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Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion

Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion
Author:
Steven Kleinman, MD
Section Editor:
Lynne Uhl, MD
Deputy Editor:
Jennifer S Tirnauer, MD
Literature review current through: Aug 2023.
This topic last updated: Apr 28, 2023.

INTRODUCTION — Red blood cell (RBC) transfusions are given to treat anemia or to replace losses after acute bleeding. In some cases, it is important to use specific modifications to optimize efficacy or minimize risk.

This topic discusses practical aspects of RBC administration in adults, including details of collection and storage, when to request specialized modifications, infusion parameters, and other considerations that may improve outcomes.

Related subjects are discussed separately:

Indications for RBC transfusion:

Adults – (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult".)

Infants and children – (See "Red blood cell transfusion in infants and children: Indications".)

Newborns – (See "Red blood cell (RBC) transfusions in the neonate", section on 'Indications for transfusion'.)

Administration of RBC transfusions in other populations:

Infants and children – (See "Red blood cell transfusion in infants and children: Administration and complications".)

Newborns – (See "Red blood cell (RBC) transfusions in the neonate", section on 'Selection of RBC products'.)

Practical aspects of platelet and plasma transfusion:

Platelets – (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Ordering platelets'.)

Plasma – (See "Clinical use of plasma components".)

COLLECTION AND STORAGE PROCEDURES

Sources of RBC units — Donated blood is obtained from volunteer donors who have undergone screening with a medical history that includes questions related to risk factors for infectious diseases. All units undergo laboratory testing for selected infectious organisms. Aspects of the donor history and laboratory testing that are used to reduce the risk of complications from blood transfusion are discussed in detail separately. (See "Blood donor screening: Overview of recipient and donor protections" and "Blood donor screening: Medical history" and "Blood donor screening: Laboratory testing".)

Units of packed RBCs are manufactured by one of the following methods:

Component separation from individual units of whole blood – The majority of RBC units are manufactured by the routine separation of donated units of whole blood (typical volume, 450 to 500 mL) into various components by centrifugation. There are a number of centrifugation protocols used and methods of plasma extraction. The components typically prepared from whole blood include packed RBCs, plasma, and sometimes platelets. The final volumes and contents of these components are listed in the table (table 1).

RBC apheresis – In the United States, 15 to 20 percent of RBC units are collected via apheresis, in which a donor who has a sufficiently high hematocrit is connected to an apheresis device that separates red cells from other blood constituents [1,2]. In the most common procedure, two RBC units are collected at the time of phlebotomy, and the other cellular and plasma constituents are infused back to the donor in the closed apheresis system. Alternatively, a single RBC unit can be collected along with a unit of platelets and/or plasma. There are at least three RBC apheresis systems that differ slightly from each other in their methods of RBC separation and storage solutions. (See 'Anticoagulant-preservative (A-P) solutions' below.)

The number of RBCs in a unit derived from whole blood may vary according to the hemoglobin level of the donor; all units will provide a minimum amount. In contrast, apheresis units are collected in such a way that the target number of RBCs per unit is more standardized. However, both collection methods provide adequate RBCs for transfusion. While the source of RBCs (whole blood-derived versus apheresis) may theoretically affect the post-transfusion hemoglobin increment, it has not been demonstrated to affect clinically important outcomes, as discussed below. (See 'Donor and component characteristics potentially affecting recipient outcome' below.)

In both cases, plastic storage bags permit separation of components while preserving sterility, and preservative solutions are used to prolong the shelf-life. (See 'Storage bags' below and 'Anticoagulant-preservative (A-P) solutions' below.)

Storage bags — Blood storage bags made from polyvinyl chloride (PVC) became available in the early 1960s. These bags permit the separation of collected blood into red cells, plasma, and platelets, in a closed and sterile environment. The plasticizer used in red cell PVC storage bags in the United States and most other jurisdictions is di-2-ethylhexyl phthalate (DEHP), which is instrumental in preserving the integrity of the red cell membrane during prolonged in vitro storage, probably as a direct result of small amounts of DEHP leaching into the stored RBC unit.

Although no deleterious effects have been linked to patient exposure to DEHP in transfused RBC units, such exposure from other medical devices has been an ongoing patient safety concern, and this concern has extended to recipients of blood transfusions, especially populations such as neonates, who might be especially vulnerable to potential adverse effects of DEHP or its more toxic metabolites. These concerns have sparked an ongoing attempt to develop a potentially less-toxic plasticizer that can also preserve red cell membrane integrity [3].

Anticoagulant-preservative (A-P) solutions — A major breakthrough in preserving blood came with the development of the first anticoagulant-preservative (A-P) solution, acid citrate dextrose (ACD), in the early 1940s. This allowed blood to be stored for up to 21 days. Prior to this, red cells could only be stored for brief periods in a citrate-glucose solution. It was not until the 1930s that blood was transfused after storage. The first blood "bank" was established at Cook County Hospital in Chicago in 1937.

During the ensuing years, significant progress was made in the development of other A-P solutions:

Citrate phosphate dextrose (CPD) – 21-day (three-week) storage

CPD-adenine – 35-day (five-week) storage

Current generation additive solutions – 42-day (six-week) storage

These additive solutions improve the RBC shelf-life by maintaining pH and other essential biochemical parameters. A benefit of the extended storage duration is that fewer collections are lost through outdating. However, as noted below, the average storage duration for RBCs is less than three weeks. (See 'RBC age/storage duration effect on clinical outcomes' below.)

In the United States, the current generation of additive solutions are denoted by the terminology AS-1, AS-3, and AS-5, representing slightly different formulations from different manufacturers. In Europe, the solution used is saline, adenine, glucose, mannitol (SAGM), which is very similar to AS-1. The volume of additive solution is smaller than the volume of plasma removed, resulting in a smaller volume and higher hematocrit than in the original unit of whole blood.

In modern practice, whole blood is collected into an anticoagulant solution. Subsequently the additive (preservative) solution is added to the manufactured RBC units through an integral bag system shortly after collection and component preparation. This or a similar procedure is used for apheresis-derived RBC units, although the details may vary slightly depending on the apheresis system used.

When CPD-adenine (CPD-A1) is used as the A-P solution, the final volume of the unit is approximately 225 to 350 mL and the hematocrit is approximately 65 to 80 percent.

When one of the AS systems is used, virtually all of the plasma is removed and replaced with approximately 100 mL of storage solution. This results in a final volume of the unit of approximately 300 to 400 mL, and a hematocrit of approximately 55 to 65 percent.

The final hematocrit of apheresis-derived units is approximately 55 to 60 percent, and the volume is targeted to be approximately 175 mL but may be higher.

There have been (and continue to be) attempts to further improve the quality of RBC units during and at the end of their 42-day storage period. To this end, a newer additive solution (AS-7) was approved by US Food and Drug Administration (FDA) in 2015 [4-6]. However, for commercial reasons, it is not in widespread use in the United States [4-6].

Units that require prolonged storage (eg, due to extremely rare blood type) can be frozen. (See 'Frozen red cells' below.)

Pre-storage leukoreduction — Each unit of whole blood or packed RBCs contains approximately two to five billion (2 to 5 x 109) leukocytes (white blood cells [WBCs]), which are collected along with the other cellular elements. These leukocytes are thought to contribute to a number of adverse effects including febrile nonhemolytic transfusion reactions (FNHTRs), human leukocyte antigen (HLA) alloimmunization, and transmission of cytomegalovirus (CMV, which resides intracellularly in WBCs), as well as other inflammatory and immunologically mediated events. In rare cases, leukocytes may contribute to transmission of intracellular bacterial organisms.

Leukoreduction refers to the selective removal of leukocytes by passing the blood through a leukocyte reduction filter, which can achieve a three to four log (99.9 to 99.99 percent) reduction in the leukocyte count of the unit, leaving the final leukocyte count <5 million (<5 x 106; the FDA-required limit) and generally <1 million. This dramatically reduces or in some cases eliminates the risks of adverse events such as FNHTRs, HLA alloimmunization, and CMV transmission [7].

Certain populations at risk for these complications should routinely receive leukoreduced blood products. This includes the following [8-10]:

Chronically transfused patients

Patients with previous FNHTRs

Patients undergoing cardiac surgery

All recipients (or potential recipients) of solid organ or hematopoietic cell transplants

All individuals with acute leukemia, and probably individuals with other malignancies

CMV seronegative at-risk patients for whom seronegative components are not supplied

Clinicians who order transfusions should familiarize themselves with the policies of their jurisdiction and local blood bank regarding leukoreduction, which may involve routine or universal pre-storage leukoreduction, provision of leukoreduced products only to patients in certain hospital wards (eg, bone marrow transplant unit, cardiac surgery suite), or the need to request leukoreduced products for selected individuals.

Leukoreduction can be performed at the time of blood collection (referred to as pre-storage leukoreduction) or at the time of transfusion (bedside leukoreduction). Pre-storage leukoreduction of RBC units is achieved by use of one of several specialized leukoreduction filters, which can be used at different points in the manufacturing process (eg, for whole blood-derived units, filtration can be done on the whole blood unit or the derived RBC unit; for RBC apheresis collections, filtration can occur during or shortly after collection). The FDA requires that leukoreduced RBC units must not lose more than 15 percent of their starting hemoglobin (RBC) content; the usual loss for most licensed systems is approximately 7 to 8 percent [11].

Bedside leukoreduction is not commonly performed. This is because pre-storage leukoreduction is preferable.

Pre-storage leukoreduction achieves a greater degree of leukocyte removal.

Pre-storage leukoreduction provides greater quality control and standardization; some staff may be unfamiliar with bedside leukoreduction filters and may use them incorrectly.

Pre-storage leukoreduction avoids the accumulation of cytokines released by leukocytes into the storage bag. These secreted cytokines may contribute to febrile nonhemolytic transfusion reactions (FNHTRs). (See "Immunologic transfusion reactions", section on 'Febrile nonhemolytic transfusion reactions'.)

Rarely, bedside leukoreduction may be associated with hypotensive reactions.

Leukoreduction does not interfere with any subsequent modifications (see 'Specialized modifications and products' below), and it adds only a small additional cost to each RBC unit. It has been suggested that the cost of leukoreduction is less than the cost of treating the consequences of using non-leukoreduced blood [12]. However, the up-front cost is higher.

If cost considerations allow, leukoreduction would ideally be performed on all cellular components intended for transfusion for all patients. The policy of universal leukoreduction is standard practice in many developed countries, while a minority of other countries (including the United States) have yet to require universal leukoreduction as the standard of care. Nevertheless, many United States blood collectors have implemented universal leukoreduction. The proportion of RBC units that are pre-storage leukoreduced in the United States has been estimated at 85 to 95 percent [13].

One issue related to routine pre-storage leukoreduction is that blood from donors with sickle cell trait may block the leukoreduction filters in some instances. The blood bank will typically employ various strategies to reduce the incidence of filter blockage (eg, cooling) and may defer certain donors if there is difficulty filtering their blood after the second failed attempt. (See "Sickle cell trait", section on 'Leukoreduction'.)

Importantly, leukoreduction is not sufficient to prevent transfusion-associated graft-versus-host disease (ta-GVHD) in susceptible populations, because a small number of viable lymphocytes remain in the unit. These individuals should receive blood that has been irradiated. (See 'Irradiation' below.)

Storage/transport temperature — Regulations require that RBC units be stored under refrigeration at controlled temperatures of 1 to 6°C to maintain the viability of the red cells and to prevent the growth of bacteria.

When transported between facilities (eg, from a blood collection facility to a hospital or between hospitals), the storage temperature must be maintained at 1 to 10°C. When units are transported from the blood bank to another part of the hospital for transfusion, they should be transported under the same controlled temperature conditions.

For hospital transfusion services that are accredited by the Association for the Advancement of Blood & Biotherapies (AABB), an AABB Standard requires that each hospital establish and validate procedures to ensure that units eligible for reissue (ie, units that have been issued for a given patient but have not been used and have subsequently been returned to the blood bank) have been maintained at an appropriate temperature while outside of the hospital blood bank (ie, between 1 to 6°C or 1 to 10°C depending on local hospital policy) [14].

In the United States, there is no FDA requirement for how long an RBC unit can be exposed to uncontrolled temperatures (eg, room temperature >10°C) before being returned to refrigerator storage and subsequently reissued to another patient.

In some other countries, policies state that RBC units must be discarded if they have been outside of controlled temperature conditions for longer than 30 or 60 minutes on any given occasion, as can occur if the unit is released to the ward for an intended patient but is not transfused and is returned to the hospital blood bank [15-17]. Policies had previously limited the duration outside of controlled temperature conditions for 30 minutes, based on historical data from the 1970s related to red cell quality and concerns about bacterial proliferation in the very uncommon circumstance where the stored RBC unit contains viable organisms [18]. However, newer studies have shown that RBC units can be maintained outside controlled temperature conditions for up to 60 minutes without either of these adverse effects, which has led some countries to extend the time to 60 minutes [15-17]. This policy change may reduce wastage of RBC units.

RBC licensure requirements — In the United States, the US Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER) regulates the collection of blood and blood components used for transfusion. All blood establishments that collect, manufacture, prepare, store under controlled conditions for further distribution, or process blood and blood products are required to register with the FDA. In addition, a blood establishment must be licensed by the FDA if it intends to distribute blood products across state lines. An FDA license indicates that the facility producing the product meets current good manufacturing practice (CGMP) standards, as is determined by inspection at regular intervals. Most blood collectors and transfusion services also seek accreditation by the AABB by demonstrating conformance with that organization's Blood Bank/Transfusion Services Standards, which are intended to maintain and enhance quality and safety.

CBER also licenses products such as blood collection containers, additive storage solutions, and cell separation (apheresis) devices. The two criteria used by the FDA to license anticoagulant-preservative (A-P) solutions and blood storage bags have not changed much over the past several decades [19,20]:

Recovery – One of the criteria is to measure the 24-hour recovery of autologous, radiolabeled red cells in healthy individuals after different intervals of storage. This is done by radiolabeling an aliquot of RBCs with radioactive chromium 51. The recovery of radiolabeled cells provides a measurement of the survival of red cells that were viable at the time of transfusion.

The recovery threshold for the percentage of circulating red cells 24 hours following infusion is set at 75 percent at the maximum allowable storage age (42 days), with some ongoing discussion about the degree of statistical variation that is allowable [21]. Acceptable survival of the cells from this small aliquot serves as a surrogate for assessing the survival of an entire RBC unit over a much longer period of time. However, while this criterion is used as a regulatory tool, there are limited data to establish its predictive value, and since its institution, it has been recognized that there is substantial inter-donor variability in this measurement [22,23].

Hemolysis – Spontaneous hemolysis during storage is considered to be a measurement of cell viability in the RBC storage bag [20]. Thus, a second criterion used by the FDA and international regulators is to set a limit for the maximum amount of spontaneous hemolysis that can occur at the end of storage. In the United States, this is set at 1 percent of the total hemoglobin content as measured in the supernatant, whereas in Europe and Canada, this criterion is set at 0.8 percent [20]. This criterion is also used as a quality control measure in blood component laboratories [22].

Further details about various RBC preparations and their use are contained in the FDA-approved Circular of Information for the Use of Human Blood and Blood Components [24]. This document is considered to be an extension of product labeling.

Changes during in vitro storage — Stored red cells are metabolically active, and this metabolic activity contributes to a number of biochemical and structural changes during in vitro storage [25,26]. Collectively, these are known as the RBC storage lesion. They include:

Potassium leakage into supernatant

Decreased 2,3 BPG

Decreases in nitric oxide

Depletion of ATP

Membrane changes (including the formation of microvesicles and microparticles)

Increased oxidative damage to lipids and proteins

Loss of deformability (leading to impairment of flow in the microvasculature)

These changes accumulate as the storage duration increases and vary between different donors and different manufacturing processes. None of these changes has been found to adversely affect clinical outcomes in transfused adults, with the possible exception of potassium leakage causing hyperkalemia in selected populations [27].

Potassium leakage from the cells into the supernatant – The potassium concentration in the supernatant of stored RBC units increases by approximately 1 mEq/L per day due to passive leakage out of the red cells. Potassium is not actively transported back into the red cells because the red cell membrane ATPase is inactive during refrigeration. Thus, while the initial concentration of extracellular potassium in an RBC unit is approximately 2 to 5 mEq/L, it rises to levels of 45 to 60 mEq/L at the end of storage. In irradiated RBC units, the potassium concentration is higher on any given day, and the peak level at the end of 42-day storage is approximately 70 to 90 mEq/L [28,29]. Despite this phenomenon, the risk of hyperkalemia from transfusion is rare in adults because the volume of the extracellular component of packed RBCs is small. The potential for clinically significant hyperkalemia is greatest in the settings of severe trauma/massive transfusion, impaired renal function, or transfusion of infants or newborns, as discussed below. (See 'Hyperkalemia' below.)

Decreased 2,3, bisphosphoglycerate (2,3 BPG) – Red cell 2,3 BPG (previously called 2,3 diphosphoglycerate [2,3 DPG]) can increase oxygen delivery to the tissues by shifting the oxyhemoglobin dissociation curve to the right. Reduced 2,3 BPG has the opposite effect (ie, it can reduce tissue oxygen delivery by shifting the curve to the left) (figure 1). Levels of 2,3 BPG in stored units of RBCs begin to decline by two weeks and can be as low as 10 percent of normal after five to six weeks. It is uncertain whether this abnormality is physiologically important, even in critically ill patients [30]. Even if it were important, the 2,3 BPG concentration in the transfused cells returns to normal within 6 to 24 hours of transfusion, resulting in normalization of oxygen release. (See "Structure and function of normal hemoglobins", section on '2,3-bisphosphoglycerate'.)

Decreases in nitric oxide (NO) – NO acts as a physiological vasodilator; it is regulated by several potential mechanisms:

An intracellular NO equivalent in red cells binds to hemoglobin to produce S-nitrosohemoglobin (SNO-Hb). Circulating red cells in turn release limited fluxes of SNO equivalents (which are also vasodilatory) in proportion to hemoglobin desaturation, matching regional blood flow with metabolic demand [31-34].

NO acts on the vascular endothelium, which can be damaged in many disease states requiring transfusion. Increased plasma-free hemoglobin (due to higher hemolysis levels in older stored RBC units or accelerated in vivo hemolysis after transfusion) may contribute to inactivation of NO at the endothelial level [35]. This may lead to vasoconstriction, oxidative stress, and possible tissue and organ damage.

A decrease in red cell SNO-Hb occurs rapidly upon RBC unit storage. In one study, red cell SNO-Hb was serially assayed in blood collected from 15 healthy volunteers and processed and stored according to standards used by the AABB [34]. By three hours after processing, red cell SNO-Hb decreased by 82 percent; levels remained low over a 42-day storage period. Preclinical models have demonstrated that RBC-dependent vasoactivity may be depressed with stored blood, and that administration of NO may attenuate this effect [31,33,36].

Theoretically, when evaluating RBC quality, it would be more pertinent to measure other parameters that might correlate better with red cell function and transfusion efficacy; these include oxygen delivery to tissues, carbon dioxide removal, and red cell binding to NO and cytokines. Several techniques are available for measuring tissue oxygenation, and their use is becoming more widespread, especially in studies of patients transfused in the intensive care unit [37].

DONOR AND COMPONENT CHARACTERISTICS POTENTIALLY AFFECTING RECIPIENT OUTCOME — Allogeneic red blood cell (RBC) units are complex biological products prepared from donated blood with significant inter-donor variability in quality and in hemoglobin dose. The impact of donor characteristics, RBC processing/manufacturing methods (including storage time), and recipient characteristics on transfusion outcomes has been a subject of increasing interest [27,38,39].

With the exception of a single randomized trial comparing outcomes of RBC transfusions from male versus female donors, the data to address donor and component characteristics have generally been collected from retrospective observational studies. Due to the large number of potentially relevant factors, such studies heavily rely on regression analyses and modeling methods.

Effect of donor age, sex, and parity on post-transfusion mortality — One randomized trial and numerous retrospective observational studies using blood donor demographic data, patient electronic medical records, and/or mortality registries have evaluated the effects of donor characteristics (age, sex, parity) on post-transfusion mortality in the recipient [40-51].

Donor sex – A large randomized trial published in 2023 (Trial Assessing Donor Sex on Recipient Mortality [iTADS]) assigned 8719 individuals requiring RBC transfusion to receive RBC units exclusively from male donors or exclusively from female donors [51]. The mean number of RBC units received was slightly >5 units per patient. There was no statistical difference in the primary outcome of survival over time nor in the secondary outcomes that were assessed (survival over specified discrete time intervals ranging from 30 days to 2 years, length of hospital stay, intensive care unit admission, and a number of severe morbidities).

Observational studies conducted before this trial had come to conflicting conclusions, with some finding no effect of donor sex and others showing increased mortality from female blood donors or discordant sex between the donor and recipient [40-46]. However, the data from the large randomized trial (iTADS) discussed above do not support the associations found in the observational study, and the findings from iTADS strongly argue against any policy that would differentiate units of blood based on donor sex.

Donor parity – Two studies showed no effect of prior pregnancies in female donors, while another study showed an increased mortality when the transfused unit was from a parous female donor [42-44]. The increased mortality was restricted to male recipients.

Donor age – Two studies showed no effect of the donor's age on recipient mortality [40,50]; two other studies showed increased mortality from younger donors, defined as <30 years old in one study and <45 years old in the other [41,48]. One of the studies that showed no mortality difference did show a slightly decreased hospital length of stay for donors <20 years old (the opposite directionality from the studies that showed a difference in mortality [50].

It is not fully understood why results from previous studies have been conflicting. One of the largest and most comprehensive studies, a retrospective analysis involving almost one million transfusion recipients, found that donor age and sex did not affect recipient mortality once the data were adjusted for the number of transfusions using a nonlinear model [40]. This statistical adjustment was required to eliminate the confounding effects of the recipient's disease severity, which created a nonlinear relationship between the number of transfusions and the risk of death. The authors suggested that these confounding effects were responsible for an earlier report (by a different set of investigators) that suggested transfusions from female and younger donors were associated with an increased risk of mortality [40,41]. This reanalysis illustrates the importance of the statistical methods chosen for analyzing these complex datasets and the influence of the methods used to control for confounders such as receipt of multiple units over a varying time course.

RBC age/storage duration effect on clinical outcomes — In the United States, units of packed RBCs can be stored refrigerated for up to 42 days. However, the inventory is constantly turning over, and few units are stored for this length of time. In a 2022 survey of >100,000 transfusions, the average storage duration of the transfused RBC units was 26 days (interquartile range [IQR], 15 to 36 days) [52].

As demonstrated in a transfused patient population, the number of transfused red cells that are removed by physiologic mechanisms within the first 24 hours after transfusion increases as the in vitro storage time of the RBC unit increases; subsequently, the survival of the remaining red cells appears to be the same regardless of their in vitro storage age [53].

Multiple randomized trials have demonstrated equivalent outcomes (mostly mortality but also severe morbidity) with transfusion of "fresh" red cells (RBC units stored for fewer days) and "standard issue" red cells (RBCs stored for the usual number of days).

As examples:

The INFORM trial (Informing Fresh versus Old Red Cell Management) randomly assigned 20,858 hospitalized adults with type A or O blood to receive shorter (mean, 13 days) versus longer (mean, 24 days) storage duration blood [54]. This trial found no difference in mortality (9.1 versus 8.7 percent) or in length of hospital stay (10 days in both arms). Analysis of kidney function in INFORM participants demonstrated no difference in the incidence of acute kidney injury (AKI; 14.4 percent with shorter storage duration versus 1.54 percent with longer storage duration; relative risk [RR] 0.94, 95% CI 0.86-1.02) [55].

Two smaller randomized trials in adults (the ABLE trial [Age of Blood Evaluation] in 2430 critically ill adults and the RECESS trial [Red Cell Storage Duration Study] in 1098 adolescents and adults undergoing cardiac surgery) also found no difference in outcomes such as mortality and length of stay with shorter or longer storage duration RBC units [56,57]. Additional laboratory analyses in a subset of the participants in each of these trials indicated no differences in coagulation or immune parameters in recipients of RBC units of different storage ages, up to 35 days [58,59].

A 2016 meta-analysis that included all but the largest trial also confirmed no clinical benefit from using RBC units with a shorter storage duration [60].

A subsequent trial (TRANSFUSE trial [Standard Issue Transfusion versus Fresher Red-Cell Use in Intensive Care]) in approximately 5000 patients in the critical care setting also found no difference with transfusion of RBC units that were stored for a shorter period of time [61].

Randomized trials in pediatric populations have also found no major differences with younger versus older blood; these trials are discussed separately. (See "Red blood cell transfusion in infants and children: Selection of blood products", section on 'Storage duration' and "Red blood cell (RBC) transfusions in the neonate", section on 'Selection of RBC products'.)

Remaining unanswered issues include whether these data can be extrapolated to adult trauma patients and/or to patients for whom the majority (or all) of the transfused units have been stored for 35 to 42 days [62].

Newer research techniques such as proteomics, metabolomics, and genomics are being applied to better understand the basis for the well-documented observations of intra- and inter-donor differences in how red cells age during in vitro storage [63]. Whether these differences affect clinical outcomes for the recipient remains to be thoroughly investigated [64,65]. Prolonged (5 to 6 week) storage may affect post-transfusion hemoglobin increment in the recipient [39]. This decreased increment also has been demonstrated in healthy volunteers transfused with autologous RBC units stored for greater than 35 days [66].

Additional information about the clinical relevance of red cell storage time is discussed in a mini symposium on RBC storage and in separate reviews and editorials published before randomized trial data were available, which discuss many of the relevant considerations [67-77].

Donor and component effect on hemoglobin increments — The amount of hemoglobin is highly variable in whole blood-derived RBC units, ranging from 50 to 80 grams prior to leukoreduction and (approximately 8 percent less for units that have undergone leukoreduction) [11,78]. This variability is due to a fixed collection volume from all donors (approximately 500 mL of whole blood), despite the variability of donor hemoglobin from 12.5 g/dL to as much as 17 to 18 g/dL. RBC units collected by apheresis have a greater standardization of hemoglobin content (approximately 60 grams), which is achieved through algorithms that are programmed into the automated apheresis machines.

The post-transfusion hemoglobin increment in recipients is highly likely to be affected by the amount of hemoglobin present in the transfused unit(s). This is challenging to demonstrate, as studies that have assessed post-transfusion hemoglobin increments do not routinely measure hemoglobin content in the RBC units due to logistical constraints. However, one clinical trial in patients with thalassemia transfused with pathogen-inactivated RBCs (a product under development) has made such measurements [78].

Two studies have found an effect of RBC storage age on post-transfusion hemoglobin increments. A study of 225 patients with myelodysplastic syndromes showed decreased hemoglobin increment with increased storage age [38]. A larger retrospective study conducted over an 8 year period (2008 to 2016) of 23,914 transfused patients who underwent 38,019 episodes in which a single RBC unit was transfused found that some donor demographic characteristics, RBC component manufacturing parameters, and recipient characteristics had a small effect on the transfusion recipient’s post-transfusion hemoglobin increment [39]. Overall, the average hemoglobin increase from a single unit transfusion was 1.0 g/dL. Factors that affected the hemoglobin increment by approximately 10 percent (approximately 0.1 g/dL) included:

Donor – Male sex and age <70 years increased the increment.

RBC collection – Apheresis collection rather than whole blood collection, gamma irradiation of the unit, and storage of the unit for 5 to 6 weeks decreased the increment.

Recipient – Female sex, increasing age, and lower body mass index increased the increment.

While each of these factors had only a small effect individually, the authors modeled scenarios in which single unit transfusion was calculated to raise the hemoglobin by as little as 0.59 g/dL to as much as 1.65 g/dL.

SPECIALIZED MODIFICATIONS AND PRODUCTS — There are a number of processes that can be used to modify red cells in an attempt to minimize complications that occur in certain patient populations.

Irradiation — RBC units can be irradiated prior to transfusion by subjecting them to 2500 cGy of irradiation, targeted to the central portion of the component, with a minimum dose of 1500 cGy delivered to any part of the component. Irradiation sources include gamma rays from either a cesium-137 or cobalt-60 blood irradiator or x-rays using a standalone machine. The 2500 cGy dose is sufficient to inactivate lymphocytes in the product.

Viable donor lymphocytes can attack recipient cells in individuals who are unable to mount an immune response against them, causing transfusion-associated graft-versus-host disease (ta-GVHD). Ta-GVHD can target all hematopoietic cells as well as other tissues, leading to bone marrow aplasia and other complications that are ultimately fatal. (See "Transfusion-associated graft-versus-host disease".)

Irradiation adds an additional minor delay in the time before a unit is available (generally less than 30 minutes). There is variability in practice regarding whether irradiation is performed just prior to issuing a unit versus maintaining an ongoing inventory of irradiated units. The latter may be especially appropriate in institutions that care for a stable number of individuals who require irradiated blood. Irradiation adds cost and reduces the shelf-life of the irradiated unit; thus, it is not done universally. The reduced shelf-life is due to a lesion induced in the red cell membrane that reduces red cell viability and accelerates leakage of potassium from red cells into the supernatant. In the United States, irradiated RBCs have a storage limit of 28 days post irradiation (not longer than 42 days in total); in some European countries, total shelf life is reduced to 28 days post collection of the unit [79-84]. (See 'Changes during in vitro storage' above.)

Irradiation is used to prevent ta-GVHD in at-risk individuals [85]. Patients at most risk include those who are severely immunocompromised and those who would fail to recognize the transfused lymphocytes as foreign, due to human leukocyte antigen (HLA) homology. (See "Transfusion-associated graft-versus-host disease", section on 'Risk factors'.)

Patient groups requiring irradiated components include the following, which are listed in the table (table 2) and discussed in more detail in a guideline from the British Committee for Standards in Haematology (BCSH) [86]:

Recipients of intrauterine or neonatal exchange transfusion; premature neonates

Individuals with congenital cell-mediated immunodeficiency states

Individuals treated with specific types of potent immunosuppressive therapies (purine analogs, antithymocyte globulin [ATG], certain monoclonal antibodies); this may include those being treated for non-Hodgkin lymphoma (NHL) or other hematologic malignancies

Recipients of hematopoietic stem cell transplant (autologous or allogeneic)

Individuals with Hodgkin lymphoma (any stage of disease)

Individuals at risk for partial HLA matching with the donor due to directed donations, HLA-matched products, or genetically homogeneous populations

Randomized trials comparing irradiated units versus non-irradiated units have not been performed. Immunocompromised patient groups have been defined based on observational evidence, case reports, reviews, and attempts to predict the degree of immunosuppression. Thus, there is a lack of consistency in the literature as to which patients must receive irradiated blood.

In some cases, the recommendation to use irradiated red cell products is indefinite (eg, individuals with Hodgkin lymphoma); in others, it may be time-limited (eg, for three months after autologous hematopoietic stem cell transplantation [six months if total body irradiation was used]; as long as GVHD is present after allogeneic hematopoietic cell transplantation). Local institutional or society guidelines should be consulted for specific recommendations.

In the United States, each hospital establishes its own policy as to which groups of patients should receive irradiated components [87]. A 2014 College of American Pathologists (CAP) survey of practices at approximately 2100 United States institutions revealed substantial differences in which diagnoses were associated with the use of irradiated units [88]. A small number of institutions performed universal irradiation of all transfused cellular components or "block" irradiation for all patients on a given service/floor or for very young patients due to undiagnosed congenital immunodeficiency.

Additional information is available in separate topic reviews. (See "Transfusion-associated graft-versus-host disease", section on 'Pathogenesis' and "Red blood cell transfusion in infants and children: Selection of blood products", section on 'Irradiated red blood cells'.)

Whole blood — Whole blood has been difficult for clinicians to obtain from blood banks due to the routine use of component separation. However, the use of whole blood has re-emerged as an option for trauma patients, leading to its increasing availability in some blood banks [89-93].

The major difference between whole blood and packed RBC units is the volume of plasma present in the unit [94]. Thus, whole blood may be appropriate for individuals who require RBCs and plasma transfusion, such as adults with acute, massive bleeding. (See "Massive blood transfusion".)

In contrast, individuals with chronic anemia or those who require fewer units of blood should be transfused with packed RBCs. In these individuals, the blood volume has already expanded to compensate for anemia. Therefore, volume expansion is not required, and circulatory overload may be a risk if plasma is also given.

The volume of a unit of whole blood is approximately 450 to 500 mL, and the hematocrit of a unit of whole blood is equivalent to the hematocrit of the whole blood donor. In contrast, packed RBC units have a smaller volume and a higher hematocrit due to removal of plasma and resuspension in a smaller volume of anticoagulant-preservative (A-P) solution. (See 'Anticoagulant-preservative (A-P) solutions' above.)

Frozen red cells — RBC units can be frozen in 40 percent glycerol. Cells prepared by this method are approved by the US Food and Drug Administration (FDA) and the Association for the Advancement of Blood & Biotherapies (AABB) for storage at -80ºC for up to 10 years [95].

A major indication for freezing RBC units is to maintain an inventory of units with rare blood group phenotypes to meet the transfusion needs of recipients with very rare red cell phenotypes (eg, Bombay phenotype) or to transfuse individuals who have developed multiple alloantibodies directed against common RBC blood group antigens. Another potential indication is for individuals with immunoglobulin A (IgA) deficiency who have circulating anti-IgA antibodies that react with IgA in the donor plasma, when an IgA-deficient donor is not available. Washed red cells are another option for these individuals. (See "Selective IgA deficiency: Management and prognosis", section on 'Reactions to blood products' and 'Washed red cells' below.)

The efficacy of frozen red cells was evaluated in a prospective, randomized trial of 57 stable trauma patients who required blood transfusion [96]. Compared with refrigerated RBC units, frozen deglycerolized RBC units were non-inferior with respect to increasing hematocrit, effects on thromboelastography parameters, and clinical outcomes.

The time and effort required for subjecting red cells to glycerolization, freezing, thawing and washing (for removal of the glycerol) immediately before infusion increase cost and delay transfusion. Thus, frozen deglycerolized RBC units are not appropriate for most other indications.

Deglycerolized RBC units must be transfused within 24 hours if prepared in an open system and within two weeks if prepared in a closed system.

Washed red cells — Units of RBCs can be washed to reduce or eliminate complications associated with the small amount of residual plasma in the unit. This approach may be indicated for individuals with the following conditions:

Severe or recurrent allergic reactions (eg, hives) associated with red cell transfusion. (See "Immunologic transfusion reactions", section on 'Management of allergic reactions'.)

IgA deficiency with circulating anti-IgA antibodies that react with IgA in the donor plasma, when an IgA-deficient donor is not available. Frozen deglycerolized red cells may be the component of choice for these individuals. (See "Selective IgA deficiency: Management and prognosis", section on 'Reactions to blood products' and 'Frozen red cells' above.)

Individuals at risk for hyperkalemia. (See 'Hyperkalemia' below.)

Washing is done in an automated system using 0.9 percent sodium chloride immediately before infusion. The shelf-life of washed blood is four hours at 20 to 24°C or 24 hours if stored at 1 to 6°C.

Frozen deglycerolized RBC units also undergo extensive washing and can be used for the same indications. (See 'Frozen red cells' above.)

Volume-reduced red cells — When circulatory overload is a concern (eg, due to congestive heart failure, renal failure), the RBC unit can be centrifuged immediately prior to transfusion to remove the storage solution and hence reduce the volume of the transfusion. Other measures to minimize the risk of transfusion-associated volume overload are discussed separately. (See "Transfusion-associated circulatory overload (TACO)", section on 'Prevention'.)

CMV-seronegative red cells — Cytomegalovirus (CMV)-negative blood components are components that test negative for the presence of CMV using serologic methods (antibody testing). CMV antibody testing is only performed on a subset of donated units to provide a sufficient inventory of CMV-negative blood components to individuals at risk of clinically serious CMV infection. (See "Blood donor screening: Laboratory testing", section on 'Cytomegalovirus'.)

Immunocompetent individuals are usually not given CMV-negative products because they are generally able to mount an immune response. At least 40 percent of the general adult population has been exposed to CMV. Exposure varies geographically and may be much higher in some areas. (See "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults", section on 'Epidemiology'.)

In contrast, certain immunocompromised individuals who are themselves CMV-negative may be at risk for serious infection if they receive a CMV-positive unit of blood. These individuals are given CMV-negative blood components (eg, RBC or platelets). Examples of individuals for whom CMV-negative components are appropriate include:

Solid organ transplant recipients

Hematopoietic stem cell transplant (HCT) recipients

Low birth weight neonates

Individuals infected with HIV

Pregnant women

If individuals with these characteristics are CMV-positive, they would likely receive CMV-positive units.

For individuals who are at risk for complications of CMV infection, another option is to use leukoreduced units. This practice is considered to be of equivalent safety to CMV-negative blood for CMV risk reduction. (See 'Pre-storage leukoreduction' above.)

ADMINISTERING THE TRANSFUSION — Important aspects of RBC administration include attention to the following [24,97]:

Informed consent — Informed consent for RBC transfusion should be obtained from the intended recipient before all non-emergency administration of blood components. According to AABB standards, elements of consent should include a description of the risks, benefits, and treatment alternatives; the opportunity for the intended recipient to ask questions; and the right of the patient to accept or refuse transfusion.

Pre-transfusion considerations

Patient identification – Practices to ensure that the intended transfusion is given to the intended recipient are critical for preventing serious transfusion reactions such as acute hemolytic transfusion reactions (AHTR) due to ABO mismatch. (See "Hemolytic transfusion reactions".)

Premedication – The routine use of premedication (eg, acetaminophen and/or antihistamines) to prevent febrile nonhemolytic or allergic transfusion reactions is not supported by data; this issue and potential exceptions are discussed separately. (See "Immunologic transfusion reactions", section on 'Febrile nonhemolytic transfusion reactions'.)

Inspection of the unit – All units should be visually inspected before transfusion. If this inspection reveals that the storage bag is not intact or the appearance of the unit is abnormal, it should not be transfused.

Venous access – Adequate venous access is necessary for RBC transfusion; techniques for venous access are discussed separately. (See "Peripheral venous access in adults" and "Central venous access in adults: General principles".)

Filters – All RBC units must be transfused through a standard 170 to 260 micron filter (contained as an integral part of a standard infusion set) designed to remove clots and aggregates.

Additional filters for leukoreduction are routinely used by many blood collectors (at the time of collection (see 'Pre-storage leukoreduction' above)) or transfusion services (at the time of administration) and are helpful in preventing febrile nonhemolytic transfusion reactions (FNHTRs). (See "Immunologic transfusion reactions", section on 'Febrile nonhemolytic transfusion reactions'.)

Blood warmers – For patients who require blood that is warmed (eg, those at risk of hypothermia or autoimmune cold-induced hemolysis), blood warmers that raise the temperature closer to body temperature are used. These must be calibrated and monitored to avoid heating of the blood cells above 40°C, which will cause hemolysis. (See "Paroxysmal cold hemoglobinuria", section on 'Treatment' and "Use of blood products in the critically ill", section on 'Complications of large-volume transfusion' and "Massive blood transfusion", section on 'Hypothermia'.)

Compatible fluids — No other intravenous solutions or medications except 0.9 percent sodium chloride for injection, ABO-compatible plasma, or albumin should be administered through the same tubing concurrently with the RBC units. Exceptions can be made if approved in the package insert approved by the US Food and Drug Administration (FDA); this approval has been granted for some isotonic, calcium-free electrolyte solutions. Dextrose-containing solutions are contraindicated; if blood is mixed with 5 percent dextrose in water, the sugar is taken up rapidly by the RBCs, followed by uptake of water and cell lysis.

The prohibition against infusion of other fluids also extends to Ringer's lactate solution. This is because Ringer's lactate contains calcium, which could interfere with the clotting system. However, some authors have advocated administering RBC and Ringer's lactate concurrently through the same line in emergency trauma cases due to the need for rapid therapy [98]. A few small in vitro studies have been performed to evaluate the safety of this practice. In summary, these studies found that for RBCs in some citrate-containing additive solutions, the clotting system appears to be unaffected provided that the RBC infusion occurs rapidly; ie, within 30 to 60 minutes [98-100]. However, these observations have not been fully validated.

These observations notwithstanding, as a general rule, calcium or calcium-containing solutions should not be combined with a blood unit due to the risk of overcoming the capacity of the anticoagulant (citrate, which chelates calcium) and causing clotting in the tubing.

When RBC units are administered through a central venous catheter with multiple lumens, other lumens can be used concurrently for infusion of medications. However, caution should be exercised if the medication is associated with known adverse effects or if it is being administered to the patient for the first time.

Medications and fluids can also be administered through the same lumen as an RBC transfusion, before or after the transfusion; in this setting, the lumen should be flushed with normal saline both before and after medication infusion [101].

Infusion rate — RBC units should be infused at a rate that delivers the needed blood efficiently while at the same time reducing the risk of volume overload. Suggested infusion rates for adults are 1 to 2 mL per minute (60 to 120 mL per hour) for the first 15 minutes and then as rapidly as tolerated. The complete infusion should not exceed four hours.

However, slower rates of infusion (possibly combined with administration of a smaller unit to comply with the four-hour infusion requirement) and/or the administration of diuretics may be indicated for patients who are predisposed to circulatory overload. (See "Transfusion-associated circulatory overload (TACO)", section on 'Prevention'.)

Post-transfusion monitoring

Hemoglobin level – The post-transfusion hemoglobin level may be accurately measured as early as 15 minutes following transfusion, as long as the patient is not actively bleeding. This practice is based on studies showing a high degree of concordance between values measured 15 minutes after the transfusion and longer intervals [102,103].

Hospitalized patients – In the inpatient setting, a post-transfusion hemoglobin either may be obtained soon after transfusion or may wait until a routinely ordered laboratory blood draw.

Ambulatory patients – For outpatients, a post-transfusion hemoglobin may be obtained but is not needed in all circumstances.

Observation following transfusion – In addition to observing the patient during transfusion, inpatients will continue to be observed for 15 to 30 minutes post-transfusion. The situation with outpatients is more variable and dependent on local institutional procedures; some institutions will observe for this length of time but others will release the patient sooner (eg, after the final set of vital signs is taken, especially if the patient has been routinely transfused at the same facility in the past).

POTENTIAL ADVERSE EFFECTS OF TRANSFUSION

Metabolic effects

Hyperkalemia — As noted above, levels of extracellular potassium in RBC units increase toward the end of the maximal storage time (see 'Changes during in vitro storage' above). However, severe hyperkalemia from transfusion of properly collected and stored (eg, not hemolyzed) RBC units is rarely seen in adults [104].

Risk factors for transfusion-related hyperkalemia include a longer storage duration of the units, a greater number of RBC units (or greater volume) transfused, a faster infusion rate, a smaller blood volume in the recipient, and the use of irradiation [104-107]. A rapid infusion rate appears to be a particularly important risk factor in neonates and children [107]. (See "Red blood cell transfusion in infants and children: Administration and complications", section on 'Metabolic toxicity'.)

Even when transfusion-associated hyperkalemia occurs, it is likely transient. Further, it is unclear how often this leads to clinical symptoms, particularly cardiac arrhythmias or cardiac arrest, for which there are only a few convincing reports [106]. One factor that might lead to cardiac symptoms is rapid infusion through a central venous catheter.

There are three clinical settings in which there is an increased risk of transfusion-related hyperkalemia:

Massive trauma – Hyperkalemia is a common occurrence in patients with severe trauma, with a prevalence of 29 percent in massively injured patients at a United States military combat support hospital in Iraq [108]. Although red cell transfusion may contribute to this, other risk factors include tissue breakdown with the release of cellular potassium into the extracellular fluid; a low cardiac output that impairs renal function; and hypocalcemia, which can increase the severity of the manifestations of hyperkalemia [105,108]. (See "Treatment and prevention of hyperkalemia in adults", section on 'Calcium' and "Massive blood transfusion", section on 'Hyperkalemia'.)

Impaired renal function – Renal excretion of the potassium load acquired from RBC transfusion limits the elevation in serum potassium. This protective effect is diminished in patients with moderate to severely impaired renal function. Such patients may require modifications in transfusion practices such as the use of fresher RBC units or washed red cells. (See 'Washed red cells' above and "Causes and evaluation of hyperkalemia in adults", section on 'Acute and chronic kidney disease'.)

Infants and newborns – Infants and newborns are at increased risk for transfusion-related hyperkalemia due to their small blood volume and the low rate of urinary excretion of a potassium load. Protective measures include the use of fresher RBC units, washed red cells, and/or a bedside potassium adsorption filter [109]. (See 'Washed red cells' above and "Red blood cell (RBC) transfusions in the neonate".)

Citrate toxicity — Whole blood is collected using a balanced citrate solution to chelate calcium and prevent the collected blood unit from clotting. (See 'Anticoagulant-preservative (A-P) solutions' above.)

Citrate toxicity from transfused RBC units is rare but could occur if the transfused citrate load was high enough to cause significant chelation of calcium, thereby resulting in low levels of ionized calcium.

The manifestations of hypocalcemia can include a sense of heightened anxiety, carpopedal spasm, tetanic contractions, and arrhythmias.

Patient populations at risk for citrate toxicity include those who receive large-volume transfusions of plasma, red cells, or whole blood (eg, as in massive transfusion) over a short period of time, especially if severe liver disease is present, as this impairs citrate metabolism. Individuals undergoing liver transplantation are one such population. Approaches to mitigating citrate toxicity are discussed separately. (See "Massive blood transfusion", section on 'Complications'.)

Citrate toxicity in individuals undergoing plasmapheresis or therapeutic plasma exchange is discussed separately. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Complications".)

Transfusion reactions — Transfusion reactions are discussed in separate topic reviews:

Acute transfusion reaction evaluation – (See "Approach to the patient with a suspected acute transfusion reaction".)

Febrile nonhemolytic reactions – (See "Immunologic transfusion reactions", section on 'Febrile nonhemolytic transfusion reactions'.)

Hemolytic transfusion reactions – (See "Hemolytic transfusion reactions".)

Allergic or anaphylactic reactions – (See "Immunologic transfusion reactions".)

Transfusion-related acute lung injury (TRALI) – (See "Transfusion-related acute lung injury (TRALI)".)

Volume overload – (See "Transfusion-associated circulatory overload (TACO)".)

Graft-versus-host disease – (See "Transfusion-associated graft-versus-host disease".)

Infection — Infection associated with transfusion is discussed in separate topic reviews:

Bacterial infection – (See "Transfusion-transmitted bacterial infection".)

Viral infection – (See "Blood donor screening: Laboratory testing", section on 'Infectious disease screening and surveillance'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anemia in adults" and "Society guideline links: Transfusion and patient blood management".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Blood transfusion (The Basics)")

SUMMARY AND RECOMMENDATIONS

Indications for RBC transfusion – Red blood cell (RBC) transfusions are given to raise the hemoglobin level in patients with anemia or to replace losses after acute bleeding. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult" and "Red blood cell transfusion in infants and children: Indications".)

Screening of donated blood – Donated blood is obtained from screened volunteers, and all units undergo laboratory testing for selected infectious organisms. (See "Blood donor screening: Overview of recipient and donor protections" and "Blood donor screening: Medical history" and "Blood donor screening: Laboratory testing".)

Collection and storage – Processes and criteria for licensure are in place to ensure quality control during manufacture and storage of RBC units. Methods of manufacture, storage solutions, storage temperature requirements, and pre-storage leukoreduction are discussed above. The preponderance of data indicate that donor age, sex, and parity do not affect survival in transfusion recipients. (See 'Collection and storage procedures' above and 'Effect of donor age, sex, and parity on post-transfusion mortality' above.)

Storage lesion – RBCs undergo a number of changes during refrigerated storage that are collectively referred to as the RBC storage lesion. These include loss of ATP, membrane changes, decreased nitric oxide (NO), decreased 2,3 bisphosphoglycerate (2,3 BPG), and potassium leakage. These changes do not adversely affect post-transfusion survival. (See 'Changes during in vitro storage' above and 'RBC age/storage duration effect on clinical outcomes' above.)

Modifications – There are a number of specialized RBC products or modifications that can be provided, either as part of hospital-wide transfusion policy or as ordered by the individual clinician (see 'Specialized modifications and products' above):

Leukoreduction, for individuals at risk for febrile nonhemolytic transfusion reactions (FNHTRs), human leukocyte antigen (HLA) alloimmunization, or cytomegalovirus (CMV) transmission

Irradiation, for individuals at risk for transfusion-associated graft-versus-host disease (ta-GVHD) (table 2)

Whole blood, for massive transfusion

Frozen RBCs, for individuals with rare blood groups

Washed RBCs, for those with severe allergic reactions, anti-IgA antibodies, or increased risk for hyperkalemia

Volume-reduced RBCs, for those at risk of transfusional volume overload

CMV-negative RBCs, for CMV-negative individuals who are immunosuppressed and at risk for serious infection from CMV

Infusion – Transfusion requires informed consent, patient identification, adequate venous access, and visual inspection of the unit of blood. With limited exceptions, no other intravenous solutions or medications except 0.9 percent sodium chloride for injection, ABO-compatible plasma, or albumin should be administered through the same tubing as the RBC unit. Suggested infusion rates for adults are 1 to 2 mL/minute (60 to 120 mL/hour) for the first 15 minutes and then as rapidly as tolerated, not exceeding four hours. If needed, a post-transfusion hemoglobin can be checked as soon as 15 minutes after transfusion. (See 'Administering the transfusion' above.)

Risks – The risk of transfusion-related hyperkalemia is increased in massive trauma, chronic kidney disease, and newborns/infants. The risk of citrate toxicity is increased in massive transfusion, especially with severe liver disease. Approaches to monitoring for and mitigating these effects, transfusion reactions, and transfusion-transmitted infections, are discussed above and separately. (See 'Potential adverse effects of transfusion' above and "Massive blood transfusion" and "Approach to the patient with a suspected acute transfusion reaction".)

Children – Administration is discussed separately. (See "Red blood cell transfusion in infants and children: Administration and complications".)

ACKNOWLEDGMENT — The UpToDate editorial staff gratefully acknowledge the extensive contributions of Arthur J. Silvergleid, MD, to earlier versions of this and many other UpToDate topics.

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Topic 7939 Version 76.0

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