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Consequences of
Transfusing Blood
Components in Patients
With Trauma:
A Conceptual Model
Allison R. Jones, RN, PhD, CCNS
Susan K. Frazier, RN, PhD
Transfusion of blood components is often required in resuscitation of patients with major trauma. Packed
red blood cells and platelets break down and undergo chemical changes during storage (known as the
storage lesion) that lead to an inflammatory response once the blood components are transfused to patients.
Although some evidence supports a detrimental association between transfusion and a patient’s outcome,
the mechanisms connecting transfusion of stored components to outcomes remain unclear. The purpose
of this review is to provide critical care nurses with a conceptual model to facilitate understanding of the
relationship between the storage lesion and patients’ outcomes after trauma; outcomes related to trauma,
hemorrhage, and blood component transfusion are grouped according to those occurring in the shortterm (≤30 days) and the long-term (>30 days). Complete understanding of these clinical implications
is critical for practitioners in evaluating and treating patients given transfusions after traumatic injury.
(Critical Care Nurse. 2017;37[2]:18-30)
nintentional injury remains a leading cause of death for persons of all ages in the United
States.1 Exsanguination is the most common cause of death within the first 48 hours of injury
for patients with major trauma, accounting for 30% to 40% of traumatic deaths.2 Approximately
1% to 3% of all patients with major trauma require transfusion of blood components, including packed red
blood cells (PRBCs), fresh frozen plasma (FFP), and platelets, to stabilize their hemodynamic state.3 In
addition, 2% of patients who receive transfusions require massive transfusion of blood components (≥ 10
units of PRBCs in a 24-hour period)4,5 for massive hemorrhage, defined as either the loss of blood equal
U
CE 1.0 hour, CERP A
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1. Describe the pathophysiology associated with severe trauma, hemorrhage, and transfusion of packed red blood cells (PRBCs) and platelets
2. Describe cellular changes associated with the storage lesion in both PRBCs and platelets
3. Identify potential consequences/outcomes associated with transfusion of PRBCs and platelets in patients with major trauma
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©2017 American Association of Critical-Care Nurses doi:https://doi.org/10.4037/ccn2017965
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to the circulating volume of the patient within 24 hours or
the loss of half of the circulating volume within 3 hours.4
The physiological and clinical consequences of traumatic injury, subsequent hemorrhage, and transfusion
are both short-term (occur within 30 days of injury)
and long-term (occur after the initial 30-day time frame).
Short-term consequences of injury, hemorrhage, and
subsequent transfusion of blood components, primarily
mortality and major complications during hospitalization, have been described, especially among patients with
trauma who received massive transfusions.6-8 Long-term
physiological and psychological consequences of traumatic injury have also been widely studied; the primary
focus has ranged from rehabilitation (physiological) to
posttraumatic stress disorder and depression (psychological).9-12 A clear understanding of the association
between transfusion of blood components in patients
with major trauma and subsequent short- and long-term
outcomes will contribute to the effective delivery of care
and improved patient recovery.
Although many reviews of trauma, hemorrhage, and
the storage lesion are available, we are unaware of any
review in which knowledge on all areas has been synthesized. Thus, the purpose of this review is to provide critical care nurses with a thorough understanding of the
biological and physiological relationships among traumatic hemorrhage, cellular breakdown of blood components during storage, and associated consequences for
patients after trauma and transfusion. Additionally, we
present a conceptual model (Figure 1) to further facilitate evaluation and care of such patients.
Pathophysiology of Trauma and
Associated Hemorrhage
Traumatic injuries are categorized as blunt or penetrating, depending on the mechanism of the injury.
Penetrating injuries (eg, stabbing or gunshot wound),
are typically relatively isolated injuries specific to the
tissues in the path of the instrument or projectile. These
injuries tend to have more severe physiological effects
than do blunt injuries and are associated with a 5-fold
increase in the likelihood of mortality (odds ratio [OR]
5.4; 95% CI, 2.4-12.0; P < .01).13 Patients with penetrating injuries are also more likely to require transfusion
of blood components, particularly massive transfusions.14,15 In contrast, blunt injuries (eg, motor vehicle
accidents) result in more broadly distributed damage
and are
usually
An understanding of the association
less severe between transfusion of blood components
than are and outcomes in patients with major trauma
penetrat- will contribute to the effective delivery of
ing inju- care and improved patient recovery.
ries. No
matter the mechanism of injury, endothelial disruption
and blood loss stimulate a coagulation cascade and
vasoconstriction to stop the hemorrhaging. During this
process, blood is shunted to the more vital organs
(brain, heart, and lungs) to ensure survival.
In the period immediately after injury, inflammatory
cytokines (eg, interleukin 6 and tumor necrosis factor _)
stimulate the recruitment of white blood cells to the site
of injury and initiate a 3-phase response that consists of
acute inflammation, repair, and remodeling. Vasoconstriction is due not only to the injury itself but also to what
is known as the lethal triad—an intricately connected
combination of hypothermia, acidosis, and coagulopathy commonly associated with trauma (Figure 2).16
Hypothermia-associated coagulopathy occurs when core
temperature decreases to less than 33°C (91.4°F).17
Acidosis also affects coagulopathy. At a pH less than
7.1, patients experience a reduced platelet count and
platelet dysfunction, increased fibrinogen breakdown,
and impaired plasma protease function.18 Coagulopathy
Authors
Allison R. Jones is an assistant professor, Department of Acute, Chronic, and Continuing Care, School of Nursing, University of Alabama,
Birmingham, Alabama. She has a clinical background in emergency and trauma nursing. In research, she focuses on the consequences of
blood component storage and transfusion, with particular interest in transfusion after trauma.
Susan K. Frazier is the director of the PhD program, a codirector of the RICH Heart Program, and an associate professor, College of Nursing,
University of Kentucky, Lexington, Kentucky. Her research focuses on cardiopulmonary interactions in a variety of critically ill patients,
including patients with acute heart failure, acute decompensated heart failure, acute respiratory distress syndrome, chronic obstructive
pulmonary disease, and multiple trauma.
Corresponding author: Allison R. Jones, RN, PhD, CCNS, 1407 16th Ave S, Birmingham, AL 35205 (e-mail: [email protected]).
To purchase electronic or print reprints, contact the American Association of Critical-Care Nurses, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 899-1712 or
(949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, [email protected].
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Short-term consequences
(≤ 30 days)
Long-term consequences
(> 30 days)
Effects of storage lesion
Coagulopathy
Vasoconstriction
Hypovolemia
Inflammation
Systemic
inflammation
Coagulopathy
Clinical
complicationsa
Physical
Hypoxia
Trauma
Hemorrhage
Transfusion
Tissue/
organ damage
Physical
Unknown
other
Effects of storage lesion
Prolonged length
Increased
of stay
morbidity and
mortality
Unknown
Cognitive
Quality of life
Figure 1 Conceptual model of trauma, hemorrhage, and transfusion.
a
Multiple organ dysfunction syndrome, pneumonia.
Major
trauma
insult
Bleeding
Tissue injury
Hypoxia
Hypotension
Loss of
blood
Shock
Acidosis
Resuscitation
Hypothermia
Hypovolaemia
Endogenous
Mitochondria
Immunology
Inflammation
Cellular responses
Molecular pathways
Acute traumatic
coagulopathy
Fibrinolysis
Dilution
Consumption of
clot factors
Lymphocytes
Thrombocytes
Systemic
Pre-existing disease
Drugs and medications
Trauma-induced
coagulopathy
Figure 2 Effects leading to trauma-induced coagulopathy.
Reprinted from Thorsen et al,16 with permission.
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Table 1
Thromboelastography measures and correlations to traditional coagulation testinga
Measures
Value
Correlation
to traditional
coagulation tests
Reference
range
Transfusion
recommendation
P
R time
Clotting factors (time to
initial fibrin formation)
PT
aPTT
5-10 min
> 10 min: FFP, cryoprecipitate
PT: < .001
aPTT: < .001
PLT: .12
K time
Fibrinogen, platelet number
(time for clot to reach 20mm clot strength)
PT
aPTT
PLT
1-3 min
> 3 min: FFP, cryoprecipitate
PT: < .001
aPTT: < .001
PLT: .02
_ Angle
Fibrinogen, platelet number
(angle from baseline to
slope of tracing, indicates
clot formation)
PT
aPTT
PLT
53°-72°
< 53°: platelets with or
without cryoprecipitate
PT: < .001
aPTT: < .001
PLT: < .001
MA
Platelet function (maximum
amplitude of tracing)
PT
aPTT
PLT
50-70 mm
< 50 mm: platelets
PT: < .001
aPTT: < .001
PLT: < .001
G value
Coagulation cascade (calculated value of clot strength)
PT
PLT
5.3-12.4
dynes/cm2
LY30
Fibrinolysis (clot lysis at
30 minutes after maximal
amplitude)
NA
0%-3%
NA
PT: .005
aPTT: -.19
PLT: .03
> 3%: tranexamic acid
NA
Abbreviations: aPTT, activated partial thromboplastin time; FFP, fresh frozen plasma; G value, calculated value of clot strength; K time, kinetic time; LY30, clot lysis at 30
minutes; MA, maximum amplitude; NA, not applicable; PLT, platelet count; PT, prothrombin time; R time, reaction time.
a
Based on information from Cotton et al20 and Semon.21
(defined as prothrombin time > 14 seconds and partial
thromboplastin time > 34 seconds) was an independent
predictor of mortality in patients with major trauma,
increasing their risk of death by 35%.19 If unresolved, this
triad produces deadly outcomes. Thus, clinicians must be
acutely aware of the interplay of temperature, pH, and
coagulation status in patients with major trauma. Interventions to correct these conditions should be considered
high priority because they will help achieve hemostasis.
Standard measures of coagulation used to determine
and evaluate the effectiveness of resuscitation strategy
include prothrombin time, activated partial thromboplastin time, and the international normalized ratio.
Although these measures reflect capability for coagulation and initiation of hemostasis, patients after trauma
present a unique challenge in the immediacy of their
coagulation needs. Clinical use of thromboelastography
(TEG) to guide resuscitation has increased as a supplement to traditional coagulation measures20,21 (Table 1,
Figure 3). TEG is based on the notion that the cessation
of hemorrhage relies on effective blood clotting22 and
involves analysis of a patient’s blood to determine the
time to clot development, strength of the developed
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Coagulation
Time
Kinetics
Fibrinolysis
Strength
Lysis
g
TEG
®
_
R
CT
MA
MCF
Ly
CL
ROTEM®
CFT
Figure 3 Thromboelastography measures.
Abbreviations: CFT, clot formation time; CL, clot lysis; CT, clotting time; Ly,
lysis; MA, maximum amplitude; MCF, maximum clot firmness; R, reaction
time; ROTEM, rotational thromboelastometry; TEG, thromboelastography.
Reprinted from Thorsen et al,16 with permission.
clot,
l andd time
i to clot
l lysis.
l i TEG results
l from
f
analysis
l i off
whole blood may be available in less than 5 minutes and
provide essential, timely data for resuscitation.22 Although
use of TEG has increased, results of a recent systematic
review23 revealed little diagnostic accuracy associated with
the use of TEG compared with traditional coagulation
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measures in resuscitation of patients with major trauma
and led to the recommendation that use of TEG be
reserved for research purposes. Nonetheless, critical care
nurses must understand the indications for TEG if this
procedure is applicable to their clinical setting and
should be able to interpret TEG results for efficient provision of care.
Transfusion of Blood Components and
Potential Consequences
Traumatic hemorrhage accounts for roughly a third of
injury-related deaths.2 Transfusion of blood components
remains the standard of care because of the associated
benefits and lifesaving qualities. However, like any medical treatment, such transfusion is not without risks. Transfusion of blood components is associated with increased
risk for morbidity and mortality in patients with trauma.
Marik and Corwin24 systematically reviewed 45 observational studies of critically ill patients; 10 of the studies
included patients with trauma, although details on injury
severity were not included. The investigators analyzed
pooled
Transfusion of older PRBCs and platelets data from
these
can worsen outcomes in already fragile
studies
patients due to biological and chemical
and found
changes known as the storage lesion.
that an
infectious complication was nearly twice as likely to
develop in patients who received transfusion of PRBCs
than in patients who had no transfusion (OR, 1.8; 95% CI,
1.5-2.2). Additionally, those who received PRBCs were
roughly 3 times more likely to experience acute respiratory distress syndrome (OR, 2.5; 95% CI, 1.6-3.3) and
almost twice as likely to die (OR, 1.7; 95% CI, 1.4-1.9).
Other investigators found similar associations between
transfusion of PRBCs and adverse clinical outcomes such
as transfusion-related acute lung injury,25 acute kidney
injury,26 and thromboembolic events.27 However, many
of these studies were retrospective and observational;
thus, the outcomes may have been due to other factors.
Transfusion of fresh whole blood may be more beneficial than transfusion of blood components in patients with
major trauma.28,29 We found that patients who received
transfusion of blood components were 3 times more likely
to die than were patients who received whole blood after
trauma, regardless of injury severity (OR, 3.164; 95% CI,
1.314-7.618).30 Only recently have investigators performed
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a randomized controlled trial to compare transfusion of
fresh whole blood with transfusion of blood components.31 Although patients who received whole blood
required fewer transfusions overall than did patients
who received blood components, the mortality rates of
the 2 groups did not differ.
Whole blood is not routinely used in patients with
major trauma because of logistic and economic problems, such as storage, screening, and sufficient donors,
thereby leaving transfusion of blood components as the
primary resuscitation option. Discussion of transfusion
of stored components and related consequences therefore necessitates understanding the storage lesion that
occurs within PRBCs and platelets. As with any treatment or procedure, care providers should understand
the risks, benefits, rationale, and current evidence associated with the care they provide.
The Storage Lesion
Current blood bank practices include rotation of
older blood components to trauma centers more likely
to use the components before the expiration date, thereby
reducing waste.32 However, transfusion of older PRBCs
and platelets creates potential for worse outcomes in
already fragile patients due to the storage lesion. The
storage lesion is a collective term for alterations that occur
in PRBCs and platelets during storage, which may be
associated with physiological consequences in patients
who receive transfusions of the components33 (Table 2).
General changes associated with the storage lesion include
cellular and morphological changes, changes in oxygenation and energy, biochemical changes, release of microparticles, and increases in inflammatory mediators. The
storage lesion develops in a predictable fashion over
time, such that longer storage time leads to a greater
disruption of cellular integrity. Accordingly, standard
expiration dates apply to stored blood components;
PRBCs are stored for a maximum of 42 days and platelets for a maximum of 5 days before transfusion risks
outweigh the benefits.50 In the following material, we
discuss the 5 areas affected by the storage lesion as
related to PRBCs and platelets.
Packed Red Blood Cells
Cellular and Morphological Changes. During
storage, PRBCs undergo changes in cell shape and membrane
integrity from normal smooth, flexible discs to spherical
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Table 2
Storage lesion alterations
Global consequences of storage lesion for packed red blood cells and platelets
Physiological consequences after transfusion
Storage lesion effects
34-45
Packed red blood cells
Cellular and morphological
changes
Irreversible change from smooth, easily
deformable discs to spheroechinocytes (less flexible, spherical cells with
protrusions)
Development of microvesicles with
procoagulant properties
Difficulty moving through smaller blood vessels
Inability to oxygenate tissues adequately
Reperfusion injury due to release of free radicals
Inflammation due to spheroechinocytes adhering to
blood vessels
Oxygenation and energy
changes
Left shift in oxyhemoglobin dissociation curve
Reduction in 2,3-diphosphoglycerate
Impaired ability to carry or deliver oxygen Impaired circulation and inadequate tissue oxygenation
Decrease in adenosine triphosphate (ATP), failure of
Switch from aerobic metabolism to
ATP pump, cellular swelling
anaerobic metabolism
Biochemical changes
Decrease in ATP
Switch from aerobic metabolism to
anaerobic metabolism
Release of microparticles
Breakdown of phospholipid membrane, Increase in free hemoglobin, free iron, cytokines, and
microparticles containing pieces of plasma membrane
microparticles released into supernaVasoconstriction, induction of hypercoagulable state,
tant
tissue damage, and inflammation
Increase in inflammatory
mediators
Result of breakdown of cellular structure and leaking of cellular contents
Failure of ATP pump, electrolyte imbalance of transfused
supernatant fluid (increased potassium), increased
lactate
Excess hydrogen ions, buildup of lactic acid, decreased pH
Irreversible cellular damage
Increase in ubiquitin and cytokine levels throughout
storage
Induction of inflammatory reaction
Platelets46-49
Cellular and morphological
changes
Irreversible change from smooth,
easily deformable plate-shaped cells
to spheroechinocytes (less flexible,
spherical cells with protrusions)
Platelet activation
Development of microvesicles
Difficulty moving through smaller blood vessels
Membrane breakdown, exposure of phosphatidylserine,
potentially early cell death
Development of procoagulant properties
Oxygenation and energy
changes
Switch from aerobic metabolism to
anaerobic metabolism
Decrease in ATP
Breakdown of plasma membrane, leaking of intracellular
contents
Potential cellular death due to membrane breakdown
Buildup of lactic acid, excess hydrogen ions, decrease
in pH
Biochemical changes
Decrease in ATP
Failure of ATP pump, electrolyte imbalance, cellular
swelling
Release of microparticles
Expression of membrane receptors,
phospholipid membrane breakdown
Release of microparticles with procoagulant and proinflammatory properties
Increase in inflammatory
mediators
Platelet activation, breakdown in
cellular structure
Development and release of inflammatory mediators
cells
ll with
ith sharp
h
protrusions,
t i
called
ll d spheroechinoh
hi
cytes.34,35 These morphological changes occur rapidly
and early in the storage period; 9.5% of cells are
abnormal (ie, are spheroechinocytes) by day 7 of storage.36 Because of their new shape and lack of flexibility, spheroechinocytes are unable to pass through the
microvasculature; the protrusions most likely cause
the cells to adhere to the endothelium.37,38 Anniss and
Sparrow39 found that the number of adherent red
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bl
bloodd cells
ll increased
i
d significantly
i ifi tl from
f
a mean off 69
(SD, 10) cells/mm2 on the first day of storage to 128
(SD, 11) cells/mm2 on storage day 42 (P < .05). Consequently, transfused PRBCs have markedly reduced
flow through the microcirculation, with less oxygen
delivered to metabolically active cells; these abnormal
erythrocytes also obstruct the microcirculation and
may result in cellular ischemia and in tissue and
organ dysfunction.37,40
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Oxygenation and Energy Changes. In cells that do
not develop into spheroechinocytes, biochemical changes
that occur during storage result in a reduction in the level
of 2,3-diphosphoglycerate (2,3-DPG), a by-product of
glycolysis in red blood cells.41 A reduction in 2,3-DPG
produces a left shift of the oxyhemoglobin dissociation
curve; thus, the ` chain of the hemoglobin molecule
has greater affinity for the oxygen molecule and will not
release oxygen at the cell. Almac and Ince42 reported that
the 2,3-DPG concentration in stored PRBCs decreased
to undetectable levels within 2 weeks of the start of storage. The increased oxygen affinity in transfused PRBCs
continues until the recipient of a transfusion produces
adequate 2,3-DPG levels that allow release of oxygen,
typically within the first few days after transfusion.43,44
However, for patients who receive massive transfusions
or replacement of their entire blood volume, lower levels
of 2,3-DPG transfused in large volumes of stored components may significantly reduce cellular oxygen concentration for several hours after transfusion.43 Thus, transfusion
of PRBCs to improve tissue oxygenation may not be as
effective as intended.
In addition, erythrocyte metabolism continues after
the start of storage because the supernatant fluid in
which the cells are stored contains glucose. In the
absence of oxygen, erythrocytes convert to anaerobic
metabolism of glucose to produce adenosine triphosphate (ATP).51 Levels of ATP in stored PRBCs initially
increase but are depleted by the end of the 42-day
period.52 This initial increase in ATP levels has been
attributed to the release of ATP in response to a
hypoxic state, in which ATP acts as a vasodilator in
vivo.53 Depletion of ATP during storage is associated
with cellular alterations. As the ATP-fueled sodiumpotassium pump within the cell membrane fails and
results in accumulation of sodium within the cell, cellular swelling leads to a stiffened cellular structure and
loss of the phospholipid membrane via formation of
microvesicles or microparticles—small pieces of the cell
membrane that encapsulate and remove intracellular
components no longer essential to cellular function.54,55
The combination of altered cellular chemistry and cellular structure results in decreased oxygenation ability,
similar to the formation of spheroechinocytes.
Biochemical Changes. Once stored PRBCs convert
to anaerobic metabolism, by-products that include lactic
acid and excess hydrogen ions are produced by the
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breakdown of fatty acids for additional energy; these
by-products ultimately lead to a reduced intracellular
pH after persistent hypoxia.56 Extracellular concentration
of potassium increases because of failure of the sodiumpotassium pump, with a reported increase in mean levels from 5.16 (SD, 1.2) mmol/L on day zero to 35.1 (SD,
4.6) mmol/L on day 28 of storage (P < .005).45 Two developments characterize irreversible cellular damage: cessation of mitochondrial function and the loss of membrane
function.56 Irreversible damage such as these developments occurs in approximately 50% of PRBCs by day 21
of storage.35 Once transfused, damaged red blood cells
may quickly succumb to apoptosis, or be removed from
the circulation in a manner similar to normal processing
of old red blood cells, thereby decreasing the overall
effectiveness of the transfused component.
Release of Microparticles. Breakdown of the cellular
membrane allows release of intracellular contents such
as lipids, free hemoglobin, free iron, and cytokines in the
form of microparticles. Release of microparticles is associated with decreased endothelial-derived nitric oxide
(a potent vasodilator and antioxidant)34 and induction
of a hypercoagulable state.57 Free hemoglobin and free
iron contribute to oxidative stress in the cells, with subsequent production of free radicals that may initiate tissue damage (eg, reperfusion injury) once transfused.34
Longer storage time is associated with greater release
of microparticles.57 When trauma centers receive older
stored PRBCs, the concentration of microparticles most
likely is substantively greater than it is in fresher cells,
a situation that can lead to clinical complications in
patients after transfusion.
Increase in Inflammatory Mediators. The storage
lesion is also associated with an increased release of
inflammatory mediators. Kor et al40 have suggested that
despite the removal of white blood cells from donated
blood, some proinflammatory molecules remain in
stored PRBCs. Ubiquitin, a protein found in all eukaryotic cells and related to inflammation through inhibition
of tumor necrosis factor _, is also released with the
breakdown of the cell membrane,58,59 and the concentration can increase significantly during PRBC storage; for
example, from a mean of 113 (SD, 33) ng/mL on day 0
to a mean of 2170 (SD, 68) ng/mL on day 42 (P < .001).59
Thus, transfusion of PRBCs may lead to development of
an inflammatory reaction and potentially subsequent
adverse outcomes.
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Platelets
Cellular and Morphological Changes. Although
similarities exist between PRBCs and platelets in the
effects of the storage lesion, the storage lesion in platelets is less well understood than that in PRBCs. Storage
of platelets stimulates a process that mimics platelet
activation in vivo,46 ultimately resulting in membrane
breakdown and alteration of the cell shape to a rounded
cell with spiny protrusions.47 Through platelet activation,
cell membrane breakdown, and exposure of phosphatidylserine (a phospholipid on the inner part of the platelet
cell membrane), platelets may become procoagulant,
whereby they support thrombin generation and premature cell death while in storage or soon after transfusion.60 Shrivastava47 reported a minimal decrease in the
efficacy of transfused platelets but noted that structurally altered platelets are removed from circulation more
rapidly than are unaltered platelets because of stimulation of the apoptosis pathway via structural change.
The most effective method of platelet storage
remains controversial. The primary challenge is the
balance between maintenance of cellular integrity and
reduction in risk for bacterial contamination. Current
standards47,61 include storage of platelets at room temperature with continuous agitation for 5 days. Previous
standards,57 however, included refrigeration of stored
platelets, intended to decrease the likelihood of bacterial contamination. Changes in these standards were
based on research findings that cold storage temperature was associated with premature platelet removal
from the circulation via the liver; therefore, cold storage reduced platelet circulation time once the cells
were transfused.48 Rumjantseva et al49 evaluated platelets stored at 4°C (39.2°F) for at least 48 hours before
transfusion into mice and found that approximately
50% of the transfused platelets were cleared from circulation within 2 hours. More recently, investigators48
suggested that refrigerated platelets might be more beneficial to trauma patients, because the cells are somewhat
activated before transfusion and therefore contribute
to more rapid hemostasis. Thus, although platelets
undergo morphological changes and activation during
storage, they remain effective after transfusion, albeit
for a shorter time than fresh platelets do.
Oxygenation and Energy Changes. Stored platelets are associated with 2 types of cellular demise that
lead to removal of the cells from a patient’s circulation;
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both types involve loss of ATP. The first type is necrotic
cell death, which involves a breakdown in the cell membrane during storage similar to the breakdown that
occurs in PRBCs, leading to leakage of the intracellular
contents into the extracellular fluid.54 The second type is
a marked loss of platelets in vivo with reduction in ATP
levels, with a maximum platelet survival of 9 to 10 days
after transfusion before apoptotic cell death occurs.62 No
matter the cause or type of cell death during storage, the
result is the same: a breakdown of the cell and activation
of a procoagulant state. Patients who require platelet
transfusion after injury therefore may require follow-up
monitoring and possibly further intervention.
Biochemical Changes. A major difference
between PRBCs and platelets is the increased production of reactive oxygen species (ROS) with platelets,
associated with the destruction of organelles, the
plasma membrane, and ultimately the cytoskeleton.60 All
other biochemical changes observed in platelets are
similar to those that occur in PRBCs (accumulation of
lactic acid, hydrogen ions, and consequent decreased
pH and electrolyte imbalances).60
Release of Microparticles. Microparticles are
released from platelets via 1 of 2 mechanisms: rupture of
the cell during storage or platelet activation. Platelet
activation includes expression of membrane receptors,
which triggers release of microparticles.63 These microparticles may
have proco- Transfusion of platelets may both
agulant prop- suppress the inflammatory response
erties, which and induce an inflammatory reaction
may make
due to microparticles released during
the platelets cell death in storage.
beneficial to
recipients.63 In addition, platelets contain 3 types of
granules with proinflammatory properties: _ granules
(primarily contain proteins such as P-selectin), dense
granules (contain small molecules, such as serotonin or
ATP), and lysosomal granules (contain degradative
enzymes).63 The mechanisms by which microparticles
trigger inflammation have not been fully elucidated, but
research57,64 suggests a link between the presence of
microparticles and an inflammatory response in patients
given platelet transfusions.
Increase in Inflammatory Mediators. In addition
to release of microparticles, platelet activation triggers
development and release of inflammatory mediators
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(thromboxane and prostaglandins), which may also
stimulate an inflammatory response in patients given
platelet transfusions.63 This response becomes exacerbated after necrotic cell death,60 especially with allogenic
transfusion of platelets, which is common in patients
with trauma.63 Inaba et al65 reported that trauma patients
who received apheresis platelets stored for 4 days and 5
days were 20% and 240% more likely, respectively, to
experience clinical complications than were patients
who received platelets stored for 3 days or less (P < .001).
Inaba et al suggested that the consequences of the storage lesion varied according to differences in storage
conditions and potential contamination and were a
potential mechanism for increased complications.
Short- and Long-term Consequences of
Transfusion of Stored Blood Components
Transfusion of stored blood components is used to
restore blood volume, provide clotting factors, and
help in achieving hemostasis. However, consequences
of the storage lesion present challenges to the successful resuscitation and recovery of patients with major
trauma who receive stored blood components. Critical
care nurses who administer these blood components
must be aware of not only the indications for and benefits of
blood
Effects of transfusion-related factors
composhould be considered in the evaluation
and provision of care for trauma patients. nent
transfusion but also the associated physiological impact. Better understanding of these outcomes may allow nurses
to anticipate potential complications and intervene to
produce better outcomes.
Reperfusion Injury
One consequence of transfusion of stored blood
components is reperfusion injury, which occurs when
tissues deprived of adequate circulation subsequently
have circulation restored. This situation is more common
in patients with major trauma than in other types of
patients.66 In highly oxygen-dependent tissues such as
the brain or heart, cellular damage can occur after seconds or minutes of oxygen deprivation, with extended
hypoxia leading to long-term tissue damage.56,67 Under
normal circumstances, cells function via aerobic metabolism; when the oxygen supply diminishes, as with
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hemorrhage, cells convert to anaerobic metabolism,
leading to an increase in the level of lactic acid and subsequent excess of hydrogen ions in the extracellular fluid
in an attempt to correct the decreased pH.56 Hydrogen
imbalances in the intracellular and intercellular environment lead to sodium absorption and an influx of calcium into the cells.68
Transfusion of blood components reintroduces the
oxygen and nutrients necessary for tissues to resume
aerobic metabolism. The presence of more oxygen than
the cells can use leads to an excess amount of ROS, or
oxygen molecules with an exposed unpaired electron.56,68
Reperfusion injury occurs when the antioxidants present in tissues and typically able to counteract ROS
become overwhelmed with the amount of ROS and
thus cannot process them efficiently.67 ROS can result
in formation of hydrogen peroxide or hydrogen radicals capable of damaging cellular DNA or causing
damage to the cell by bonding with the phospholipid
membrane, leading to cell death.56,68 Cellular destruction initiates an inflammatory response whereby neutrophils are recruited to the site of injury.69 Neutrophils
further contribute to cellular damage through release
of ROS and restriction of circulation to the site of injury.70
In recent years, the focus of reperfusion injury and its
associated outcomes has primarily included areas such as
cardiac arrest and resuscitation, hypoxic-ischemic brain
injury, and stroke.67 A growing body of literature also
exists on transfusion of blood components during
organ transplantation and associated reperfusion
injury.71,72 However, patients with major trauma are
vulnerable to reperfusion injury, depending on the
extent of their injuries, the amount of blood lost, and
time to definitive care, including transfusion of blood
components. For example, Kunimatsu et al73 reported
that ROS development was greatest in the first 15
minutes after reperfusion in patients with “global
brain ischemia.” Thus, patients with major trauma
and hemorrhage may be at risk for reperfusion injury
if blood loss is severe and transfusion of blood components is required. Therefore, monitoring of changes
in mental status and cognitive function may be indicated. Despite current understanding of reperfusion
injury, little research has been done on neurological
consequences of transfusion of blood components,
although studies in both animals74,75 and humans76 are
being done.
www.ccnonline.org
Vasoconstriction
Traumatic injury and hemorrhage induce vasoconstriction to preserve body heat. Guidelines from the
Advanced Trauma Life Support manual (9th edition)77
suggest that initial treatment for blood loss include
infusion of 1 L of crystalloids followed by transfusion of
blood components. However, fluids and blood components are often stored in cool or cold settings, and rapid
infusion may lead to further vasoconstriction. Warmers
are used during resuscitation to increase the temperature of infused fluids to normal core body temperature
(37°C or 98.6°F), although this goal may not be accomplished, depending on the infusion flow rate and original
temperature of the infused fluid.78 Thus, vasoconstriction
in patients hypothermic due to trauma and exposure to
the elements may worsen with resuscitation efforts,
leading to reduction of perfusion to metabolically active
tissues. Similar to the situation in reperfusion injury,
continuous evaluation for signs and symptoms related
to oxygen-dependent tissues such as the heart and brain
should be considered.
inflammatory response (signaling of inflammatory
mediators) and a simultaneous anti-inflammatory
response in the form of gene suppression for leukocyte production.83 In a large prospective study84 of more
than 1200 patients with major trauma, systemic inflammatory response syndrome was diagnosed in more
than 90% of the patients within the first 7 days after
injury, although this value decreased to 50% by the
third week. The anti-inflammatory response that
immediately follows injury may extend beyond the
immediate recovery period, persisting beyond 28 days
in some instances.83 When combined with traumatic
endothelial damage and other factors such as comorbid conditions, this anti-inflammatory state can lead to
complications such as acute respiratory distress syndrome and multiple organ failure.69 Consequently,
severely injured patients have an increased risk for
infection via open wound or invasive procedures and
for development of inflammatory complications during
hospitalization. The extent of long-term effects of an
impaired immune reaction remains unknown.
Inflammation
One consequence of the storage lesion is the release of
microparticles.79 The more dead cells in a container of a
stored blood component, the more microparticles are present when that blood component is transfused, a situation
than may increase the likelihood of a transfusion- related
reaction. Signs normally associated with such reactions are
those also normally associated with inflammation (eg,
fever, rash, erythema); the signs occur within minutes or
hours of transfusion and can normally be treated once
identified.80 Although transfused PRBCs include microparticles and induce inflammation, platelet transfusions can
induce approximately 3 times more reactions than do
PRBC transfusions.81 Vamvakas and Blajchman82 have suggested that microparticles from platelets suppress immune
response in recipients after transfusion. Thus, transfusion
of platelets may both suppress the inflammatory response
and induce an inflammatory reaction. However, the extent
of the relationship between microparticles and clinical
complications after transfusion, particularly in the longterm, remains unclear and requires further investigation.
Clinical Complications
Transfusions have long been associated with poorer
clinical outcomes.65,66,85 In a meta-analysis of 21 studies,
Wang et al85 evaluated outcomes of patients according
to transfusion of older blood components (9 to 42 days
in storage) compared with younger blood components
(<2 days to <21 days in storage). These investigators analyzed pooled data from 3 of 7 studies in which adverse
outcomes associated with PRBC transfusion aside from
mortality
were evalu- An understanding of the consequences
associated with PRBC and platelet
ated and
transfusion after trauma provides
concluded
that transfu- critical care nurses an opportunity to
sion of older optimize patients’ outcomes.
PRBCs was
associated with greater risk for pneumonia (OR, 1.17;
95% CI, 1.08-1.27) and multiple organ dysfunction syndrome (OR, 2.26; 95% CI, 1.56-3.25). Conversely, in a
randomized controlled trial, the Age of Blood Evaluation, investigators86 found no difference in clinical outcomes among patients who received older blood
components (storage ≥8 days) compared with patients
who received fresh blood components (storage <8 days),
regardless of the reason for admission and the volume
Impaired Immune Reaction
Trauma induces a change in roughly 80% of the
leukocyte transcriptome, resulting in a systemic
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CriticalCareNurse
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27
of blood components transfused. Although the proposed
association between storage time and development of
complications is still controversial,27,34 the impact of
transfusion-related factors (component storage time,
variability in storage environment, volume transfused)
should be considered in the evaluation and provision
of care for patients with trauma who require transfusion.
Evidence-Based Conceptual Model
Short-term outcomes are commonly evaluated in
patients given transfusions after major trauma, but few
investigators have examined long-term clinical effects
of transfusion of blood components. The conceptual
model shown in Figure 1 represents the current state of
knowledge of the relationship between traumatic injury,
hemorrhage, and transfusion of blood components and
both short- and long-term consequences. Areas on the
top half of the model denote short-term consequences,
whereas areas on the bottom denote long-term consequences. Visualization of these relationships may enhance
understanding of the physiological processes, associated
treatment strategies, and evaluation and care of patients
given transfusion of blood components after major
trauma. As indicated by the area at the bottom, righthand corner of the figure, opportunities for exploration
of the long-term consequences are essentially unlimited.
Future areas of research may include chronic organ dysfunction, cognitive dysfunction, physical disability,
awareness of disability and effect on daily life, rehabilitation requirements, and return to work or baseline status.
Conclusions
Trauma affects a high number of persons annually,
and severely injured patients may require transfusion of
blood components during resuscitation. Current standards for preservation of blood components allow
extended storage periods, which are associated with a
storage lesion that may produce deleterious cellular
effects. The conceptual model (Figure 1) illustrates the
association between trauma, hemorrhage, and potential
outcomes related to transfusion of blood components.
A clear understanding of the consequences associated
with such transfusions provides critical care nurses an
opportunity to optimize patients’ outcomes via early
evaluation and appropriate intervention and management. &&1
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Acknowledgments
The authors acknowledge Drs Terry Lennie, Debra Moser, Patricia K. Howard,
and Heather Bush for their support in the development of the manuscript.
This research was completed as part of a doctoral dissertation by Dr Jones at
the University of Kentucky.
Financial Disclosures
None reported.
Now that you’ve read the article, create or contribute to an online discussion about
this topic using eLetters. Just visit www.ccnonline.org and select the article you want
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See also
To learn more about trauma patients, read “Association of Injury
Factors, Not Body Mass Index, With Hospital Resource Usage in
Trauma Patients” by Lee et al in the American Journal of Critical Care,
July 2016;25:327-334. Available at www.ajcconline.org.
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