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Blood Transfusions forBurn Patients
https://t.me/medicina_free
RayhanTariq, ChristopherHoman, MingqiangLi,
andHenryLiu
35
Introduction
An estimated 180,000 deaths annually are caused by burnsrelated injury worldwide [1]. Nearly 500,000 people receive
medical treatment for burn-related events, and 3500 burn
patients die annually from their burn injury in the United
States alone. There were 40,000 burn patients hospitalized in
the United States in 2016, including 30,000 at hospital burn
centers [2]. The length of hospitalization is approximately
calculated for an average of 1day per 1% burned total body
surface area (TBSA) and increases with age and the presence
of inhalation or other co-existing injuries [3].
Anemia is one of the major challenging consequences
after severe burn injury and often requires blood transfusion.
There are two types of anemia that present in burn patients:
anemia due to acute blood loss and due to critical illness.
During the rst 1–2 weeks after severe burn injury, acute
blood loss anemia develops from thermal injury and repeated
surgical procedures for the burn wounds as well as from
intrinsic physiologic changes such as decreased hematopoiesis, red blood cell (RBC) sequestration, and increased RBC
destruction [4, 5]. Anemia of critical illness prevails usually
after week 3 and is multifactorial, and it can be caused by an
imbalance between decreased production (dampened erythropoiesis, reduced erythropoietin production, nutritional
decits) and increased destruction (amplied sequestration,
abnormal RBC morphology, increased metabolism and
inammatory response) of RBCs [6]. Burn patients with
>20% TBSA usually need intensive care hospitalization with
the probability of multiple blood transfusions over the course
of hospitalization. Burn patients were transfused a mean of
14units of packed RBCs during their hospitalization.
Massive blood transfusion is often common and substantial in burn patients as mentioned above. Blood transfusion
carries its own risks which include immunosuppression,
transfusion-related lung injury (TRALI), transfusionassociated circulatory overload (TACO), and infection transmission. A correlation between blood transfusions and
infection in burn patients is well-documented for many years
[6, 7]. One multicenter retrospective study and one retrospective single center study both reported an increased risk
of blood stream infection by 11% for each unit transfused [7,
8]. An increased mortality has also been reported with
increased transfusion rate.
Hypercoagulability and coagulopathy are also major
challenging consequences of severe burn injury and require
early detection and extensive intervention. A burn injury can
potentially induce a systemic hypercoagulable state shortly
after admission and during period of recovery. This hypercoagulability is usually driven by tissue injury, excessive
inammatory response, and hypoperfusion. A coagulopathic
status, such as disseminated intravascular coagulopathy
(DIC), is associated with severe burn injuries greater than
40% TBSA [9]. Risk of coagulopathy and excessive bleeding leads to a wide range of clinical presentation in hemostatic proles in burn patients including anemia; normo-,
hyper-, and hypocoagulability; and hyperbrinolysis.
R. Tariq · C. Hoffman
Thomas Jefferson University Hospital, Department of
Anesthesiology, Philadelphia, PA, USA
M. Li
Xiangyang Central Hospital, Department of Anesthesiology,
Xiangyang, Hubei, China
H. Liu (
*)
Department of Anesthesiology and Perioperative Medicine,
Milton S. Hershey Medical Center, Penn State College of
Medicine, Hershey, PA, USA
© Springer Nature Switzerland AG 2021
C. S. Scher et al. (eds.), Essentials of Blood Product Management in Anesthesia Practice,
https://doi.org/10.1007/978-3-030-59295-0_35
Epidemiology ofBlood Transfusion
inBurn Injury
Several studies have described the transfusion need in burn
patients in relationship between percentage of TBSA burn and
the transfusion rate. Birdsell etal. reported in a study with 109
pediatric burn patients that 100% of children with ≥30%
353
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R. Tariq et al.
TBSA received a blood transfusion, but no blood transfusions
were given for TBSA ≤5% [8]. Yogore etal. described in a
study with 1282 burn patients that 5.7% of patients with ≤10%
TBSA burn, 21% patients with 11 to 20% TBSA burn, 39%
patients with 21–30% TBSA burn, and 62% patients with
>30% TBSA burn required blood transfusion [10]. Palmieri
etal. noted that 74.7% of 620 patients with ≥20% TBSA burn
from 21 medical centers needed blood transfusion(s) [6].
Posluszny et al. found that 88.7% of patients with ≥20%
TBSA required a blood transfusion(s) [11]. Wu etal. described
that 86.5% of 133 patients with ≥40% TBSA demanded blood
transfusion(s) and 97.7% demanded a plasma transfusion(s)
[12]. Lu et al. reported a necessity for blood transfusion in
71.9% of 89 patients with 15–65% TBSA and a necessity for
plasma transfusion(s) in 44.9% [13].
It is noteworthy the historical rate of blood transfusion as
it relates to TBSA burn percentage. The transfusion rate has
been documented in several studies in earlier days. Graves
etal. noted an average of 19.7units in patients with >10%
TBSA [7]. Vasko etal. found that patients with >10% TBSA
received an average of 8.94 units and patients with >30%
TBSA required 17units [14]. Palmieri etal. described that
patients with ≥20% TBSA were transfused on average with
13.7 ± 1.1 units and patients with burns ≥50% TBSA
received >30units of RBC transfusion. Patients with >40%
TBSA required at least 11units of RBCs [6]. Posluszny etal.
showed that patients with >40% TBSA demanded on average a blood transfusion of 20units [11]. Wu etal. reported
that patients with ≥40% TBSA were given an average of
68.2units of blood [12].
These numbers showed the liberal trend for blood transfusion in burn patients traditionally. The Transfusion
Requirements in Critical Care (TRICC) trial for stable ICU
patients triggered a shift from traditionally liberal transfusion strategy (hemoglobin 10–12g/dL) toward a currently
more restrictive strategy (hemoglobin 7–8g/dL), supported
by outcomes that a restrictive strategy was at least as safe as
the liberal strategy and was able to decrease hospital mortality in restrictive group [15]. Burn patients were excluded in
the TRICC trial and its following studies. In 2017, a large,
multicenter, randomized, and prospective trial of blood
transfusion investigation, entitled “Transfusion Requirement
in Burn Care Evaluation (TRIBE),” compared the restrictive
strategy of blood transfusion versus the liberal strategy in
patients with burn injury >20% TBSA [16]. The results
showed no statistically signicant differences in mortality,
hospital length of stay, ICU stay, or safety [16].
Burn Injury andCoagulopathy
While blood transfusion in a burn patient may reduce the
adverse effect associated with anemia, blood transfusion is
associated with some side effects of its own. The major side
effects include pulmonary edema, volume overload, immune
suppression, TRALI, and potentially coagulopathy.
Transfusion-related coagulopathy is usually secondary to
massive transfusion which leads to dilutional coagulopathy.
Burn injury is a known disruptor of coagulation cascade displaying a wide range of presentations from sub-clinical
manifestation to fulminant DIC.The underlying pathophysiology is the propagation of both thrombosis and brinolysis
mediated by inammatory cytokines and release of tissue
factors. The natural anticoagulants are subsequently depleted.
The hypothermia and hemodilution secondary to aggressive
uid resuscitation also contribute to the coagulation abnormality. These changes resemble those disturbances in major
trauma or sepsis [17]. Because of previously mentioned reasons, it is very helpful to obtain a dynamic measurement of
blood coagulation for an accurate assessment of the current
coagulation status for the management of these burn patients.
This can be achieved quickly and point-of-care basis by viscoelastic testing of blood in current medical practice.
Correction of the coagulopathic defects decreases the associated morbidity and mortality. Empirical evidence suggests
that viscoelastic tests such as thromboelastography can better guide transfusion when used in complement with the traditional blood coagulation tests [18]. The use of specic
blood components could somewhat limit the patients’ exposure to the risk associated with blood products. However, it
seems like the use of viscoelastic testing or specic blood
component products (cryoprecipitate, brinogen concentrate, and prothrombin complex concentrate) is still not
widely adopted, especially in developing countries [19].
TRIBE Trial andtheOptimal Blood
Transfusion Threshold inBurn Patients
It is widely accepted now that restrictive blood transfusion is
as effective as liberal strategy in ICU patients. This is largely
the result of the 1999 Transfusion Requirements in Critical
Care (TRICC) trial. However, the TRICC trial was not
designed to be specic to burn patients and considered a mix
of all the ICU patients. Burn patients have some unique
pathophysiological alterations. A hypermetabolic state, prolonged hospitalization, and need for multiple surgeries are
some of the characteristic features of severe burn injury in
critical care facility. The Transfusion Requirement in Burn
Care Evaluation (TRIBE) trial is one of the rst major prospective, randomized, controlled clinical trials that focused
particularly on transfusion-related issues in burn patients. The
goal of TRIBE was to compare outcomes under a restrictive
blood transfusion policy (maintaining a hemoglobin level at
7–8 g/dL) to a traditional transfusion policy (maintaining
hemoglobin at 10–11g/dL) [16]. In this TRIBE clinical trial,
345 patients across 18 medical centers were randomized to a
restrictive (hemoglobin level at 7–8 g/dL) or liberal (hemoglobin level at 10–11 g/dL) transfusion strategy throughout
hospitalization. The median blood transfusion in restrictive
35 Blood Transfusions forBurn Patients
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355
group was 8units, i.e., half of the 16units in the liberal group.
Patients were studied during their entire hospital stay including any ICU stay and surgical procedures. The authors found
no difference in incidence of bloodstream infections, organ
dysfunction, mechanical ventilation days, time to wound
healing, and 30-day mortality. This well-designed clinical
trial presents high-quality evidence that a conservative blood
management therapy is non-inferior to liberal approach in
burn patients while reducing exposure to blood products and
conserving this very valuable commodity.
Summary
In the United States, nearly 500,000 people will need certain
medical treatment for burn-related injuries, and 3500 burn
patients die from their burn injury annually. Risks of excessive bleeding and sepsis cause a wide range of abnormal
hemostatic proles in burn patients including anemia;
normo-, hyper-, and hypocoagulability; and hyperbrinolysis. Correction of the coagulopathic defects decreases the
associated morbidity and mortality. Viscoelastic tests such as
thromboelastography and other point-of-care tests can better
guide transfusion practice and management of coagulation
problems when used in complement with the traditional
blood coagulation tests. These measured decits of platelets,
brinogen, and factors then be then replenished with more
specic blood components. The TRIBE trial identied the
optimal blood transfusion threshold in burn patients. The
TRIBE trial was a well-designed prospective randomized
multicenter trial that showed similar outcomes in a restrictive
(hemoglobin 7–8 g/dL) versus liberal (hemoglobin 10–11 g/
dL) transfusion strategy. A restrictive blood transfusion was
well tolerated in burn patients while reducing exposure to
blood products and providing economic benets by reducing
blood consumption and hospital stay.
References
1. WHO, fact sheets [Internet]. Burns; Available from: https://www.
who.int/news-room/fact-sheets/detail/burns. Accessed on 28 Aug
2019.
2. National Burn Repository: Report of Data from 2017.
American Burn Association.
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A+Report+of+Data+from+2005-2015+&gs_l=psy-ab.1.0.33i29
9l2.4172.4172..10004...0.0..0.324.500.0j1j0j1......0....2j1..gws-
wiz.....0....10001%3A0%2C154.GAJ2PGw0Atw. Accessed on 28
Aug 2019.
3. Taylor SL, Sen S, Greenhalgh DG, Lawless M, Curri T,
Palmieri TL. Real-time prediction for burn length of stay
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5. Loebl EC, Marvin JA, Curreri W, Baxter CR.Erythrocyte survival
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6. Palmieri TL, Caruso DM, Foster KN, Cairns BA, Peck MD, Gamelli
RL, etal. Effect of blood transfusion on outcome after major burn
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7. Graves TA, Ciof WG, Mason AD Jr, McManus WF, Pruitt BA
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8. Birdsell DC, Birch JR.Anemia following thermal burns: a survey of 109 children. Can J Surg. 1971;14(5):345–50. PMID:
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9. King DR, Namias N, Andrews DM.Coagulation abnormalities following thermal injury. Blood Coagul Fibrinolysis. 2010;21(7):666–
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10. Yogore MG 3rd, Boral L, Kowal-Vern A, Patel H, Brown S,
Latenser BA.Use of blood band services in a burn unit. J Burn
Care Res. 6:835–41.
11. Posluszny JAGR. Anemia of thermal injury: combined acute
blood loss anemia and anemia of critical illness. J Burn
Care Res. 2006;27(6):835–41.
BCR.0000245418.73538.25. PMID: 17091079.
12. Wu G, Zhuang M, Fan X, Hong X, Wang K, Wang H, etal. Blood
transfusions in severe burn patients: epidemiology and predictive factors. Burns. 2016;42(8):1721–7. https://doi.org/10.1016/j.
burns.2016.06.002. PMID: 27576934.
13. Lu RP, Lin FC, Ortiz-Pujols SM, Whinna HC, Cairns BA, Key
NS.Blood utilization in patients with burn injury and association
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Pagliarello G, et al. A multicenter, randomized controlled
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NEJM199902113400601. PMID: 9971864.
16. Palmieri TL, Holmes JH, Arnoldo B, Peck M, Potenza B, Cochran
A, etal. Transfusion requirement in burn care evaluation (TRIBE):
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S, et al. Measuring coagulation in burns: an evidence-based
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org/10.1177/2059513117728201
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M.Monitoring and treatment of coagulation abnormalities in burn
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Prehospital Transfusions by First
https://t.me/medicina_free
Providers
Marie-ChristineWright, ChikezieN.Okeagu,
AlainaL.Broussard, KeithP.Delaune, ShukanPatel,
ElyseM.Cornett, andAlanDavidKaye
36
Introduction
In 1628, English physician William Harvey published his
landmark work, Exercitatio Anatomica de Motu Cordis et
Sanguinis in Animalibus (commonly De motu cordis), in
which he described the circulation of blood in the body by
the heart. Although it was widely accepted that blood played
an essential role in the sustenance of life, little was known
about how it was delivered to the tissues to serve this vital
function. In fact, the prevailing belief theorized by Galen
~1500years earlier stated that blood was continuously produced and distributed by the liver and completely absorbed
by the tissues [1]. His discovery led to intense investigation
M.-C. Wright
University of Toledo School of Medicine, Department of
Pediatrics, Toledo, LA, USA
e-mail: Marie.wright@utoledo.edu
C. N. Okeagu
Department of Anesthesiology, LSU School of Medicine,
New Orleans, LA, USA
cokeag@lsuhsc.edu
e-mail:
A. L. Broussard · K. P. Delaune
Ochsner Clinic, Department of Anesthesiology,
New Orleans, LA, USA
e-mail:
Alaina.broussard@ochsner.org; keith.delaune@ochsner.org
S. Patel
Department of Anesthesiology, LSU Health Sciences Center,
New Orleans, LA, USA
e-mail:
spat23@lsuhsc.edu
E. M. Cornett (
Department of Anesthesiology, LSU Health Shreveport,
Shreveport, LA, USA
e-mail: ecorne@lsuhsc.edu
A. D. Kaye
Departments of Anesthesiology and Pharmacology, Toxicology
and Neurosciences, Louisiana State University School of
Medicine-Shreveport, Shreveport, LA, USA
LSU Health Shreveport School of Medicine, New Orleans, LA, USA
Tulane School of Medicine, New Orleans, LA, USA
e-mail: akaye@lsuhsc.edu
*)
into blood circulation, resulting in successful transfusion
experiments in animals within a few decades of the publication of De motu cordis, and ultimately culminating in the
successful transfusion of human blood by Dr. James
Blunndell in 1818 [2, 3]. Today, blood transfusion is the most
common procedure performed in US hospitals [4].
The indications for blood transfusion are vast and include
a number of conditions that result in blood loss and anemia,
including hemorrhage [5]. Hemorrhage is responsible for up
to 40% of deaths in trauma [6]. Massive hemorrhage also
presents a host of physiological derangements that jeopardize
the survival of trauma patients. Recognized as the “triad of
death,” the combination of hypothermia, metabolic acidosis,
and coagulopathy, when present, portends a poor prognosis
(see Fig.36.1). Severe hemorrhage can directly lead to hypothermia. Failure to control hemorrhage leads to increased
sympathetic tone, which diverts blood away from non-vital
organs in an attempt to preserve perfusion of vital organs.
This eventually leads to a mismatch between oxygen demand
and oxygen delivery, forcing the body to rely on anaerobic
metabolism, which results in the accumulation of acidic compounds such as lactic acid and ketone bodies. It also results in
a drop in pH and the development of metabolic acidosis. In an
attempt to control the massive blood loss, the body activates
the coagulation cascade, and clotting factors are quickly
depleted leading to a consumptive coagulopathy. Furthermore,
these derangements each can potentiate each other leading to
worsening acidosis, coagulopathy, and hypothermia [7–10].
The recognition that promptly addressing these factors
gives patients the best chance at a favorable outcome has led
to the development of various damage control resuscitation
(DCR) strategies [11]. Transfusion of blood products is a
staple of DCR protocols and one of the rst tools employed
upon the arrival of the patient at a trauma center [6, 10, 11].
However, elements of the triad can present within minutes,
long before patients arrive at the hospital [12, 13]. In fact, up
to 56% of trauma patients die before arrival at the hospital
[14]. As such, there has been much interest in resuscitation
© Springer Nature Switzerland AG 2021
C. S. Scher et al. (eds.), Essentials of Blood Product Management in Anesthesia Practice,
https://doi.org/10.1007/978-3-030-59295-0_36
357
358
Coagulopathy
Metabolic AcidosisHypothermia
M.-C. Wright et al.
https://t.me/medicina_free
Rapid
Hemorrhage
Fig. 36.1 Triad of death
measures that can be initiated prior to arrival at the hospital,
and this includes the administration of prehospital blood
transfusions (PHBT) [11, 14–17].
Developed with inuence from treatment regimens for soldiers injured during military conict, modern DCR aims to
mitigate rapid hemorrhage, with a balanced ratio of plasma,
platelets, and red blood cells to mimic reconstituted whole
blood [18, 19]. Traditionally, crystalloid-based resuscitation in
the prehospital setting has been common; however there has
been recent interest in developing approaches that emphasize
earlier transfusion of blood [11, 20]. While administering
blood products should theoretically help to curb the physiological effects of hemorrhage and lead to increased survival,
research into the outcomes of these protocols has yielded
mixed results. A randomized trial by Sperry et al. demonstrated that prehospital administration of thawed plasma
resulted in a lower 30-day mortality than standard resuscitation with crystalloid solution (23% vs 33%) [20]. Shackelford
et al. also found reduced 24-hour and 30-day mortality in
those that received prehospital transfusion (red cells within
30minutes of injury) in the US military combat setting [21].
Contrarily, Moore etal. found no difference in a 28-day mortality in trauma patients receiving plasma vs saline [22].
Similarly, a recent systematic review and meta- analysis examining the effectiveness of PHBT in reducing mortality by
Rijnhout etal. could not nd conclusive benet of PHBT [23].
Aside from the equivocal outcomes data, there is additional controversy surrounding prehospital transfusion. The
practice of administering blood outside of the hospital setting carries with it inherent feasibility and logistical issues.
For instance, there are legitimate concerns regarding the
availability and storage of blood products [17]. Blood products need to be stored at acceptable temperatures and have to
be utilized before expiration. Moreover, warming of blood
products before administration is advised [23, 24]. Failure to
do so will worsen hypothermia and exacerbate the physiologic derangements of the triad [8, 9, 13, 23]. Ensuring that
these requirements are met can be expensive [23, 24].
Furthermore, as there is not time to determine the blood type
of a trauma victim in the setting of life-threatening traumatic
hemorrhage, universal donor types must be on hand to avoid
inciting immunological rejection of the donor blood and
worsening the patient’s condition. Additionally, even if blood
is properly cross-matched or universal donor blood is used,
there can be negative reactions to blood transfusion such as
anaphylaxis, circulatory overload, and lung injury that rst
responders administering transfusions outside of the hospital
may be ill-equipped to deal with [20, 23].
Despite these potential risks, very few patients are
reported to have these complications [20, 23]. A lack of standardization of PHBT protocols makes it difcult to denitively determine their contribution to mortality prevention in
trauma, and the promise that has been shown by some studies suggests that PHBT may in fact provide benet if protocols can be optimized. The prospect of being able to reduce
the percentage of negative outcomes associated with traumatic hemorrhage makes further exploration into the concept
a worthwhile endeavor. This chapter will explore different
aspects of PHBT.It will provide an overview of the different
blood products available for transfusion and discuss in more
detail aspects of storage and transportation and guidelines
for PHBT. Finally, we will further discuss recent clinical
ndings and potential considerations for the future of PHBT.
Blood Products
Blood donation is highly regulated in the United States by the
Food and Drug Administration (FDA). Blood donors must be
between 16 and 65 years of age, must weigh at least 110
pounds, and exclude those with certain medical conditions or
other infectious etiologies [25]. Donors are also screened for
recent travel exposures, new tattoos or piercings, hemoglobin
concentration, blood pressure, medications, and pregnancy
[25]. In addition to screening questionnaires, blood is tested
for different infectious diseases after donation including HIV,
hepatitis B and C, WNV, HTVL, CMV, EBV, syphilis, and
Chagas [25]. Blood facilities in the United States are frequently inspected and are required to meet high-quality standards which are outlined in the Public Health Service Act 42
and enforced by the FDA to ensure the US blood supply is as
safe as possible [26]. Whole blood is collected from donors
and should be separated into components within 5–8hours
via refrigerated centrifugation [27]. Apheresis is an alternative blood collection method which collects specic components of blood while simultaneously returning the remaining
blood back to the donor using ltration techniques [27].
Whole blood is an unprocessed blood product which contains all components of physiologic circulating blood includ-
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359
ing red blood cells (RBC), plasma, platelets, and leukocytes
[27]. Since whole blood contains multiple different elements,
there are many adverse reactions that can occur when foreign
blood is given to a recipient [27]. Antigens on a red blood cell,
such as “A” or “B,” determine a person’s blood type as “A,”
“B,” “AB,” or “O.” Rh factor is another antigen that determines
if blood type is “positive” or “negative” [25]. If ABO blood
type is not correctly matched beforehand, antibodies can be
formed against the foreign antigen and can cause fatal acute
hemolytic transfusion reactions [25]. To avoid this type of
reaction, if a blood type is unknown, the universal blood donor
“O negative” should be given [25]. Whole blood can be stored
at a licensed blood bank for 35days at 1–6°C in an anticoagulant solution, citrate phosphate dextrose adenine (CPDA-1)
[27]. The US military occasionally uses “warm fresh whole
blood” (WFWB) donated from “walking blood banks” (WBB)
in combat- related trauma [28]. WFWB expires after storage at
room temperature for 24hours or refrigerated for 8hours [28].
The biggest disadvantage for using WFWB in traumatic combat situations is the risk of acute hemolytic reaction. This is
related to mismatched blood types and the possibility of transmitting infections [28]. The advantages for using whole blood
transfusions is that whole blood contains all natural blood
components in physiologic ratios without preservatives or
additives and can be stored as one modality allowing easier
access in emergency situations [28]. A 2009 study by Spinella
etal. demonstrated that WFWB is associated with an improved
30-day survival in combat-related patients with hemorrhagic
shock compared to component blood transfusion [28]. Due to
the physiologic components of whole blood, easier storage,
and access, whole blood may be advantageous to prevent hemorrhagic mortality before rst responders reach the hospital
with a critical patient.
Packed red blood cells (PRBCs) are blood products that
contain 200 mL of concentrated RBCs to a hematocrit of
75% [29]. PRBCs are used to quickly increase oxygencarrying capacity in patients who are severely anemic (hemoglobin<7g/dl) or have severe occult blood loss [29]. After
receiving 1 unit of PRBC, a patient’s hemoglobin and hematocrit are expected to rise by 1g/dl and 3%, respectively [29].
As with whole blood, ABO compatibility is essential to avoid
transfusion reactions [25]. Packed red blood cells are also
available to certain populations as “washed,” “leukoreduced,” or “irradiated.” Washed red cells are washed with
sterile saline which removes 98% of plasma, platelets, and
cellular debris and reduces leukocyte concentration [29].
Washed PRBCs are indicated in patients with a history of
allergic reaction to transfusion and IgA deciency but must
be used within 24hours of saline washing [29]. Leukoreduced
red cells are PRBCs with 99.9% of leukocytes ltered out
reducing the risk of CMV, EBV, and HTLV infections and
febrile reactions [29]. Irradiated red cells are gammaradiated PRBCs which kill all lymphocytes [29]. This blood
product is indicated to prevent donor versus host disease in
immunocompromised patients, lymphoma patients, stem
cell and marrow transplant patients, and intrauterine transfusions [29]. PRBCs can be stored at 1–6°C at a blood bank
for up to 42days. When dispensed, PRBCs can be stored in
a blood bank cooler for 6 hours [27]. Transfusion with
PRBCs can play an important role in prehospital treatment of
patients who experience hemorrhagic shock because the
highly concentrated hemoglobin allows for a rapid increase
in oxygen-carrying capacity which is vital for organ function
in patients who have lost severe amounts of blood.
Fresh frozen plasma (FFP) contains all clotting factors,
protein C, protein S, antithrombin III, albumin, immunoglobulins, tissue factor pathway inhibitor, and brinogen [30].
These elements are separated from whole blood and must be
frozen within 6hours of phlebotomy to preserve clotting factors [30]. FFP is indicated in patients with signicant coagulation factor deciencies including congenital deciencies,
microvascular bleeding with elevated PT and PTT, dilutional
coagulopathy related to massive blood replacement, disseminated intravascular coagulation, and coagulopathy secondary
to liver pathology [29]. FFP is also used in urgent reversal of
warfarin therapy and in combination with plasmapheresis to
treat thrombocytopenic purpura and hemolytic uremic syndrome [29]. FFP expires after 1year in a blood bank freezer
at ≤18°C but must be used 5days after thawing [27].
Liquid plasma (LP) contains the same blood components as
FFP, but it is immediately stored at 1–6°C instead of freezing
after phlebotomy. Liquid plasma expires 5days after the whole
blood that it was extracted from, so approximately 26–40days
depending on anticoagulation solution used [27]. Liquid
plasma contains less clotting factors than FFP, for example,
clotting factors V and VIII begin to decrease after 6hours [27].
The longer shelf life of LP compared to thawed FFP is advantageous for adequate supplies of plasma. ABO compatibility is
also a concern for plasma transfusions, but the matching system is opposite to that of RBC compatibility [31]. Since plasma
contains only antibodies, as opposed to antigens that are located
on RBCs, the universal plasma donor type is AB plasma which
contains no antibodies [31]. Liquid plasma may play a larger
role in prehospital transfusion in the future related to its longer
shelf life as compared to thawed FFP.
Platelets are an essential component of clot formation in the
blood. Platelets can be collected from single whole blood,
pooled whole blood (platelets from 4–6 donors), or apheresis
procedures [29]. Prophylactic platelet transfusions are indicated in thrombocytopenic patients or bleeding surgical patients
when the platelet count is below 50,000 or below 100,000 if the
risk of bleeding is clinically signicant [29]. They are also
needed in patients with microvascular bleeding with known
platelet dysfunction but contraindicated in idiopathic thrombocytopenia purpura (ITP) [29]. Platelets are stored at room temperature (20–24°C) with continuous gentle agitation to avoid
clot formation, but the shelf life is only 5days [29].
Cryoprecipitate is a blood product that contains concentrated factor VIII, factor XIII, brinogen, bronectin, and von
Willebrand’s factor [29]. Cryoprecipitate is indicated for pro-
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Table 36.1 Blood products analyzed by components, expiration date,
and storage requirements
Blood product Composition
Whole blood Unprocessed RBC,
Packed red
blood cells
(PBRCs)
Fresh frozen
plasma (FFP)
Liquid plasma
(LP)
Cryoprecipitate Clotting factors VIII
Platelets Platelets only 5days 20–24°C
plasma, platelets,
clotting factors, and
leukocytes in
physiologic ratios
RBCs only (small
residual plasma and
leukocytes unless
radiated or ltered)
All clotting factors,
antithrombin III,
albumin,
immunoglobulin,
brinogen protein C
and S, and tissue
factor pathway
inhibitor
Same as FFP, but less
clotting factors, never
frozen
and XIII, von
Willebrand factor,
brinogen, and
bronectin
Expiration
date Storage
21days in
CPD or
CP2D
35days in
CPDA-1
42days 1–6°C
365days
5days after
thaw
5days after
expiration
of whole
blood
extracted
from
(21+5 or
35+5)
365days
1–6°C
≤−18°C
1–6°C
before
transfusion
1–6°C
≤−18°C
with
continuous
gentle
agitation
phylaxis in perioperative patients with congenital brinogen
deciencies, patients with von Willebrand’s disease that is
unresponsive to DDAVP or currently bleeding, and correction
of microvascular bleeding in massive blood transfusions with
bronectin concentrations between 80 and 100 mg/dl [29].
Blood bronectin concentration can be raised by 50mg/dl with
administration of one unit of cryoprecipitate per 10 kg [29].
Cryoprecipitate transfusion allows for replenishment of important end components for the formation of brin clots and does
not require ABO matching before use [25]. For these reasons,
cryoprecipitate may also play an important role in prehospital
treatment when massive transfusion protocol is needed.
Currently, the massive transfusion protocol requires
PRBC, FFP, and platelets transfused in a 1:1:1 ratio for
“damage control resuscitation” in hemorrhaging patients
with severe trauma [32]. These traumatic scenarios are seen
daily throughout the United States by rst responders.
Massive transfusion achieves the goals of quickly enhancing
oxygen-carrying capacity and correcting intravascular volume depletion and trauma-induced coagulopathies while
administering in a 1:1:1 ratio to prevent dilutional coagulopathy [32]. Prehospital transfusions of hemorrhaging
patients can address these fatal problems before reaching a
medical facility (Table36.1).
Transportation, Storage, andExpiration
Prehospital transfusions by rst providers may improve outcomes in patients; however, implementing such protocols in
Emergency Medical Services (EMS) in the United States is
futile if the blood products reaching patients are of lesser quality
than those received at a hospital. Intense oversight and regulation are needed to preserve blood product quality from the time
of deployment until administration in the eld. Unfortunately,
such tight regulations can be logistical barriers to the widespread implementation of prehospital transfusion practices. Of
these barriers, the regulation of temperature during transport
remains the most difcult aspect of bringing blood into the eld.
Above ideal temperatures, the blood products may expire rapidly, making the practice of bringing blood on every emergency
call (where they might not be used) extremely costly. Maintaining
a lower temperature minimizes the metabolic activity of the
blood, prolonging its shelf life. Freezing the blood, however, is
not feasible—at temperatures below 2°C, the red blood cells
may become dehydrated and subsequently hemolyze.
Additionally, ice crystal formation can cause RBC membrane
damage [33]. That being said, whole blood and pRBCs are not
the only products used in transfusion, and unfortunately, different products are best maintained at different temperatures.
The tight control of temperature maintains the standard of
care, ensuring patients receive the same quality of blood
products administered in the Emergency Room. These temperatures, in addition to preventing damage and contamination, prolong the shelf life of the products. Shelf life is
generally described as the maximum time at which administered products are still effective. The American Association
of Blood Banks (AABB) works closely with the FDA to produce standards for temperature targets in both the storage
and transport of each blood product [34]. The following
descriptions of each type of blood products’ recommended
storage/transportation temperatures and expiration dates are
from the 2018 AABB Temperature Standards [35].
The AABB recommends the storage of pRBC preparations at a temperature between 1 and 6°C and transportation
at a temperature between 1 and 10 °C. The shelf life for
pRBCs is determined by the time at which 75% of transfused
red blood cells are still viable in the circulation 24hours after
administration. Depending on the specic anticoagulant
used, shelf life varies from 21 to 42days.
For platelet preparations, the AABB recommends storage
at temperatures between 20 and 24°C (room temperature)
with continuous agitation. During transportation platelet
preparations should be kept at the same temperature; how-
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ever continuous agitation is not necessary. The continuous
agitation in storage has been thought to reduce platelet
hypoxia and the subsequent damaging decrease in pH due to
lactic acid production [36]. The shelf life for platelet products is generally only 5days.
The AABB recommends FFP storage at temperatures less
than or equal to −18°C.At these temperatures, the shelf life
is up to 12 months from the date of collection (up to
36months if kept at temperatures below −25°C). However,
FFP must be thawed before administration, and once thawed,
the shelf life decreases to between 1 and 5days depending on
the preparation.
For cryoprecipitate, the AABB recommends storage at
temperatures less than or equal to −18°C.Similar to FFP,
cryoprecipitate also has to be thawed. Once thawed it should
be kept at room temperature until administration; however, it
quickly expires within 6 hours.
As mentioned earlier, a major obstacle for the systematic
implementation of prehospital transfusions is the transport
of these products into the eld at temperatures meeting the
demands of regulatory laws and recommendations.
Specialized containers used for transport are primarily built
around their ability to keep whole blood and blood components at the target temperature for transport. Such containers
are usually coolers of some sort with the ability to be
remotely monitored and controlled to maintain a very specic temperature, regardless of the external environment.
Coolers seem to be preferred over the use of standard blood
product refrigerators due to the mobility of coolers in the
eld. The two main components of these storage devices are
an insulated container and a coolant insert or packet. One
commonly used product is Pelican BioThermal’s (USA)
Crēdo™ Medic Pack Series 4 EMT cooler, capable of holding 2units of pRBCs and 2units of plasma. The Medic Pack
consists of an outer carrying shell, a middle vacuum pack
container, and an internal thermal container lled with
heavy water [37]. The heavy water is frozen (for at least
8hours) prior to use and once used thaws to around 3.8°C,
the melting point of heavy water. Results of testing showed
the pack could maintain blood product temperatures
between 1 and 6°C for runs up to 24hours [38]. Similarly,
companies have started production on coolers made specically for temperature- sensitive blood/medication transport.
FaraeTec’s (USA) LifeBox 50 consists of a rugged outer
shell (unlike the Crēdo™ Medic Pack) with a reticulated
polystyrene shell beneath it, a carbon aerogel vacuum-insulated panel, a zero- permeability vapor barrier for panel protection, and an inner plastic corrugated lining [39]. The
LifeBox, like the Crēdo™ Medic Pack, contains a phase
change material to help maintain target temperatures.
Neither box requires batteries for operation, giving them
both an advantage over more expensive options. However,
these containers are not cheap. Investigations into more
affordable options (containers not specically made for
such extreme temperature control) found that safe storage
and transport weren’t possible with simpler, cheaper materials [40]. It can be postulated that as more EMS departments
throughout the country adopt prehospital transfusion protocols, companies will develop more optimal storage containers perhaps at a more affordable price.
With the advent of prehospital transfusions in the eld,
much of what has been implemented does not follow a nationally standardized protocol. A few EMS programs throughout
the country have successfully implicated protocols that make
prehospital transfusions by EMS personnel effective both
medically and nancially. Departments must take care to
maintain low wastage and misuse of an already diminished
national supply of blood. To mitigate this risk, it’s imperative
that EMS departments engage in a partnership with a local
hospital or blood bank to allow rotation of the EMS’s blood
supplies. Short shelf lives mean that products not used in the
eld may go to waste; therefore “exchanging” them for newer
supplies from a local hospital or blood bank ensures that the
near-expiration blood products will likely be used quickly in
the hospital setting [41]. Certain EMS departments have also
implemented a standard that all onboard units of blood or
blood components are to be from different donations, allowing rst providers to continue to administer indicated products if one of the units causes a transfusion reaction [38].
EMS stations have used other equipment in the introduction of prehospital transfusion protocols. In some instances,
temperature probes were added to the specialized coolers,
able to display the temperature on the dashboard of an ambulance, personnel department of an aircraft, or remotely to a
supervisor. EMS stations also invested in specialized refrigeration units that allow for precise temperature control of
stored blood products [38]. Such refrigerators have advanced
technology including triple-redundant thermometers with
software that can send texts and alert staff in cases of malfunction or rising temperatures [42]. Some programs incorporated devices including point-of-care hemoglobin meters
to assist in determining if transfusion is indicated.
Additionally, portable warming devices are necessary to
allow rst providers to rapidly heat blood products for transfusion of large amounts. In experimental trials, one of these
warming devices, the Warrior Lite, was able to warm blood
products from 10°C to 35°C at a rate of 200mL/min [43].
The process of integrating prehospital transfusions into
emergency medical services in the eld is not without logistical complications. Each department must decide if implementing such protocols is cost-effective for their area.
Factors to consider include the incidence of shock/trauma in
the area, availability of a local hospital system and/or blood
bank to establish a blood-sharing program with, cost of tting emergency vehicles and stations with the appropriate
equipment, and equipment upkeep. Equipment such as coolers are the victims of excessive wear and tear due to the
demanding environment rst providers operate in daily. Not
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only are these coolers expensive, but the process of preconditioning and installation are expensive and time-consuming
[38]. Wastage of expensive blood products due to misuse,
poor storage protocols, or uncontrollable factors (i.e., vehicle
breakdown) may also contribute to increased costs. It is also
expensive, yet exceedingly important, to train all personnel
in the storage, transportation, and administration per protocol of these products [44]. Departments also must implement
strict documentation protocols, which can be time- consuming
for personnel. Much of the current research on prehospital
transfusions by rst providers understandably focuses on
indication criteria for transfusion and patient outcomes.
However, as more EMS departments throughout the country
develop prehospital transfusion programs, more research
should be directed at the cost-effectiveness of these programs
to determine if the process can be nancially streamlined.
All of the logistical barriers discussed above have prevented widespread implementation of such practices in EMS
throughout the United States. Historically, the US military
has carried blood products in medical evacuation helicopters
for some time [45]. The timeline of different departments
implementing similar practices is hard to delineate. The
Norwegian Helicopter Emergency Medical Services has
reportedly deployed aircraft with blood on board intermittently for the last 30years before nally making it standard
for every ight to carry blood products in 2013 [17]. Australia
seems to be one of the rst to implement prehospital transfusions in civilian air ambulances circa 2011, with the United
Kingdom following soon after [46]. In 2016, a study showed
that of 235 helicopter emergency medical services in the
United States, only 25.3% carried blood products. Of those
that did, only 60% carried blood products on every ight [47].
Since then many different emergency services such as Life
Flight (USA) have implemented prehospital transfusion protocols where possible. Interestingly, since 2009, cruise lines
have successfully implemented protocols for warm fresh
whole blood transfusion (WFWB) using donors on- board
[17]. Reportedly in 2017, Cypress Creek EMS and Harris
County Emergency Services District 48 of Harris County,
Texas, were the rst to carry and transfuse whole blood to
patients as a civilian ground EMS service in the United States
[41]. In 2018, San Antonio, Texas, became the rst metropoli-
tan area to equip paramedics and seven re departments with
whole blood for prehospital transfusions [48]. As research on
the results of these programs surfaces, the United States can
anticipate the implementation of similar practices in EMS
departments throughout the country. As the prevalence of prehospital blood transfusions further increases, more research
should highlight the main logistical barriers to program incorporation and allow the healthcare community to delineate
areas of improvement that increase the cost-effectiveness of
these programs, standardize protocols for transfusion, and
most importantly improve patient outcomes.
Guidelines forTransfusion andRisks
Guidelines for transfusions vary from hospital to hospital and
from society to society; however the general purpose and
backbone of various guidelines all express the same thing.
During a surgical procedure, the responsibility of transfusing
blood usually falls on the anesthesiologist; as such the
American Society of Anesthesiologists has published its own
guidelines on the subject. These guidelines are broken down
into four sections: Patient Evaluation, Preadmission Patient
Preparation, Preprocedure Preparation, and Intraoperative and
Postoperative Management of Blood Loss (see Table36.2).
Transfusion in critical care and trauma medicine has different guidelines than that of a preplanned surgery. However,
the overall goal of both scenarios is the same which is to
stabilize the patient and prevent any long-term complications, if possible. The American College of Critical Care
Medicine in conjunction with the Society of Critical Care
Medicine has transfusion recommendations relating to seven
areas: (1) critically ill, (2) sepsis, (3) patients at risk for or
with acute lung injury or ARDS, (4) neurological injury and
disease, (5) RBC transfusion risks, (6) alternatives to RBC
transfusion, and (7) strategies to reduce transfusions. See
Table36.3.
The American Association of Blood Banks has also put
forth their own guidelines for transfusions; however in the
surgical and acute setting, guidelines by the ASA and
ACCCM may be more practical. The AABB sets forth its
guidelines in the form of two recommendations. See
Table36.4.
In many instances, a RBC transfusion is critical to the survival of the patient; however, transfusion reactions do occasionally occur and should be accounted for any time blood
products are given. Acute intravascular hemolytic transfusion reactions occur when red blood cells break down due to
either a complement-mediated immune mechanism (usually
secondary to ABO incompatibility) or physical damage to
the cells (osmotic or temperature related). Severe complications such as shock and DIC are often related to ABO incompatibility and less so with physical damage. Signs of ABO
incompatibility in the operating room include hypotension,
shock, and fever. If ABO incompatibility is suspected, the
transfusion should be stopped immediately, and supportive
measures to maintain blood pressure should be done.
Transfusion of blood products such as platelets, FFP, and
cryoprecipitate will help in decreasing the consumptive
coagulopathy [52]. Syndromes such as transfusion- associated
circulatory overload (TACO) and transfusion-related acute
lung injury (TRALI) usually occur 6hours after transfusion
which involve respiratory distress and are oftentimes lifethreatening. TACO is characterized by pulmonary hydrostatic edema, while TRALI presents as pulmonary
permeability edema [53]. TRALIs are caused by donor anti-
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bodies in plasma containing blood components (FFP, platelets, RBCs) interacting with antigens on the patient’s
granulocytes. This reaction subsequently results in granulocyte aggregation and complement activation in the lung capillaries, leading to fever, hypoxemia, acute respiratory
distress, and increased peak airway pressure. The symptoms
Table 36.2 Transfusion guidelines set forth by the American Society
of Anesthesiologists [
Patient evaluation
1. Review of previous medical records, paying particular attention
to history of previous blood transfusion and current medications
(warfarin, clopidogrel, aspirin, or other NOACs)
2. History of congenital coagulopathies, thrombotic events, and
risk factors for organ ischemia
3. Efforts should be made to discuss the possible need for a
transfusion, and the risk and benets of such a procedure and
patient preferences toward a blood transfusion should also be
elicited
4. Current labs should be checked, a physical exam performed,
and any additional labs ordered
Preadmission patient preparation
1. For patients with CKD, renal insufciency, or transfusion
refusal, erythropoietin with or without iron may be used to help
lower risks
2. For patients on anticoagulants, discontinuation should only be
done after consulting with the proper specialist
3. For patients on antiplatelet agents, discontinuation is desired
before the start of the procedure
4. For patients undergoing procedures where signicant blood loss
is expected, blood products should be available on short notice
Pre-procedure preparation
1. A restrictive RBC strategy should be used
(a) Transfusion requirements for hemoglobin’s ranging between
6 and 10g/dL should be based on current or potential
bleeding, intravascular volume status, signs of end-organ
ischemia, and cardiopulmonary reserve
(b) Administration of RBCs should be done unit by unit
(c) A protocol for avoidance of transfusions may be used as a
strategy to reduce blood loss for patients whom transfusion
is refused or is not possible
(d) Massive transfusion protocol may be implemented when
available as a method to optimize RBC delivery in
massively bleeding patients
2. Reversal of anticoagulants
(a) For urgent reversal of warfarin, administer prothrombin
complex concentrates or FFP
(b) Admitter vitamin K for selected patients for nonurgent
reversal of warfarin, except when rapid restoration of
anticoagulation after surgery is required
3. Antibrinolytics for prophylaxis of excessive blood loss
(a) For patients undergoing cardiopulmonary bypass, the use of
antibrinolytic therapy for prophylaxis of the use of
allogenic blood transfusions is recommended
(b) Antibrinolytic therapy for prophylaxis should be
considered in certain orthopedic surgery
(c) Antibrinolytic therapy for prophylaxis should be
considered in liver surgery and other clinical circumstances
at high risk for excessive bleeding
4. Acute normovolemic hemodilution (ANH)
(a) Consider ANH to reduce the need for allogeneic blood
transfusion in patients at high risk for excessive bleeding (e.g.,
major cardiac, orthopedic, thoracic, or liver surgery), if possible
49]
Table 36.2 (continued)
Intraoperative and postoperative management of blood loss
1. Allogenic RBC transfusion
(a) Administer blood without consideration of length of storage
(b) Leukocyte-reduced blood may be used for reducing
complications with allogenic blood transfusion
2. Reinfusion of recovered RBCs
(a) Reinfuse recovered RBCs as a blood-sparing intervention
when applicable
3. Intraoperative and postoperative patient monitoring
(a) Visual assessment of the surgical eld in collaboration with
the surgeon to look for any excessive bleeding should be
performed periodically
(b) Inspect suction canisters, surgical sponges, and surgical
drains to access for a quantitative measurement of blood
loss
(c) Monitor perfusion of vital organs using standard ASA
monitors (i.e., blood pressure, heart rate, oxygen saturation,
EKG)
(d) In patients where anemia is suspected, the monitoring of
hemoglobin and hematocrit levels is vital and should
account for estimated blood loss
(e) In patients where coagulopathy is suspected, monitoring
coagulations studies such as INR, aPTT, and brinogen
concentration may be warranted
(f) Signs and symptoms of transfusions reactions should be
looked for periodically (hyperthermia, urticaria, respiratory
distress, etc.). Should these symptoms occur, stop the
transfusion immediately
4. Treatment of excessive bleeding
(a) Ordering a platelet count before transfusion may be
benecial; however it is often times not possible.
Anticoagulation drug status should also be assessed in
patients with excessive bleeding
(b) If at all possible, order coagulation studies such as PT, INR,
and aPTT before transfusion with FFP
(c) Fibrinogen levels should be monitored before the infusion of
cryoprecipitate
(d) In patients with excessive bleeding and platelet dysfunction,
desmopressin may be considered. Topical agents such as
brin glue or thrombin gel may be used as well
(e) If the cause of the excessive bleeding is brinolysis, then
agents such as ɛ-aminocaproic acid or tranexamic acid may
be used
(f) If the coagulations studies reveal an increased INR, then
PCCs may be used
(g) After all other approaches have been exhausted, one may
consider using recombinant factor VII to alleviate the
bleeding
(h) Concentrated brinogen may also be benecial
are similar to the symptoms seen in transfusion-related circulatory overload, but fever sets TRALI apart [54]. Platelet
transfusion often puts the patient at risk for bacterial contamination. Platelets are stored at 20–24 degrees Celsius
which facilitates growth of bacteria. There has been a large
decline in the number of transfusion reaction cases related to
new screening methods to detect contamination being implemented. However, contaminated products are occasionally
missed by screening, as such patients who develop hyperthermia and hypotension after a transfusion should be suspected for having bacterially contaminated products given to
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