Anticoagulation In Children Research Articles

A Comparison of the Anticoagulation Efficacy and Safety of Epoprostenol to Heparin and Citrate in Children Receiving Continuous Renal Replacement Therapy

Introduction: Anticoagulants are used in continuous renal replacement therapy (CRRT) to prolong filter life. There are no prior investigations directly comparing epoprostenol to more commonly used forms of anticoagulation in children. Therefore, the primary aim of this study was to assess the efficacy and safety of epoprostenol as compared to heparin and citrate anticoagulation in a pediatric cohort. Methods: We performed a retrospective analysis of all patients <18 years of age admitted to an academic quaternary care children’s hospital from 2017–2022 who received epoprostenol, heparin, or citrate exclusively for CRRT anticoagulation. Efficacy was evaluated by comparing the hours to the first unintended filter change and the ratio of filters used to CRRT days. Safety was assessed by evaluating changes in platelet count and vasoactive-ionotropic score (VIS). Results: Of 101 patients, 44 received epoprostenol (43.6%), 38 received heparin (37.6%), and 19 received citrate (18.8%). The first filter change was more commonly planned in patients receiving anticoagulation with epoprostenol (43%) as compared to citrate (11%) or heparin (29%) (p = 0.034). Of those patients where the first filter change was unintended (n = 33), there were greater median hours until the filter was replaced in those receiving epoprostenol (29) when compared to citrate (21) (p = 0.002) or heparin (18) (p = 0.003). There was a smaller median ratio of filters used to days on therapy in the patients that received epoprostenol (0.53) when compared to citrate (1) (p = 0.003) or heparin (0.75) (p = 0.001). For those receiving epoprostenol, there was no significant decrease in platelet count when comparing values prior to CRRT initiation through 7 days of therapy. There was no significant difference in VIS when comparing values prior to CRRT initiation through the first 2 days of CRRT. Conclusions: Epoprostenol-based anticoagulation is effective when compared to other anticoagulation strategies used in pediatric CRRT with a favorable side effect profile.

Impact of inflammation and steroids on anti-coagulation in children supported on a ventricular assist device.

Critically ill pediatric patients supported on ventricular assist devices (VADs) are increasingly being anticoagulated on bivalirudin, but with difficulty monitoring anticoagulation. Activated partial thromboplastin time (aPTT) has recently been shown to poorly correlate with bivalirudin plasma concentrations, while dTT had excellent correlation. However, aPTT is the more common monitoring test and dTT testing is rarely used. In addition, effects of frequent clinical VAD scenarios (such as inflammation) on the accuracy of aPTT and dTT testing remains uncertain. We reviewed the effects of clinical scenarios (infection/inflammation, chylothorax, and steroids administration) on anticoagulation monitoring in 10 pediatric VAD patients less than 3years at Cincinnati Children's Hospital Medical Center from 10/27/2020 to 5/6/2022 using bivalirudin for anticoagulation. There were 16 inflammation/infection, 3 chylothorax, and 6 steroids events. Correlation between dTT and aPTT was significantly lower after infection/inflammation, with dTT increasing prior to inflammation/infection while aPTT remained unchanged. In addition, steroids are administered to VAD patients to reduce inflammation and thus additionally stabilize anticoagulation. However, this anticoagulation stabilization effect was reflected more accurately by dTT compared to aPTT. In children requiring VAD support utilizing bivalirudin anticoagulation, inflammation/infection is a common occurrence resulting in anticoagulation changes that may be more accurately reflected by dTT as opposed to aPTT.

Urokinase prophylactic anticoagulation in children with nephrotic syndrome: a multicenter retrospective cohort study

ObjectiveTo analyze the clinical effect of urokinase on the prevention of thrombosis in children with primary nephrotic syndrome.MethodsA total of 370 children diagnosed with primary nephrotic syndrome (PNS) in the Children’s Hospital of Soochow University and Zibo Maternal and Child Health Hospital from January 2018 to December 2022 were selected as the research objects. The patients were divided into a urokinase adjuvant therapy group and non-urokinase adjuvant therapy group according to the application of drugs. The clinical data of the children were collected, including sex, age, drug application, bleeding during treatment, and telephone follow-up, to record whether thromboembolism occurred in the acute stage and remission stage. The clinical pattern of PNS, renal biopsy, histopathological type, and related laboratory indexes before and after treatment were recorded.ResultsA total of 313 patients were treated with urokinase and 57 patients were not. More thrombotic events was observed in non-urokinase group compared to the urokinase group(2 versus 0 episodes, p = 0.02). The thrombotic events observed included one patient had pulmonary embolism combined with right ventricular thrombosis, and another had intracranial venous thrombosis. More minor bleeding events occurred in urokinase group compared to the non-urokinase group(7 versus 1 episodes, p = 1.0). No major bleeding events occurred in either group.ConclusionThe rational prophylactic use of urokinase anticoagulation in children with PNS can prevent the formation of thromboembolism and has good safety.

Real-world experience with edoxaban for anticoagulation in children at risk for coronary artery thrombosis.

Direct oral anticoagulants have the potential to improve care in children requiring chronic anticoagulation. Edoxaban has favourable pharmacokinetics that could benefit younger patients but data on long-term safety and efficacy for specific paediatric indications are lacking. We present a single-centre experience using edoxaban in children who require chronic anticoagulation for large coronary artery aneurysms secondary to Kawasaki disease. Weight-based dosing of once-daily oral edoxaban was offered as alternative to standard anticoagulation for patients aged 1-18 years. Chart review was performed for a median follow-up period of 49 months on edoxaban. Steady-state pharmacokinetics and pharmacodynamics of edoxaban were also explored. Sixteen patients on chronic therapy with edoxaban were included. No major bleeding events were reported. Two patients experienced coronary artery thrombosis after 23 and 38 months on edoxaban, 7 and 11 years after diagnosed with Kawasaki disease, respectively. This predicts 70% event-free rate at 12 years from diagnosis. Area under the curve estimates over the dosing interval of 24 hours were similar to those reported in adults. Edoxaban use is feasible and well-tolerated for long-term use in paediatric population. We suggest appropriate exposure using weight-based once-daily dosing strategy that may be comparable to standard-of-care anticoagulation in prevention of coronary artery thrombosis. Larger studies are needed to evaluate long-term safety and efficacy of edoxaban in this population.

A comparative study of the effects of citrate and heparin anticoagulation on coagulation function and efficacy in children with septic shock undergoing continuous blood purification

To compare the effects of citrate and heparin anticoagulation on coagulation function and efficacy in children with septic shock undergoing continuous blood purification (CBP), and to provide guidance for CBP anticoagulation in children with septic shock. A case control study was conducted. Thirty-seven children with septic shock admitted to the pediatric intensive care unit (PICU) of the First Affiliated Hospital of Gannan Medical University from July 2019 to September 2022 were enrolled as the research subjects. The patients were divided into citrate local anticoagulation group and heparin systemic anticoagulation group according to different anticoagulation methods. The baseline data, the level of coagulation indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), D-dimer] before treatment and 1 day after weaning from CBP, serum inflammatory mediators [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypersensitivity C-reactive protein (hs-CRP), procalcitonin (PCT)], bleeding complications during CBP and 7-day mortality were collected. A total of 37 cases were enrolled finally, including 17 cases with citric acid local anticoagulation and 20 cases with heparin systemic anticoagulation. There was no statistically significant difference in general data such as gender, age, and body weight of children between the two groups. There were no statistically significant differences in baseline levels of coagulation indicators and inflammatory mediators before treatment of children between the two groups. One day after weaning from CBP, both groups showed varying degrees of improvement in coagulation indicators compared with those before treatment. Compared with before treatment, the PT of the heparin systemic anticoagulation group was significantly shortened after 1 day of weaning (s: 11.82±2.05 vs. 13.64±2.54), APTT and TT were significantly prolonged [APTT (s): 51.54±12.69 vs. 35.53±10.79, TT (s): 21.95±4.74 vs. 19.30±3.33], D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 4.94±3.94), with statistically significant differences (all P < 0.05). While in the citrate local anticoagulation group, only APTT was significantly prolonged after treatment compared with that before treatment (s: 49.28±10.32 vs. 34.34±10.32, P < 0.05). There were no statistically significant differences in other coagulation indicators compared with before treatment. Compared with the citric acid local anticoagulation group, the PT of the heparin systemic anticoagulation group was significantly shortened after treatment (s: 11.82±2.05 vs. 13.61±3.05, P < 0.05), and the D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 3.77±2.38, P < 0.01). The levels of inflammatory mediators in both groups were significantly reduced 1 day after CBP weaning compared with those before treatment [citric acid local anticoagulation group: hs-CRP (mg/L) was 12.53±5.44 vs. 22.65±7.27, PCT (μg/L) was 1.86±1.20 vs. 3.30±2.34, IL-6 (ng/L) was 148.48±34.83 vs. 202.32±48.62, TNF-α (ng/L) was 21.38±7.71 vs. 55.14±15.07; heparin systemic anticoagulation group: hs-CRP (mg/L) was 11.82±4.93 vs. 21.62±8.35, PCT (μg/L) was 1.90±1.08 vs. 3.18±1.97, IL-6 (ng/L) was 143.81±33.41 vs. 194.02±46.89, TNF-α (ng/L) was 22.44±8.17 vs. 56.17±16.92, all P < 0.05]. However, there was no statistically significant difference between the two groups (all P > 0.05). There was no statistically significant difference in bleeding complication during CBP and 7-day mortality in children between the citrate local anticoagulation group and the heparin systemic anticoagulation group (5.9% vs. 30.0%, 17.6% vs. 20.0%, both P > 0.05). Heparin for systemic anticoagulation and regional citrate anticoagulation can significantly reduce the levels of IL-6, TNF-α, hs-CRP and PCT in children with septic shock, and relieve inflammatory storm. Compared with citric acid local anticoagulation, heparin systemic anticoagulation can shorten the PT and reduce the level of D-dimer in children with septic shock, which may benefit in the prevention and treatment of disseminated intravascular coagulation (DIC).

Novel blood product transfusion regimen to prevent clotting and citrate accumulation during continuous renal replacement therapy with regional citrate anticoagulation in children.

Introduce a novel protocol to prevent clotting and citrate accumulation (CA) from blood product transfusion (BPT) during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in children. We prospectively compared fresh frozen plasma (FFP) and platelet transfusions between the two BPT protocols, direct transfusion protocol (DTP) and partial replacement of citrate transfusion protocol (PRCTP), in terms of the risks of clotting, citric accumulation (CA), and hypocalcemia. For DTP, blood products were directly transfused without any adjustment to the original RCA-CRRT regimen. For PRCTP, the blood products were infused into the CRRT circulation near the sodium citrate infusion point, and the dosage of 4% sodium citrate was reduced depending on the dosage of sodium citrate in the blood products. Basic information and clinical data were recorded for all children. Heart rate, blood pressure, ionized calcium (iCa) and various pressure parameters were recorded before, during and after BPT, as well as coagulation indicators, electrolytes, and blood cell counts before and after BPT. Twenty-six children received 44 PRCTPs and 15 children received 20 DTPs. The two groups had similar in vitro ionized calcium (iCa) concentrations (PRCTP: 0.33 ± 0.06 mmol/L, DTP: 0.31 ± 0.04 mmol/L), total filter lifespan (PRCTP: 49.33 ± 18.58, DTP: 50.65 ± 13.57 h), and filter lifespan after BPT (PRCTP: 25.31 ± 13.87, DTP: 23.39 ± 11.34 h). There was no visible filter clotting during BPT in any of the two groups. The two groups had no significant differences in arterial pressure, venous pressure, and transmembrane pressure before, during, or after BPT. Neither treatment led to significant decreases in WBC, RBC, or hemoglobin. The platelet transfusion group and the FFP group each had no significant decrease in platelets, and no significant increases in PT, APTT, and D-dimer. The most clinically significant changes were in the DTP group, in which the ratio of total calcium to ionized calcium (T/iCa) increased from 2.06 ± 0.19 to 2.52 ± 0.35, the percentage of patients with T/iCa above 2.5 increased from 5.0% to 45%, and the level of in vivo iCa increased from 1.02 ± 0.11 to 1.06 ± 0.09 mmol/L (all p < 0.05). Changes in these three indicators were not significant in the PRCTP group. Neither protocol was associated with filter clotting during RCA-CRRT. However, PRCTP was superior to DTP because it did not increase the risk of CA and hypocalcemia.

Thromboprophylaxis for Coagulopathy Related to COVID-19 in Pediatrics: A Narrative Review.

In addition to harming the respiratory system, COVID-19 can affect multiple organs. Children may develop a specific complication of COVID-19 called multisystem inflammatory syndrome in children (MIS-C) which could influence the vascular system of children and cause multiple coagulopathies in the body. Information on the use of thromboprophylaxis in this condition was collected via the review of various articles. In general, different factors in immune system responses can trigger the initiation of thrombotic events. Studies have shown that starting anticoagulant prophylaxis, which contributes to decreased thrombotic events, is dependent on the patient's condition and D-dimer levels. However, further studies on pediatric populations are needed to establish the role of anticoagulants in children with this condition.

Efficacy and safety of direct oral anticoagulants in children in real clinical practice

Introduction. As well as standard anticoagulants, direct oral anticoagulants (DOAC) have been approved for treatment of thromboembolism in children, recently. Several clinical trials provide promising data on efficacy and safety of DOAC in children and young adults. But further studies aimed at evaluating the efficacy and safety of these drugs in children and adolescents are still needed.The aim of the study is to evaluate the safety and effectiveness of the use DOACs in children.Materials and methods. We have retrospectively analyzed the medical records of patients (0–17 years) of from 2013 to 2022 at our tertiary care Centre and selected patients, who were treated with apixaban, rivaroxaban or dabigatran for more than 14 days. Patients with arterial thrombosis, children, who were treated with combined anticoagulant therapy and those who were unable for follow-up were excluded. We assessed the rates of bleeding and recurrent venous thromboembolism (VTE).Results. There were 67 patients, who were treated with DOAC in our center. Patients were divided into 2 groups: those, who received prophylactic anticoagulation (group 1 – 6 patients), and patients, who received DOAC therapy after venous thromboembolism (group 2 – 61 patients). The median follow-up time was 46 (25–365) days in the group 1, and 4 months (2 weeks – 36 month) in the group 2. There were no VTE episodes and 1 minor bleeding in group 1, while 1 (2 %) major, 4 (6 %) minor bleeding episodes in group 2. There were 4 (6 %) patients with recurrent VTE in group 2.Conclusion. The majority of patients in this study received rivaroxaban (79 %). We found a moderately increased recurrence rate of VTE, which could be the result of a long follow-up period, and a comparable rate of bleeding, all of which were associated with rivaroxaban therapy. In the future, of particular interest, in our opinion, are prospective studies of DOACs as primary antithrombotic prophylaxis, as well as secondary prophylaxis in the highest-risk groups, and the results of an analysis of their use in real clinical practice.

Epidemiology of anticoagulation for children supported by extracorporeal membrane oxygenation in the United States: A Pediatric Hospital Information System database study.

Due to the risk of thrombosis, nearly all children supported by extracorporeal membrane oxygenation (ECMO) receive systemic anticoagulation. While heparin has traditionally been used, there are reports of increased use of direct thrombin inhibitors. We sought to describe the use of anticoagulation in children supported by ECMO in the United States using a large administrative database. We performed a retrospective cohort study of children supported by ECMO within the Pediatric Health Information System (PHIS) database. Pediatric encounters involving ECMO from 2012 to 2020 were identified. Data regarding demographics, diagnoses, anticoagulation, complications, and outcomes were extracted for eligible encounters. Eleven thousand five hundred ninety-five encounters that involved ECMO were identified. Fifty-four percent were male with an age range of 0-17years and a median (IQR) age of 0 (0-2) years. Unfractionated heparin (UFH) only was used in 94% (95% CI: 93.6-94.5%) of encounters and UFH followed by bivalirudin in 5% (95% CI: 4.3-5.1%) of cases. There was a significant difference in the use of bivalirudin from 2012 to 2020 (p < 0.001). Differences in anticoagulation regimens were observed between infants and children (p = 0.004) and between those with and without cardiac indications for ECMO (p < 0.001). Four percent (95% CI: 4.1-4.8%) of encounters were associated with diagnostic coding for thrombosis and differences in occurrence of thrombosis were observed between different anticoagulant regimens (p < 0.001). Though the majority of children on ECMO in the United States receive heparin anticoagulation, there is an increase in use of direct thrombin inhibitors. Prospective studies must evaluate the efficacy of different anticoagulants in this patient population.

Pharmacokinetics of a microdosed cocktail of three direct oral anticoagulants in children with congenital heart defects: study protocol for a single-centre clinical trial (DOAC-Child)

IntroductionDirect oral anticoagulants (DOACs) are direct inhibitors of coagulation factor Xa and are frequently used in adults for different indications such as deep vein thrombosis or non-valvular atrial fibrillation. Paediatric...

Anticoagulation Use for Secondary Prophylaxis Against Recurrent Venous Thromboembolism in Hospitalized Children: A Report from the Children's Hospital-Acquired Thrombosis (CHAT) Consortium

Introduction: Most venous thromboembolism (VTE) in children are provoked and have an overall low risk for recurrence, especially if the original provoking factor is mitigated. Nonetheless, certain factors heighten VTE recurrence risk, including hospitalization. In fact, the rate of VTE in hospitalized children has increased more than 200% since 20011. This staggering discovery emphasizes the dire need for more effective tactics aimed at VTE prevention. Historically, pediatric providers have been hesitant to initiate pharmacologic (i.e. anticoagulant) measures in children for a number of reasons. In our recent survey of practice patterns of secondary prevention against recurrent VTE in pediatrics, we found low use (<25%) of pharmacologic prophylaxis in high-risk children2. Additionally, most respondents did not feel comfortable initiating secondary pharmacologic prophylaxis in younger children2. In the wake of the COVID-19 pandemic, numerous trials have been conducted to evaluate anticoagulation for VTE prevention in affected individuals. The recently published COVID-19 Anticoagulation in Children- Thromboprophylaxis trial showed safety of low-dose enoxaparin in children hospitalized with COVID-19 or multisystem inflammatory syndrome in children (MIS-C)3. Furthermore, trials of direct oral anticoagulants have also shown safety and efficacy in secondary VTE prevention in children4. Importantly, these studies have consistently demonstrated low rates of bleeding. Methods: The CHAT Registry is an IRB-approved registry that captures clinical data on hospital-acquired VTE in children <21 years of age and non-VTE controls. Subjects were enrolled from 2012-2021 across 8 participating pediatric hospitals. Using this REDCap database, we performed a retrospective study of enrolled subjects to explore trends for secondary anticoagulation prophylaxis use in hospitalized children. Subjects (cases and controls) were included if they had a history of VTE. Descriptive statistics were used to analyze demographics/characteristics and VTE prophylaxis measures. Results: Fifty-two subjects (%) out of 2219 total CHAT subjects (1273 cases, 946 controls) reviewed had a prior history of VTE. Characteristics of these subjects are presented in Table 1. The mean age was 9.6 years with a slight male predominance (54%). Regarding VTE prophylaxis (Figure 1), 18 (35%) received VTE prophylaxis (mechanical and/or pharmacologic) during hospitalization. Of these, 11 subjects (61%) were prescribed pharmacologic prophylaxis either alone (8) or in combination with mechanical prophylaxis (3). The remaining seven (39%) received only mechanical prophylaxis. Four subjects were already on anticoagulation at the time of admission. Forty-four (85%) subjects experienced a hospital-acquired VTE recurrence. Only 16 (36%) of these had received some method of VTE prophylaxis. Of those who did not receive pharmacologic prophylaxis, only 3 had a documented contraindication. The most commonly documented contraindications to pharmacologic prophylaxis pertained to risk of bleeding, and included uncorrected coagulopathy, ongoing/uncontrolled hemorrhage and thrombocytopenia. The median time between admission and VTE event was 9 days. Conclusion: There is a high rate of recurrent VTE in hospitalized children with a history of prior VTE. These results underscore the significance of implementing consistent pharmacologic prophylaxis in high-risk children where appropriate. As the landscape is actively changing in terms of available anticoagulant formulations available for children, providers may feel more confident in initiating secondary pharmacologic prophylaxis particularly as new data confirm the safety. Nevertheless, ongoing definitive studies are required to better understand which particular factors yield the highest rates of VTE and hence warrant pharmacologic prophylaxis above standard mechanical measures. We want to acknowledge the CHAT Consortium sites who contributed to the CHAT Registry. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Edoxaban for Thromboembolism Prevention in Pediatric Patients With Cardiac Disease

BackgroundStandard of care (SOC) anticoagulation for thromboembolism (TE) prevention in children with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exists for alternate use of direct oral anticoagulants in children. ObjectivesThe investigators aimed to obtain safety and efficacy data for edoxaban in children. MethodsWe performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients <18 years of age with cardiac disease (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease] trial). Patients were randomized 2:1 to age- and weight-based oral edoxaban once daily vs SOC for 3 months (main study period), stratified by cardiac diagnosis. Both groups could continue in an open-label edoxaban extension arm through 1 year. The primary endpoint was adjudicated clinically relevant bleeding (CRB). The main secondary endpoint was symptomatic TE or asymptomatic intracardiac thrombosis. ResultsThe modified intention-to-treat cohort included 167 children. One patient per group experienced a nonmajor CRB in the main period. Treatment-emergent adverse events occurred in 46.8% (51 of 109) with edoxaban and 41.4% (24 of 58) with SOC. One SOC patient experienced 2 TE events (DVT with PE). Among 147 children in the extension, 1 CRB event (0.7%) and 4 TEs occurred (2.8%; 2 strokes and 2 of 33 Kawasaki disease patients with coronary artery thromboses and/or myocardial infarctions). ConclusionsEdoxaban is a potential alternative mode of thromboprophylaxis in children with cardiac disease showing low rates of CRB and TEs with advantages of once daily dosing and infrequent monitoring requirement. (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots] (Thrombotic Events) in Children at Risk Because of Cardiac Disease trial; NCT03395639).

Results of an international survey on adherence with anticoagulation in children, adolescents, and young adults: Communication from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis

BackgroundThe ISTH Scientific and Standardization Committee (SSC) Subcommittee on Pediatric/Neonatal Thrombosis and Hemostasis convened a working group on medication adherence to begin to understand the current state of clinical practice to inform priority areas for efforts to improve adherence for children, and adolescents and young adults (AYA) prescribed anticoagulants. ObjectivesWe sought to survey an international group of clinicians involved in anticoagulation management in children and/or AYA about perceptions of medication on health outcomes, clinical practice related to medication adherence, and barriers to assessing and improving medication adherence. MethodsClinicians involved in anticoagulation management in children and/or AYA were surveyed via REDCap®. Descriptive statistics were used to summarize demographic and clinical characteristics and responses to multiple choice and Likert‐type questions. Free‐text answers were coded based on the Behaviour Change Technique Taxonomy and the Expert Recommendations for Implement Change project. Results and ConclusionsThere were 200 participants, 90% of whom were pediatric hematology/oncology physicians. Based on the results, which demonstrate that clinicians are concerned about impact of poor medication adherence and have limited resources to identify and improve adherence, the working group has identified next steps to further understand impact of medication adherence on anticoagulation‐related health outcomes, address the need for validated measures to assess medication adherence for all anticoagulants prescribed to this population, and develop an intervention and implementation research agenda to improve outcomes.

P1720: HOW TO IMPROVE THE TIME IN THERAPEUTIC RANGE (TTR) OF ANTICOAGULATED CHILDREN DURING THE COVID-19 PANDEMIC: TELECONTROL VERSUS TRADITIONAL HOSPITAL CONTROL

Background: The Covid-19 pandemic generated added difficulty in carrying out oral anticoagulation controls in children, due to limited travel to health centers for the mobility restrictions. Children there is greater difficulty in maintaining adequate coagulation times, measured in times in therapeutic range (TTR) due to the significant individual variability in anticoagulant medication that can cause thrombotic or hemorrhagic complications. We proposed carrying out controls at home telematically as an alternative to traditional hospital controls, avoiding travel during the pandemic and evaluating the safety of the results and the quality of life (QoL) Aims: To assess the efficacy of remote control in children with chronic oral anticoagulation compared to patients with hospital control based on the analysis of TTR during covid-19 pandemic as well as QoL Methods: Observational and longitudinal study comparing 2 cohorts: remote control group and hospital control group. During 2020, the patients were included in the remote control group in accordance with the usual clinical practice, keeping in hospital control those children who had to follow specific treatments in the hospital (cancer treatments). Classified the patients according INR ranges and age: 3 groups INR ranges established (1.8-2.2; 2.2-2.5 and 2.5-3) according to medical criteria and 3 age groups (0-6 yrs, 7-12 yrs, and 13-16 yrs). In January 2021, TTR data defined in both groups were collected according to Rosendaal’s methodology. Given the complexity of the TTR due to the pharmacokinetic variability of the antivitamin K drugs, which means that the specific determination in one day does not correspond to the INR values ​​that the patient will present on the days between the controls, we calculated the TTR of each patient by the fraction (number of INR in therapeutic range/total number of INR). We distributed patients into 4 groups: Group A: patients with less than 25% TTR. Group B: patients who have been between 25%-50% of TTR. Group C: patients who have been between 50%-75% of TTR. Group D:patients who have more 75% of TTR Results: 44 patients were included: 23 remotely controlled (mean age 8.4 yrs) vs. 21 hospitalized (mean age 9.1). Reasons for anticoagulation: surgery, catheters, cancer, heart disease and vasculitis. Controls outside the therapeutic range were on average higher in the hospital group (15.1 vs 3.3), maintaining these differences for all ages and INR ranges. 91% children in remote control spend more than 75% in TTR compared to 13% of the hospital group, being significant in children older than 7 years, with INR 2.2-2.5 and with catheters or heart disease. 5 children in the remote-control group with 100% of their determinations in TTR. 16 bleeding events were documented, 12 in hospital group(4 major bleedings)and 4 bleedings (all minor) in remote control. 15 thrombotic events (14 hospital control vs 1 in remote control). 81 doses of low molecular weight heparin (LMWH) and 31 doses of vitamin K (VK) were administered to hospital control children vs. 15 doses of LMWH and 6 vials VK to remote control children Summary/Conclusion: Remote control of anticoagulation in children is an effective and safe alternative to traditional hospital control, with very high TTR results. Using this type of control to avoid travel during mobility restrictions due to the covid-19 pandemic led to improved results, with fewer emergency visits related to anticoagulation, with a lower rate of bleeding or thrombotic complications, and less need for LMWH support. or VK compared with children with hospital control

Bivalirudin or Unfractionated Heparin for Anticoagulation in Pediatric Patients on Continuous Flow Ventricular Assist Device Support: Single-Center Retrospective Cohort Study

Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited. Retrospective cohort study. Single tertiary-quaternary referral center. All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020. Not applicable. Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09-0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47-13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a "washout" in eight cases with concern for pump thrombosis-six had resolution of the pump thrombosis, while two needed pump exchange. Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin "washout" was successful in medical management of six of eight cases of possible pump thrombosis.

Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation in Children with Liver Dysfunction/Failure.

Regional citrate anticoagulation (RCA) is an option but citrate accumulation is risk and it is a giving up cause for this situation. This retrospective study was conducted in the pediatric intensive care unit (PICU) between May 2019 and April 2021. We investigated 47 patients with liver failure (LF) in our PICU, and RCA during continuous renal replacement therapy (CRRT) was applied to 10 (21.3%) of them. Half of them were male (n: 5/10), their mean age was 104.7 ± 66.20 months. Nine of them needed vasoactive support during follow-up. The most common indication for CRRT was hepatorenal syndrome (40%). There was no significant difference between liver transaminases and liver function tests before and after CRRT (p > 0.05). In terms of citrate toxicity of the patients, there was no significant difference between total calcium/ionized calcium, lactate level, pH and bicarbonate values before and after CRRT (p > 0.05). The mean total CRRT time was 110.2 ± 118.2 h, and the mean circuit lifespan was 43.8 ± 48.7 h; the mean number of circuits was 2.7 ± 2.4. Total Ca/ionized Ca >2.5 was a clinically relevant endpoint, but no patient interrupted dialysis for this cause. There was no complication about RCA. This study did not observe any adverse effects on acid-base status, transaminases, an increase in bilirubin during RCA-CRRT treatment in pediatric patients with LF. Total calcium/ionized calcium ratio, serum lactate level and prothrombin time level should be closely monitored daily in terms of citrate accumulation in this patient group.

Practical Considerations for Use of Direct Oral Anticoagulants in Children.

Direct oral anticoagulants (DOACs) provide an attractive alternative for the management and prevention of thrombosis in pediatric patients. With multiple ongoing and published pediatric trials and recent regulatory approval of dabigatran and rivaroxaban, the landscape of pediatric anticoagulation is rapidly changing. However, as pediatricians gain experience with these drugs, it is important to be mindful of pediatric-specific considerations that may limit the use of DOACs in certain children and adolescents. While there is increasing adult data and experience, there is a paucity of real-world evidence to guide the use of these drugs in children who would not have met clinical trial inclusion criteria. In this mini review, we summarize pediatric specific data, areas for future research, and practical considerations for the use of DOACs in children and adolescents.

Secondary thrombosis prevention practice patterns in pediatrics: Results of an international survey

BackgroundPediatric venous thromboembolism (VTE) rates continue to increase. Although most children present with transient provoking factors, some have persistent prothrombotic risks beyond the initial treatment period warranting secondary anticoagulation. Current pediatric VTE guidelines provide limited recommendations in this regard. ObjectivesOur primary objective was to identify key influences on pediatric thrombosis physicians’ decisions to initiate secondary anticoagulation. MethodsWe targeted pediatric hematologists/oncologists internationally using Duration of Therapy for Thrombosis in Children, Children’s Hospital Acquired Thrombosis consortium, and Venous Thromboembolism Network US pediatric subgroup membership rosters, who self‐identified as primary outpatient thrombosis providers. Of 124 total surveys distributed, 61 complete surveys were evaluable. We defined secondary anticoagulation as anticoagulant use beyond the initial treatment period, on a daily basis (extended) or limited to periods of superimposed clinical risk factors (episodic). ResultsPediatric thrombosis physicians surveyed indicated that they prescribe secondary anticoagulation in <25% of children despite persistent risks. Among those who indicated use of secondary anticoagulation, the preferred modality was extended anticoagulation in children with a history of recurrent unprovoked VTE (98%), chronic central venous catheter (74%), and potent thrombophilia (73%). Episodic anticoagulation was preferred in children with a history of mild thrombophilia (54%). Respondents were more likely to prescribe secondary anticoagulation for adolescents as opposed to children <12 years old. ConclusionsAmong pediatric thrombosis physicians surveyed, they perceived the prevalence of persistent prothrombotic risks to be high in children who have completed a course of anticoagulation for provoked VTE; however, estimated use of secondary anticoagulation was low. Studies involving real‐world data are needed to further evaluate use of secondary anticoagulation in this setting.

Anticoagulation in Pediatric Patients.

Special aspects of anticoagulation in children include the different epidemiology of thrombosis, developmental changes in the coagulation system, age-dependent pharmacokinetics of anticoagulants, risk of bleeding, and practical hurdles to anticoagulation. The classical anticoagulants so far used in children have several limitations, resulting in the need for regular monitoring. The pharmacological properties of direct oral anticoagulants (DOACs) and the special challenges of anticoagulation in children make the DOACs particularly attractive for children. All DOACs have pediatric development programs, targeting various indications for prevention and treatment of thrombosis. Child-appropriate formulations have been developed, age-specific dosing information generated, and safety and efficacy evaluated in ongoing phase 3 trials. Rivaroxaban and dabigatran have already been authorized for children for treatment of acute venous thrombosis and for extended secondary prevention. Their safety and efficacy have been demonstrated comparable to that of standard-of-care anticoagulants, without need for monitoring. Further studies are ongoing, which are expected to lead to pediatric authorizations of DOACs for primary venous thromboembolic event prevention in some high-risk settings. More real-life data will be necessary from postmarketing studies and registries to complement the evidence base for DOAC use in children, particularly in the youngest age groups and special disease populations.

Ontogeny of Pediatric Pharmacogenetics: Celebrating the Past and Vision for the Future.

Ontogeny of Pediatric Pharmacogenetics: Celebrating the Past and Vision for the Future.