A note from the Chair · BloodNet: The Pediatric Critical Care Blood Research Network 1 Spring 2018 BloodNet has really grown these last few years. We now have 113 members, from 58

BloodNet: The Pediatric Critical Care Blood Research Network 1 Spring 2018

BloodNet has really grown these last

few years. We now have 113

members, from 58 sites, in 8 countries.

We are the largest network on

transfusion research!

These last few months, we have

published 15 peer-reviewed articles.

Our Scientific Committee has reviewed

14 manuscripts, including the majority

of the TAXI manuscripts, as well as 4

protocols or grants.

Allan Doctor has received two new

grants totaling $5 million for his work

on ErythoMer, a nano-scale synthetic

red blood cells that can deliver oxygen

throughout the body. Stacey Valentine,

Scot Bateman, and Phil Spinella

secured grants for TAXI, from NICHD,

NHLBI R13, SABM-Haemonetics

Research Starter Grant, and

Washington University Children's

Discovery Institute Grant. Marianne

Nellis and Oliver Karam have

submitted two proposals for NHLBI

grants.

BloodNet members have also been

presenting two sessions at the AABB

meeting in San Diego, and will be

presenting at the PAS meeting in

Toronto and a whole-day workshop at

the World Congress in Singapore.

BloodNet has also started a research

collaboration with the pediatric group

of ISBT, the International Society of

Blood Transfusion. This should allow

us to collaborate on new projects and

enroll patients in new centers.

As from the fall, BloodNet meetings will

last a whole day, to allow for more

discussion time.

BloodNet has decided not to ask for

annual fees, but to ask for a $100 fee

to attend the meetings, in order to

cover for the costs. This will also help

us invite speakers to talk about new

methods, designs, or perspectives, to

stimulate our own research projects.

We will also allow industry to present

blood-related research projects, for a

certain fee.

Finally, BloodNet has a new logo, a

new website (BloodNetResearch.org),

and a new Twitter account

(@BloodNet_PALISI)!

We are looking forward to seeing you

all at our next meeting, in Boston, on

September 5, 2018!!!

Dr. Oliver Karam, MD, PhD

Chair

A note from the Chair

Coronado Bay Resort, San Diego


Sheila Hanson presented a summary

of a recently completed study by

members of the Hemostasis and

Thrombosis subgroup.

Although it is routine to administer

pharmacologic prophylaxis for venous

thromboembolism to adults after

trauma, the paucity of pediatric-

specific evidence on the risk-benefit

ratio of prophylaxis limits the adoption

of adult-driven practice.

The objective was to determine

whether venous thromboembolism

prophylaxis in post pubertal children

after trauma is not inferior to its effect

in similar adults.

We conducted a propensity score-

matched cohort study using data from

the Trauma Quality Improvement

Program from 2015-2016, in patients

≤21 years old with severe trauma,

traumatic brain injury, central venous

catheterization or mechanical

ventilation.

In this propensity score-matched

cohort study using data from the

Trauma Quality Improvement

Program, the effect of low molecular

weight heparin for venous

thromboembolism prophylaxis was not

inferior to that of adults in post-pubertal

children but inferior in pre-pubertal

children.

In conclusion, low molecular weight

heparin, when received within 72 hours

after admission, may prevent venous

thromboembolism in post-pubertal

children at high risk of venous

thromboembolism after trauma.

Oliver Karam presented the findings

from his recently completed

International Survey on Clinically

Relevant Bleeding in Critically Ill

Children. Bleeding, a feared

complication of critical illness, is

frequent in critically ill children.

However, the concept of clinically

relevant bleeding is ill-defined.

Although there have been many

definitions of bleeding, only one has

been developed to evaluate critically ill

adults, and none for critically ill

children. Our objective was to identify

the factors that influence pediatric

intensivists’ perception of clinically

relevant bleeding.

We designed a web-based survey sent

to 526 pediatric critical care physicians

and nurse practitioners who are

members of the Pediatric Acute Lung

Injury and Sepsis Investigators

(PALISI) group, as well as pediatric

critical care physicians who

participated in two transfusion-related

studies. We asked respondents to

qualify the clinical significance of 106

bleeding characteristics, using a 9-

point Likert scale.

The response rate was 40%, with

respondents from 16 countries.

Bleeding characteristics most

frequently identified as definitively

clinically relevant were those in critical

locations (especially when the

bleeding leads to organ failure),

requiring interventions, physiological

repercussions, and duration of

bleeding. Quantifiable bleeding > 5

ml/kg/hr for more than one hour was

also frequently considered as clinically

relevant. Respondents also identified

the following characteristics as

clinically irrelevant: dressings required

to be changed no less than every 6

hours, streaks of blood in oro- or

nasogastric tubes, streaks of blood in

endotracheal tubes or blood in

endotracheal tubes only during

suctioning, lightly blood-tinged urine,

quantifiable bleeding < 1 ml/kg/h, and

non-coalescing petechia. Perception of

bleeding was not influenced by

Relative effectiveness of pharmacologic prophylaxis against venous thromboembolism in

children after trauma

International Survey on Clinically Relevant Bleeding in Critically Ill Children

BloodNet: The Pediatric Critical Care Blood Research Network 3 Spring 2018 geographical location or the

experience of the respondent.

In conclusion, this international survey

provides a better understanding of the

factors that influence pediatric

intensivists’ perception of clinically

relevant bleeding. The respondents’

perception of bleeding is not captured

by currently available bleeding scores.

It is therefore important to develop a

validated definition of clinically relevant

bleeding in critically ill children.

Oliver Karam also presented a new

protocol:

A fifth of all critically ill children will

have at least one episode of clinically

relevant bleeding during their

admission in a pediatric critical care

unit. As these bleeding events may

have dramatic adverse consequences,

clinicians may opt to transfuse

hemostatic blood products, such as

plasma, platelets, whole blood, and/or

cryoprecipitate. Surprisingly, there are

currently no data on the proportion of

critically ill children who suffer bleeding

events and who are transfused with

hemostatic blood products. We do

know that more than a third of plasma

and platelet transfusions are

administered to bleeding critically ill

children, but not all bleeding patients

are transfused. A physician’s decision

to transfuse is based on many different

factors, such as the anatomic location

and amount of bleeding, the

physiological effects of bleeding, the

coagulation and platelet tests, and the

severity of the underlying disease. Yet,

there are no data regarding those

factors that are predictive of the

transfusion of hemostatic blood

products. The lack of data regarding

when and why transfusion is employed

is a major obstacle to the design of

clinical trials targeting specific

interventions to stop or prevent

bleeding. A better understanding of

these factors could aid the

development of clearer guidelines,

better therapies, and decrease

unnecessary transfusions.

Therefore, we propose a study that will

determine the epidemiology of

hemostatic blood product transfusion

in bleeding critically ill children.

We will conduct a multicenter,

prospective, cohort observational

study at eight pediatric critical care

units, enrolling 385 consecutive

critically ill patients who are bleeding.

For aim 1, we will evaluate the

proportion of bleeding critically ill

children who are transfused with

hemostatic blood products. For aim 2,

we will identify predictive factors for the

transfusion of these blood products in

bleeding critically ill children. For aim 3,

we will compare the physician’s

perceived severity of bleeding with an

objective assessment of the severity of

the bleeding.

An understanding of the epidemiology

of hemostatic blood transfusions to

treat bleeding in critically ill children will

facilitate the design of trials targeting

interventions to stop or prevent

bleeding. Furthermore, identifying the

predictive factors and the perceived

severity of bleeding will enable the

development of interventions to

decrease unnecessary transfusions.

Sheila Hanson provided an update

from the group she leads.The group

has been active, with a wide range of

areas of interest. Recently completed

studies include: Massive Transfusion

(Spinella), Role of Platelet Function

and Microparticles in CPB (Meyer),

VTE Prophylaxis in Pediatric Trauma

(Hanson, Faustino), Survey of

Bleeding and Thrombosis in CHD

(Nelson, Hanson, Spinella), and

Platelet function in Chromosome 18

anomalies (Meyer).

There are several funded and

unfunded ongoing studies in CVC-

associated thrombosis (Faustino),

platelet aggregation in CHD (Nelson),

Platelet microparticles in CPB (Meyer),

prothrombotic state in childhood

disease (Meyer) and multiple studies in

thrombin generation (Spinella,

Nelson). In addition, there are 8 studies

ongoing, using the first harvest data

from the pediatric ECMO data registry,

Update from the Thrombosis and Hemostatis Subgroup meeting

Transfusion of Hemostatic Blood Products in Critically Ill Children

BloodNet: The Pediatric Critical Care Blood Research Network 4 Spring 2018 PEDECOR, established in

collaboration with BloodNet.

Proposed studies with plans to seek

funding in the near future include:

Prophylaxis in trauma or surgical

patients (Faustino, Hanson),

Prophylaxis in Intubated Adolescents

(Faustino), Cold vs warm platelet

transfusion trial (Spinella, Steiner,

Zantec), Mechanisms of traumatic

coagulopathy (Nair, Russell, Spinella),

tPA dwell to prevent CVC thrombosis

(Hanson).

Please contact one of the study

investigators if interested in

collaboration.

Marianne Nellis presented a protocol

focusing on Pediatric Plasma and

Platelet Transfusions in the Recipient

Epidemiology and Donor Evaluation

Study-III (REDS-III) database.

Over 230,000 units of plasma and

platelets are prescribed to children in

the US annually. However, little is

known about their efficacy and safety,

as divergent views exist regarding their

benefits and harms. This lack of

knowledge is reflected in the published

guidelines for pediatric plasma and

platelet transfusions which are based

primarily on expert opinion and, at

times, considered controversial. Initial

studies of plasma and platelet

transfusion practices have

demonstrated marked variability in

utilization.

The use of plasma and platelet

transfusions in children is driven by the

experience of the providers, not data.

To prescribe these products in the

safest, most efficacious manner, it is

important to understand the

epidemiology of pediatric plasma and

platelet transfusions.

The Recipient Epidemiology and

Donor Evaluation Study-III (REDS-III),

supported by the NHLBI as of 2011, is

an initiative collecting information from

donors and recipients, and offers a

unique opportunity to study plasma

and platelet transfusions in children.

Though designed to focus on adults,

the database contains information on

approximately 1700 plasma

transfusions and 2800 platelet

transfusions in children admitted to the

hospital. These numbers are nearly

four times larger than any pediatric

study on the transfusion of either

product published to date, and have

yet to be analyzed.

The proposed research project will

describe the epidemiology, product

safety profiles, and efficacy of plasma

and platelet transfusions in children,

using the REDS-III database. We will

(1) examine the thresholds at which

plasma and platelets are prescribed to

children, according to different clinical

settings; (2) determine if

characteristics of the plasma and

platelet products influence their

efficacy and safety in children; and (3)

describe the effects of plasma and

platelet transfusions on hemostatic

tests in children.

Pediatric Plasma and Platelet Transfusions in the Recipient Epidemiology and Donor

Evaluation Study-III (REDS-III)


You can rely on BloodNet to support

your research and enhance your

success. The success of BloodNet is

built on the success of each of its

members.

What BloodNet will do for you:

1. When you present a research

project at BloodNet, BloodNet

members will provide feedback

which will help you better define

your specific goals and research

strategy.

2. When you are ready to apply for

funding, BloodNet’s Scientific

Committee will review your

proposal and provide feedback,

and will provide a letter of support

in order to maximize the likelihood

of getting funding.

3. When you start enrolling patients

in your study, BloodNet will help

you identify participating centers

and will provide counselling to help

overcome the difficulties that may

arise.

4. When you present your preliminary

results, BloodNet will provide input

for data interpretation, will help

with any aspect requiring their

assistance and will identify specific

discussion points.

5. When you draft a manuscript,

BloodNet’s Scientific Committee

will provide a review of the

manuscript.

What you must do for BloodNet:

1. Present projects that are fit with

BloodNet aims at BloodNet

meetings, not just PALISI. The

Scientific Committee will select

projects that will be presented at

PALISI meetings for BloodNet.

2. Respect ownership and

confidentiality for any research

project endorsed by BloodNet. It is

all about trust.

3. BloodNet expects recognition for

its input and support and requests

authorship on manuscript

submissions for projects endorsed

and presented at BloodNet

meetings.

Therefore, here are some ground

rules:

1. All projects that are presented at a

BloodNet meeting will undergo a

vote by the members attending the

meeting before being formally

endorsed by BloodNet. The three

voting options will be “not

endorsed, because not relevant to

BloodNet’s research strategy”,

“not endorsed, because project not

yet sufficiently defined”, or “yes,

project is endorsed”. The vote will

be electronic, at the end of each

presentation, based on a simple

majority.

2. If a project is voted “not endorsed,

because project not yet sufficiently

defined”, a member of the

Scientific Committee will be

designated to work with the

primary investigator, with a goal to

present again at the next BloodNet

meeting.

3. All BloodNet projects must be

presented at BloodNet meetings,

not only at the wider PALISI

meeting. The Scientific Committee

will select projects that will be

presented at PALISI meetings for

BloodNet.

4. All research projects endorsed by

BloodNet are listed in a log that will

keep track of research topic

ownership.

5. The grant proposal of any

endorsed project is expected to be

reviewed by BloodNet’s Scientific

Committee prior to grant

application.

6. An update on all endorsed projects

is expected at least once a year,

either during a meeting and/or in

the newsletter. A project must be

presented at a BloodNet meeting

at least once every two years.

7. The manuscript of any endorsed

project is expected to be reviewed

by BloodNet’s Scientific

Committee prior to submission.

8. The manuscript of any endorsed

project is expected to recognize

BloodNet as a co-author,

indicating “XX, YY, and ZZ; on

behalf of BloodNet”

9. Members who attend any

BloodNet meeting are expected to

pay for meeting expenses on a per

meeting basis.

Transgressions of these ground rules

will be reviewed by the Executive

Committee, who will be responsible for

determining the appropriate response.

Introducing BloodNet Ground Rules


2018

Nellis ME, Karam O, Mauer E, Cushing M,

Davis P, Steiner ME, Tucci M, Stanworth

SJ, Spinella PC, on behalf of the Pediatric

Acute Lung Injury and Sepsis Investigators

(PALISI) network, BloodNet, and the P3T

Investigators. Platelet Transfusions

Practices in Critically Ill

Children. Critical Care Medicine 2018.

Schmidt AE, Gore E, Henrichs KF, Conley

G, Dorsey C, Bjugstad KB, Refaai

MA, Blumberg N, Cholette JM.

Oxidation Reduction Potential (ORP)

is Predictive of Complications

Following Pediatric Cardiac Surgery.

Pediatr Cardiol. 2018 Feb;39(2):299-306

Stolla M, Henrichs K, Cholette JM,

Pietropaoli AP, Phipps RP, Spinelli

SL, Blumberg N. Haem is associated

with thrombosis in neonates and

infants undergoing cardiac surgery for

congenital heart disease. Vox Sang.

2018 Jan;113(1):72-75.

Nellis ME, Karam O. Assessing our

current practice: point prevalence

studies in transfusion medicine.

Transfusion. 2018 (Epub ahead of print)

Hassan NE, Reischman DE, Fitzgerald

RK, Faustino EVS; Prophylaxis Against

Thrombosis Practice (PROTRACT) Study

Investigators and the Pediatric Acute Lung

Injury and Sepsis Investigators

(PALISI)/BloodNet

Investigators. Hemoglobin Levels

Across the Pediatric Critical Care

Spectrum: A Point Prevalence Study.

Pediatr Crit Care Med. 2018 (Epub ahead

of print)

Muszynski JA, Reeder RW, Hall MW, Berg

RA, Shanley TP, Newth CJL, Pollack MM,

Wessel D, Carcillo J, Harrison R, Meert

KL, Dean JM, Jenkins T, Tamburro RF,

Dalton HJ; Eunice Kennedy Shriver

National Institute of Child Health and

Human Development Collaborative

Pediatric Critical Care Research Network

(CPCCRN). RBC Transfusion Practice in

Pediatric Extracorporeal Membrane

Oxygenation Support. Crit Care Med.

2018 (Epub ahead of print)

Gurney JM, Spinella PC. Blood

transfusion management in the

severely bleeding military patient. Curr

Opin Anaesthesiol. 2018 Apr;31(2):207-

214.

Shah S, Coppolino K, Menocha S, Beceiro

S, Nateri J, Spinella PC, Nicol K, Hall MW,

Muszynski JA; investigators of the PALISI

BloodNet network. Immunomodulatory

Effects of Plasma Products on

Monocyte Function in vitro. J Trauma

Acute Care Surg. 2018 [Epub ahead of

print]

Remy KE, Hall MW, Cholette J,

Juffermans NP, Nicol K, Doctor

A, Blumberg N, Spinella PC, Norris PJ,

Dahmer MK, Muszynski JA; Pediatric

Critical Care Blood Research Network

(Blood Net). Mechanisms of red blood

cell transfusion-related

immunomodulation. Transfusion. 2018.

[Epub ahead of print]

Yazer MH, Cap AP, Spinella PC, Alarcon

L, Triulzi DJ. How do I implement a

whole blood program for massively

bleeding patients? Transfusion. 2018

[Epub ahead of print]

Yazer MH, Seheult J, Kleinman S, Sloan

SR, Spinella PC. Who’s afraid of

incompatible plasma? A balanced

approach to the safe transfusion

of bloodproducts containing ABO-

incompatible plasma. Transfusion. 2018

Feb;58(2):532-538.

Sivertsen J, Braathen H, Lunde

THF, Spinella PC, Dorlac W, Strandenes

G, Apelseth TO, Hervig TA, Kristoffersen

EK, Diagnostic Study LI. Preparation of

leukoreduced whole blood for

transfusion in austere environments;

effects of forced filtration, storage

agitation, and high temperatures on

hemostatic function. J Trauma Acute

Care Surg. 2018 [Epub ahead of print]

Cannon JW, Neff LP, Pidcoke HF, Aden

JK, Spinella PC, Johnson MA, Cap AP,

Borgman MA. The evolution of pediatric

transfusion practice during combat

operations 2001-2013. J Trauma Acute

Care Surg. 2018 [Epub ahead of print]

Remy KE, Yazer MH, Saini A, Mehanovic-

Varmaz A, Rogers SR, Cap CAP, Spinella

PC. Effects of Platelet Sparing

Leukocyte Reduction and Agitation

Methods on In Vitro Measures of

Hemostatic Function in Cold-Stored

Whole Blood. J Trauma Acute Care Surg.

2018 [Epub ahead of print]

Cholette JM, Pietropaoli AP, Henrichs KF,

Alfieris GM, Powers KS, Gensini F,

Rubenstein JS, Sweeney D, Phipps R,

Spinelli SL, Refaai MA, Eaton

MP, Blumberg N. Elevated free

hemoglobin and decreased haptoglobin

levels are associated with adverse

clinical outcomes, unfavorable

physiologic measures, and altered

inflammatory markers in pediatric

cardiac surgery patients.Transfusion.

2018. doi: 10.1111/trf.14601. [Epub ahead

of print]

2017

Schmidt AE, Henrichs KF, Kirkley SA,

Refaai MA, Blumberg

N. Prophylactic Preprocedure Platelet

Transfusion Is Associated With

BloodNet Publications 2017-2018

Jennifer Muszynski


Increased Risk of Thrombosis

and Mortality. Am J Clin Pathol. 2017 Dec

20;149(1):87-94.

Refaai MA, Cahill C, Masel D, Schmidt AE,

Heal JM, Kirkley SA, Blumberg N. Is It

Time to Reconsider the Concepts of

“Universal Donor” and “ABO

Compatible” Transfusions? Anesth

Analg. 2017 (Epub ahead of print)

Demaret P, Karam O, Tucci M, Lacroix J,

Behal H, Duhamel A, Lebrun F, Mulder A,

Leteurtre S. Anemia at pediatric

intensive care unit discharge:

prevalence and risk markers. Ann

Intensive Care. 2017 Oct 24;7(1):107

Sahai T, Henrichs K, Refaai M, Heal JM,

Kirkley SA, Schmidt AE, Mendler JH,

Masel D, Liesveld J, Aquina C, Blumberg

N. ABO identical and washed blood

transfusions as candidate strategies to

reduce early mortality in

acute promyelocytic leukemia. Leuk

Res. 2017 Nov;62:1-3

Camazine MN, Karam O, Colvin R,

Leteurtre S, Demaret P, Stanworth

S, Muszynski JA, Spinella PC for the

PLASMATV investigators and the Pediatric

Critical Care Blood Research

Network. Outcomes related to the use

of frozen plasma or pooled

solvent/detergent treated plasma in

critically ill children. Pediatric Critical

Care Medicine. 2017: 18(5):e215-e223.

PMID: 28350560.

Cholette JM, Swartz MF, Rubenstein J,

Henrichs KF, Wang H, Alfieris GM, Powers

KS, Daugherty LE, Gensini F, Blumberg

N. Outcomes using a conservative vs.

liberal red blood cell transfusion

strategy in infants requiring cardiac

surgery. Ann Thorac Surg 2017;103:206-

15.

Karam O, Demaret P, Duhamel A, Shelfer

A, Spinella PC, Tucci M, Leteurtre S,

Stanworth SJ; Plasma TV

investigators. Factors influencing

plasma transfusion practices

in paediatric intensive care units around

the world. Vox Sang. 2017: 112(2); 140-

149. PMID 28176380

Muszynski JA, Spinella PC, Cholette JM,

Acker JP, Hall MW, Juffermans NP, Kelly

DP, Blumberg N, Nicol K, Liedel J, Doctor

A, Remy KE, Tucci M, Lacroix J, Norris JP

for the Pediatric Critical Care Blood

Research Network. Transfusion‐related

immunomodulation: review of the li

terature and implications for pediatric

critical illness. Transfusion. 2017 57(1):

195-206. PMID: 27696473.

Executive Committee

Oliver Karam, MD, PhD, Chair, Children’s Hospital of Richmond at VCU, Richmond, VA

Marisa Tucci, MD, Vice-Chair, Ste-Justine Hospital, Montreal, Quebec

Philip C. Spinella, MD, FCCM, Washington University School of Medicine, St. Louis, Missouri

Allan Doctor, MD, Washington University School of Medicine, St. Louis, Missouri

Jacques Lacroix, MD, St. Justine Hospital, Montreal, Quebec

Robert Parker, MD, Stony Brook University Hospital, Stony Brook, NY

Marie Steiner, MD, MS, University of Minnesota Children’s Hospital, Minneapolis, Minnesota

BloodNet Coordinator

Grace Henderson, Children’s Hospital of Richmond at VCU, Richmond, VA

Subgroup leadership

Jennifer Muszynski, MD, Nationwide Children’s Hospital, OH

Sheila Hanson, MD, Children's Hospital of Wisconsin, WI

Scientific Steering Committee

Marisa Tucci, MD, Chair, Ste-Justine Hospital, Montreal, Quebec

Neil Blumberg, MD, University of Rochester Medical Center, Rochester, NY

Allan Doctor, MD, Washington University School of Medicine, St. Louis, Missouri

Cassandra Josephson, MD, Emory University School of Medicine, Atlanta, GA

Jacques Lacroix, MD, St. Justine Hospital, Montreal, Quebec

Naomi Luban, MD, Children’s National Medical Center, Washington D.C.

Phillip Norris, MD, Blood Systems Research Institute, San Francisco, CA

Robert Parker, MD, Stony Brook University Hospital, Stony Brook, NY

Chris Silliman, MD, PhD, University of Colorado Denver School of Medicine, Denver, CO

Philip C. Spinella, MD, FCCM, Washington University School of Medicine, St. Louis, Missouri

Marie Steiner, MD, MS, University of Minnesota Children’s Hospital, Minneapolis, Minnesota

Find us on the web:

http://www.bloodnetresearch.org/

Connect on Twitter:

@BloodNet_PALISI

Or email Grace Henderson:

[email protected].

BloodNet Leadership

Connect with BloodNet

Documents

A note from the Chair · BloodNet: The Pediatric Critical Care Blood Research Network 1 Spring 2018 BloodNet has really grown these last few years. We now have 113 members, from 58