Transfusion of Blood and Blood Products:

Indications and Complications

SANJEEV SHARMA, MD; POONAM SHARMA, MD; and LISA N. TYLER, MD
Creighton University School of Medicine, Omaha, Nebraska

Red blood cell transfusions are used to treat hemorrhage and to improve oxygen delivery to tissues. Transfusion of
red blood cells should be based on the patient’s clinical condition. Indications for transfusion include symptomatic
anemia (causing shortness of breath, dizziness, congestive heart failure, and decreased exercise tolerance), acute
sickle cell crisis, and acute blood loss of more than 30 percent of blood volume. Fresh frozen plasma infusion can be
used for reversal of anticoagulant effects. Platelet transfusion is indicated to prevent hemorrhage in patients with
thrombocytopenia or platelet function defects. Cryoprecipitate is used in cases of hypofibrinogenemia, which most
often occurs in the setting of massive hemorrhage or consumptive coagulopathy. Transfusion-related infections
are less common than noninfectious complications. All noninfectious complications of transfusion are classified
as noninfectious serious hazards of transfusion. Acute complications occur within minutes to 24 hours of the
transfusion, whereas delayed complications may develop days, months, or even years later. (Am Fam Physician.
2011;83(6):719-724. Copyright © 2011 American Academy of Family Physicians.)

B
lood transfusion can be a life- sickle cell crisis (for stroke prevention), or
saving procedure, but it has risks, acute blood loss of greater than 1,500 mL or
including infectious and nonin- 30 percent of blood volume.4 Patients with
fectious complications. There is symptomatic anemia should be transfused
debate in the medical literature concern- if they cannot function without treating the
ing the appropriate use of blood and blood anemia.4 Symptoms of anemia may include
products. Clinical trials investigating their fatigue, weakness, dizziness, reduced exer-
use suggest that waiting to transfuse at lower cise tolerance, shortness of breath, changes
hemoglobin levels is beneficial.1,2 This review in mental status, muscle cramps, and
will consider the indications for transfusion angina or severe congestive heart failure.
of blood and blood products, and will dis- The 10/30 rule—transfusion when a patient
cuss common noninfectious complications has a hemoglobin level less than or equal to
associated with transfusion. 10 g per dL (100 g per L) and a hematocrit
level less than or equal to 30 percent—was
Red Blood Cells used until the 1980s as the trigger to trans-
Packed red blood cells (RBCs) are prepared fuse, regardless of the patient’s clinical
from whole blood by removing approxi- presentation.4,5
mately 250 mL of plasma. One unit of packed In 1999, a randomized, multicenter, con-
RBCs should increase levels of hemoglobin trolled clinical trial evaluated a restrictive
by 1 g per dL (10 g per L) and hematocrit by transfusion trigger (hemoglobin level of 7 to
3 percent. In most areas, packed RBC units 9 g per dL [70 to 90 g per L]) versus a lib-
are filtered to reduce leukocytes before eral transfusion trigger (hemoglobin level
storage, which limits febrile nonhemolytic of 10 to 12 g per dL [100 to 120 g per L])
transfusion reactions (FNHTRs), and are in patients who were critically ill.1 Restric-
considered cytomegalovirus safe.3 tive transfusion practices resulted in a 54
RBC transfusions are used to treat hemor- percent relative decrease in the number
rhage and to improve oxygen delivery to tis- of units transfused and a reduction in the
sues. Transfusion of RBCs should be based 30-day mortality rate. The authors recom-
on the patient’s clinical condition.4 Indi- mended transfusion when hemoglobin is
cations for RBC transfusion include acute less than 7 g per dL, and maintenance of a
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 SORT: KEY RECOMMENDATIONS FOR PRACTICE

Evidence
Clinical recommendation rating References Comments

The threshold for transfusion of red blood cells should be a hemoglobin A 1, 2, 6 RCTs in adults and
level of 7 g per dL (70 g per L) in adults and most children. children with a critical
illness
A restrictive transfusion strategy (hemoglobin level of 7 to 9 g per dL B 2 RCT in children with a
[70 to 90 g per L]) should not be used in preterm infants or children critical illness
with cyanotic heart disease, severe hypoxemia, active blood loss, or
hemodynamic instability.
Transfusion of plasma should be considered in a patient who has an C 8 Consensus conference
International Normalized Ratio greater than 1.6 with active bleeding, or recommendations
in a patient receiving anticoagulant therapy before an invasive procedure.
Platelets should not be transfused in patients with thrombotic C 10, 11 Guidelines based on case
thrombocytopenic purpura or heparin-induced thrombocytopenia reports
unless a life-threatening hemorrhage has occurred.

RCT = randomized controlled trial.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.
org/afpsort.xml.

hemoglobin level between 7 to 9 g per dL.1 A recently per dL (85 to 95 g per L). The liberal transfusion trig-
updated Cochrane review supports the use of restrictive
ger was a hemoglobin level of 9.5 g per dL, with a target
transfusion triggers in patients who do not have cardiac
level of 11 to 12 g per dL (110 to 120 g per L). Patients
disease.6 in the restrictive group received 44 percent fewer blood
A similar study was carried out in critically ill chil-
transfusions, with no difference in rates of multiple organ
dren.2 The restrictive transfusion trigger was a hemoglo-
dysfunction syndrome or death. The restrictive transfu-
bin level of 7 g per dL, with a target level of 8.5 to 9.5 g
sion strategy is useful for children who are stable patients
in intensive care. It should not be used in
preterm neonates or in children with severe
Table 1. Indications for Transfusion of Plasma Products
hypoxemia, active blood loss, hemodynamic
instability, or cyanotic heart disease.2
Indication Associated condition/additional information
Plasma
International Normalized Inherited deficiency of single clotting factors Plasma products available in the United
Ratio > 1.6 with no virus-safe or recombinant factor States include fresh frozen plasma and
available—anticoagulant factors II, V, X, or XI
thawed plasma that may be stored at 33.8 to
Prevent active bleeding in patient on
anticoagulant therapy before a procedure
42.8°F (1 to 6°C) for up to five days. Plasma
Active bleeding
contains all of the coagulation factors. Fresh
Emergent reversal of Major or intracranial hemorrhage
frozen plasma infusion can be used for rever-
warfarin (Coumadin) Prophylactic transfusion in a surgical
sal of anticoagulant effects. Thawed plasma
procedure that cannot be delayed has lower levels of factors V and VIII and
Acute disseminated With active bleeding and correction of is not indicated in patients with consump-
intravascular underlying condition tion coagulopathy (diffuse intravascular
coagulopathy coagulation).3
Microvascular bleeding ≥ 1 blood volume (replacing approximately Plasma transfusion is recommended in
during massive 5,000 mL in an adult who weighs 155.56 lb patients with active bleeding and an Interna-
transfusion [70 kg])
tional Normalized Ratio (INR) greater than
Replacement fluid for Thrombotic thrombocytopenic purpura;
apheresis in thrombotic hemolytic uremic syndrome
1.6, or before an invasive procedure or sur-
microangiopathies gery if a patient has been anticoagulated.7,8
Hereditary angioedema When C1 esterase inhibitor is unavailable9 Plasma is often inappropriately transfused
for correction of a high INR when there is no
Information from references 7 through 9. bleeding. Supportive care can decrease high-
normal to slightly elevated INRs (1.3 to 1.6)

720  American Family Physician www.aafp.org/afp Volume 83, Number 6 ◆ March 15, 2011
 Table 2. Indications for Transfusion of   Table 4. Indications for Transfusion of
Platelets in Adults Cryoprecipitate

Platelet count Adults Neonates (continued)

Prophylactic transfusion indications (x 103 per µL) Hemorrhage after cardiac Anticoagulant factor XIII
surgery deficiency
Major surgery or invasive procedure, no ≤ 50
Massive hemorrhage or Congenital
active bleeding
transfusion dysfibrinogenemia12
Ocular surgery or neurosurgery, no active ≤ 100
Surgical bleeding Congenital fibrinogen
bleeding
Neonates deficiency
Surgery with active bleeding < 50 (usually)
Anticoagulant factor VIII von Willebrand disease*
> 100 (rarely)
deficiency*
Stable, nonbleeding < 10
Stable, nonbleeding, and body < 20 *—Use when recombinant factors are not available.
temperature > 100.4°F (38°C) or
Information from references 12 and 15.
undergoing invasive procedure

Information from reference 9.

platelets in these conditions can result in further throm-

bosis.10,11 One unit of apheresis platelets should increase
Table 3. Indications for Transfusion of   the platelet count in adults by 30 to 60 × 103 per µL
Platelets in Neonates (30 to 60 × 109 per L).3 In neonates, transfusing 5 to 10 mL
per kg of platelets should increase the platelet count by
Platelet count 50 to 100 × 103 per µL (50 to 100 × 109 per L).12 One
(x 103 per µL) Indications apheresis platelet collection is equivalent to six pooled
random donor platelet concentrates.13
< 20 Always transfuse
Spontaneous bleeding through intact endothelium
20 to < 30 Consider transfusion; transfuse for clinical
does not occur unless the platelet count is no greater
reasons (e.g., active bleeding, lumbar
puncture) than 5 × 103 per µL (5 × 109 per L).9 One randomized
30 to 50 Transfuse if any of the following controlled trial evaluated a threshold for prophylactic
indications exist: platelet transfusion in patients with acute myeloid leuke-
First week of life with birth weight mia.14 Patients were randomized based on platelet trans-
< 1,000 g (2 lb, 4 oz) fusion triggers of 10 × 103 per µL (10 × 109 per L) or
Intraventricular or intraparenchymal 20 × 103 per µL (20 × 109 per L). Patients in the lower trig-
cerebral hemorrhage ger group received 21.5 percent fewer transfusions than
Coagulation disorder the higher trigger group. Gastrointestinal bleeding was
Sepsis or fluctuating arterial venous more common in the lower trigger group; however, there
pressures
was no difference in blood transfusions between groups.
Invasive procedure
Tables 29 and 39-12 give indications for platelet transfusion
Alloimmune neonatal thrombocytopenia*
in adults and neonates, respectively.
*—Select a donor (possibly the mother) whose platelets lack the caus-
ative antigen. If the mother’s platelets are used, unit must be washed, Cryoprecipitate
irradiated, and resuspended in plasma that is ABO compatible with Cryoprecipitate is prepared by thawing fresh frozen
the neonate.
plasma and collecting the precipitate. Cryoprecipitate
Information from references 9 through 12.
contains high concentrations of factor VIII and fibrino-
gen. Cryoprecipitate is used in cases of hypofibrinogen-
emia, which most often occurs in the setting of massive
without transfusion of plasma. Table 1 gives indications hemorrhage or consumptive coagulopathy. Indications
for plasma transfusion.7-9 for cryoprecipitate transfusion are listed in Table 4.12,15
Each unit will raise the fibrinogen level by 5 to 10 mg per
Platelets dL (0.15 to 0.29 µmol per L), with the goal of maintain-
Platelet transfusion may be indicated to prevent hem- ing a fibrinogen level of at least 100 mg per dL (2.94 µmol
orrhage in patients with thrombocytopenia or platelet per L).15 The usual dose in adults is 10 units of pooled
function defects. Contraindications to platelet transfu- cryoprecipitate.3,15 Recommendations for dosing regimens
sion include thrombotic thrombocytopenic purpura in neonates vary, ranging from 2 mL of cryoprecipitate per
and heparin-induced thrombocytopenia. Transfusion of kg to 1 unit of cryoprecipitate (15 to 20 mL) per 7 kg.12

March 15, 2011 ◆ Volume 83, Number 6 www.aafp.org/afp American Family Physician  721
Blood Transfusion
Table 5. Noninfectious Serious Hazards  
of Transfusion

Acute
Transfusion Complications Acute hemolytic reaction
Transfusion-related complications can be categorized Allergic reaction
as acute or delayed, which can be divided further into Anaphylactic reaction
the categories of noninfectious (Table 5 16) and infectious Coagulation problems in massive transfusion
(Table 6 16,17). Acute complications occur within minutes Febrile nonhemolytic reaction
to 24 hours of the transfusion, whereas delayed compli- Metabolic derangements
cations may develop days, months, or even years later. Mistransfusion (transfusion of the incorrect product to the
The AABB (formerly known as the American Associa- incorrect recipient)
tion of Blood Banks) uses the term “noninfectious seri- Septic or bacterial contamination
ous hazards of transfusion” to classify noninfectious Transfusion-associated circulatory overload
complications.16 Transfusion-related infections are Transfusion-related acute lung injury
less common because of advances in the blood screen- Urticarial reaction
ing process; the risk of contracting an infection from Delayed
transfusion has decreased 10,000-fold since the 1980s.17 Delayed hemolytic reaction
Noninfectious serious hazards of transfusion are up to Iron overload
1,000 times more likely than an infectious complica- Microchimerism
tion.16 However, there has been no progress in prevent- Overtransfusion or undertransfusion
ing noninfectious serious hazards of transfusion, despite Post-transfusion purpura
improvements in blood screening tests and other related Transfusion-associated graft-versus-host disease
medical advances. Therefore, patients are far more likely Transfusion-related immunomodulation
to experience a noninfectious serious hazard of transfu-
Adapted with permission from Hendrickson JE, Hillyer CD. Noninfec-
sion than an infectious complication.17 tious serious hazards of transfusion. Anesth Analg. 2009;108(3):760.

Acute Transfusion Reactions

ACUTE HEMOLYTIC REACTIONS
Hemolytic transfusion reactions are caused by immune Table 6. Infectious Complications of Blood
destruction of transfused RBCs, which are attacked Transfusions
by the recipient’s antibodies. The antibodies to the
antigens of the ABO blood group or alloantibodies to Complication Estimated risk
other RBC antigens are produced after immunization
Hepatitis B virus 1 in 350,000
through a previous transfusion or pregnancy. There
Hepatitis C virus 1 in 1.8 million
are two categories of hemolytic transfusion reactions:
Human T-lymphotropic virus 1 in 2 million
acute and delayed. Nonimmune causes of acute reac- 1 or 2
tions include bacterial overgrowth, improper storing, Human immunodeficiency virus 1 in 2.3 million
infusion with incompatible medications, and infusion Creutzfeldt-Jakob disease Rare*
of blood through lines containing hypotonic solutions Human herpesvirus 8 Rare*
or small-bore intravenous tubes.16,18,19 Malaria and babesiosis Rare*
In acute hemolytic transfusion reactions, there is Pandemic influenza Rare*
a destruction of the donor’s RBCs within 24 hours of West Nile virus Rare*
transfusion. Hemolysis may be intravascular or extra-
vascular. The most common type is extravascular *—Exact risk unknown.
hemolysis, which occurs when donor RBCs coated with Information from references 16 and 17.
immunoglobulin G (IgG) or complement are attacked in
the liver or spleen.17 Intravascular hemolysis is a severe
form of hemolysis caused by ABO antibodies. Symp- intravascular coagulation, need for dialysis, and death
toms of acute hemolytic transfusion reactions include secondary to complications.18
fever, chills, rigors, nausea, vomiting, dyspnea, hypoten- The incidence of acute hemolytic reactions is approxi-
sion, diffuse bleeding, hemoglobinuria, oliguria, anuria, mately one to five per 50,000 transfusions.19 From 1996
pain at the infusion site; and chest, back, and abdominal to 2007, there were 213 ABO-incompatible RBC transfu-
pain.19 Associated complications are clinically significant sions with 24 deaths.17 Systems using bar codes for blood
anemia, acute or exacerbated renal failure, disseminated and patient identification have decreased errors.17

722  American Family Physician www.aafp.org/afp Volume 83, Number 6 ◆ March 15, 2011
 Blood Transfusion

ALLERGIC REACTIONS FEBRILE NONHEMOLYTIC TRANSFUSION REACTIONS

Allergic reactions range from mild (urticarial) to life An FNHTR is defined as a rise in body temperature of
threatening (anaphylactic). Urticarial allergic reactions at least 1.8°F (1°C) above 98.6°F (37°C) within 24 hours
are defined by hives or pruritus.20 Patients experiencing after a transfusion; it may involve rigors, chills, and dis-
allergic transfusion reactions have been sensitized to the comfort.10 The fever occurs more often in patients who
antigens in the donor unit. These antigens are soluble, and have been transfused repeatedly and in patients who have
the associated reaction is dose-dependent. Allergic trans- been pregnant.25 Leukoreduction, which is the removal
fusion reactions occur in 1 to 3 percent of transfusions.16 or filtration of white blood cells from donor blood, has
Patients with anaphylactic transfusion reactions, like decreased FNHTR rates.26 FNHTRs are caused by platelet
those with urticarial reactions, may present with hives, transfusions more often than RBC transfusions and have
but they are distinct in that they also develop hypotension, an incidence that ranges from less than 1 percent to more
bronchospasm, stridor, and gastrointestinal symptoms.16 than 35 percent.16
Anaphylaxis occurs in response to a recipient’s presensiti- Two mechanisms have been proposed to explain
zation to a variety of proteins in donor plasma. For exam- FNHTRs: a release of antibody-mediated endogenous
ple, anaphylaxis occurs because of donor IgA being infused pyrogen, and a release of cytokines. Common cytokines
into a recipient who is IgA deficient and has preexisting that may be associated with FNHTRs include interleu-
circulating anti-IgA.17 In addition, anti–human leukocyte kin-1, interleukin-6, interleukin-8, and tumor necrosis
antigen (HLA) antibodies and anticomplement antibodies factor.25 FNHTR is a diagnosis of exclusion that can be
have been linked to anaphylactic reactions, which are esti- made only after ruling out other causes of fever (e.g.,
mated to occur in one in 20,000 to 50,000 transfusions.21 hemolysis, sepsis).
Prevention of anaphylactic transfusion reactions
TRANSFUSION-ASSOCIATED CIRCULATORY OVERLOAD
includes avoiding plasma transfusions with IgA in patients
known to be IgA deficient. Cellular products (e.g., RBCs, Transfusion-associated circulatory overload is the result
platelets) may be washed to remove plasma in patients with of a rapid transfusion of a blood volume that is more
an IgA deficiency.16 The best precaution is observation of than what the recipient’s circulatory system can handle.
the patient during the initial 15 minutes of transfusion. It is not associated with an antibody-mediated reaction.
Those at highest risk are recipients with underlying car-
TRANSFUSION-RELATED ACUTE LUNG INJURY diopulmonary compromise, renal failure, or chronic ane-
Transfusion-related acute lung injury (TRALI) is non- mia, and infants or older patients.17 Signs and symptoms
cardiogenic pulmonary edema causing acute hypoxemia include tachycardia, cough, dyspnea, hypertension, ele-
that occurs within six hours of a transfusion and has a vated central venous pressure, elevated pulmonary wedge
clear temporal relationship to the transfusion.22 Patients pressure, and widened pulse pressure. Cardiomegaly and
with TRALI do not have any other risk factors for acute pulmonary edema are often seen on chest radiography.27
lung injury. Antineutrophil cytoplasmic antibodies or The diagnosis is made clinically, but may be assisted
anti-HLA antibodies activate the recipient’s immune by measuring brain natriuretic peptide levels, which are
system, resulting in massive pulmonary edema.17,23 Acti- elevated in response to an increase in filling pressure.28
vated neutrophils in the lungs may also secrete proteo- A study comparing patients who have transfusion-
lytic enzymes, leading to more tissue damage.24 Optimal associated circulatory overload with patients who have
methods for detecting these antibodies in donated prod- TRALI found significantly greater levels of brain natri-
ucts have yet to be determined.16 uretic peptide in those with transfusion-associated cir-
Donor products that contain large amounts of plasma culatory overload.28 Transfusion of lower volumes or at a
from multiparous women are associated with TRALI. slower rate may help prevent it.16 The treatment is diure-
Mortality in the United Kingdom decreased significantly sis to decrease volume overload.
after donor plasma from men was used exclusively.17
In 2006, TRALI was the leading cause of transfusion- Delayed Transfusion Reactions
related mortality, contributing to 50.7 percent of TRANSFUSION-ASSOCIATED GRAFT-VERSUS-HOST DISEASE
transfusion-related deaths.16 The TRALI working group Transfusion-associated graft-versus-host disease is a
of the AABB recommends using male-predominant consequence of a donor’s lymphocytes proliferating and
plasma for transfusions.17 Because this policy excludes a causing an immune attack against the recipient’s tissues
large number of female donors, maintaining an adequate and organs. It is fatal in more than 90 percent of cases.16
supply of plasma and platelets is a concern. Patients vulnerable to this condition are those who are

March 15, 2011 ◆ Volume 83, Number 6 www.aafp.org/afp American Family Physician  723
Blood Transfusion

immunocompromised or immunocompetent and who 9. Liumbruno G, Bennardello F, Lattanzio A, Piccoli P, Rossetti G; Italian
are receiving transfusion with shared HLA haplotypes Society of Transfusion Medicine and Immunohaematology (SIMTI) Work
Group. Recommendations for the transfusion of plasma and platelets.
(i.e., donor is a relative).17 Symptoms include rash, fever, Blood Transfus. 2009;7(2):132-150.
diarrhea, liver dysfunction, and pancytopenia occurring 10. British Committee for Standards in Haematology, Blood Transfusion
one to six weeks after transfusion.16 Task Force. Guidelines for the use of platelet transfusions. Br J Haema-
tol. 2003;122(1):10-23.
Risk factors include a history of fludarabine (Oforta)
11. Schiffer CA, Anderson KC, Bennett CL, et al. Platelet transfusion for
treatment, Hodgkin disease, stem cell transplant, intensive patients with cancer: clinical practice guidelines of the American Society
chemotherapy, intrauterine transfusion, or erythroblasto- of Clinical Oncology. J Clin Oncol. 2001;19(5):1519-1538.
sis fetalis. Other probable risk factors include a history of 12. Poterjoy BS, Josephson CD. Platelets, frozen plasma, and cryoprecipi-
tate: what is the clinical evidence for their use in the neonatal intensive
solid tumors treated with cytotoxic drugs, transfusion in
care unit? Semin Perinatol. 2009;33(1):66-74.
premature infants, and recipient-donor pairs from homog- 13. Slichter SJ. Platelet transfusion therapy. Hematol Oncol Clin North Am.
enous populations.29 Gamma irradiation of blood products 2007;21(4):697-729, vii.
keeps the donor lymphocytes from proliferating and can 14. Rebulla P, Finazzi G, Marangoni F, et al. The threshold for prophylac-
tic platelet transfusions in adults with acute myeloid leukemia. Gruppo
prevent transfusion-associated graft-versus-host disease.16
Italiano Malattie Ematologiche Maligne dell’Adulto. N Engl J Med.
1997;337(26):1870-1875.
The Authors 15. Callum JL, Karkouti K, Lin Y. Cryoprecipitate: the current state of knowl-
edge. Transfus Med Rev. 2009;23(3):177-188.
SANJEEV SHARMA, MD, is an associate professor in the Department of 16. Hendrickson JE, Hillyer CD. Noninfectious serious hazards of transfu-
Family Medicine at Creighton University School of Medicine, Omaha, Neb. sion. Anesth Analg. 2009;108(3):759-769.
POONAM SHARMA, MD, is an associate professor in the Department of 17. Vamvakas EC, Blajchman MA. Transfusion-related mortality: the ongo-
Pathology at Creighton University School of Medicine. ing risks of allogeneic blood transfusion and the available strategies for
their prevention. Blood. 2009;113(15):3406-3417.
LISA N. TYLER, MD, is an assistant professor in the Department of Pathol- 18. Gaines AR, Lee-Stroka H, Byrne K, et al. Investigation of whether the
ogy at Creighton University School of Medicine. acute hemolysis associated with Rh(o)(D) immune globulin intravenous
(human) administration for treatment of immune thrombocytopenic
Address correspondence to Sanjeev Sharma, MD, Creighton University
purpura is consistent with the acute hemolytic transfusion reaction
Medical Center, 601 N. 30th St., Omaha, NE 68131 (e-mail: ssharma@
model. Transfusion. 2009;49(6):1050-1058.
creighton.edu). Reprints are not available from the authors.
19. Lichtiger B, Perry-Thornton E. Hemolytic transfusion reactions in
Author disclosure: Nothing to disclose. oncology patients: experience in a large cancer center. J Clin Oncol.
1984;2(5):438-442.
20. Reutter JC, Sanders KF, Brecher ME, Jones HG, Bandarenko N. Inci-
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724  American Family Physician www.aafp.org/afp Volume 83, Number 6 ◆ March 15, 2011