a note from the chair · bloodnet: the pediatric critical care blood research network 1 spring 2018...
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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
BloodNet: The Pediatric Critical Care Blood Research Network 2 Spring 2018
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)
BloodNet: The Pediatric Critical Care Blood Research Network 5 Spring 2018
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
BloodNet: The Pediatric Critical Care Blood Research Network 6 Spring 2018
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
BloodNet: The Pediatric Critical Care Blood Research Network 7 Spring 2018
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/
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@BloodNet_PALISI
Or email Grace Henderson:
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