):158-180

Purpose Of Review: This article reviews risk factors, recurrence risk, evaluation, management, and outcomes of arterial ischemic stroke in children and young adults.

Recent Findings: The risk for recurrence and mortality appear to be low for neonatal and childhood stroke. Most children have relatively mild deficits, but those who have greater neurologic deficits, poststroke epilepsy, or strokes early in life are at risk for lower overall cognitive function. Stroke recurrence and long-term mortality after stroke in young adults are greater than originally thought. Cognitive impairments, depression, and anxiety are associated with higher levels of poststroke unemployment and represent targets for improved poststroke care. Poststroke care in young adults involves more than medical management. Self-reported memory and executive function impairments may be more severe than what is detected by objective measures. Assessment of possible cognitive impairments and appropriate management of psychological comorbidities are key to maximizing the long-term functional outcome of stroke survivors.

Summary: Childhood and young adult stroke survivors survive for many more years than older patients with stroke. To ensure that these survivors maximize the productivity of their lives, neurologists must not only optimize medical management but also recognize that impairments in cognition and mood may be remediable barriers to long-term functional independence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/CON.0000000000000438DOI Listing
February 2017

Thrombocytopenia Pitfalls: Misdiagnosing Type 2B von Willebrand Disease as Ethylenediaminetetraacetic Acid-Dependent Pseudothrombocytopenia.

J Pediatr 2016 Aug 20;175:238-238.e1. Epub 2016 May 20.

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2016.04.077DOI Listing
August 2016

Molecular structural analysis of a novel and de-novo mutation in the SERPINC1 gene associated with type 1 antithrombin deficiency.

Br J Haematol 2017 05 21;177(4):654-656. Epub 2016 Apr 21.

Department of Pediatrics, Division of Hematology/Oncology, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.14090DOI Listing
May 2017

Impact of aerobic exercise on haemostatic indices in paediatric patients with haemophilia.

Thromb Haemost 2016 06 25;115(6):1120-8. Epub 2016 Feb 25.

Manuel Carcao, MD, MSc, Division of Haematology-Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON - M5G 1X8, Canada, Tel.: +1 416 813 5367, Fax: +1 416 813 5327, E-mail:

Unlabelled: This study investigated the impact of aerobic exercise on laboratory assessments of haemostatic activity in boys (5-18 years of age) with haemophilia A (HA) or B (HB), examining the hypothesis that laboratory coagulation parameters temporarily improve with exercise. Thirty subjects meeting eligibility criteria (19 HA; 11 HB; mean age: 12.8 years) were invited to participate. They underwent a replacement factor washout period and were advised against strenuous activity for three days prior to the planned intervention. At study visit, baseline blood samples were drawn prior to exercise on a stationary cycle ergometer, aiming to attain 3 minutes (min) of cycling at 85 % of predicted maximum heart rate. Blood work was repeated 5 min (t5) and 60 min (t60) post exercise completion. Samples were assessed for platelet count (PC), factor VIII activity (

Fviii: C), von Willebrand antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo) and platelet function analysis (PFA-100); maximum rate of thrombus generation (MRTG) in blood was measured via thromboelastography and plasma peak thrombin generation (PTG) via calibrated automated thrombography. Mean duration of exercise was 13.9 (± 2.6) min. On average, t5 samples showed significant elevation, relative to baseline in PC, FVIII:C, VWF:Ag, VWF:RCo and PTG, while

Fviii: C, VWF:Ag, VWF:RCo and MRTG were significantly elevated in t60 samples. Within the cohort, participants with severe HA showed no change in

Fviii: C levels with exercise. The greatest improvement in haemostatic indices was observed in post-adolescent males with mild-moderate HA, who thus represent the group most likely to benefit from a reduction of bleeding risk in the setting of exercise.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1160/TH15-09-0757DOI Listing
June 2016

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

Semin Thromb Hemost 2016 Feb 15;42(1):18-29. Epub 2016 Jan 15.

Division of Haematology/Oncology, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, Canada.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0035-1568877DOI Listing
February 2016

aPTT in children receiving UFH: time for a change?

Blood 2015 Oct;126(18):2075-6

NATIONWIDE CHILDREN'S HOSPITAL; THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2015-08-664037DOI Listing
October 2015