1 Venous Thromboembolism Prophylaxis – Pediatric – Inpatient Consensus Care Guideline Note: Active Table of Contents – Click each header below to jump to the section of interest Table of Contents INTRODUCTION ................................................................................................................................... 3 SCOPE .................................................................................................................................................. 3 RECOMMENDATIONS........................................................................................................................... 3 METHODOLOGY ................................................................................................................................... 8 COLLATERAL TOOLS & RESOURCES ..................................................................................................... 10 APPENDIX A. PEDIATRIC VTE PROPHYLAXIS RISK FACTORS AND ASSESSMENT ................................... 11 REFERENCES ....................................................................................................................................... 13 Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 2 Content Expert: Monica Bogenschutz, PharmD – Pharmacy mbogenschutz@uwhealth.org Contact for Changes: Anne Rose, PharmD – Pharmacy arose@uwhealth.org Guideline Author: Yafang Cheng, PharmD Workgroup Members: Jessica Bergsbaken, PharmD – Pharmacy Monica Bogenschutz, PharmD – Pharmacy Ashton Nell, BSN, RN, CCRN – Nursing Erin Robinson, PharmD – Pharmacy Anne Rose, PharmD – Pharmacy Allison Samuel, PharmD – Pharmacy Jessica Stafford Draper, APNP – Pediatric Trauma Joshua Vanderloo, PharmD – Pharmacy Reviewers: Christina Amend, MD – Pediatric Hematology/Oncology Sarah Mc Dermott, DO, MBS – Pediatric Hematology/Oncology Michael Wilhelm, MD – Pediatric Intensive Care Unit Committee Approvals: Inpatient Anticoagulation Subcommittee: April 2023 Pharmacy & Therapeutics Committee: April 2023 Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 3 Introduction Venous thromboembolism (VTE) is a life-threatening condition associated with increased morbidity, mortality, duration of hospital stay, and health care expenditures.1 In the pediatric population, VTE is increasingly being recognized as a complication of contemporary health care.2 The estimated annual incidence of VTE among hospitalized pediatric patients is upwards of 60 events per 10,000 admissions and has been increasing over time. Infants are at the greatest risk of thromboembolism, with a second peak in incidence noted during adolescence. Although VTE is far less common in children than adults, several underlying factors place children at risk for developing VTE. One of the greatest risks for VTE in children is the insertion of central venous catheters, which is common in the inpatient setting. Other acquired conditions frequently associated with VTE in children include infection, trauma, surgery, and immobility. There is no standardized and validated thromboprophylaxis risk tool established in the pediatric population. This guideline provides recommendations on the evaluation of both risk of VTE and risk of bleeding in pediatric patients based on identified risk factors, as well as appropriate VTE prophylaxis modalities if applicable. Scope Intended Users: Physicians, advanced practice providers, pharmacists, and nurses who provide care to hospitalized pediatric patients Objective: To provide recommendations and guidance for the prevention of VTE in hospitalized pediatric patients. Target Population: Any pediatric patient admitted to the hospital who is 6 months of age or older. The recommendations for pharmacologic strategies used to prevent VTE would apply to pediatric patients receiving unfractionated heparin (UFH), low molecular weight heparin (LMWH), or a direct oral anticoagulant (DOAC). Patients younger than 6 months of age are excluded from this guideline due to insufficient data to describe screening for VTE and prophylactic anticoagulation use in this population. This guideline is not intended to provide recommendations for the treatment of VTE. Recommendations 1. Prevention of VTE in hospitalized pediatric patients3 1.1 All hospitalized patients 6 months of age or older should be evaluated for both bleeding and VTE risk within 24 hours of admission, upon transferring level of care, and periodically during hospital stay (every 48-72 hours).4-6 (UW Health GRADE Low quality evidence, strong recommendation) 2. Evaluation of Bleeding Risk 2.1 There is no universally validated model or tool to assess bleeding risk with the use of chemical DVT prophylaxis in pediatric patients. 2.2 Recommendations for specific factors associated with increased bleeding risk are included in Table 1.4-8 (UW Health GRADE Very low quality evidence, strong recommendation) 2.2.1 If a patient meets at least one of the following criteria of the “Chemical Prophylaxis NOT Recommended” list in Table 1, avoid chemical prophylaxis as risk outweighs benefit. (UW Health GRADE Very low quality evidence, strong recommendation) 2.2.2 If patient meets at least one of the following criteria in the “Consider Avoiding Chemical Prophylaxis” list in Table 1, consider avoiding chemical prophylaxis. (UW Health GRADE Very low quality evidence, conditional recommendation) 2.2.2.1 Consider consulting hematology for recommendations if patient considered at high risk for VTE, but also with high bleeding risk.6 2.2.2.2 Uncontrolled hypertension is defined as systolic or diastolic blood pressure greater than 95th percentile for age, height, and gender.4 Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 4 2.2.2.3 Coagulopathy is defined as INR >1.5, APTT >44 seconds, fibrinogen <100 g/dL, or platelet <50,000/microliter.4 Table 1: Bleeding Risk Factors Chemical Prophylaxis NOT Recommended Consider Avoiding Chemical Prophylaxis Intracranial hemorrhage Intracranial mass Brain ischemia/acute stroke Recent lumbar puncture (< 24 hours ago) Active bleeding Coagulopathy Recent thrombolytic therapy (< 24 hours) Neurosurgical procedure Pelvic fracture within past 48 hours Uncontrolled hypertension Recent aspirin or antiplatelet use (< 5-7 days ago) 3. Evaluating VTE risk in medical, surgical, and trauma patients 3.1 There is no universally validated model or tool to assess VTE risk in medical, surgical, or trauma pediatric patients. 3.2 Table 2 and Table 3 should be used to assess VTE risk.4-6,8-18(UW Health GRADE Very low quality evidence, strong recommendation) 3.2.1 Reduced mobility is defined as decrease in movement from baseline or those unable to participate in physical therapy. 3.2.2 Active infection includes diagnostically confirmed bacterial infections and/or viral infections including COVID-19 infection. 3.2.3 Central venous access device is defined as a non-tunneled catheter, tunneled catheter, or peripherally inserted central catheter (PICC). 3.2.4 Major burn is defined as more than 50% of body surface area. 3.2.5 Major surgery is defined as an operation lasting longer than 45 minutes. 3.2.6 Critically ill is defined as patients in the critical care setting or ICU (inotropic support, mechanically ventilated, etc.). 3.2.7 Autoimmune disorders associated with thrombosis include Kawasaki’s disease, inflammatory bowel disease, systemic lupus erythematosus, nephrotic syndrome, multisystem inflammatory syndrome in children (MIS-C), etc. 3.2.8 Thrombophilic conditions include defects of antithrombin, protein C or S deficiency, factor V Leiden, homocystinuria, or prothrombin gene mutation. 3.2.9 Active malignancy is defined as receiving chemotherapy and/or radiation in the previous 6 months. 3.2.10 Estrogen therapy includes oral contraceptives or estrogen replacement currently taking or taken within the past 2 weeks. 3.2.11 Obesity is defined as BMI greater than 95th percentile for age. 3.3 Risk Factor Stratification definitions 3.3.1 Low VTE risk: • No altered mobility and 0-2 risk factors 3.3.2 Moderate VTE risk: • No altered mobility and 3-4 risk factors • Altered mobility and 0-2 other risk factors 3.3.3 High VTE risk: • No altered mobility and ≥ 5 risk factors • Altered mobility and ≥ 3 other risk factors Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 5 Table 2: VTE Risk Factors Acute Conditions Reduced mobility longer than 48 hours Central venous access device Active infection Major trauma or burn Major surgery Pregnancy Critically ill Hypoalbuminemia Blood transfusion within previous 48 hours Chronic Medical Conditions Post-pubertal and/or age 12 years or older Autoimmune disorders associated with thrombosis Thrombophilic condition Active malignancy Smoking Estrogen therapy Obesity Historical Factors Asparaginase within previous 30 days Recent surgery within past 30 days History of thrombosis* Family history of VTE in a 1st degree relative < 40 years old at time of clot *For patients with prior history of central line-associated VTE, see section 6.3 below Table 3: VTE Risk Assessment8 Risk Factor Stratification Recommendation Low VTE Risk • Early Ambulation • No prophylaxis necessary Moderate VTE Risk High VTE Risk and High Bleed Risk • Early Ambulation • Mechanical Prophylaxis High VTE Risk and Low Bleed Risk • Early Ambulation • Mechanical Prophylaxis and consider pharmacologic Prophylaxis 4. VTE prophylaxis options 4.1 Mechanical prophylaxis: methods may include sequential compression device (SCD), graduated compression stockings (GCS), or consulting physical therapy and/or occupational therapy to assist with movement of the patient.4-6,8,10,11,19 4.1.1 Contraindications to mechanical prophylaxis4,19 (UW Health GRADE Low quality evidence, strong recommendation) • Extremity has acute fracture • Extremity has peripheral IV access • Skin condition affecting extremity (i.e. dermatitis, burn, etc.) • Unable to achieve correct fit due to patient size • Lower extremity peripheral arterial insufficiency Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 6 4.2 Patients identified as high VTE risk should be evaluated to possibly receive the corresponding prophylaxis based on individual considerations. (See Table 4) (UW Health GRADE Low quality evidence, strong recommendation) 4.2.1 Enoxaparin is the preferred pharmacologic prophylaxis agent for pediatric patients.20,21 (UW Health GRADE Low quality evidence, strong recommendation) 4.2.1.1 Use of subcutaneous (SQ) injections is preferred due to lack of evidence of intravenous administration in the prophylactic setting. 4.2.1.2 Avoid enoxaparin or heparin if patient has hypersensitivity to enoxaparin, heparin, pork products, or any component of the formulation.4 (UW Health GRADE Low quality evidence, strong recommendation) Table 4: VTE Prophylaxis Regimens* in High VTE Risk Patients1,4,7,8,21-24 Patient Population Weight VTE Prophylaxis Regimens Normal Renal Function < 60 kg • Enoxaparin 0.5 mg/kg SQ every 12 hours (max 60 mg/day)a > 60 kg • Enoxaparin 40 mg SQ every 24 hoursb (consider 30 mg SQ every 12 hours for total knee arthroplasty) • Heparin 5000 units SQ every 12 hoursa Renal Impairment (CrCl < 30 mL/min/1.73m2) < 60 kg • Enoxaparin 0.5 mg/kg SQ every 24 hoursa > 60 kg • Enoxaparin 30 mg SQ every 24 hours a • Heparin 5000 units SQ every 12 hoursa aUW Health GRADE Low quality evidence, strong recommendation bUW Health GRADE Low quality evidence, conditional recommendation *For patients with prior history of central line-associated VTE, see section 6.3 below 5. Rivaroxaban, an oral anticoagulant with FDA approval in the pediatric population, may be considered for prophylaxis in patients with high VTE risk if appropriate based on patient characteristics.25-27 (UW Health GRADE Low quality evidence, conditional recommendation) 5.1 Consider rivaroxaban for VTE prophylaxis in patients appropriate for use based on below criteria due to emerging evidence in the pediatric population, and consider hematology consult if needing assistance determining appropriateness. (UW Health GRADE Very low quality evidence, conditional recommendation) 5.2 Rivaroxaban may be used based on individual considerations.26 (UW Health GRADE Low quality evidence, strong recommendation) 5.2.1 Only use rivaroxaban in infants weighing at least 2.6 kg whose serum creatinine is less than the 97.5th percentile and children or adolescents with eGFR > 50 mL/min/1.73 m2 (UW Health GRADE Low quality evidence, strong recommendation) 5.2.2 Patients should receive at least five days of parenteral anticoagulation and at least ten days of enteral feeding prior to starting rivaroxaban for VTE prophylaxis. (UW Health GRADE Low quality evidence, strong recommendation) 5.2.3 See Lexicomp drug monograph for rivaroxaban dosing based on patient age, weight, and interacting medications (i.e. certain antiseizure medications, etc.) 6. VTE prophylaxis in unique pediatric populations 6.1 Rivaroxaban for thromboprophylaxis after Fontan procedure28 6.1.1 Rivaroxaban may be used for thromboprophylaxis after Fontan procedure based on individual considerations listed under 5.2.1 and 5.2.2. (UW Health GRADE Low quality evidence, strong recommendation) 6.1.2 See Lexicomp drug monograph for rivaroxaban dosing based on patient age and weight 6.2 Pediatric patients with COVID-19 infection29 Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 7 6.2.1 Pharmacologic VTE prophylaxis is recommended in patients aged 12 years and older who are hospitalized for COVID-19 infection, unless contraindicated. (UW Health GRADE Low quality evidence, strong recommendation) 6.2.1.1 If pharmacologic VTE prophylaxis is contraindicated, consider mechanical VTE prophylaxis. (UW Health GRADE Low quality evidence, strong recommendation) 6.2.1.2 For patients less than 12 years old, follow usual VTE prophylaxis recommendations. (UW Health GRADE Low quality evidence, strong recommendation) 6.2.2 Consider checking D-dimer, and if elevated but the patient does not have an active thromboembolism, consider starting VTE prophylaxis at any patient age.30,31 (UW Health GRADE Very low quality evidence, conditional recommendation) 6.3 Pediatric patients with history of central line-associated thrombosis 6.3.1 Prior history of thrombosis, whether associated with a central line or not, is a known risk factor for subsequent thrombosis 6.3.2 Consider therapeutic anticoagulation with heparin or enoxaparin, rather than prophylactic anticoagulation, in patients with a history of central-line associated thrombosis if any future central line is placed based on emerging evidence and if appropriate for the patient32 (UW Health GRADE Low quality evidence, conditional recommendation) 6.3.3 If using therapeutic anticoagulation, reference UW Health documents “Therapeutic Dosing of Unfractionated Heparin – Pediatric/Neonatal – Inpatient/Emergency Department” and “Enoxaparin Dosing and Monitoring for Therapeutic Use – Pediatric – Inpatient” for guidance on dosing and required monitoring 7. Anticoagulation monitoring3,22 7.1 Complete blood count (CBC) 7.1.1 Obtain baseline CBC within 48 hours of initiation of enoxaparin or heparin. (UW Health GRADE Very low quality evidence, strong recommendation) 7.2 Anti-Xa5,21 7.2.1 Routine anti-Xa levels are not recommended with the use of enoxaparin, heparin, or rivaroxaban at prophylactic doses.1 7.2.2 May consider checking anti-Xa level if the patient experiences active bleeding or has evidence of renal dysfunction while receiving enoxaparin.22 (UW Health GRADE Very low quality evidence, conditional recommendation) 7.2.3 If an anti-Xa level is deemed necessary, it should be drawn 4-6 hours after enoxaparin administration with a target anti-Xa goal of 0.1-0.3 units/mL.21 Disclaimer Clinical practice guidelines assist clinicians by providing a framework for the evaluation and treatment of patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit the clinical condition contemplated by a guideline and that a guideline will rarely establish the only appropriate approach to a problem. Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 8 Methodology Development Process Each guideline is reviewed and updated a minimum of every 3 years. All guidelines are developed using the guiding principles, standard processes, and styling outlined in the UW Health Clinical Practice Guideline Resource Guide. This includes expectations for workgroup composition and recruitment strategies, disclosure and management of conflict of interest for participating workgroup members, literature review techniques, evidence grading resources, required approval bodies, and suggestions for communication and implementation. Methods Used to Collect the Evidence: The following criteria were used by the guideline author and workgroup members to conduct electronic database searches in the collection of evidence for review. Literature Sources: • Electronic database search (e.g., PubMed) • Hand-searching journals, external guidelines, and conference publications Time Period: All studies to date Search Terms: • VTE prophylaxis AND pediatrics • VTE risk factors AND pediatrics • Enoxaparin use in pediatrics for VTE prophylaxis • Heparin use in pediatrics for VTE prophylaxis • Direct oral anticoagulant use in pediatrics for VTE prophylaxis Methods to Select the Evidence: All observational studies, randomized clinical trials, and systematic reviews/meta analyses in English were considered for the guideline development. Methods Used to Formulate the Recommendations: The workgroup members created recommendations internally via a consensus process using discussion of the literature and expert experience/opinion. If issues or controversies arose where consensus could not be reached, the topic was escalated appropriately per the guiding principles outlined in the UW Health Clinical Practice Guideline Resource Guide. Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations: Internally developed recommendations, or those adopted from external sources without an assigned evidence grade, were evaluated by the guideline workgroup using an algorithm adapted from the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (see Figure 1). Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 9 Figure 1. GRADE Methodology adapted by UW Health Rating Scheme for the Strength of the Evidence/Recommendations: GRADE Ranking of Evidence High We are confident that the effect in the study reflects the actual effect. Moderate We are quite confident that the effect in the study is close to the true effect, but it is also possible it is substantially different. Low The true effect may differ significantly from the estimate. Very Low The true effect is likely to be substantially different from the estimated effect. GRADE Ratings for Recommendations For or Against Practice Strong Generally should be performed (i.e., the net benefit of the treatment is clear, patient values and circumstances are unlikely to affect the decision.) Conditional May be reasonable to perform (i.e., may be conditional upon patient values and preferences, the resources available, or the setting in which the intervention will be implemented.) Recognition of Potential Health Care Disparities: None identified Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 10 Collateral Tools & Resources The following collateral tools and resources support staff execution and performance of the evidence- based guideline recommendations in everyday clinical practice. Metrics • Prevention of VTE with the therapy that is most appropriate based on individual patient VTE and bleeding risk • Rate of central venous catheter (CVC) related VTEs • Rate of non-CVC VTE events Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 11 Appendix A. Pediatric VTE Prophylaxis Risk Factors and Assessment Table 2: VTE Risk Factors Acute Conditions Reduced mobility longer than 48 hours Central venous access device Active infection Major trauma or burn Major surgery (during admission) Pregnancy Critically ill Hypoalbuminemia Blood transfusion within previous 48 hours Chronic Medical Conditions Post-pubertal and/or age 12 years or older Autoimmune disorders associated with thrombosis Thrombophilic condition Active malignancy/cancer Smoking Estrogen therapy Obesity Historical Factors Asparaginase within previous 30 days Recent surgery within past 30 days History of thrombosis* Family history of VTE in a 1st degree relative < 40 years old at time of clot *For patients with prior central-line associated VTE, see section 6.3 below Table 3: VTE Risk Assessment8 Risk Factor Stratification Recommendation Low VTE Risk • Early Ambulation • No prophylaxis necessary Moderate VTE Risk High VTE Risk and High Bleed Risk • Early Ambulation • Mechanical Prophylaxis High VTE Risk and Low Bleed Risk • Early Ambulation • Mechanical Prophylaxis and consider pharmacologic Prophylaxis Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 12 Table 4: VTE Prophylaxis Regimens* in High VTE Risk Patients1,4,7,8,21-24 Patient Population Weight VTE Prophylaxis Regimens Normal Renal Function < 60 kg • Enoxaparin 0.5 mg/kg SQ every 12 hours (max 60 mg/day)a > 60 kg • Enoxaparin 40 mg SQ every 24 hoursb (consider 30 mg SQ every 12 hours for orthopedic procedures) • Heparin 5000 units SQ every 12 hoursa Renal Impairment (CrCl <30 mL/min/1.73m2) < 60 kg • Enoxaparin 0.5 mg/kg SQ every 24 hoursa > 60 kg • Enoxaparin 30 mg SQ every 24 hours a • Heparin 5000 units SQ every 12 hoursa aUW Health GRADE Low quality evidence, strong recommendation bUW Health GRADE Low quality evidence, conditional recommendation *For patients with prior central-line associated VTE, see section 6.3 below Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions 13 References 1. Raffini L, Trimarchi T, Beliveau J, Davis D. Thromboprophylaxis in a pediatric hospital: a patient-safety and quality-improvement initiative. Pediatrics. May 2011;127(5):e1326-32. doi:10.1542/peds.2010-3282 2. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics. Oct 2009;124(4):1001-8. doi:10.1542/peds.2009- 0768 3. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. Jun 2008;133(6 Suppl):381s- 453s. doi:10.1378/chest.08-0656 4. Mahajerin A, Webber EC, Morris J, Taylor K, Saysana M. 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Jan 2020;7(1):e18-e27. doi:10.1016/s2352-3026(19)30219-4 27. Mills K, Hill C, King M, et al. Just DOAC: Use of direct-acting oral anticoagulants in pediatrics. Am J Health Syst Pharm. Mar 21 2023;80(7):412-422. doi:10.1093/ajhp/zxac387 28. McCrindle BW, Michelson AD, Van Bergen AH, et al. Thromboprophylaxis for Children Post-Fontan Procedure: Insights From the UNIVERSE Study. J Am Heart Assoc. Nov 16 2021;10(22):e021765. doi:10.1161/jaha.120.021765 29. National Institutes of Health. Therapeutic management of hospitalized children with COVID-19. In: COVID-19 treatment guidelines. National Institutes of Health; Updated August 8, 2022. Accessed April 10, 2022. https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-of-children/hospitalized- children-therapeutic-management/. 30. Goldenberg NA, Sochet A, Albisetti M, et al. Consensus-based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illness. J Thromb Haemost. Nov 2020;18(11):3099-3105. doi:10.1111/jth.15073 31. Sochet AA, Morrison JM, Jaffray J, et al. Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID- 19: A Phase 2 Trial. Pediatrics. Jul 1 2022;150(1)doi:10.1542/peds.2022-056726 32. Clark HH, Ballester L, Whitworth H, Raffini L, Witmer C. Prevention of recurrent thrombotic events in children with central venous catheter-associated venous thrombosis. Blood. Jan 20 2022;139(3):452-460. doi:10.1182/blood.2021013453 Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2023 Effective 4/20/2023. Contact CCKM@uwhealth.org for previous versions