REVIEW

CURRENT
OPINION What is new in the blood bank for trauma
resuscitation
Roman Dudaryk a, Aaron S. Hess b, Albert J. Varon a, and John R. Hess c

Purpose of review
The aim of the present review was to describe recent changes in blood banking thinking, practice, and
products that affect trauma care.
Recent findings
Prompt balanced hemostatic resuscitation of major hemorrhage from trauma improves outcome and
reduces blood use. New blood processes and products can help deliver appropriate doses of procoagulant
plasma and platelets quicker and more safely. New processes include holding larger inventories of thawed
plasma with risk of wastage and rapid plasma thawers. New products in the blood bank include group A
or group A low-titer B thawed plasma and AB or A liquid (never-frozen) plasma for resuscitation, prepooled
cultured whole blood–derived platelets in plasma, and prepooled cryoprecipitate in varying pool sizes.
Single-donor apheresis or pooled whole blood–derived platelets in additive solution, designed to reduce
plasma-related transfusion reactions, are also increasingly available but are not an appropriate blood
component for hemorrhage control resuscitation because they reduce the total amount of administered
plasma coagulation factors by 10%.
Summary
Early initiation of balanced massive transfusion protocols leading to hemostatic resuscitation is lifesaving.
Changing blood product availability and composition will lead to higher complexity of massive transfusion.
It is critical that anesthesiologists understand the composition of the available new blood products to use
them correctly.
Video abstract
http://links.lww.com/COAN/A38
Keywords
damage control resuscitation, hemorrhage control resuscitation, platelet additive solutions

The transfusion medicine community is wor-

INTRODUCTION
The approach to resuscitation of the trauma patient
with massive uncontrolled bleeding has evolved
markedly over the past decade [1]. From the Advanced
Trauma Life Support paradigm of first restoring circu-
lating volume and oxygen delivery, then controlling
vascular bleeding, and finally fixing coagulation, we
have moved to balanced ‘hemorrhage control’ or
‘damage control’ resuscitation across the continuum
of prehospital, emergency room, operative, and post-
operative care [2]. This new approach appears to save
both lives and resources [3 ,4,5]. Along the way, we
&
ried about the availability of the conventional uni-
versal donor blood products, group O RhD-negative
(O Neg) red blood cells (RBCs) and group AB fresh
frozen plasma (FFP), and about alternatives to FFP
and conventional platelets in plasma [9,10]. O Neg
RBCs are frequently in short supply and are needed
a
Division of Trauma Anesthesiology, University of Miami Miller School of
Medicine, Miami, Florida, bDepartment of Anesthesia, University of Wis-
consin Hospital and Clinics, Madison, Wisconsin and cDepartment of
Laboratory Medicine, University of Washington School of Medicine,

Seattle, Washington, USA

have become much more sophisticated about the uses
and limits of the conventional blood components
[6,7]. Just as we are becoming comfortable with the
new paradigm of 1 : 1 : 1 resuscitation, blood bankers
are changing the components and making new ones
available to meet national demands for blood avail-
ability and safety [8].
Correspondence to John R. Hess, MD, MPH, FACP, FAAAS, Professor of
Laboratory Medicine and Hematology, University of Washington School
of Medicine; Medical Director, Transfusion Service, Harborview Medical
Center, 325 N. Ninth Ave., Seattle, WA 98104, USA.
E-mail: hessj3@uw.edu
Curr Opin Anesthesiol 2015, 28:206–209
DOI:10.1097/ACO.0000000000000156

www.co-anesthesiology.com Volume 28 ! Number 2 ! April 2015

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


KEY POINTS
! Apheresis plasma, liquid plasma, and group A plasma
are all being made to increase the supply of plasma for
immediate use in trauma.
! Prepooled whole blood platelets and prepooled
cryoprecipitate will speed the delivery of platelets and
cryoprecipitate for trauma patients.
! ‘Platelets in additive solution’ contain 180 ml less
plasma than normal apheresis platelets and are not
appropriate for hemostatic resuscitation if alternatives
are available.
for O Neg patients, infants, and remote care
situations without laboratory support. Using O
Neg units in trauma only for women of childbear-
ing potential or RhD-alloimmunized individuals
helps preserve this precious national resource. Six
percent of the population is O Neg and, by heavily
recruiting such donors, 10 or 11% of the RBCs in the
system are O Neg. AB donors are more rare – only
4% of individuals – and the decision not to use
women as plasma donors to prevent transfusion-
related acute lung injury reduces the availability of
AB FFP by half. Whole blood–derived AB FFP is
almost always in short supply, and as a result there
are a series of new plasma products. These are
discussed below. Anesthesiologists need to be aware
that a new low-plasma platelet product, platelets
in platelet additive solution, can reduce the
delivery of coagulation factors in damage control
resuscitation [11].
ALTERNATIVES TO WHOLE BLOOD-
DERIVED FRESH FROZEN PLASMA
FFP is plasma that is frozen within 8 h of collection.
When made from whole blood, it is approximately
80% plasma and 20% anticoagulant with an Inter-
national Normalization Ratio of approximately 1.1.
Thawed, it can be kept for up to 24 h. Most blood
collected in the USA, however, comes from mobile
blood drives and the plasma is not frozen until 8 h
after collection. Such plasma is called FP24, indicat-
ing that it was frozen within 24 h of collection, and
it is in most respects identical to FFP. Relabeled as
thawed plasma, both FFP and FP24 can be kept
thawed for up to 5 days, which makes allowance
for storage in the emergency room [12 ]. Most trans-
&
fusion services view all of these products as equiv-
alent when given in compatible blood types.
Plasma can also be collected by apheresis, return-
ing the platelets and RBCs to the donor at the time of
collection. Because there are no associated iron losses,
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Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
New blood products for trauma resuscitation Dudaryk et al.
the limit on donation of six times a year does not
apply and the US Food and Drug Administration
allows apheresis plasma donors to donate up to
600 ml per donation up to twice a week and 24 times
in a year, similar to apheresis platelet donors. This
plasma is then broken down into 200 ml units. The
plasma is more concentrated in apheresis plasma
because the anticoagulant solution uses twice the
concentration of citrate in half the volume resulting
in units that are approximately 90% plasma. Unfortu-
nately, AB apheresis plasma is uncommon because
AB donors are uncommon, apheresis procedures
are relatively time-consuming and expensive, and
the donors tend to be used as platelet donors rather
than plasma donors [13].
LIQUID PLASMA
Liquid plasma (LQP) also known as ‘never-frozen
plasma’ is a blood product left over from the 1960s
and 1970s, when whole blood in citrate phosphate
and dextrose could be stored for only 21 days. At the
end of those 21 days, the plasma could be separated
and kept for another 5 days. As a result of those
never-rescinded regulations, it is legal to keep never-
frozen plasma for a total of 26 days because most
blood is collected into citrate phosphate and dex-
trose. Ten years ago, only one hospital in the USA
was doing this, but use is now spreading under the
pressure of maintaining liquid inventories for
immediate use. With this extended shelf life, LQP
can also be used in prehospital settings. Initial con-
cerns about its safety and effectiveness have been
addressed [14]. A recent study [15] compared the
hemostatic potential of LQP with thawed FFP in
vitro, demonstrating superiority of LQP in terms of
thrombin generation and the dynamics of clot for-
mation and strength on thromboelastogram. Retro-
spective analysis of a large transfusion database from
Sweden comparing use of FFP with that of LQP [16]
demonstrated a lower mortality at 14 days after
transfusion in the LQP group, providing more evi-
dence that LQP is as well tolerated as FFP. Several
trauma centers have already included LQP in their
massive transfusion protocol (MTP), and in the near
future we are likely to see increased utilization of
this product as more suppliers make it available.
TYPE A PLASMA
Early administration of FFP during hemostatic resus-
citation requires around-the-clock availability of
thawed units. After thawing, those units must be
used within 5 days or discarded. To prevent waste, if
not used within 3–4 days, AB FFP units are fre-
quently allocated to general use and dispensed as
www.co-anesthesiology.com 207
Trauma and transfusion
universal donor thawed plasma. In low-volume
trauma centers, this practice leads to increased use
and wastage of AB FFP, to a degree that suppliers
are not able to meet the increased demand for this
valuable commodity.
Recently, use of type A thawed plasma has been
proposed as an alternative to type AB in initial stages
of MTP before type-specific FFP is available [17]. Type
A plasma is widely available: 40% of the American
population shares this blood group. On the basis of
population frequencies of 45% type O and 40% type
A, type A plasma can be safely transfused in approxi-
mately 85% of patients admitted to a trauma center.
If used in the remaining 15% of patients (type B and
type AB), the theoretical risk of hemolytic transfu-
sion reaction is limited by the generally low levels of
anti-B antibodies in most North American donors. If
only units with a low titer of anti-B antibody are
selected, the risk can be further mitigated. Groups at
Dartmouth-Hitchcock Medical Center and the Uni-
versity of Massachusetts, Worchester, have each pub-
lished experience using this scheme [18 ,19]. In both
&
series, only a few units were allowed to be adminis-
tered, with additional FFP being type compatible.
Data from three of the sites in the Pragmatic
Randomized Optimal Plasma and Platelet Ratios
(PROPPR) trial are in press with some group B and
AB patients receiving up to nine group A units, but
the total numbers of patients in all of the series
combined is small because numbers of B and AB
patients are small [20 ]. It is worth mentioning that
&&
development and implementation of such an
approach still carries an increased risk of transfusion
reaction that has to be accepted by the hospital
transfusion committee and treating physicians.
RAPID THAWING DEVICES
FFP is stored frozen at "308C, and thawing requires
approximately 25 min of immersion with agitation
in a 378C water bath. There is one company in North
America that sells a microwave licensed for thawing
FFP without damaging the plasma with local over-
heating, and the device can thaw 1 U in 6 min and
2 U in 10–12 min [21]. A pair of such units can
markedly speed the release and improve the pace
of plasma release in massive transfusion situations.
Anesthesiologists serving on transfusion commit-
tees can help transfusion services justify the cost
of these devices to hospital administrators. There is a
need for such better and cheaper devices as well.
PREPOOLED CRYOPRECIPITATE
Decreased fibrinogen concentration has been linked
to trauma-induced coagulopathy. An updated
208 www.co-anesthesiology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
European guideline on the management of bleeding
following trauma [22] recommends maintaining the
fibrinogen concentration above 1.5–2.0 g/l (150–
200 g/dl). This can be achieved by either fibrinogen
concentrate, which is not approved for this use in the
USA, or cryoprecipitate. Although cryoprecipitate is
included in the vast majority of MTPs, the recently
published Prospective Observational Multicenter
Major Transfusion (PROMMTT) study [23 ] indi-
&&
cated that the majority of patients did not receive
cryoprecipitate or received it very late. One of the
obvious explanations for this delay is the labor-inten-
sive and time-consuming process of pooling multiple
small units of cryoprecipitate into pools that usually
contain 5–6 U of single-donor cryoprecipitate. The
process can take a technologist much of an hour at a
time when the transfusion service is very busy [24].
Such a delay can be avoided by prepooling the cry-
oprecipitate component immediately after separ-
ation from plasma but prior to freezing. This
product has been available from a few blood centers
for more than a decade, but increasing demand is
leading to increasing availability. Pooled cryopreci-
pitate can be rapidly thawed as a pool contains only
60–120 ml and will allow timely correction of a low
fibrinogen content in bleeding trauma patients. As a
unit of cryoprecipitate typically contains 200–
350 mg of fibrinogen, a pool will contain 1–2 g. A
trauma dose for an adult will generally be of the order
of two pools and may need to be repeated.
NEW PLATELET PRODUCTS
Platelets are critical in injury care and an important
part of MTPs [25]. Platelets, however, carry the high-
est risk of bacterial contamination among all blood
products, at approximately 1 in 2000 U collected, so a
pool of five is estimated to have a risk of contami-
nation approximately 1 in 400 [26]. It is not uncom-
mon for a trauma patient to receive four or five sets of
pooled platelets, which can increase the risk of pla-
telet-related sepsis to below 1 in 100. Such patients
frequently have complex injuries and multiple sour-
ces of potential infection, which make the diagnostic
connection to platelet transfusion difficult. Platelet
pools made from whole blood with sterile connec-
tion technology have no increased risk of pooling-
associated contamination. Routine surveillance cul-
tures taken at 24 h after pooling detect approximately
70% of contaminated pools, which significantly
reduces the chance of bacterial contamination from
transfusion of multiple pooled units to a single
patient – bringing it closer to the 1 : 5000 risk associ-
ated with conventional apheresis platelets.
Platelets in additive solution are another new
product that is available in blood banks of some
Volume 28 ! Number 2 ! April 2015

centers. In this product, 65% of the normal 300 ml
of plasma in apheresis platelet units is replaced by a
saline nutrient solution [27]. The lost plasma will
reduce the total plasma in 6 U of RBC, 6 U of FFP, and
this unit of apheresis platelets by just over 10% and
have the effect of reducing the concentration of
administered plasma coagulation factors from 65
to 58% of normal. This is half of the difference in
administered plasma concentrations, 65 vs. 52%, in
the 1 : 1 : 1 and 1 : 1 : 2 plasma : platelet : RBC unit
ratio arms of the PROPPR trial [28 ]. In trauma
&
patients, this product should be avoided if alterna-
tive preparations of platelets are available.
CONCLUSION
Hemostatic resuscitation with early, high-ratio
(1 : 1) administration of RBCs to FFP is becoming
the standard of care of bleeding trauma patients
requiring massive transfusion. Medical societies in
both the USA and Europe have recognized the vital
importance of this approach to the care of the
critically injured. Increasing demand and limited
supply of AB plasma motivates the transfusion
and trauma communities to search for other prod-
ucts and processes to make plasma for resuscitation
available quickly. Type A-low-B titer plasma and
LQP are becoming new alternative products for early
FFP administration. Prepooled cryoprecipitate and
whole blood platelet pools will further improve
efficiency and quality of MTPs. Well observed series
of cases are urgently needed to compare these new
blood products with current standards of care.
Acknowledgements
J.R.H. was supported in part by the US National Heart
Lung and Blood Institute through the PROPPR trial
U01HL077863.
Financial support and sponsorship
None.
Conflicts of interest
J.R.H. is the inventor of the AS-7 RBC additive solution.
He receives patent royalties from the US Army and the
University of Maryland and has received consulting fees
from Haemonetics Corporation, licensee of the patents.
REFERENCES AND RECOMMENDED
READING
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& of special interest
&& of outstanding interest
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www.co-anesthesiology.com 209