Current practices in pediatric hospital‐acquired thromboembolism: Survey of the Children's Hospital Acquired Thrombosis (CHAT) Consortium

Abstract

Background

A rise in hospital‐acquired venous thromboembolism (HA‐VTE) in children has led to increased awareness regarding VTE prophylaxis and risk assessment. Despite no consensus exists regarding these practices in pediatrics.

Objective

To describe common practices in VTE prophylaxis, VTE risk assessment models, and anticoagulation dosing strategies in pediatric hospitals that are members of the Children's Hospital Acquired Thrombosis (CHAT) Consortium.

Methods

An electronic survey of 44 questions evaluating practices surrounding pediatric HA‐VTE risk assessment and prevention was distributed between August 9, 2021, and August 30, 2021, to the primary investigators from the 32 institutions within the CHAT Consortium.

Results

The survey response rate was 100% (n = 32). In total, 85% (n = 27) of the institutions assess HA‐VTE, but only 63% (n = 20) have formal hospital guidelines. Within the institutions with formal guidelines, 100% (n = 20) include acute systemic inflammation or infection and presence of a central venous catheter (CVC) as risk factors for VTE. Pharmacologic prophylaxis is prescribed at 87% (28) of institutions, with enoxaparin being the most frequent (96%, n = 27). Variability in responses persisted regarding risk factors, risk assessment, thromboprophylaxis, dosing of prophylactic anticoagulation or anticoagulant drug monitoring. A majority of providers were comfortable providing thromboprophylaxis across all age groups. In addition, the global coronavirus disease 2019 increased the providers' use of prophylactic anticoagulation 78% (n = 25).

Conclusion

Practices among institutions are variable in regard to use of HA‐VTE prophylaxis, risk assessment, or guideline implementation, highlighting the need for further research and a validated risk assessment model through groups like the CHAT Consortium.

Essentials

• •The rate of children getting blood clots in the United States is increasing.
• •Our survey redemonstrated variability in practices in preventing blood clots in children.
• •Most of our physicians were comfortable using blood thinners to prevent clots in all ages.
• •In those surveyed, coronavirus disease 2019 increased interventions to prevent blood clots in children.

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1. INTRODUCTION

Pediatric hospital‐acquired venous thromboembolism (HA‐VTE) incidence has seen a marked increase over the past 20 years from 5.3 to 106 cases per 10,000 admissions.^{1., 2., 3., 4.} Many attributeincreased incidence to improved outcomes for pediatric patients with chronic medical conditions or critical illness undergoing more invasive measures.^{5., 6.} Furthermore, in recent history, there has been a heightened awareness brought on by thrombotic complications in hospitalized children due to the hypercoagulability associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causing the coronavirus disease 2019 (COVID‐19) global pandemic.^{7., 8., 9.} Despite increased incidence and awareness, there are still no validated or standardized guidelines for assessing HA‐VTE risk or applying thromboprophylaxis measurements in children.

In 2012, to overcome paucity of guidelines, the Children's Hospitals' Solutions for Patient Safety (SPS), a quality improvement network of over 130 children's hospitals aiming to reduce hospital‐acquired conditions, created recommendations based on expert opinion for HA‐VTE prevention including risk factors and prevention strategies, such as the use of sequential compression devices and pharmacologic prophylaxis based on the level of VTE risk.¹⁰ These recommendations are still not standardly implemented by children's hospitals.^{6., 11., 12., 13.} The multicenter Children's Hospital‐Acquired Thrombosis (CHAT) Consortium created a registry to identify HA‐VTE risk factors and developed two HA‐VTE risk assessment models (RAMs) to be applied to children upon hospital admission.^{6., 13., 14.} The first of these RAMs was created to identify HA‐VTE risk for all hospitalized children at hospital admission, while the second RAM focused on those who were critically ill at admission or transfer into an intensive care unit.^{6., 13.} The highest‐risk variables for HA‐VTE identified by the CHAT RAM for hospitalized children included both presence of a central venous catheter (CVC) and complete immobility defined by Braden mobility score 1¹⁵ upon admission.⁶

To identify the current HA‐VTE practices and implementation of guidelines for pediatric HA‐VTE risk assessment and prevention strategies, we surveyed members of the US‐based, multicenter CHAT Consortium. Here, we describe the results of that survey, discuss the variability of practice among pediatric providers, and demonstrate the further need for validation of RAMs and guidelines for VTE prevention.

2. METHODS

A survey of 44 questions was designed by the authors and distributed to the principal investigators at the US‐based CHAT Consortium sites. Institutional review board approval was not required due to the nature of the survey; however, an exempt application was submitted to both institutional review boards at the University of North Carolina School of Medicine in Chapel Hill, North Carolina, and Children's Hospital Los Angeles in Los Angeles, California. The survey was voluntary, and participation implied consent.

The survey questions, which focused on practices surrounding HA‐VTE risk factors, use of risk assessment models, VTE prophylaxis, and anticoagulation dosing strategies in pediatric hospitals, are provided in the Appendix S1. Some questions included skip patterns and diversions, thus not all participants were required to complete the survey in its entirety. Some questions allowed multiple responses by each participant. The survey was designed and administered electronically using a commercial web‐based survey tool (Qualtrics), distributed from August 9, 2021, through August 30, 2021. Only the principal investigators from each CHAT site were sent the survey, and each individual indicated their institutions, thus allowing for only one survey response per institution. The principal investigator was asked to answer on behalf of their institution, and we interpret their answers as reflective of the practices of the institution at large. Duplicated responses or unfinished responses were not included for analysis.

We used a 5‐point Likert scale with answers ranging from extremely comfortable to extremely uncomfortable to gauge participants' comfort level with pharmacologic prophylaxis within various age groups. Enoxaparin dosing for pharmacologic prophylaxis use was defined within the survey as 40 mg every 24 h for adult dosing and 0.5 mg/kg every 12 h for pediatric dosing. Survey results were reported as descriptive statistics.

3. RESULTS

3.1. Demographics

Thirty‐two participants across all CHAT Consortium sites responded (response rate, 100%) and were included in the analysis. Sixty‐six percent (n = 21) identified themselves as pediatric hematologists alone, while 31% (n = 10) identified themselves as pediatric hematologists and oncologists. The majority of participants (88%, n = 28) practice in an academic medical center, while only 12% (n = 4) practice in a community‐based hospital (Table 1).

TABLE 1.

Participant demographics reported across the 32 CHAT Consortium institutions

Demographic	Number of institutions (%)
Primary specialty
Pediatric hematology	21 (66)
Pediatric hematology/oncology	10 (31)
Pediatric intensive care	1 (3)
Years since primary fellowship completed
<5	8 (26)
5–10	12 (39)
>10	11 (35)
Region of United Statesa
West	5 (16)
Midwest	11 (34)
South	9 (28)
Northeast	7 (22)
Facility type
Stand‐alone children's hospital	18 (56)
Combined adult and pediatric hospital	13 (44)

Abbreviation: CHAT, Children's Hospital Acquired Thrombosis.

^aBased on US Census Bureau Regions and Divisions.⁴⁵

3.2. VTE risk factors and risk assessments

Assessment of HA‐VTE risk in children occurs at 85% (n = 27) of the institutions in at least one hospital unit, but only 63% (n = 20) have established formal guidelines (Table 2, Figure 1). Of the 27 institutions that have a HA‐VTE risk assessment process, RAM application occurs upon hospital admission in 78% (n = 21), while 48% (n = 13) administer the RAM at the time of clinical status change. Daily risk assessments are rarely completed (15%, n = 4). The most common medical group to perform the HA‐VTE risk assessments are residents or attending physicians (51%, n = 14; and 48%, n = 13, respectively) followed by fellows (41%, n = 11) and bedside nurses (37%, n = 10). Forty‐five percent (n = 15) of institutions have a dedicated thrombosis and coagulation service.

TABLE 2.

Characteristics of the 32 CHAT institutions regarding HA‐VTE practices as reported by participants

Characteristics	Number of institutions (%)
Number of HA‐VTEs diagnosed yearly
10–20	6 (19)
20–40	7 (22)
40–60	3 (9)
>60	13 (41)
I do not know	3 (9)
Institutional practices
Dedicated pediatric thrombosis and coagulation service	15 (45)
QI project for HA‐VTE risk assessment and prevention in place	16 (50)
Performs risk assessments for HA‐VTE	27 (84)
HA‐VTE prophylaxis guidelines in place	20 (63)
Pharmacologic prophylaxis provided to <18‐year‐olds	28 (87)

Abbreviations: HA‐VTE, hospital‐acquired venous thromboembolism; QI, quality improvement.

FIGURE 1.

Provider responses regarding venous thromboembolism risk assessment practices and thromboprophylaxis practices

All 20 institutions with formal HA‐VTE guidelines consider acute systemic inflammation or infection and presence of a CVC as risk factors (Table 3). Sixty percent (n = 12) base their recommendations on the expert opinion–based SPS VTE Prevention Bundle,¹⁰ originally published in 2012, and have implemented the SPS RAM at their hospital, while 20% (n = 4) of the institutions implemented the published, yet unvalidated, CHAT RAM.⁶

TABLE 3.

Reported VTE risk factors included in the risk assessment models

Risk Factors	Number of institutions (%)
Acute systemic inflammation or infection	20 (100)
Central line	20 (100)
Age of patient	19 (95)
Chronic inflammatory condition	19 (95)
Current or recent use of estrogen	19 (95)
Inherited thrombophilia	19 (95)
Personal history of thrombosis	19 (95)
Altered mobility	18 (90)
Critically ill	18 (90)
Family history of VTE in first‐degree relative	18 (90)
Malignancy	18 (90)
Acquired thrombophilia	17 (85)
Obesity based on BMI	17 (85)
Recent orthopedic procedure	17 (85)
Bloodstream infection	16 (80)
Trauma	16 (80)
Cyanotic heart disease or low‐flow state	15 (75)
Burns	12 (60)
Protein‐losing disorders	12 (60)
Recent nonorthopedic surgical procedure	11 (55)
Diabetic ketoacidosis	10 (50)
Severe dehydration	10 (50)
Mechanical ventilation	9 (45)
Othera	3 (15)

Abbreviations: BMI, body mass index; COVID‐19, coronavirus disease 2019; TPN, total parenteral nutrition; VTE, venous thromboembolism.

^aOther responses included use of TPN, length of stay >7 days, spinal cord injury, pregnancy, COVID‐19 infection, smoking or vaping, testosterone therapy.

3.3. Pharmacologic prophylaxis

All participants felt “extremely comfortable” or “somewhat comfortable” prescribing prophylactic anticoagulation in patients older than 12 years of age. Eighty‐nine percent (n = 24) felt “extremely comfortable” or “somewhat comfortable” with prophylaxis in the 1 to 11 years age group. Finally, 65% (n = 17) felt “extremely comfortable” or “somewhat comfortable” with prophylactic anticoagulation in neonates. Only 19% (n = 5) felt “somewhat uncomfortable” or “extremely uncomfortable” in the neonatal age group. Hesitation in those participants was associated with concerns of bleeding risk (n = 4), lack of evidence or studies (n = 4), and pain inflicted by needle administration of medication (n = 2). Similar concerns with less frequency were identified in patients 1–11 years old.

Eighty‐seven percent (n = 28) of participants use pharmacologic prophylaxis in individuals less than 18 years old in certain clinical cases. Only 75% (n = 21) of participants administer routine pharmacologic prophylaxis for patients considered “high risk” for thrombosis. Pharmacologic prophylaxis was routinely prescribed in the pediatric intensive care unit (ICU) (64%, n = 18) or cardiac ICU (54%, n = 15), while a minority provided prophylaxis for the neonatal ICU (21%, n = 6). In only a minority of cases were individual groups of patients provided with prophylactic anticoagulation regardless of their age. The most common groups who did receive such prophylaxis were cardiac patients, gastroenterology patients, and orthopedic patients (each 14%, n = 14), while the least common groups are oncology and pulmonary patients (each 4%, n = 1) (Table 4).

TABLE 4.

HA‐VTE prophylaxis provided to the following groups of patients regardless of age at various institutions as reported by participants

Patient groups	Number of institutions (%)
Cardiac	4 (14)
Gastroenterology	4 (14)
Hematology	2 (7)
Nephrology	2 (7)
Oncology	1 (4)
Orthopedic	4 (14)
Pulmonary	4 (14)
Rheumatology	0 (0)
Surgical	3 (11)
None	10 (36)
I do not know	6 (21)

Abbreviation: HA‐VTE, hospital‐acquired venous thromboembolism.

3.4. Anticoagulant choice and dosing

The most used anticoagulants for prophylaxis are enoxaparin (96%, n = 27) or unfractionated heparin (64%, n = 18). Forty‐three percent (n = 12) of participants report using a direct oral anticoagulant with some patients (rivaroxaban or apixaban). Only one participant reported using aspirin in some patients for VTE prophylaxis.

Dosing regimens of enoxaparin varied among participants. Participants use adult dosing over pediatric dosing based on weight of >50 kg (71%, n = 20) and/or age >16 years old (57%, n = 16). Pubertal development is less often considered (14%, n = 4). For adolescent patients weighing >60 kg, 48% (n = 13) of participants use adult dosing, while only 33% (n = 9) use pediatric dosing with varying maximum dosing. For obese adolescents (i.e., >100 kg), only 30% (n = 8) use 0.5 mg/kg twice daily dosing for enoxaparin, and 37% (n = 10) use dosing of 40 mg every 24 h. Many institutions use twice‐daily dosing for obese patients, with varying maximum doses including 30 mg (11%, n = 3), 40 mg (11%, n = 3), and 60 mg (3%, n = 1).

Sixty‐one percent (n = 17) of the participants using enoxaparin consider measuring anti‐Xa levels depending on the patient, while 18% (n = 5) answered yes regardless of patient factors. If anti‐Xa levels were measured, 27% (n = 6) of participants use a goal anti‐Xa level of 0.1–0.3 units/ml, while 50% (n = 11) use a goal of 0.2 to <0.5 units/ml. Eleven percent (n = 3) of participants state they check anti‐Xa levels with obese patients or their institutions have specific obesity‐based dosing.

3.5. Influences of SARS‐CoV‐2

Twenty‐five of 32 (78%) participants stated that the COVID‐19 pandemic changed their practice regarding prophylactic anticoagulation. ranged from increased frequency of VTE prophylactic anticoagulation (88%, n = 22) to increased number of patients within the hospital assessed for HA‐VTE (36%, n = 9) or increased frequency of HA‐VTE risk assessment (52%, n = 13). SARS‐CoV‐2 increased the dosing of prophylaxis for enoxaparin at one institution, while leading to an increase in dosing frequency from once daily to twice daily at another institution. Thirty‐one percent (n = 8) of institutions monitor anti‐Xa levels more often and one institution increased the goal for anti‐Xa levels from 0.1–0.3 to 0.2–0.4 units/ml.

3.6. CHAT Consortium participation

Most participants are currently enrolling patients into CHAT studies (84%, n = 27). Though very few have made changes to their protocols since participating in CHAT (15%, n = 4), most would change their current hospital risk model if CHAT were to establish a validated RAM (88%, n = 28).

4. DISCUSSION

Practices of individual pediatric hematologists continue to demonstrate variation surrounding VTE prophylaxis and treatment.^{16., 17., 18., 19.}survey of the CHAT Consortium is no different regarding HA‐VTE risk assessment and prophylaxis practices. The providers in survey did not have uniformity in terms of optimal HA‐VTE RAM implementation use, patient population to assess for HA‐VTE or provide thromboprophylaxis, thromboprophylaxis dosing regimen, or prophylactic anticoagulation monitoring. These findings are most interesting given that there is overlying enthusiasm within group to identify children at the highest risk of HA‐VTE and best prevention techniques.

While the rate of HA‐VTE is increasing in pediatric populations,^{1., 2., 3.} there is a paucity of pediatric studies characterizing the practices of pediatric hospitals surrounding VTE prophylaxis. Adult literature suggests benefits from thromboprophylaxis for both medical and surgical patients,²⁰ but to date there is no published consensus regarding pediatric dosing, regimen, or comfort level. Of the published pediatric guidelines, the most frequently agreed‐upon risk factors include CVC, exogenous estrogen, and immobility.²¹ However, other reviews have found discrepancies even in the use of CVC as a risk factor.²² Still, 100% of our providers agreed with CVC being a risk factor, while estrogen use and immobility were thought to be less contributory (95% and 90%, respectively). Beyond these previously identified risks, our survey results show concern for the impact of systemic inflammation, which is in line with previous CHAT studies.^{6., 13.}

Our survey elucidated specific concerns with prescribing prophylaxis in the pediatric population. Top reasons given for discomfort in prescribing pharmacologic prophylaxis in younger children include the risk of bleeding, lack of available evidence, and lack of oral prophylactic options. Despite these comments, comfort with pharmacologic prophylaxis in younger children was relatively high overall, with only 19% who felt uncomfortable in neonates. Though primary prophylaxis is not discussed in the American College of Chest Physicians (CHEST) guidelines, they do discuss prophylaxis in neonates with high‐risk conditions (such as with CVCs or undergoing cardiac procedures), which may explain why many providers felt comfortable with prophylaxis in neonatal populations.²³ A study looking at Pediatric Health Information System data from January 2008 to September 2015 noted that only 1% of hospitalized children received pharmacologic thromboprophylaxis, 5% received mechanical compression, and 0.4% received both.²⁴ In study, the rates of prophylaxis increased with age (10–12 years old, 0.5%; 16–18 years old, 1.6%), reflecting the comfort with thromboprophylaxis identified from our survey participants.²⁴ Incongruous with these findings, only 27% of providers were prescribing pharmacologic prophylaxis to those <1 year old. continues to highlight the issues within field and the need for standardized care practices.

In addition, our survey identified variability in enoxaparin dosing for obese patients and adolescents as well as drug monitoring in those populations. In obese children, dosing guidance for thromboprophylaxis is nebulous,²⁵ which is reflected by our participants' responses. Not only were they less likely to be dosed on the basis of a defined pediatric regimen, but the use of standard adult dosing decreased as well. The majority of participants (61%, n = 17) stated that routine monitoring of enoxaparin as thromboprophylaxis was decided on a case‐by‐case basis, while a minority (18%, n = 5) said they routinely monitor regardless of the clinical scenario. When anti‐Xa levels were monitored, 50% aimed for an anti‐Xa level of 0.2–0.4 units/ml, despite studies in pediatrics, specifically the Prophylaxis of Thromboembolism in Kids Trial (PROTEKT), recommending a goal anti‐Xa level of 0.1–0.3 units/ml.^{26., 27.} Though generally not measured, studies in adults will target prophylactic anti‐Xa levels with enoxaparin of 0.2–0.4 units/ml, when used.^{28., 29., 30.} Unfortunately, a randomized controlled trial has yet to be completed to determine the efficacy of targeting a specific anti‐Xa level for children.

More research is needed to elucidate opportunities to establish common practice parameters for thromboprophylaxis as our survey shines light upon the lack of a current, standard approach in pediatrics. SARS‐CoV‐2 has brought topic to the forefront of pediatric practice^{7., 8., 9., 31., 32.} acting as a catalyst to consider ways of delineating and potentially establish expert consensus across sites. Seventy‐eight percent (n = 25) of participants stated that the growing COVID‐19 pandemic changed their hospital practices regarding prophylactic anticoagulation. Reflecting these changes, a consensus paper published in the Journal of Thrombosis and Haemostasis through the Pediatric/Neonatal Hemostasis and Thrombosis Subcommittee of the ISTH Scientific and Standardization Committee provided recommendations for anticoagulant thromboprophylaxis for children hospitalized with COVID‐19 or multisystem inflammatory syndrome in children. They discussed thromboprophylaxis for those with symptomatic COVID‐19–related illnesses as low‐dose low‐molecular‐weight heparin twice‐daily dosing targeting an anti‐Xa activity level of 0.2 to <0.5 units/ml, with consideration given to additional risk factors for thrombosis.³³ More recently, a Phase 2 trial was published that demonstrated the safety of 0.5 mg/kg/dose twice‐daily dosing with a maximum dose of 60 mg to target an anti‐Xa activity level of 0.2–0.49 IU/ml.³⁴ These recommendations were published after our participants responded and would likely have increased the number of individuals who would have changed their practice. As our body of knowledge continues to grow with COVID‐19, so should our prophylaxis guidelines and practices until consensus can be reached. As with much in pediatrics, we turn to recent publications in adult literature. First, in those who are critically ill with COVID‐19, the research recommends prophylactic dosing of anticoagulation over intermediate or therapeutic intensity anticoagulation.^{35., 36.} Conversely, in those who are not critically ill, the literature suggests therapeutic over prophylactic anticoagulation.^{35., 37., 38.} These findings are reflected in the recent American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID‐19 and the new 2020 CHEST COVID‐19 guidelines with updates from 2022.^{39., 40., 41., 42., 43.} As new literature surrounding topic is published, including growing work in pediatrics as was already indicated, use of thromboprophylaxis will likely continue to increase in these clinical scenarios.

Limitations of survey are similar to those found in other surveys of medical care providers. First, there is no ability for verification of responses. Particularly with survey, there were no clinical scenarios or definitions of some of the risk factors (i.e., acute systemic inflammation), and the population surveyed may limit generalizability. The participants, all members of the CHAT Consortium, who responded already have a heightened awareness over HA‐VTE. To point, however, the responses of a more generalizable audience would likely represent even more heterogeneity. CHAT Consortium participants also represent few community hospitals, thus also limiting is generalizability. Also, the responses provided may not truly depict the hospital incidence of thrombosis or the decisions that are made in actual clinical practice. Though we acknowledge these limitations, we have results from a robust and comprehensive survey of pediatric providers regarding VTE prophylaxis practices, risk assessment, implementation, comfort, and dosing strategies, including changes during the COVID‐19 pandemic published to date.^{16., 17., 44.}

5. CONCLUSION

survey has demonstrated that practices, even among a small subset of providers, is widely variable regarding assessing and managing HA‐VTE risk in children.variability emphasizes the need for consensus guidelines regarding appropriate thromboprophylaxis practices for children and adolescents. The CHAT Consortium aims to provide validated RAMs through its ongoing prospective study as well as future safety and efficacy trials for thromboprophylaxis use in children to standardize the approach and treatment to prophylaxis against HA‐VTE.

AUTHOR CONTRIBUTIONS

The study was conceived by CMA, JJ, and YLA. CMA, JJ, AS, and YLA edited the survey questions and analyzed and edited data. CMA, JJ, AS, BRB, GY, NAG, and YLA edited and participated in final manuscript preparation. All authors approved the final version of the manuscript.

FUNDING INFORMATION

CMA received grant funding to support her fellowship training on the Research Training in Hematology grant from the National Institutes of Health National Heart, Lung, and Blood Institute (grant number 5T32HL007149). JJ received grant funding for study from the National Institutes of Health from the National Center for Advancing Translational Science (grant number UL1TR001855), the Children's Hospital Saban Research Mentored Career Development Award and the Hemostasis and Thrombosis Research Society Mentored Research Award, supported by an independent educational grant from Takeda Pharmaceuticals U.S.A. The remaining authors have no relevant financial disclosures.

RELATIONSHIP DISCLOSURE

The following relationships are in addition to the above funding. NAG received research support and salary support from the National Institutes of Health, National Heart, Lung, and Blood Institute for clinical and translational investigation in venous thromboembolism in patients less than 21 years old. He received consultancy fees from Anthos Therapeutics, Bayer, Boehringer‐Ingelheim, Daiichi Sankyo, Janssen, and the Academic Research Organization CPC Clinical Research for roles in clinical trial oversight committees (e.g., steering, data and safety monitoring) in pharmaceutical industry‐sponsored pediatric clinical trials of antithrombotic agents. YLA, YG, BRB, and AS have no relevant conflicts of interests to disclose.

ETHICS STATEMENT

Study was submitted to the IRB, but was exempt from UNC, CHLA, and CHAT consortium IRB.

A. APPENDIX

CHAT Consortium participating site principal investigators who responded to the survey on behalf of their institution were as follows (alphabetically by site): John Fargo: Pediatric Hematology/Oncology, Akron Children's Hospital, Northeast Ohio Medical University, Akron, OH. Shelly Crary: Division of Pediatric Hematology‐Oncology, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, AR. Riten Kumar: Thrombosis and Anticoagulation Program, Dana Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA. Gary Woods: Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine Department of Pediatrics, Atlanta, GA. Shalu Narang: Rutgers New Jersey Medical School, Hemostasis and Thrombosis Program, Newark Beth Israel Medical Center & Children's Hospital of New Jersey, RWJBarnabas Health, Newark, NJ. James Cooper: Children's Hospital of Pittsburgh of UPMC, Division of Pediatric Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA. Mike Silvey: Division of Hematology/Oncology/Bone Marrow Transplant, Kansas City Regional Hemophilia Treatment Center, Children's Mercy Kansas City, University of Missouri, Kansas City School of Medicine, Kansas City, MO. Kate Garland: Pediatric Hematology, Center for Bleeding and Clotting Disorders, Children's Minnesota, University of Minnesota, Minneapolis, MN. Arash Mahajerin: Division of Hematology, CHOC Children's Hospital, Orange, CA. Lori Luchtman‐Jones: Division of Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH. Marcela Torres: Hematology and Oncology Center, Cook Children's, Fort Worth, TX. Jordan Wright: Hematology/Oncology Department, Comprehensive Care Center for Cancer and Blood Disorders, Dayton Children's Hospital, WSU School of Medicine, Dayton, OH. Kristy Pahl: Duke Children's Hospital & Health Center, Division of Pediatric Hematology‐Oncology, Department of Pediatrics, Duke University Medical Center, Durham, NC. Katherine Armstrong: Children's Cancer Institute, Hackensack Meridian Children's Health at Joseph M. Sanzari Children's Hospital, Hackensack, New Jersey. Chi Braunreiter: Helen DeVos Children's Hospital, Spectrum Health, MSU College of Human Medicine, Grand Rapids, MI. Nihal Bakeer: Indiana Hemophilia and Thrombosis Center, Indianapolis, IN. Anthony Sochet: Johns Hopkins All Children's Hospital, Johns Hopkins University, School of Medicine, St. Petersburg, FL. Marie Hogan: Division of Hematology and Oncology, School of Medicine, Oregon Health & Science University. Shveta Gupta: Hemophilia and Thrombosis Center, Haley Center for Cancer and Blood Diseases, Arnold Palmer Hospital for Children, Orlando Health, Orlando, FL. Christine Knoll: Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ. Kerry Hege: Pediatric Hematology/Oncology North Program, Riley Hospital for Children at IU Health. Indiana University School of Medicine, Indianapolis, IN. Beverly Schaefer: Roswell Park Cancer Institute, WNY Blood Care, Oishei Children's Hospital, Pediatric Hematology and Oncology, UBMD Pediatrics, Buffalo, NY. Arun Panigrahi: Division of Pediatric Hematology/Oncology, University of California, Davis, Sacramento, CA. Courtney Thornburg: Hemophilia and Thrombosis Treatment Center, Rady Children's Hospital San Diego, University of California‐San Diego, San Diego, CA. Kristin Shimano: Department of Pediatrics, Children's Cancer & Blood Diseases Program, UCSF Benioff Children's Hospital, San Francisco, CA. Sanjay Ahuja: Pediatric Hematology/Oncology. Rainbow Babies and Children's Hospital, University Hospital Cleveland Medical Center, Cleveland, OH. Angela Weyand: Pediatric Hematology Oncology, C. S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI. Alexander Boucher: University of Minnesota Physicians, University of Minnesota Masonic Children's Hospital, Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota Medical School, Minneapolis, MN. Yasmina Abajas: Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of North Carolina School of Medicine, Chapel Hill, NC. Anjali Subbaswamy: Department of Pediatrics, University of New Mexico, Albuquerque, NM. Osman Khan: The Jimmy Everest Center for Cancer and Blood Disorders in Children, Oklahoma Center for Bleeding and Clotting Disorders, University of Oklahoma Health Sciences Center University of Oklahoma, Oklahoma City, OK. Colleen Druzgal: Department of Pediatrics, School of Medicine, University of Virginia, Charlottesville, VA. Deanna Maida: South Texas Comprehensive Hemophilia Treatment Center, Pediatric Hematology/Oncology, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX. Allison Wheeler: Department of Pediatrics, Pediatric Hematology, Vanderbilt University Medical Center, Nashville, TN. Lynn Malec: Pediatric Hematology‐Oncology, Children's Wisconsin, Pediatrics Comprehensive Center for Bleeding Disorders, Medical College of Wisconsin, Milwaukee, WI. Brian Branchford: Versiti Medical Sciences Institutes, Department of Pediatrics, Division of Pediatric Hematology/Oncology/Bone Marrow Transplant, Medical College of Wisconsin and Children's Wisconsin. Nicole Elena Kucine: NewYork‐Presbyterian, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Weill Medical College of Cornell University, New York, NY. Stephanie Prozora; Yale Hemophilia Treatment Center, Section of Hematology Oncology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT.

Supporting Information

Appendix S1