Just DOAC: Use of direct-acting oral anticoagulants in pediatrics
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Purpose: The aim of this article is to provide an overview of the current literature for direct-acting oral anticoagulant (DOAC) use in pediatric patients and summarize ongoing trials.
Summary: In treatment of venous thromboembolism (VTE) in pediatric patients, evidence supports use of both dabigatran and rivaroxaban. Dabigatran has been shown to be noninferior to standard of care (SOC) in terms of efficacy, with similar bleeding rates. Similarly, treatment with rivaroxaban in children with acute VTE resulted in a low recurrence risk and reduced thrombotic burden, without increased risk of bleeding, compared to SOC. Treatment of pediatric cerebral venous thrombosis as well as central venous catheter-related VTE with rivaroxaban appeared to be both safe and efficacious and similar to that with SOC. Dabigatran also has a favorable safety profile for prevention of VTE, and rivaroxaban has a favorable safety profile for VTE prevention in children with congenital heart disease. Many studies with several different DOACs are ongoing to evaluate both safety and efficacy in unique patient populations, as well as VTE prevention.
Conclusion: The literature regarding pediatric VTE treatment and prophylaxis is growing, but the need for evidence-based pediatric guidelines remains. Additional long-term, postauthorization studies are warranted to further elucidate safety and efficacy in clinical scenarios excluded in clinical trials. Additional data on safety, efficacy, and dosing strategies for reversal agents are also necessary, especially as the use of DOACs becomes more common in the pediatric population.
Kimberly Mills
Carolyn Hill
Morgan King
Jennifer L Pauley
M Petrea Cober
Norman E Fenn
Nicole E Omecene
Tara Smith
Caroline Sierra
Am J Health Syst Pharm
. 2023 Jan 5;zxac387. doi: 10.1093/ajhp/zxac387. Online ahead of print.
2023
English
Risk of venous thromboembolism in pediatric hospitalized patients undergoing noncardiac surgery: A report from the Children's Hospital-Acquired Thrombosis consortium
Background: Surgery is a known risk factor for hospital-acquired venous thromboembolism (HA-VTE) in children.
Objectives: To assess whether the odds of HA-VTE differs across six anatomic sites of noncardiac surgery and to identify risk factors for HA-VTE in these children.
Methods: This was a multicenter, case-control study. Anatomic sites of surgery and risk factors for HA-VTE were collected on hospitalized pediatric patients who had undergone a single noncardiac surgery and developed HA-VTE (cases), and those who did not develop HA-VTE (controls), via the Children's Hospital-Acquired Thrombosis (CHAT) Registry. Logistic regression estimated the odds ratio (OR) and 95% confidence intervals (CIs) between six anatomic sites of surgery and 16 putative HA-VTE risk factors. Variables with a p value of 0.10 or less in unadjusted analyses were included in adjusted models for further evaluation. The final model used backward selection, with a significance level of 0.05.
Results: From January 2012 to March 2020, 163 cases (median age, 5.7 years; interquartile range [IQR], 0.3-14.2) and 208 controls (median age of 7.5 years; IQR, 3.7-12.9) met our criteria. There was no statistically significant increased odds of VTE among the types of noncardiac surgery. In the final adjusted model, central venous catheter (CVC; OR, 14.69; 95% CI, 7.06-30.55), intensive care unit (ICU) stay (OR, 5.31; 95% CI, 2.53-11.16), and hospitalization in the month preceding surgery (OR, 2.75; 95% CI, 1.24-6.13) were each independently significant risk factors for HA-VTE.
Conclusion: In children undergoing noncardiac surgery, placement of CVCs, admission/transfer to the ICU, or hospitalization in the month prior to surgery were positively associated with HA-VTE.
Elizabeth T Stephens
Anh Thy H Nguyen
Julie Jaffray
Brian Branchford
Ernest K Amankwah
Neil A Goldenberg
E Vincent S Faustino
Neil A Zakai
Amy Stillings
Emily Krava
Guy Young
John H Fargo
Res Pract Thromb Haemost
. 2022 Oct 13;6(7):e12810. doi: 10.1002/rth2.12810. eCollection 2022 Oct.
2022
English
TSP-1 (thrombospondin-1) deficiency protects APOE(-/-) mice against leptin-induced atherosclerosis.
atherosclerosis; leptin; obesity; smooth muscle; thrombospondins
OBJECTIVE: Hyperleptinemia, hallmark of obesity, is a putative pathophysiologic trigger for atherosclerosis. We previously reported a stimulatory effect of leptin on TSP-1 (thrombospondin-1) expression, a proatherogenic matricellular protein implicated in atherogenesis. However, a causal role of TSP-1 in leptin-driven atherosclerosis remains unknown. Approach and Results: Seventeen-weeks-old ApoE(-/-) and TSP-1(-/-)/ApoE(-/-) double knockout mice, on normocholesterolemic diet, were treated with or without murine recombinant leptin (5 µg/g bwt, IP) once daily for 3 weeks. Using aortic root morphometry and en face lesion assay, we found that TSP-1 deletion abrogated leptin-stimulated lipid-filled lesion burden, plaque area, and collagen accumulation in aortic roots of ApoE(-/-) mice, shown via Oil red O, hematoxylin and eosin, and Masson trichrome staining, respectively. Immunofluorescence microscopy of aortic roots showed that TSP-1 deficiency blocked leptin-induced inflammatory and smooth muscle cell abundance as well as cellular proliferation in ApoE(-/-) mice. Moreover, these effects were concomitant to changes in VLDL (very low-density lipoprotein)-triglyceride and HDL (high-density lipoprotein)-cholesterol levels. Immunoblotting further revealed reduced vimentin and pCREB accompanied with augmented smooth muscle-myosin heavy chain expression in aortic vessels of leptin-treated double knockout versus leptin-treated ApoE(-/-); also confirmed in aortic smooth muscle cells from the mice genotypes, incubated ± leptin in vitro. Finally, TSP-1 deletion impeded plaque burden in leptin-treated ApoE(-/-) on western diet, independent of plasma lipid alterations. CONCLUSIONS: The present study provides evidence for a protective effect of TSP-1 deletion on leptin-stimulated atherogenesis. Our findings suggest a regulatory role of TSP-1 on leptin-induced vascular smooth muscle cell phenotypic transition and inflammatory lesion invasion. Collectively, these results underscore TSP-1 as a potential target of leptin-induced vasculopathy.
Ganguly R; Khanal S; Mathias A; Gupta S; Lallo J; Sahu S; Ohanyan VA; Patel A; Storm K; Datta S; Raman P
Arteriosclerosis, Thrombosis, and Vascular Biology
2020
2020-12-17
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1161/ATVBAHA.120.314962" target="_blank" rel="noreferrer noopener">10.1161/ATVBAHA.120.314962</a>
Step by Step: Advancing the Understanding of Local Vascular Control.
Editorials; vasodilation; hypoxia; dilation; endothelium; arterial pressure
Chilian William M; Yin Liya; Ohanyan Vahagn
Arteriosclerosis, thrombosis, and vascular biology
2020
2020-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1161/ATVBAHA.120.313811" target="_blank" rel="noreferrer noopener">10.1161/ATVBAHA.120.313811</a>
Hepatic Forkhead Box Protein A3 Regulates ApoA-I (Apolipoprotein A-I) Expression, Cholesterol Efflux, and Atherogenesis
activation; Atherosclerosis; Cardiovascular System & Cardiology; cholesterol efflux; fatty-acids; FOXA3; FOXA3; gene; Hematology; high-density-lipoprotein; increased; Liver; Macrophages; mice lacking; nuclear factor 3-gamma; transport
OBJECTIVE: To determine the role of hepatic FOXA3 (forkhead box A3) in lipid metabolism and atherosclerosis. Approach and Results: Hepatic FOXA3 expression was reduced in diabetic or high fat diet-fed mice or patients with nonalcoholic steatohepatitis. We then used adenoviruses to overexpress or knock down hepatic FOXA3 expression. Overexpression of FOXA3 in the liver increased hepatic ApoA-I (apolipoprotein A-I) expression, plasma HDL-C (high-density lipoprotein cholesterol) level, macrophage cholesterol efflux, and macrophage reverse cholesterol transport. In contrast, knockdown of hepatic FOXA3 expression had opposite effects. We further showed that FOXA3 directly bound to the promoter of the Apoa1 gene to regulate its transcription. Finally, AAV8 (adeno-associated virus serotype 8)-mediated overexpression of human FOXA3 in the hepatocytes of Apoe-/- (apolipoprotein E-deficient) mice raised plasma HDL-C levels and significantly reduced atherosclerotic lesions. CONCLUSIONS: Hepatocyte FOXA3 protects against atherosclerosis by inducing ApoA-I and macrophage reverse cholesterol transport.
Li Yuanyuan; Xu Yanyong; Jadhav Kavita; Zhu Yingdong; Yin Liya; Zhang Yanqiao
Arteriosclerosis, Thrombosis, and Vascular Biology
2019
2019-08
<a href="http://doi.org/10.1161/ATVBAHA.119.312610" target="_blank" rel="noreferrer noopener">10.1161/ATVBAHA.119.312610</a>
Safe Readministration of Intravenous Thrombolysis in Recurrent Basilar Thrombosis.
Aged; Basilar Artery; Basilar Artery – Drug Effects; Basilar Artery – Physiopathology; Basilar Artery/diagnostic imaging/*drug effects/physiopathology; Cerebral Angiography – Methods; Cerebral Angiography/methods; Computed Tomography Angiography; Drug Administration Schedule; Fibrinolytic Agents – Administration and Dosage; Fibrinolytic Agents – Adverse Effects; Fibrinolytic Agents/*administration & dosage/adverse effects; Humans; Infusions; Intracranial Thrombosis; Intracranial Thrombosis – Drug Therapy; Intracranial Thrombosis – Physiopathology; Intracranial Thrombosis/diagnostic imaging/*drug therapy/physiopathology; Intravenous; Magnetic Resonance Imaging; Male; medication safety; Recombinant Proteins – Administration and Dosage; Recombinant Proteins/administration & dosage; Recurrence; recurrent stroke; Repeat Procedures; Retreatment; thrombolysis; Thrombolytic Therapy – Adverse Effects; Thrombolytic Therapy – Methods; Thrombolytic Therapy/adverse effects/*methods; Thrombosis; Time Factors; Tissue Plasminogen Activator – Administration and Dosage; Tissue Plasminogen Activator – Adverse Effects; Tissue Plasminogen Activator/*administration & dosage/adverse effects; Treatment Outcome; Treatment Outcomes
We report a patient who had recurrence of stroke in the basilar artery territory because of repeat thrombosis, and was administered intravenous recombinant tissue plasminogen activator (IV-rtPA) twice within a span of 3 weeks without any adverse events, with radiological evidence of successful thrombolysis. Because of minor and improving stroke symptoms with IV-rtPA, endovascular therapy was not performed and there was radiological evidence of recanalization with IV-rtPA alone. This report adds to the very limited literature on the topic demonstrating safe and successful use of repeat IV thrombolysis following a previous recent stroke.
Khan Alina; Itrat Ahmed
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
2018
2018-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jstrokecerebrovasdis.2017.09.066" target="_blank" rel="noreferrer noopener">10.1016/j.jstrokecerebrovasdis.2017.09.066</a>
Cardiovascular Effects of Exposure to Cigarette Smoke and Electronic Cigarettes: Clinical Perspectives From the Prevention of Cardiovascular Disease Section Leadership Council and Early Career Councils of the American College of Cardiology.
atherogenesis; Cardiovascular Diseases – Etiology; Cardiovascular Diseases/*etiology; Electronic Cigarettes – Adverse Effects; Electronic Nicotine Delivery Systems/*adverse effects; Epigenesis; Genes; Genetic; genetic and epigenetic effects; Humans; Impact of Events Scale; Scales; smoke-free legislation; Smoking – Complications; Smoking – Legislation and Jurisprudence – United States; Smoking Cessation; Smoking/*adverse effects/legislation & jurisprudence; thrombosis; tobacco cessation; United States
Cardiovascular morbidity and mortality as a result of inhaled tobacco products continues to be a global healthcare crisis, particularly in low- and middle-income nations lacking the infrastructure to develop and implement effective public health policies limiting tobacco use. Following initiation of public awareness campaigns 50 years ago in the United States, considerable success has been achieved in reducing the prevalence of cigarette smoking and exposure to secondhand smoke. However, there has been a slowing of cessation rates in the United States during recent years, possibly caused by high residual addiction or fatigue from cessation messaging. Furthermore, tobacco products have continued to evolve faster than the scientific understanding of their biological effects. This review considers selected updates on the genetics and epigenetics of smoking behavior and associated cardiovascular risk, mechanisms of atherogenesis and thrombosis, clinical effects of smoking and benefits of cessation, and potential impact of electronic cigarettes on cardiovascular health.
Morris Pamela B; Ference Brian A; Jahangir Eiman; Feldman Dmitriy N; Ryan John J; Bahrami Hossein; El-Chami Mikhael F; Bhakta Shyam; Winchester David E; Al-Mallah Mouaz H; Sanchez Shields Monica; Deedwania Prakash; Mehta Laxmi S; Phan Binh An P; Benowitz Neal L
Journal of the American College of Cardiology
2015
2015-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jacc.2015.07.037" target="_blank" rel="noreferrer noopener">10.1016/j.jacc.2015.07.037</a>