Blood product transfusion in the critical care setting

Daryl J. Kora and Ognjen Gajicb

a

Department of Anesthesiology/Division of Critical

Care Medicine and bDepartment of Medicine/Division
of Pulmonary and Critical Care Medicine,
Multidisciplinary Epidemiology and Translational
Research in Intensive Care (METRIC) Research Group,
Mayo Clinic, Rochester, Minnesota, USA
Correspondence to Daryl J. Kor, MD, Department of
Anesthesiology, Mayo Clinic, 200 First Street SW,
Rochester, MN 55905, USA
Tel: +1 507 255 6051; fax: +1 507 255 4267;
e-mail: kor.daryl@mayo.edu
Current Opinion in Critical Care 2010,
16:309316

Purpose of review
The past two decades have witnessed an extensive re-evaluation of transfusion therapy
in the intensive care unit (ICU). The purpose of this review is to present the current state
of knowledge regarding blood transfusion in the critically ill and to identify gaps in our
current understanding for future research.
Recent findings
Accumulating evidence suggests a lack of efficacy with red blood cell (RBC), plasma,
and platelet transfusion in the majority of critically ill patients. Evidence has also
increasingly exposed previously under-recognized transfusion risks. The result is a
growing number of recommendations for more restrictive RBC, plasma, and platelet
transfusion strategies. An important exception to a more conservative transfusion
practice occurs in patients with major trauma and life-threatening bleeding. Delaying
RBCs, plasma and platelet component therapies in this population can promote the
lethal triad of coagulopathy, acidosis, and hypothermia with a resultant increase in
bleeding, greater transfusion requirements, and higher mortality.
Summary
Although we have made substantial progress in understanding the role of blood
transfusion in the ICU, multiple important knowledge gaps persist. Future studies are
needed to better define and characterize the impact of RBC storage, male-only plasma
and platelet donor procurement procedures, and transfusion strategies in those
requiring massive transfusion and with acute local or global tissue ischemia.
Keywords
leukocyte reduction, massive transfusion, red blood cell storage lesion, transfusionrelated acute lung injury, transfusion-related immune modulation
Curr Opin Crit Care 16:309316
2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
1070-5295

Introduction
In the past two decades, we have witnessed increased
scrutiny regarding efficacy and risk of the once unquestioned therapy of blood transfusion. Whereas primarily
targeted at red blood cell (RBC) administration [1],
similar concerns have been raised for other component
therapies as well [2,3]. In perhaps no other environment
has this re-evaluation been more extensive than the
intensive care unit (ICU). With the notable exception
of acute blood loss, enhanced understanding of the efficacy (or lack thereof) and risk of blood product administration has led to a pervasive trend to more conservative
RBC, plasma, and platelet strategies. Nonetheless,
numerous controversies and knowledge gaps persist.
This review will address the current evidence-based
indications for RBC, platelet, and plasma transfusions.
We will address recent changes in transfusion strategies
for patients with major trauma/massive transfusion as well
as the major risks associated with transfusion therapy. We
will specifically focus on the leading cause of transfusionrelated mortality and transfusion-related acute lung
1070-5295 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

injury (TRALI). This review will not address the use

of blood product substitutes, transfusion practices in the
critically ill pediatric population or the specific component therapies of cryoprecipitate, factor concentrates,
or granulocyte infusions.

Red blood cell transfusion

The section of the review will focus on RBC transfusion
in the ICU. Emphasis will be placed on indications,
efficacy, risks, and implementation of evidence-based
practice.
Red blood cell transfusion: indications

Clinical practice guidelines for RBC administration were

recently developed by a joint planning group with multispecialty collaboration [1]. After thorough review of the
literature, the only well established recommendation for
RBC transfusion remains acute hemorrhage with hemodynamic instability or inadequate oxygen delivery. In the
absence of major bleeding, conservative transfusion practices (maintain hemoglobin > 7 g/dl) are recommended
DOI:10.1097/MCC.0b013e32833bc4a4

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

310 Intravenous fluids

for nearly all other critically ill populations, including

trauma, those requiring mechanical ventilation, and those
with stable cardiac disease [1].

and reduced red cell deformability have been proposed

as potential mechanisms of microcirculatory occlusion
and resultant tissue ischemia [8].

A possible exception to conservative RBC transfusion

practice is in the early phases of local or global tissue
ischemia as seen in patients with acute coronary syndrome (ACS) and severe sepsis/septic shock. Regarding
the former, evidence suggesting an appropriate transfusion threshold remains conflicting and inconclusive
[1]. Nonetheless, available data support RBC transfusion
at a slightly higher hemoglobin concentration (8 g/dl)
[4]. Similarly, the RBC transfusion threshold in patients
with severe sepsis or septic shock is poorly defined.
Although current guidelines suggest a liberal transfusion
practice in the acute phase of sepsis resuscitation (hematocrit 30 as needed to achieve an ScvO2 70%) [5];
these recommendations are based on a single-center
study [6] which was not specifically designed to address
transfusion practice.

Red blood cell transfusion: risks

Red blood cell transfusion: efficacy

Few studies outside the setting of acute hemorrhage have

shown meaningful benefit with RBC transfusion [1,7].
Despite the intention to increase end-organ oxygen utilization, multiple evaluations have failed to identify an
increase in this endpoint with the administration of
allogeneic RBCs [8]. Whereas the timing of intervention
(early vs. late after shock onset) may explain some of the
conflicting results [6,9], the adverse microcirculatory
effects of stored RBCs provide additional explanation.
Rapid decline in S-nitrosohemoglobin concentrations

Concern over the potential transmission of blood-borne

pathogens such as human immunodeficiency virus (HIV)
has led to a heightened awareness of the risks associated
with allogeneic RBC transfusion. Chief among these
concerns are the association of RBC transfusion with
infection [7], pulmonary complications such as TRALI
[10,11] and transfusion-associated circulatory overload
(TACO) [12], multiorgan failure [13], and risk-adjusted
mortality [14,15]. Whereas the causative factors associating transfusion with adverse outcomes remain poorly
defined, much interest has been placed on the issues
of a RBC storage lesion and transfusion-related immune
modulation (TRIM).
The various changes that occur within both the RBC and
storage media during ex-vivo preservation have been
collectively termed the RBC storage lesion (Fig. 1).
These alterations can be extensive and are primarily
classified into three broad categories: biochemical, biomechanical, and immunologic [16]. Reduced accumulation of inflammatory cytokines achieved by prestorage
leukoreduction has decreased the incidence of febrile
reactions associated with transfusion of stored RBCs.
However, other changes related to the storage lesion
have not been impacted by prestorage leukoreduction,
and the overall clinical significance of this procedure
remains unclear. Recently, Koch and colleagues [14]

Figure 1 Putative biologic and physiologic consequences of red blood cell storage

Adapted with permission from Kor et al. [16].

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Blood product transfusion in the critically ill Kor and Gajic 311

performed a large, single-center, retrospective review of

RBC transfusion in patients undergoing cardiac surgery.
When compared to those who received fresh blood
(14 days old), patients who received older blood
(>14 days old) had a higher rate of in-hospital mortality
(1.7 vs. 2.8%, P 0.004). However, concerns over the
unequal distribution of patients who received massive
transfusion tempered the results of this study. Although
several additional studies have suggested the presence of
higher mortality with increasing RBC storage age, findings to the contrary exist as well [17]. Prospective clinical
trials comparing conventional vs. fresh (<7 days old) RBC
transfusion are currently under way.

plasma product, fresh frozen plasma (FFP). We will

specifically address indications, efficacy, and risk.

Allogeneic RBC administration has also been noted to

have profound affects on recipient immune function, a
condition known as TRIM. Substantial epidemiologic
evidence associates TRIM with an increased risk for
nosocomial infections [7]. This association has been
noted in multiple surgical populations in addition to those
who are critically ill. Interestingly, recent evidence
suggests a diminution of the association between RBC
transfusion and adverse outcome [18]. This shift has been
postulated to be the result of a move to leukoreduced
blood [19] and is supported by a randomized controlled
trial comparing cardiac surgery patients who received
nonleukocyte-reduced RBC transfusions to patients
who received leukocyte-reduced RBC product [20]. In
this investigation, transfusion with leukoreduced RBCs
was associated with fewer postoperative infections and
reduced hospital mortality. Although substantial evidence supports the use of leukoreduced blood in cardiac
surgery, these findings have not been consistently reproduced in other populations [21].

(1) Replacement of inherited single coagulation factor

deficiencies for which no virus-safe fractionated product exists [25].
(2) Replacement of specific protein deficiencies such as
C-1 esterase inhibitor [26].
(3) Replacement of multiple coagulation factor deficiencies with associated severe bleeding and/or disseminated intravascular coagulation [25].
(4) As a component of plasma exchange in patients with
thrombotic thrombocytopenic purpura [25].
(5) Reversal of warfarin anticoagulation when severe
bleeding is present and prothrombin complex concentrates are not available [25].
(6) Prevention of dilutional coagulopathy in patients
with major trauma and/or massive hemorrhage [27].
(7) Prevention of bleeding in patients with advanced
liver disease and prolonged coagulation tests who
are planned to undergo an invasive procedure [25].

Implementation of evidence-based transfusion in the

intensive care unit

Despite the growing body of literature suggesting a lack

of efficacy with RBC administration in most clinical
situations, approximately 4050% of patients admitted
to the ICU will receive at least 1 allogeneic RBC unit [1].
The mean number of RBC transfusions per ICU patient
is estimated to be 5 units with the average pretransfusion
hemoglobin being 8.5 g/dl [1]. Interestingly, it has been
shown that fewer than one in five patients are transfused
for active bleeding [1] with most transfusions simply
being for a low hemoglobin level [22]. Education, feedback and the use of simple decision support tools have
had remarkable success in reducing inappropriate transfusion in the ICU [23].

Fresh frozen plasma

This section of the review will address plasma administration in the ICU. Though multiple plasma products
exist, we will focus on the most commonly administered

Fresh frozen plasma: indications

Each year, more than 3 million units of FFP are transfused in the US alone [24]. Despite efforts to educate care
providers and limit the number of inappropriate plasma
transfusions, FFP utilization continues to increase. In
light of the limited number of indications for FFP
administration (given below), much of this use appears
to lack evidence-based support.
Evidence-based indications for FFP administration:

Indeed, recent estimates indicate that at some institutions, up to 83% of FFP transfusions do not follow
published guidelines [28]. In the US, the most common
reason for FFP administration is an attempt to normalize
an elevated preprocedural international normalized ratio
(INR) [29]. Importantly, available evidence does not
support this practice. In contrast, FFP administration
in the setting of massive bleeding is often delayed and
inadequate, promoting dilutional coagulopathy, need for
massive transfusion, and potentially catastrophic consequences [27].
In the ICU, the three primary indications for FFP include
the replacement of multiple coagulation factor deficiencies with associated severe bleeding, disseminated
intravascular coagulation, and the prevention of dilutional coagulopathy in patients with major trauma who
require massive transfusion (discussed below) [25]. FFP
is not indicated in patients with isolated coagulation
factor deficits for which specific factor concentrates are
available. Additionally, the use of FFP to reverse the
effect of anticoagulation is generally not recommended
[30]. In the absence of bleeding or need for emergent

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

312 Intravenous fluids

Figure 2 International normalized ratio and coagulation reserve

This discordance is largely explained by the nonlinear,

exponential relationship between clotting factor levels and
coagulation test results (Fig. 2) [29]. As the ability to form
in-vivo thrombus is dependent on actual coagulation factor
levels, these finding are significant. One must also appreciate that whereas FFP administration often normalizes a
markedly elevated INR, coagulation factor levels rise and
associated bleeding risk falls only modestly (Table 1) [34].
Furthermore, multiple studies have noted an inability of
FFP to correct INR values ranging from 1.1 to 1.85 [28,32].
This lack of efficacy is in part explained by the INR of an
FFP unit, which is frequently on the upper limits of normal
or even beyond the normal range [28]. Thromboelastography (TEG) is an attractive alternative to traditional
coagulation screening tests which may better reflect
in-vivo clotting activity [35].

Coagulation 100
factors (%)
Zone of normal hemostasis
(physiologic reserve)

50
30
Zone of
therapeutic
anticoagulation

PT (sec) 12 13 14 15 16 17 18 19 20 21 22
INR 1.0

1.3

1.7 2.0 2.2

3.0

General relationship between the concentration of coagulation factors

and the result of the prothrombin time (PT) test. Adapted with permission
from Dzik [29].

Fresh frozen plasma: risks

The three most notable complications with plasma transfusion include allergic reactions, TACO and TRALI.
Allergic reactions can vary in severity from mild pruritus
to anaphylaxis with the latter being extremely rare.
Although also believed rare, TACO has an estimated
incidence of 111% of patients transfused. This incidence is almost certainly an underestimate due to poor
syndrome recognition and under-reporting. TACO
develops quickly, typically within minutes to hours of
transfusion and usually in patients with already compromised cardiac function and volume overload. Prompt
volume reduction with diuresis typically results in rapid
improvement, but ventilatory support may be needed.
The associated mortality is reported between 5 and 15%
[36]. In patients at risk for TACO (e.g. reduced left
ventricular systolic function, diastolic dysfunction, renal
failure, pre-existing volume overload), reduced transfusion rates and diuretic administration are recommended.
TRALI will be discussed in detail later in this review.

high-risk surgery, vitamin K is a preferred therapy. When

emergency anticoagulant reversal is needed, prothrombin
complex concentrates (PCCs) are preferred when available as they appear to provide more consistent normalization of coagulation status with an improved safety
profile [30]. Finally, the use of FFP to correct coagulation
abnormalities in patients with liver disease is similarly
controversial as numerous evaluations note a poor correlation between coagulation test results and risk of bleeding in this patient population.
Fresh frozen plasma: efficacy

Importantly, available evidence is notable for a lack of

correlation between mild-to-moderate coagulation test
abnormalities and the development of procedural bleeding
or need for RBC administration [24,31,32]. In part, this can
be described by the poor correlation between laboratory
test results and actual plasma coagulation factor levels [33].

Table 1 Changes in the vitamin K-dependent clotting factors and international normalized ratio following the administration of
approximately 800 ml fresh frozen plasma in warfarin-treated patients
Factor II

Factor VII

Factor IX

Factor X

INR

Patient

Pre

Post

Pre

Post

Pre

Post

Pre

Post

Pre

Post

1
2
3
4
5
6
7
8
9
10
11
12
Median
Range

3
1
4
17
2
3
11
30
8
3
1

3
130

12
14
21
33
14
12
16
29
19
17
19

17
1233

5
18
0
33
7
3
24
65
2
5
5

5
065

12
42
26
47
15
9
27
59
9
25
19

19
959

4
17
0
47
6
12
22
62
9
10
6

10
062

12
32
21
63
10
19
36
62
13
20
13

19
1063

0
2
0
13
9
6
10
10
18
2
1

6
018

20
20
23
27
17
18
24
22
29
15
18

20
1529

15.3
6.2
20
2.9
11.1
17.1
3.4
3.1
10.1
7.8
22
3.7
8.95
2.922

2.8
1.8
2.3
1.7
2
3.4
2
1.9
3.8
2.5
2
1.6
2
1.63.8

All clotting factor values in IU/dl. Modified from Makris et al. [34].

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Blood product transfusion in the critically ill Kor and Gajic 313

Platelets
This section of the review will address platelet use in the
ICU. We will specifically focus on indications, transfusion
thresholds, and risks associated with platelet component
therapy.

well tolerated. Unfortunately, the presence of multiple

comorbid conditions, coexisting bleeding diatheses, and
need for invasive procedures in ICU populations prevents
generalization of these study results. Furthermore, the
available evidence evaluating prophylactic platelet transfusion in the critically ill are conflicting [38,43], further
preventing definitive recommendations.

Platelets: indications

Indications for platelet transfusion include thrombocytopenia and platelet function disorders [37]. Although
inherited disorders are very rare, thrombocytopenia is
frequently encountered in the ICU. It has been estimated
that more than 40% of patients requiring ICU care will
have a platelet count below 150  109/l at some point
during their ICU stay and greater than 25% will have a
platelet count below 100  109/l [38,39]. Furthermore,
the presence of thrombocytopenia in the ICU has been
associated with major bleeding, increased ICU and HOS
length of stay, and mortality.
The most frequent clinical indication for platelet transfusion in the ICU is prophylaxis for presumed bleeding risk
in the setting of thrombocytopenia [40,41]. This is followed closely by transfusion for active bleeding and prophylaxis for a planned invasive procedure. Whereas evidence suggests bleeding risk is minimal when the platelet
count exceeds 50  109/l, risk is believed to increase
dramatically when platelet counts fall below 10  109/l
[37]. Importantly, the characterization of bleeding risk
associated with thrombocytopenia has been performed
primarily in patients with bone marrow failure and compromised thrombopoiesis. This precludes an accurate estimation of bleeding risk in most ICU populations and
presents an opportunity for meaningful future research.
Platelets: transfusion thresholds

Although evidence suggests that the platelet count triggering platelet transfusion in the ICU most often ranges
from 40 to 50  109/l [39], Cameron et al. [41] described a
more liberal transfusion practice in the perioperative
setting with an average pretransfusion platelet count of
85  109/l in patients having noncardiac surgery and
102  109/l in patients undergoing cardiopulmonary
bypass. We emphasize that whereas platelet dysfunction
is clearly present in patients undergoing cardiopulmonary
bypass surgery, it is not believed to increase their risk of
bleeding when compared to other surgical populations
[41]. Indeed, with the exception of patients with massive
bleeding, higher transfusion thresholds (>50  109/l) are
generally difficult to justify.
Randomized controlled trials provide guidance on appropriate platelet transfusion thresholds in patients with
leukemia or bone marrow failure due to chemoradiation
or other hematologic disorders [42]. In this setting, a
transfusion threshold of 10  109/l has been shown to be

While recognizing these limitations, current guidelines for

patients with disseminated intravascular coagulation
(DIC), massive bleeding, or need for invasive procedures
suggest a platelet transfusion threshold of 50  109/l. Still
higher thresholds (100  109/l) are recommended for
specific surgeries with heightened concern for periprocedural bleeding (neurosurgery and ophthalmic surgery)
[44]. We emphasize that these thresholds are based primarily on expert opinion and the treatment of bleeding or its
prophylaxis in patients with disorders of platelet number or
function remains a matter of debate [37]. Indeed, it maybe
prudent to avoid prophylactic strategies altogether, transfusing platelets for thrombocytopenic patients only when
there is evidence of active bleeding [45,46]. If prophylactic
platelet transfusion is pursued, recent data suggest lowdose transfusion can reduce the quantity of platelets
transfused without increasing bleeding risk [47].
Platelets: risks

Importantly, platelet transfusions have been associated

with worse outcome in certain critically ill populations
[43]. As with FFP, platelets are high plasma volume
products and share many of the same risks, including
TRALI, TACO, acute hemolysis, and anaphylaxis [48]. A
unique concern with platelet administration is transfusion-related sepsis [49] with bacterial contamination of
platelets being the third leading cause of transfusionrelated mortality [50]. Storage of platelets at room
temperature provides a favorable environment for bacterial contamination with resultant septic transfusion
[49]. This risk increases with duration of storage [49]
and whereas more effective microbial testing strategies
[48] have reduced the rate of this complication, a substantial false-negative testing rate persists [49]. Finally,
platelet component therapy has also been associated with
thrombotic complications such as acute in-stent thrombosis [51].

Massive transfusion
Hemorrhage lags only neurologic injury as the second
leading cause of death in patients sustaining major
trauma [52]. Importantly, uncontrolled hemorrhage can
propagate the lethal triad of coagulopathy, acidosis, and
hypothermia and each of these abnormalities can exacerbate the others. If left uncorrected, there is a progressive
deterioration in each parameter leading to additional
bleeding, greater transfusion requirements, and ulti-

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

314 Intravenous fluids

mately death. It should be noted that coagulopathy can

develop quickly in this population and may actually occur
before significant resuscitation has occurred [53]. Importantly, the presence of abnormalities in coagulation correlate with adverse outcome [53] and this association has
raised interest in the aggressive replacement of coagulation factors in patients with serious injury requiring
massive transfusion [5456].
The momentum for a more aggressive FFP transfusion
practice in the setting of massive hemorrhage originated in
the military [57] and has been extended into the civilian
population [35,5458]. In a recent, retrospective evaluation of a massively transfused civilian patient population
(>10 units of RBC), Teixeira and colleagues [27] noted a
significant reduction in mortality in those who had FFP
transfused more aggressively. Others have reported similar
improvements in mortality with more liberal use of FFP
[54,56] and multiple authors now recommend FFP : RBC
ratios varying between 1 : 1 and 1 : 2 [35,55,58]. However,
the inherent limitations of retrospective trials and potential
for survival bias [59] prevent full endorsement of aggressive FFP transfusion practices without further study. This
is clearly an area in which well designed prospective
clinical trials are needed.
Appreciating that thrombocytopenia also occurs frequently in the setting of massive transfusion, platelet
component practices in this clinical setting have been
extensively re-evaluated as well [54,55]. Zink et al. [54]
recently noted substantial reductions in both RBC transfusions and mortality when liberal platelet transfusion
practices were utilized early in the course of resuscitation.
Others have shown a similar mortality benefit with the
aggressive use of platelet component therapy [60]. These
findings are particularly notable considering the
traditional platelet transfusion threshold value of
50  109/l is not typically encountered until much later
in the resuscitation process. Importantly, this recommendation fails to account for the coexistence of coagulopathy, acidosis, hypothermia, and comorbid disease, not
to mention the frequent use of antiplatelet medications in
this population [12]. As a result, recommended transfusion threshold values are unlikely to provide meaningful
guidance in this population and liberal platelet transfusion strategies are increasingly recommended [54,55].
Although the optimal ratio of platelet components to
RBC and plasma units remains poorly defined, multiple
authors suggest a ratio of 1 : 1 : 1 [54,56]. As with FFP,
further prospective studies are needed prior to full endorsement of these recommendations.

Transfusion-related acute lung injury

TRALI is defined as new acute lung injury (ALI) occurring within 6 h of transfusion, with clear temporal

relationship to transfusion, in patients with (possible

TRALI) or without (TRALI) additional risk factors for
ALI [61]. It is now recognized as the leading cause of
mortality associated with blood transfusion [62].
Although all blood products can lead to this serious
complication, high plasma volume products such as
FFP and platelets carry the greatest risk [62,63]. Stainsby
and colleagues [64] recently noted that TRALI occurs
56 times more frequently with high plasma volume
components when compared to RBCs. Interestingly,
the majority of reported deaths resulting from TRALI
follow administration of a single unit of FFP [65].
The association of platelet administration with TRALI is
also strongly supported by both preclinical [66] and
clinical data [62,6769]. The intriguing work of Looney
et al. [66] recently noted a substantial fall in lung neutrophil sequestration and subsequent TRALI when
animals were rendered thrombocytopenic prior to lipopolysaccharide (LPS) priming and an antimajor histocompatibility complex class I monoclonal antibody (antiMHC I mAb) challenge (two-hit model of TRALI). In
this same investigation, administration of antiplatelet
therapy prior to insult also provided lung protection.
Of note, the liberal use of platelet components in patients
requiring massive transfusion has not been consistently
associated with increased risk of TRALI [3,54].
In 2001, Palfi and colleagues [70] noted a greater degree
of hypoxemia and elevated levels of the inflammatory
marker, tumor necrosis factor a, in critically ill patients
who received plasma from multiparous female donors
when compared to those who received male-donor
plasma. We subsequently published similar findings
[71] and multiple additional investigations have confirmed the association between alloimmunized donor
status and risk of TRALI in the transfusion recipient
[68,69,72,73]. Due to the primary role of antileukocyte
antibodies in TRALI, new blood banking strategies have
been adopted. In October of 2003, the UK National
Blood Service recommended use of FFP and buffy
coat-derived pooled platelet components from male
donors only. Similar policy changes were subsequently
introduced in the Netherlands and the US. Recently,
Chapman and colleagues [62] reported the UK experience with their male-only donor policy. The results note
an impressive fall in highly likely/probable TRALI due
to both FFP and platelet transfusion. In contrast, a
recently published retrospective database investigation
challenges the change in plasma procurement strategy
noting a lower frequency of respiratory complications in
cardiac surgery patients receiving exclusively female
donor plasma transfusion compared to a matched cohort
who received exclusively male donor plasma [74]. A
National Institutes of Health (NIH)-sponsored, prospective investigation being performed at the University of

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Blood product transfusion in the critically ill Kor and Gajic 315

CaliforniaSan Francisco and Mayo Clinic will further

define TRALI mechanisms and the effects of recent
changes in donor procurement strategies.

14 Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications
after cardiac surgery. N Engl J Med 2008; 358:12291239.
15 Marik PE, Corwin HL. Acute lung injury following blood transfusion: expanding
the definition. Crit Care Med 2008; 36:30803084.
16 Kor DJ, Van Buskirk CM, Gajic O. Red blood cell storage lesion. Bosn J Basic
Med Sci 2009; 9 (Suppl 1):2127.

Conclusion
The past two decades have witnessed an extensive reevaluation of transfusion therapy in the ICU. Accumulating evidence refutes the efficacy of RBC, plasma, and
platelet transfusion in the majority of critically ill
patients. Simultaneously, investigations have increasingly exposed previously under-recognized transfusion
risks such as nosocomial infection and TRALI. With the
notable exception of acute blood loss, this improved
understanding has led to recommendations for more
conservative RBC, plasma, and platelet transfusion strategies. Importantly, numerous knowledge gaps persist.
Well designed prospective studies are needed to better
define and characterize important issues such as the
impact of RBC storage duration, transfusion-related
immune modulation, and donor procurement procedures.
Different transfusion strategies with particular focus on
the timing of intervention and specific clinical endpoints
need to be investigated in patients with major trauma and
acute local or global tissue ischemia.

References
1

Napolitano LM, Kurek S, Luchette FA, et al. Clinical practice guideline: red
blood cell transfusion in adult trauma and critical care. Crit Care Med 2009;
37:31243157.

Marwaha N, Sharma RR. Consensus and controversies in platelet transfusion.

Transfus Apher Sci 2009; 41:127133.

Watson GA, Sperry JL, Rosengart MR, et al. Fresh frozen plasma is independently associated with a higher risk of multiple organ failure and acute
respiratory distress syndrome. J Trauma 2009; 67:221230.

Aronson D, Dann EJ, Bonstein L, et al. Impact of red blood cell transfusion on
clinical outcomes in patients with acute myocardial infarction. Am J Cardiol
2008; 102:115119.

Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008.
Crit Care Med 2008; 36:296327.
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the
treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368
1377.

Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: a
systematic review of the literature. Crit Care Med 2008; 36:26672674.

Kiraly LN, Underwood S, Differding JA, Schreiber MA. Transfusion of aged

packed red blood cells results in decreased tissue oxygenation in critically
injured trauma patients. J Trauma 2009; 67:2932.

Marik PE, Sibbald WJ. Effect of stored-blood transfusion on oxygen delivery in

patients with sepsis. J Am Med Assoc 1993; 269:30243029.

10 Alexander BB, Marc M, Christopher CS. Transfusion-related acute lung injury

(TRALI): a clinical review with emphasis on the critically ill. Br J Haematol
2009; 9999.
11 Chaiwat O, Lang JD, Vavilala MS, et al. Early packed red blood cell transfusion
and acute respiratory distress syndrome after trauma. Anesthesiology 2009;
110:351360.
12 Piccin A, Cronin M, Murphy C, et al. Transfusion associated circulatory
overload (TACO) incidence and risk factors. ASH Ann Meeting Abstracts
2009; 114:3157.
13 Zallen G, Offner PJ, Moore EE, et al. Age of transfused blood is an independent risk factor for postinjury multiple organ failure. Am J Surg 1999;
178:570572.

17 van de Watering L, Lorinser J, Versteegh M, et al. Effects of storage time of red

blood cell transfusions on the prognosis of coronary artery bypass graft
patients. Transfusion 2006; 46:17121718.
18 Broessner G, Lackner P, Hoefer C, et al. Influence of red blood cell transfusion
on mortality and long-term functional outcome in 292 patients with spontaneous subarachnoid hemorrhage. Crit Care Med 2009; 37:18861892.
19 Bilgin YM, van de Watering LM, Versteegh MI, et al. Effects of allogeneic
leukocytes in blood transfusions during cardiac surgery on inflammatory
mediators and postoperative complications. Crit Care Med 2010;
38:546552.
20 Bilgin YM, van de Watering LM, Eijsman L, et al. Double-blind, randomized
controlled trial on the effect of leukocyte-depleted erythrocyte transfusions in
cardiac valve surgery. Circulation 2004; 109:27552760.
21 Englehart MS, Cho SD, Morris MS, et al. Use of leukoreduced blood does not
reduce infection, organ failure, or mortality following trauma. World J Surg
2009; 33:16261632.
22 Corwin HL, Gettinger A, Pearl RG, et al. The CRIT study: anemia and blood
transfusion in the critically ill: current clinical practice in the United States. Crit
Care Med 2004; 32:3952.
23 Rana R, Afessa B, Keegan MT, et al. Evidence-based red cell transfusion in
the critically ill: quality improvement using computerized physician order entry.
Crit Care Med 2006; 34:18921897.
24 Segal JB, Dzik WH. Paucity of studies to support that abnormal coagulation
test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 2005; 45:14131425.
25 OShaughnessy DF, Atterbury C, Bolton Maggs P, et al. Guidelines for the use
of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol
2004; 126:1128.
26 Prematta M, Gibbs JG, Pratt EL, et al. Fresh frozen plasma for the treatment of
hereditary angioedema. Ann Allergy Asthma Immunol 2007; 98:383388.
27 Teixeira PG, Inaba K, Shulman I, et al. Impact of plasma transfusion in
massively transfused trauma patients. J Trauma 2009; 66:693697.
28 Holland LL, Foster TM, Marlar RA, Brooks JP. Fresh frozen plasma is
ineffective for correcting minimally elevated international normalized ratios.
Transfusion 2005; 45:12341235.
29 Dzik WH. Predicting hemorrhage using preoperative coagulation screening
assays. Curr Hematol Rep 2004; 3:324330.
30 Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin
K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:160S198S.
31 Gajic O, Dzik WH, Toy P. Fresh frozen plasma and platelet transfusion for
nonbleeding patients in the intensive care unit: benefit or harm? Crit Care Med
2006; 34:S170S173.
32 Abdel-Wahab OI, Healy B, Dzik WH. Effect of fresh-frozen plasma transfusion
on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion 2006; 46:12791285.
33 Chowdhury P, Saayman AG, Paulus U, et al. Efficacy of standard dose and
30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 2004; 125:6973.
34 Makris M, Greaves M, Phillips WS, et al. Emergency oral anticoagulant reversal:
the relative efficacy of infusions of fresh frozen plasma and clotting factor
concentrate on correction of the coagulopathy. Thromb Haemost 1997;
77:477480.
35 Johansson PI, Stensballe J. Effect of haemostatic control resuscitation on
mortality in massively bleeding patients: a before and after study. Vox Sang
2009; 96:111118.
36 Popovsky MA. Transfusion and the lung: circulatory overload and acute lung
injury. Vox Sang 2004; 87 (Suppl 2):6265.
37 Tosetto A, Balduini CL, Cattaneo M, et al. Management of bleeding and of
invasive procedures in patients with platelet disorders and/or thrombocytopenia: guidelines of the Italian Society for Haemostasis and Thrombosis
(SISET). Thromb Res 2009; 124:e13e18.
38 Stephan F, Hollande J, Richard O, et al. Thrombocytopenia in a surgical ICU.
Chest 1999; 115:13631370.
39 Arnold DM, Crowther MA, Cook RJ, et al. Utilization of platelet transfusions in
the intensive care unit: indications, transfusion triggers, and platelet count
responses. Transfusion 2006; 46:12861291.

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

316 Intravenous fluids

40 Greeno E, McCullough J, Weisdorf D. Platelet utilization and the transfusion
trigger: a prospective analysis. Transfusion 2007; 47:201205.

58 Jansen JO, Thomas R, Loudon MA, Brooks A. Damage control resuscitation

for patients with major trauma. Br Med J 2009; 338:b1778.

41 Cameron B, Rock G, Olberg B, Neurath D. Evaluation of platelet transfusion

triggers in a tertiary-care hospital. Transfusion 2007; 47:206211.

59 Snyder CW, Weinberg JA, McGwin G Jr, et al. The relationship of blood
product ratio to mortality: survival benefit or survival bias? J Trauma 2009;
66:358362; discussion 62-4.

42 Diedrich B, Remberger M, Shanwell A, et al. A prospective randomized trial of

a prophylactic platelet transfusion trigger of 10  10(9) per L versus
30  10(9) per L in allogeneic hematopoietic progenitor cell transplant
recipients. Transfusion 2005; 45:10641072.

60 Perkins JG, Cap AP, Spinella PC, et al. An evaluation of the impact of
apheresis platelets used in the setting of massively transfused trauma
patients. J Trauma 2009; 66:S77S84; discussion S-5.

43 Pereboom IT, de Boer MT, Haagsma EB, et al. Platelet transfusion during liver
transplantation is associated with increased postoperative mortality due to
acute lung injury. Anesth Analg 2009; 108:10831091.

61 Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel. Transfusion
2004; 44:17741789.

44 Samama CM, Djoudi R, Lecompte T, et al. Perioperative platelet transfusion:

recommendations of the Agence Francaise de Securite Sanitaire des Produits de Sante (AFSSaPS) 2003. Can J Anaesth 2005; 52:3037.

62 Chapman CE, Stainsby D, Jones H, et al. Ten years of hemovigilance reports

of transfusion-related acute lung injury in the United Kingdom and the impact
of preferential use of male donor plasma. Transfusion 2009; 49:440452.

45 Slichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients. Transfus Med Rev 2004; 18:153167.

63 Gajic O, Yilmaz M, Iscimen R, et al. Transfusion from male-only versus female

donors in critically ill recipients of high plasma volume components. Crit Care
Med 2007; 35:16451648.

46 Wandt H, Schaefer-Eckart K, Frank M, et al. A therapeutic platelet transfusion

strategy is safe and feasible in patients after autologous peripheral blood stem
cell transplantation. Bone Marrow Transplant 2006; 37:387392.
47 Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of prophylactic platelet
transfusions and prevention of hemorrhage. N Engl J Med 2010; 362:600
613.
48 Tormey CA, Sweeney JD, Champion MH, et al. Analysis of transfusion
reactions associated with prestorage-pooled platelet components. Transfusion 2009; 49:12421247.
49 Eder AF, Kennedy JM, Dy BA, et al. Bacterial screening of apheresis platelets
and the residual risk of septic transfusion reactions: the American Red Cross
experience (20042006). Transfusion 2007; 47:11341142.
50 Spiess BD, Royston D, Levy JH, et al. Platelet transfusions during coronary
artery bypass graft surgery are associated with serious adverse outcomes.
Transfusion 2004; 44:11431148.
51 Cornet AD, Klein LJ, Groeneveld AB. Coronary stent occlusion after platelet
transfusion: a case series. J Invasive Cardiol 2007; 19:E297E299.
52 Tieu BH, Holcomb JB, Schreiber MA. Coagulopathy: its pathophysiology and
treatment in the injured patient. World J Surg 2007; 31:10551064.
53 Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma
2003; 54:11271130.
54 Zink KA, Sambasivan CN, Holcomb JB, et al. A high ratio of plasma and
platelets to packed red blood cells in the first 6 h of massive transfusion
improves outcomes in a large multicenter study. Am J Surg 2009; 197:565
570; discussion 70.

64 Stainsby D, MacLennan S, Thomas D, et al. Guidelines on the management of

massive blood loss. Br J Haematol 2006; 135:634641.
65 Holness L. Analysis of fatalities reported to the FDA. Consensus Conference:
towards an understanding of TRALI 2004; Toronto, Ontario, Canada.
66 Looney MR, Nguyen JX, Hu Y, et al. Platelet depletion and aspirin treatment
protect mice in a two-event model of transfusion-related acute lung injury.
J Clin Invest 2009; 119:34503461.
67 Vlaar AP, Binnekade JM, Prins D, et al. Risk factors for the onset of transfusion
related acute lung injury (TRALI) in critically ill patients: a retrospective nested
case control study. Am J Respir Crit Care Med 2009; 179:A4636-.
68 Keller-Stanislawski B, Reil A, Gunay S, Funk MB. Frequency and severity of
transfusion-related acute lung injury: German haemovigilance data (2006
2007). Vox Sang 2010; 98:7077.
69 van Stein D, Beckers EA, Sintnicolaas K, et al. Transfusion-related acute lung
injury reports in the Netherlands: an observational study. Transfusion 2010;
50:213220.
70 Palfi M, Berg S, Ernerudh J, Berlin G. A randomized controlled trial of
transfusion-related acute lung injury: is plasma from multiparous blood donors
dangerous? Transfusion 2001; 41:317322.
71 Gajic O, Rana R, Winters JL, et al. Transfusion-related acute lung injury in the
critically ill: prospective nested case-control study. Am J Respir Crit Care Med
2007; 176:886891.

55 Sihler KC, Napolitano LM. Massive transfusion: new insights. Chest 2009;
136:16541667.

72 Wright SE, Snowden CP, Athey SC, et al. Acute lung injury after ruptured
abdominal aortic aneurysm repair: the effect of excluding donations from
females from the production of fresh frozen plasma. Crit Care Med 2008;
36:17961802.

56 Shaz BH, Dente CJ, Nicholas J, et al. Increased number of coagulation

products in relationship to red blood cell products transfused improves
mortality in trauma patients. Transfusion 2010; 50:493500.

73 Tynell E, Andersson TM, Norda R, et al. Should plasma from female donors be
avoided? A population-based cohort study of plasma recipients in Sweden
from 1990 through 2002. Transfusion 2010 [Epub ahead of print].

57 Spinella PC, Perkins JG, Grathwohl KW, et al. Effect of plasma and red blood
cell transfusions on survival in patients with combat related traumatic injuries.
J Trauma 2008; 64:S6977; discussion S-8.

74 Welsby IJ, Troughton M, Phillips-Bute B, et al. The relationship of plasma

transfusion from female and male donors with outcome after cardiac surgery.
J Thorac Cardiovasc Surg 2010. [Epub ahead of print].

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.