Blood Product Transfusion

in Adults:​Indications, Adverse
Reactions, and Modifications
Jay S. Raval, MD;​Joseph R. Griggs, DO;​and Anthony Fleg, MD, MPH
University of New Mexico School of Medicine, Albuquerque, New Mexico

Millions of units of blood products are transfused annually to patients in the United States. Red blood cells are transfused to
improve oxygen-carrying capacity in patients with or at high risk of developing symptomatic anemia. Restrictive transfusion
thresholds with lower hemoglobin levels are typically clinically equivalent to more liberal thresholds. Transfusion of plasma
corrects clinically significant coagulopathy in patients with or at high risk of bleeding. Mildly abnormal laboratory coagula-
tion values are not predictive of clinical bleeding and should not be corrected with plasma. Transfused platelets prevent or
treat bleeding in patients with thrombocytopenia or platelet dysfunction. Cryoprecipitate is transfused to treat hypofibrin-
ogenemia. Many adverse reactions can occur during or after blood product transfusion. Transfusion-associated circulatory
overload (i.e., volume overload) is the most common cause of mortality associated with blood products. Modifications to
blood products can prevent or decrease the risks of transfusion-related adverse reactions. It is critical to quickly recognize
when a reaction is occurring, stop the transfusion, assess, and support the patient. Reporting a reaction to the blood bank
is part of ensuring patient safety and supporting hemovigilance efforts. (Am Fam Physician. 2020;​102(1):​30-38. Copyright ©
2020 American Academy of Family Physicians.)

The transfusion of blood products is a from the AABB (formerly the American Associ-
common medical procedure, with more than ation of Blood Banks) and others are provided in
16 million units transfused annually in the Table 1.2-9 For conditions that do not have specific
United States.1 However, there are associated guidelines, consider the patient’s clinical situa-
hazards. When considering transfusion of any tion and risk of adverse reactions for the trans-
blood product, it is good practice to consider the fusion threshold;​however, most clinical trials
patient’s relevant laboratory data, overall clinical demonstrate that patients do equally well with
circumstances, feasible alternatives, and adjuncts restrictive transfusion thresholds (hemoglobin
to transfusion.2 These factors should be part of the less than 7 to 8 g per dL [70 to 80 g per L]) com-
informed consent process. pared with liberal thresholds (hemoglobin less
than 10 g per dL [100 g per L]).2,3,6
Indications
RED BLOOD CELLS PLASMA
Red blood cells (RBCs) are transfused to increase Plasma is transfused to correct a clinically sig-
oxygen-carrying capacity in patients with or at nificant coagulopathy in patients with or at
high risk of developing symptomatic anemia. high risk of bleeding. Typical plasma dosing is
In adults, RBCs are typically infused 1 unit at 10 to 20 mL per kg of body weight. Guidelines
a time and increase hemoglobin by 1 g per dL for plasma transfusion are provided in Table
(10 g per L). Guidelines for RBC transfusion 2.4,6-12 The transfusion threshold of plasma for

CME This clinical content conforms to AAFP criteria for CME. See CME Quiz on page 11.
Author disclosure:​ Dr. Raval is involved in research in the field of therapeutic apheresis, in particular opti-
mizing the use of therapeutic plasma exchange, red cell exchange, and extracorporeal photopheresis.
He has received funding to serve as a medical advisor and speaker for Terumo BCT, Alexion, and Sanofi
Genzyme on these topics. This manuscript addresses practical blood banking and transfusion medicine
and is unrelated to the areas of therapeutic apheresis for which Dr. Raval has received funding;​the other
authors have no relevant financial affiliations.

30  American
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 BLOOD PRODUCT TRANSFUSION

TABLE 1 TABLE 2

Red Blood Cell Transfusion Guidelines Plasma Transfusion Guidelines in Adults

in Adults Use for bleeding patients with multifactorial or global
Use a restrictive transfusion threshold hemoglobin level ≤ 7 g coagulopathies.
per dL (70 g per L) for hospitalized adult patients, including
Use as a replacement of specific factor deficiencies when no
those who are critically ill, who are hemodynamically stable.
recombinant products or concentrates exist or are readily
Use a restrictive transfusion threshold hemoglobin level ≤ 8 g available.
per dL (80 g per L) for patients undergoing orthopedic or car-
Use for warfarin (Coumadin) anticoagulation-related
diac surgery, or who have preexisting cardiovascular disease.
life-threatening bleeding or intracranial hemorrhage.*
Recommendations do not apply to patients with acute
Use as a replacement fluid with certain therapeutic plasma
coronary syndrome, severe thrombocytopenia, and chronic
exchange procedures to treat diseases such as thrombotic
transfusion-dependent anemia because of insufficient
thrombocytopenic purpura.
evidence.
For traumatic injury requiring massive transfusion, with massive
Do not transfuse more than 1 unit at a time to nonbleeding
hemorrhage (> 15% total blood volume loss) or hemorrhagic
patients without reassessing the patient's clinical status and
shock, transfuse red blood cells, plasma, and platelets in ratios
associated laboratory parameters.
of 1:​1:​1 to 2:​1:​1 until bleeding is no longer life-threatening.
Do not transfuse for iron deficiency without associated
Do not transfuse most patients with other conditions in the
hemodynamic instability.
absence of massive transfusion, surgery, bleeding, or supra-
For traumatic injury requiring massive transfusion, with massive therapeutic anticoagulation.
hemorrhage (> 15% total blood volume loss) or hemorrhagic
*—Four-factor prothrombin complex concentrates should be used
shock, transfuse red blood cells, plasma, and platelets in ratios
initially, when available, to reverse warfarin anticoagulation in these
of 1:​1:​1 to 2:​1:​1 until bleeding is no longer life-threatening.
settings.
Information from references 2-9. Information from references 4 and 6-12.

most adults should be an international normalized ratio

greater than 1.5 to 1.6 in patients with active bleeding or at TABLE 3
high risk of bleeding;​however, some facilities set a higher
threshold.4-8,11 Platelet Transfusion Guidelines in Adults
Mildly abnormal laboratory coagulation tests poorly pre- Use in hospitalized adult patients with therapy-induced
dict the occurrence of bleeding.6,12 A thorough bleeding his- hypoproliferative thrombocytopenia and platelet count
≤ 10,000 per µL (10 × 109 per L).
tory can help assess future bleeding risk and the need for
additional coagulation testing.13 Prophylactic plasma trans- Use for elective central venous catheter placement and plate-
fusion in patients with coagulation abnormalities before let count < 20,000 per µL (20 × 109 per L).

surgical or interventional procedures does not nullify Use for elective diagnostic lumbar puncture, major elective
bleeding risk.6-8 The utility of prophylactic plasma trans- non-neuraxial surgery, or interventional procedures and
platelet count < 50,000 per µL (50 × 109 per L).
fusion in surgical patients without massive hemorrhage or
for warfarin (Coumadin) anticoagulation reversal without Use for neuraxial surgery and platelet count < 100,000 per µL
intracranial hemorrhage is unclear because of the low qual- (100 × 109 per L).
ity of published evidence.11 Four-factor prothrombin com- For traumatic injury requiring massive transfusion, with massive
plex concentrate is now the preferred product for warfarin hemorrhage (> 15% total blood volume loss) or hemorrhagic
anticoagulation reversal.7,8 shock, transfuse red blood cells, plasma, and platelets in ratios
of 1:​1:​1 to 2:​1:​1 until bleeding is no longer life-threatening.

PLATELETS Use for active bleeding in association with qualitative platelet

defects regardless of platelet count.
Platelets are transfused to prevent or treat bleeding asso-
ciated with thrombocytopenia or platelet dysfunction. In Do not transfuse prophylactically to those undergoing
adults, 1 unit of apheresis platelets increases platelet counts cardiac surgery with cardiopulmonary bypass but not
thrombocytopenia.
by 30,000 to 50,000 per µL (30 to 50 × 109 per L). Trans-
fusion thresholds vary considerably based on the clinical Information from references 4, 6-9, and 14-18.
situation.14-16

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 TABLE 4

Noninfectious Acute Adverse Reactions of Transfusion

Acute reaction Key features* Treatment
Guidelines for platelet transfusion Acute hemolytic Acute kidney injury Supportive care;​transfusion
in adults are provided in Table 3.4,6- transfusion reaction Anemia of compatible blood
9,14-18
The transfusion threshold of Chills products;​ maintenance
platelets for most adults before sur- of urine output
Death
gery or childbirth should be a platelet Disseminated intravascu-
count of less than 50,000 per µL (50 × lar coagulation
109 per L).4,6-9,14-18 The utility of plate- Dyspnea
Fever
let transfusion for patients receiv-
Hematuria
ing antiplatelet therapy who have
Hemolysis
intracranial hemorrhage is unclear
Pain
because of the low quality of pub- Rigors
lished evidence.15 Shock

CRYOPRECIPITATE Allergic and anaphy- Dyspnea Supportive care;​antihis-

lactic or anaphylactoid Hypotension tamines;​ bronchodilators;​
Cryoprecipitate contains coagulation transfusion reaction glucocorticoids;​ epinephrine;​
Localized angioedema
factors VIII and XIII, fibrinogen, and consideration of washed or
Pruritus
von Willebrand factor. Initially used volume-reduced blood prod-
Shock
for factor VIII deficiency, cryoprecip- Urticaria
ucts for severe and refractory
cases
itate is primarily transfused to cor- Wheezing
rect acquired hypofibrinogenemia.
Transfusion thresholds typically are Febrile nonhemolytic Chills Supportive care;​ antipyretics;​
transfusion reaction Hypertension meperidine (Demerol);​trans-
fibrinogen levels less than 100 to 150 fusion of leukoreduced blood
Rigors
mg per dL (1 to 1.5 g per L) but may products;​consideration of
Tachycardia
vary depending on the clinical situ- washed or volume-reduced
Tachypnea
ation. One unit of cryoprecipitate (15 Temperature increase
blood products for severe
and refractory cases
to 20 mL) per 5 to 7 kg of body weight ≥ 1°C (1.8°F)
increases fibrinogen concentration by
Transfusion-associated Bilateral pulmonary inter- Supportive care;​ diuresis;​
up to 100 mg per dL.6-10 stitial infiltrates
circulatory overload dialysis;​placement of patient
Chills into sitting position
Adverse Reactions Dyspnea
If a reaction is suspected during trans- Fever
fusion, stop the infusion immediately Hypertension
and provide supportive care.6-8 Many Hypoxemia
findings associated with benign and Jugular venous distention
life-threatening transfusion reactions Peripheral edema
are nonspecific and overlap;​there- Pleural effusions
fore, mild signs and symptoms should Tachycardia
Tachypnea
not be minimized. For any reaction,
the implicated blood product bag, Transfusion-related Bilateral pulmonary inter- Supportive care
clinical reaction summary, and post- acute lung injury stitial infiltrates
transfusion blood and urine sam- Blood pressure changes
ples from the patient should be sent Chills
Dyspnea
to the blood bank to facilitate reac-
Fever
tion investigation. If a reaction is
Hypoxemia
suspected after the transfusion has
Tachycardia
ended, a reaction summary and post- Tachypnea
transfusion blood and urine samples
should be sent. See Tables 4,6-9,19,20 Note:​Supportive care involves cardiovascular and pulmonary supportive measures.

5,6-9,19,20 and 6 21 for information about *—Key features are listed in alphabetical order.
noninfectious and infectious transfu- Information from references 6-9, 19, and 20.
sion complications.

32  American Family Physician www.aafp.org/afp Volume 102, Number 1 ◆ July 1, 2020
 BLOOD PRODUCT TRANSFUSION

IMMUNE-MEDIATED REACTIONS accompanied by chills, rigors, hypertension, tachycar-

Febrile Nonhemolytic Transfusion Reaction (FNHTR). dia, and tachypnea. This is caused by recipient antibodies
FNHTRs occur in 1% of transfusion episodes.7-9,19,20 They binding to white blood cells (WBCs) in the blood product,
are characterized by a temperature increase of 1°C (1.8°F) or proinflammatory cytokines produced within the prod-
or greater within four hours of transfusion and may be uct.19 This reaction is a diagnosis of exclusion, made only
after other more serious reactions and
any contributions from an underlying
TABLE 5 illness are ruled out. There should be
no evidence of hemolysis or new bac-
Noninfectious Delayed Adverse Reactions of Transfusion terial infection. Treatment with anti-
Delayed reaction Key features* Treatment pyretics and meperidine (Demerol)
can help control signs and symptoms.
Alloimmunization Difficulty obtaining compatible Restrictive transfusion
cellular blood products strategy;​ transfusion Universal pretransfusion use of anti-
Hemolysis of compatible blood pyretics is not beneficial.22 However,
Occurs when antigen-negative
products their use in patients with a history of
patients are transfused with FNHTRs may allow for completion
antigen-positive blood products of transfusions.23 Prestorage leukore-
Platelet refractoriness duction of cellular blood products can
Production of antibodies help decrease the risk of FNHTRs (see
against foreign antigens
Modifications). Washing and volume
Delayed hemolytic Anemia Supportive care;​transfu- reduction also decrease FNHTRs with
transfusion reaction Chills sion of compatible blood platelet transfusion.7-9,19
products
Dark urine Allergic Transfusion Reaction. Aller-
Dyspnea gic transfusion reactions occur with
Fever frequencies varying from 0.4% of RBC
Jaundice transfusions to 4.1% of platelet trans-
Pain
fusions.7-9,14,19,20 Allergic transfusion
Rigors
reactions are mediated by immuno-
Posttransfusion Bleeding Supportive care;​intrave- globulin E (IgE) antibodies binding to
purpura Death nous immunoglobulin;​ allergens, ultimately resulting in the
glucocorticoids;​ thera- release of histamine. Allergic transfu-
Petechiae
peutic plasma exchange
Purpura sion reactions range in severity from
Rapid-onset thrombocytopenia the most common form of isolated
Transfusion- Abdominal pain Supportive care
cutaneous involvement to localized
associated graft- Death
angioedema and respiratory involve-
versus-host disease
Diarrhea ment to hypotension, shock, and
Erythema complete cardiovascular collapse.
Fever Anaphylactic or anaphylactoid reac-
Hepatic dysfunction tions, the most severe presentation of
Maculopapular rash allergic transfusion reactions, occur
Nausea in 8 per 100,000 units of blood prod-
Pancytopenia ucts transfused.20 They typically occur
Vomiting during transfusion or within four
hours after transfusion. Depending
Iron overload Cardiomyopathy Restrictive transfusion
Endocrine organ dysfunction strategy;​iron chelation on reaction severity, antihistamines,
Hepatic injury
therapy glucocorticoids, bronchodilators, and
epinephrine are all possible treat-
Note:​Supportive care involves cardiovascular and pulmonary supportive measures. ments.19,20 Volume reduction and
*—Key features are listed in alphabetical order. washing decrease allergic transfusion
Information from references 6-9, 19, and 20. reaction rates. Pretransfusion use of
antihistamines or glucocorticoids has

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 BLOOD PRODUCT TRANSFUSION

directed against foreign paternal antigens.29 Based on this

TABLE 6 role of WBC antibodies, risk reduction measures that screen
or defer these higher-risk multiparous female donors have
Estimated Risks of Potentially Infectious markedly decreased rates of TRALI, the previous leading
Units in U.S. Blood Supply* cause of transfusion-associated mortality.30 Treatment con-
Transfusion-transmitted sists of supportive care only because diuresis, steroids, and
Pathogen infection risk per unit immunosuppressants are not helpful.25
Bacteria-triggering sepsis 1 in 100,000 Hemolytic Transfusion Reaction (HTR). An HTR is
typically the antibody-mediated destruction of RBCs in
Hepatitis B virus 1 in 2,000,000
a patient and can be attributed to incompatible RBCs or
Hepatitis C virus 1 in 2,000,000 plasma.7-9,19 These reactions can be acute (occurring in less
HIV 1 in 2,000,000
than 24 hours) or delayed (occurring at 24 hours or more),
and hemolysis is classified as intravascular or extravas-
Cytomegalovirus 1 in 3,000,000 cular. The most common cause of acute HTRs is human
Human T-lymphotropic virus 1 in 3,000,000 error.19,20 HTRs can be nonimmune in origin because of
improper storage or administration, causing mechanical,
Chagas disease 1 in 3,000,000 or less
thermal, or osmotic hemolysis.19,20 Hemolysis, fever, chills,
Malaria 1 in 3,000,000 or less jaundice, acute kidney injury, pain, shock, disseminated
West Nile virus 1 in 3,000,000 or less intravascular coagulation, and death are all possible com-
plications. Supportive care is recommended for patients
Zika virus 1 in 3,000,000 or less experiencing HTRs.
Babesiosis Variable Transfusion-Associated Graft-Versus-Host Disease
(TAGVHD). TAGVHD is a rare but almost universally fatal
Variant Creutzfeldt-Jakob disease Theoretical
complication. It results from viable donor lymphocytes
*—These frequencies represent residual risks for all blood products surviving, engrafting, and targeting recipient tissues.7-9,19,20
after the use of available testing and interventions to reduce patho-
gen transmission. Importantly, pathogen inactivation strategies in
Patients at the highest risk of TAGVHD are typically
the U.S. blood supply decrease, but do not eliminate, risks. Not all severely immunocompromised (e.g., bone marrow trans-
facilities use all nonmandatory testing and interventions to reduce plant recipients, inherited deficiencies of cellular immu-
pathogen transmission.
nity, severe lymphopenia with absolute lymphocyte counts
Information from reference 21. of less than 300 to 500 per µL [0.30 to 0.50 × 109 per L]).
Classical findings including rash, fever, nausea, vomiting,
diarrhea, pancytopenia, and liver injury can occur within
not been demonstrated to prevent the recurrence of mild five to 10 days of transfusion, with complete marrow aplasia
allergic transfusion reactions despite widespread prac- within 21 days.19,20 Management is supportive only. Irradi-
tice.19,20,22,23 In patients with severe allergic transfusion reac- ation or pathogen inactivation can prevent TAGVHD (see
tions, assess for IgA or haptoglobin deficiency. Modifications).
Transfusion-Related Acute Lung Injury (TRALI). TRALI
is defined as nonhydrostatic, noncardiogenic pulmonary NONIMMUNE-MEDIATED REACTIONS
edema occurring typically within six hours of transfu- Transfusion-Associated Circulatory Overload. Transfu-
sion.7-9,14,19,20,24 The current understanding of the pathophys- sion-associated circulatory overload occurs when the blood
iology is that antibody-dependent and -independent product infusion volume leads to iatrogenic cardiogenic
mechanisms result in neutrophil activation, endothelial pulmonary edema.7-9,19,24 Blood product volumes range from
injury, capillary leakage with exudative fluid extravasation, 150 mL for a dose of cryoprecipitate to 300 mL for a single
and ultimately acute lung injury. Findings include dyspnea, RBC unit or platelets to liters for a weight-appropriate dose
tachypnea, tachycardia, hypoxemia, fever, chills, blood pres- of plasma. Unlike with other fluids, little volume from blood
sure changes, and bilateral pulmonary interstitial infiltrates products enters the third space, making them much riskier
observed on chest radiography.24-27 Platelets have the highest to infuse from an intravascular volume perspective. Rates
risk of causing TRALI at 1 per 100,000 units, with RBCs of transfusion-associated circulatory overload range from
and plasma at 0.5 and 0.4 per 100,000 units, respectively.14,28 1% to 8%19,31,32​; diminished heart and kidney function, com-
Blood products donated by multiparous females pose pensated anemia, preexisting positive-fluid balance, cancer
a higher TRALI risk due to preformed WBC antibodies diagnosis, plasma ordered for reversing anticoagulation,

34  American Family Physician www.aafp.org/afp Volume 102, Number 1 ◆ July 1, 2020
 BLOOD PRODUCT TRANSFUSION

and extremes of age are all parameters associated with Transfusion-Transmitted Infection. Aside from bacterial
increased transfusion-associated circulatory overload risk. contamination, blood-borne infectious organisms can be
Findings in transfusion-associated circulatory over- transmitted by transfusion. Volunteer donors have their
load are clinically similar to TRALI:​new-onset or wors- histories queried and limited physical examinations per-
ening dyspnea, tachypnea, tachycardia, hypoxemia, fever, formed to assess for increased transfusion-transmitted
chills, hypertension, and bilateral pulmonary interstitial infection risk. Patients who continue on to donation have
infiltrates observed on chest radiography.19,24,31 Findings their blood tested for a variety of infectious agents. Despite
that differ from TRALI include jugular venous disten- blood products being safer today than in the past, there are
tion, peripheral edema, and elevated N-terminal pro-brain small but real risks of transfusion-transmitted infections
natriuretic peptide level.33 The most important aspect (Table 6).21
of managing transfusion-associated circulatory over-
load is to recognize it. Passive reporting of transfusion- Modifications
associated circulatory overload underestimates its inci- Blood product modifications can be effective in decreasing
dence.31,32 Prompt action with supportive care and diuresis transfusion risks (Table 7).6-9,19,20
or dialysis is required.
Transfusion-associated circulatory overload is the lead- LEUKOREDUCTION
ing cause of transfusion-associated mortality.30 Strategies Leukoreduction is WBC removal from RBCs or platelets.
to reduce transfusion-associated circulatory overload in This process cannot eliminate all WBCs.7-9 Leukoreduction
patients at high risk include slow transfusion over four decreases the risk of three different complications:​FNHTRs,
hours and volume reduction (see Modifications). Although transfusion-associated cytomegalovirus (CMV), and
prophylactic peritransfusion diuresis has not been shown to human leukocyte antigen alloimmunization. Most cellular
reduce transfusion-associated circula-
tory overload,20 diuresis as part of an
TABLE 7
overall strategy for optimizing volume
status may be beneficial.
Blood Product Modifications
Septic Reaction. Sepsis from a
transfusion is attributed to bacte- Modification Description
rial growth in a blood product and Leukoreduction Decreases white blood cells in cellular blood products;​reduces
occurs in 1 per 100,000 units trans- risks of FNHTRs, human leukocyte antigen alloimmunization,
fused.20,21 Platelets have the highest transfusion-associated CMV

rates of bacterial contamination (up Irradiation T lymphocytes rendered unable to replicate;​prevents donor cell
to 1 in 3,000 units), most commonly engraftment in severely immunosuppressed transfusion recipients
with normal skin flora such as Staph- and transfusion-associated graft-versus-host disease

ylococcus and Streptococcus, because Washing Removes and replaces the acellular fluid in cellular blood products;​
of their unique storage require- reduces risks of FNHTRs, ATRs, cell-free hemoglobin, hyperkalemia
ments.14,20 Symptoms typically occur Volume Decreases volume of acellular fluid in cellular blood products;​
within 24 hours of transfusion. To reduction reduces risks of transfusion-associated circulatory overload,
confidently diagnose a septic trans- FNHTRs, ATRs, hemolytic transfusion reactions, cell-free hemoglo-
bin, hyperkalemia
fusion reaction, the patient and
implicated blood product should Hemoglobin S Donor red blood cells are screened for the absence of sickling
have the same microorganism iso- negative hemoglobins;​use in patients with sickling disorders
lated 34;​however, a presumed reaction CMV risk Screens for CMV-seronegative donors or produces risk-reduced
can be diagnosed if growth occurs reduction products by leukoreduction;​use in pregnant women and the
only in the transfused product. severely immunocompromised
Prompt recognition and rapid initi- Pathogen Kills organisms with nucleic acids using ultraviolet light–based
ation of empiric antimicrobial ther- inactivation technology;​donors typically screened and tested;​produces the
apy are essential. Broad-spectrum equivalent of an irradiated product
antibiotics are recommended, as are ATRs = allergic and anaphylactic or anaphylactoid transfusion reactions;​CMV = cytomegalo-
agents that can treat Pseudomonas virus;​FNHTRs = febrile nonhemolytic transfusion reactions.
and other gram-negative organisms Information from references 6-9, 19, and 20.
if an RBC unit is implicated.34

July 1, 2020 ◆ Volume 102, Number 1 www.aafp.org/afp American Family Physician 35

 BLOOD PRODUCT TRANSFUSION

BEST PRACTICES IN HEMATOLOGY

Recommendations from the Choosing Wisely Campaign

Recommendation Sponsoring organization

Avoid transfusion of red blood cells for arbitrary hemoglobin or hematocrit thresholds Society of Hospital Medicine (Adult)
and in the absence of symptoms or active coronary disease, heart failure, or stroke.

Do not transfuse red blood cells in hemodynamically stable, nonbleeding patients Critical Care Societies Collaborative–
in the intensive care unit with a hemoglobin concentration greater than 7 g per dL Critical Care
(70 g per L).

Do not routinely transfuse stable, asymptomatic hospitalized patients with a hemo- American College of Obstetricians and
globin level greater than 7 to 8 g per dL (70 to 80 g per L). Gynecologists

Do not transfuse more than the minimum number of red blood cell units necessary American Society of Hematology and
to relieve symptoms of anemia or to return a patient to a safe hemoglobin range American Academy of Family Physicians
(7 to 8 g per dL in stable, noncardiac inpatients).

Do not administer plasma or prothrombin complex concentrates for nonemergent American Society of Hematology
reversal of vitamin K antagonists (i.e., outside of the setting of major bleeding, intra-
cranial hemorrhage, or anticipated emergent surgery).

Do not transfuse plasma in the absence of active bleeding or significant laboratory Society for the Advancement of Blood
evidence of coagulopathy. Management

Do not routinely transfuse patients with sickle cell disease for chronic anemia or American Society of Hematology
uncomplicated pain crisis without an appropriate clinical indication.

Source:​For more information on the Choosing Wisely Campaign, see https://​w ww.choosingwisely.org. For supporting citations and to search
Choosing Wisely recommendations relevant to primary care, see https://​w ww.aafp.org/afp/recommendations/search.htm.

blood products in the United States are leukoreduced before because RBCs are hemolyzed, and platelets are activated
they are stored. and lost. It may also decrease blood product shelf-life.

IRRADIATION VOLUME REDUCTION

Irradiation of cellular blood products is performed to avoid In patients who are at risk of developing transfusion-
TAGVHD in susceptible patients.7-9 This process prevents associated circulatory overload or who need to have offend-
WBCs from replicating, which prevents TAGVHD. Irra- ing substances removed from cell-free fluid in cellular blood
diated cellular blood products should be transfused to products (similar to those requiring washed products), vol-
patients with hematologic malignancies, bone marrow ume reduction can be considered.7-9,19 By decreasing cell-
transplantation, inherited immune system disorders, and free fluid volume containing plasma and storage solution,
other conditions and situations that make patients suscep- the overall blood product volume is reduced;​however, vol-
tible to TAGVHD. Conditions such as HIV, sepsis, solid ume reduction is time- and labor-intensive and may also
metastatic tumors, and solid organ transplantation do not decrease blood product shelf-life.
require irradiated blood products.
HEMOGLOBIN S NEGATIVE
WASHING Patients with hemoglobin S disease or other sickle cell dis-
Washing removes cell-free fluid from cellular blood eases cannot donate blood;​however, patients with only the
products and replaces it with an alternative fluid, which sickle cell trait can. Although RBCs from these donors are
decreases the risk profile of these products.7-9,19 Patients suitable for most patients, a patient with a sickle cell disease
with a history of documented severe allergic transfusion should not receive these units.35
reactions, a diagnosis of IgA deficiency, or sensitivity to
extracellular hemoglobin or potassium may benefit. Wash- CMV RISK REDUCTION
ing is a time- and labor-intensive manipulation that pro- CMV is an intracellular virus that can cause complications
duces a quantitatively and qualitatively inferior product in specific patient populations if transfused, including

36  American Family Physician www.aafp.org/afp Volume 102, Number 1 ◆ July 1, 2020
 BLOOD PRODUCT TRANSFUSION

SORT:​KEY RECOMMENDATIONS FOR PRACTICE

Evidence
Clinical recommendation rating Comments

The transfusion threshold of red blood cells for most adults A Systematic reviews of RCTs evaluating red blood cell
should be a hemoglobin level ≤ 7 to 8 g per dL (70 to 80 g transfusion thresholds demonstrate identical outcomes
per L) in patients with asymptomatic anemia. 2,3 in patients transfused via restrictive vs. liberal strategies

The transfusion threshold of plasma for most adults should C Consensus recommendations for plasma transfusion
be an international normalized ratio > 1.5 to 1.6 in patients based on weak evidence from RCTs, clinical trials, and
with active bleeding or at high risk of bleeding.4-8,11 observational studies

The transfusion threshold of platelets for most adults should A Systematic reviews of RCTs and observational studies
be a platelet count ≤ 10,000 per µL (10 × 109 per L) in evaluating platelet transfusion thresholds
patients prophylactically to prevent spontaneous bleeding in
hypoproliferative thrombocytopenia.14-16

The transfusion threshold of platelets for most adults before C Consensus recommendations for platelet transfusion
surgery or childbirth should be a platelet count < 50,000 per based on poor evidence from observational studies
µL (50 × 109 per L).4,6-8,14-18

Do not routinely administer pretransfusion antipyretics or A Systematic reviews of RCTs evaluating pretransfusion
antihistamines to prevent transfusion reactions.19,20,22,23 medication strategies

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 https://​w ww.aafp.
org/afpsort.

pregnant women (and their fetuses), bone marrow trans- erence texts in Transfusion Medicine, and relevant information
plant recipients, patients with HIV, and other immuno- from the U.S. Food and Drug Administration, Centers for Disease
Control and Prevention, and AABB. Search dates:​May 1, 2019,
compromised populations.7-9 For these patients, CMV
and March 1, 2020.
risk-reduced blood products are recommended. Leukore-
duction produces products with a decreased CMV risk
profile comparable to that of blood products from CMV- The Authors
seronegative donors.7-9,36 JAY S. RAVAL, MD, is senior director of transfusion medicine
and therapeutic pathology and an associate professor in the
PATHOGEN INACTIVATION Department of Pathology at the University of New Mexico
School of Medicine (Albuquerque), and an adjunct associate
Pathogen inactivation is a process through which the
professor in the Department of Pathology and Laboratory
nucleic acid–containing elements within a blood product Medicine at the University of North Carolina School of Medi-
are intentionally damaged, producing pathogen-reduced cine (Chapel Hill).
blood product.7-9 This inactivation does not eliminate the
need for routine processes surrounding blood donation. JOSEPH R. GRIGGS, DO, is director of the University of New
Mexico Sandoval Regional Medical Center Blood Bank and
The pathogen inactivation process also injures the nucleic an assistant professor in the Department of Pathology at the
acids in WBCs and produces the equivalent of an irra- University of New Mexico School of Medicine.
diated blood product. Currently, pathogen inactivation
technology can only be applied to plasma and platelets. ANTHONY FLEG, MD, MPH, is director of the University of
New Mexico School of Medicine Preceptorship Program
This article updates a previous article on this topic by Sharma, and an associate professor in the Department of Family and
et al. 37 Community Medicine at the University of New Mexico School
of Medicine.
Data Sources:​ PubMed and Cochrane Library searches were
performed using the key terms transfusion, blood, indication, Address correspondence to Jay S. Raval, MD, MSC08 4640,
reaction, treatment, prevention, manipulation, and modification. 1 University of New Mexico, Albuquerque, NM 87131 (email:​
The searches were restricted to human studies and included jraval@​salud.unm.edu). Reprints are not available from the
meta-analyses, randomized controlled trials, clinical trials, and authors.
reviews. Also searched were Essential Evidence Plus, critical ref-

July 1, 2020 ◆ Volume 102, Number 1 www.aafp.org/afp American Family Physician 37

 BLOOD PRODUCT TRANSFUSION

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38  American Family Physician www.aafp.org/afp Volume 102, Number 1 ◆ July 1, 2020