Blood and Blood Components

Key Concepts

Red blood cell transfusion is indicated only to increase oxygen delivery at the tissue level.
One unit of packed red blood cells (PRBCs) can be expected to raise an adult’s hemoglobin level by 1 g/dL. A similar increase is expected in children following the transfusion of 10 mL/kg of PRBCs.
Controlled trials have supported newer, restrictive, red cell transfusion strategies. Pending further trials, a transfusion trigger of a hemoglobin level below 7 to 8 g/dL is appropriate for most stable hospitalized patients.
Platelet transfusions are typically used prophylactically for counts less than 10 K/μL in adults without bleeding. For patients undergoing central venous catheter placement, a level of 20 K/μL is recommended. Patients undergoing lumbar puncture and non-neuroaxial surgery should be prophylactically transfused to a level of 50 K/μL.
Prospective and retrospective reports have suggested a benefit to massive transfusion protocols, with most advocating a 1 : 1 : 1 ratio of fresh frozen plasma (FFP) to platelets to PRBCs.
When available, low-titer whole blood is safe and effective for transfusion and provides a physiologic mix of blood products.
When available, prothrombin complex concentrate (PCC) should be given over FFP for reversal of vitamin K antagonism in the setting of a life-threatening bleeding. When PCC is not available, FFP can be used for this purpose, but is considered a second-line therapy.
Transfusion reactions can vary from minor symptoms to fatal systemic reactions. If any transfusion reaction is suspected, the transfusion should be stopped while the cause and extent of the reaction is investigated.
An intravascular hemolytic transfusion reaction is usually the result of ABO incompatibility and typically results in immediate symptoms that can include fever, chills, headache, nausea, vomiting, sensation of chest restriction, severe joint or low back pain, burning sensation at the site of the infusion, and feeling of impending doom. Treatment involves stopping the transfusion, fluid resuscitation, and monitoring for the development of renal failure and disseminated intravascular coagulation (DIC).
Transfusion-related acute lung injury (TRALI) is now the leading cause of reported transfusion-related mortality. Treatment involves stopping the transfusion and providing supportive respiratory care, which may include noninvasive positive-pressure ventilation (NIPPV) or intubation and mechanical ventilation.
Improved techniques for selecting and testing blood donors has dramatically reduced the risk of viral transmission of disease by transfusion.

Foundations

Background and Importance

The modern blood transfusion era began with identification of the ABO red cell antigen system in the early 1900s. The subsequent discovery that adding citrate enabled the storage of anticoagulated blood led to the establishment of the first blood banks in the United States in the 1930s, and blood banking expanded rapidly after World War II. In subsequent decades, transfusion research focused primarily on critical issues such as developing component therapy, prolonging the storage life of blood products, and reducing the risk of transfusion reactions and transfusion-related infections. In 2015, approximately 11.4 million red blood cell units, 2.7 million plasma units, and 2 million platelet units were transfused in US acute care hospitals.

Anatomy, Physiology, and Pathophysiology

Sound transfusion decision making is informed by a thorough working knowledge of the underlying physiology and pathophysiology, as well as familiarity with the key clinical trials that support up-to-date, evidence-based guidelines. This knowledge facilitates the effective ordering and interpretation of laboratory tests, delivery of blood products, and management of common or serious complications.

Blood Banking

Red blood cell (RBC) storage methods aim to ensure viability of at least 75% of the cells 24 hours after infusion. Blood collection bags contain an anticoagulant that ensures a shelf life of 35 days and a hematocrit of 70% to 80% for packed RBCs (PRBCs). Additive solutions provide additional nutrients and extend maximum storage to 42 days.

A number of biochemical and structural changes have been documented to occur during red cell storage, including loss of deformability, leakage of potassium, irreversible membrane changes, and biochemical alterations that have the potential to affect the ability of RBCs to unload oxygen in the microcirculation. These changes worsen with increased storage duration and have been collectively referred to as the storage lesion. A number of observational studies and a few randomized prospective trials have reported conflicting results as to whether these changes are clinically relevant. The most recent four, large randomized trials have found no statistically significant difference in patient outcomes based on the age of the transfused blood product. Due to methodological limitations however, these results are not yet universally considered definitive. ³

Blood Typing

Blood typing refers to the process by which blood is categorized by the antigens expressed on the red blood cells and the antibodies contained in the serum. There are currently over 30 known blood type systems, with the most important systems being the ABO and Rh systems. Kell, Duffy, and Kidd are examples of other blood type systems which generally have less of an impact on clinical practice.

Within the ABO system, there are type A and type B antigens. Red blood cells can express either, both, or neither of these antigens on their cell membranes. Throughout the first year of life, antibodies are formed against whichever antigens are not expressed on an individual’s red blood cells. Type O blood, for instance, describes red blood cells that express neither type A nor type B antigens and thus is associated with anti-A and anti-B antibodies in the serum ( Fig. 108.1 ). This seemingly spontaneous production of antibodies is theorized to be triggered by natural exposure to similar antigens in food, bacteria, or the environment and is unique to the ABO blood type system. Conversely, if type A, B, or both antigens are expressed on an individual’s red blood cells (as is the case for type A, type B, and type AB blood respectively), the immune system recognizes these naturally occurring antigens as self-antigens and antibodies are not produced. Antibodies against antigens from other blood type systems can certainly be formed, but they generally require an exposure to red blood cells that express those antigens, for instance through blood transfusions or pregnancy. The “natural” production of ABO antibodies combined with the fact that ABO antigens and antibodies cause agglutination and hemolysis when mixed, means that patients can suffer from severe or even fatal transfusion reactions the first time they receive a PRBC transfusion from an ABO incompatible donor.

Fig. 108.1, Overview of red blood cell ABO grouping.

The second most clinically important blood type system is the Rh system. There are numerous known antigens in this system, but the D antigen is the most immunogenic. When a blood type is described as positive or negative (as in AB+), the report is referring to the presence or absence of the RhD antigen. Unlike in the ABO system, the mixing of Rh antigens and antibodies from a single transfusion is unlikely to result in a severe hemolytic reaction. This blood type system is most clinically relevant in the setting of pregnancy (or potential future pregnancies). If through a previous blood transfusion or pregnancy, an RhD negative mother has been exposed to RhD and subsequently developed anti-RhD antibodies, these antibodies can cross the placenta and into the fetal circulation. If the fetus is RhD positive, prolonged mixture of antigen and antibody can result in hemolytic disease of the newborn. Therefore, unstable hemorrhaging female patients who are not post-menopausal should receive O− blood, while male patients and postmenopausal female patients can receive O+ blood. Of note, hemolytic disease of the newborn is not seen with an ABO incompatible mother and fetus, as the vast majority of anti-ABO antibodies are IgM, which do not cross the placenta.

Type and Screen

An individual blood type and screen test includes ABO grouping, Rh typing, and antibody screen for unexpected, non-ABO/Rh antibodies. ABO grouping tests patient red cells with anti-A and anti-B serum and also with A and B red cells. Rh typing is accomplished by adding a commercial anti-D reagent to patient RBCs. To complete the antibody screen, the patient’s serum is combined with commercially prepared mixtures of red cells expressing clinically significant antigens. The incidence of unexpected antibodies in the general population is low (<1%–2%), but a positive screen prompts further compatibility testing. In ideal circumstances, type-specific, yet uncrossmatched, blood can generally be made available within 15 minutes of receiving a sample of the patient’s blood.

Type and Crossmatch

When a unit of blood is ordered for transfusion, a crossmatch follows the initial type and screen. In an ideal situation, blood identical to the patient’s own ABO and Rh group is utilized. Local blood supplies, however, might dictate that a nonidentical but compatible unit be used. Patients with blood group AB are known as universal recipients—they can receive packed red blood cells from any of the ABO groups, given their lack of anti-A and anti-B antibodies. Type O is commonly referred to as the universal donor of packed red blood cells, given the lack of A and B antigens.

A crossmatch procedure involves mixing the recipient’s serum with donor RBCs and observing for agglutination as a final compatibility test before transfusion. If the antibody screen is negative, an abbreviated crossmatch at room temperature serves as a final check for ABO incompatibility. An antibody screen and abbreviated crossmatch requires at least 45 to 60 minutes to complete. If the antibody screen is positive, a complete crossmatch is generally required before transfusion. This requires the mixture of donor RBCs and recipient serum be incubated to 37°C (98.6°F) with the addition of antihuman globulin (Coombs reagent) to promote agglutination. Many blood banks also substitute a computer crossmatch for patients whose blood has been tested at least twice in their system. Complete crossmatch testing can take up to several hours, or even days, leading to delays in many urgent or emergent situations. If complete compatibility testing following a positive antibody screen would substantially delay transfusion of blood products to a critically ill patient, the emergency clinician may choose to bypass this step. Direct communication with the blood bank will facilitate determination of the best course of action.

Titer Testing for Whole Blood Donation

Although patients with type O blood are considered to be universal donors of packed red cells (PRBCs), whole blood from type O donors contains plasma and therefore may contain a concentration of anti-A and anti-B antibodies that can cause destruction of the recipient’s type A or B RBCs. A strategy to mitigate this issue is either to transfuse only type-specific whole blood or to test donors or, more commonly, donor blood in advance to identify those with a “low titer” for anti-A and anti-B antibodies. Donors with a titer less than 256 saline dilution (immediate spin method) are designated low titer O universal whole blood (LTOWB) donors. A recent study showed LTOWB does not cause hemolysis when used in resuscitation of non–group O civilian trauma patients when up to 4 units are given. LTOWB may be fresh (fresh whole blood, FWB) or stored (stored whole blood, SWB).

The use of LTOWB was standard practice in wartime settings for decades. In civilian practice in the United States, however, it has generally been unavailable and rarely used, comprising less than 1% of transfusions. More recently, interest in the use of whole blood has been growing, including the use of banked and fresh warm whole blood, despite the associated logistic hurdles. In wartime settings, individuals designated as low-titer could be called upon to donate FWB acutely if needed. In the civilian setting, SWB is used on an as needed basis.

Management

Decision Making

Considerations in patient selection for blood product transfusion in the emergency care setting include the cause of the deficit, severity of symptoms, likelihood of ongoing hemorrhage, tissue oxygen requirements, and the patient’s ability to compensate for decreased oxygen-carrying capacity. These considerations are influenced by the patient’s age, underlying medical conditions, and hemodynamic stability. Clinical evaluation, including appearance (pallor, diaphoresis), mentation, heart rate, blood pressure, and nature of the bleeding (active, controlled, uncontrolled), as well as laboratory evaluation all inform transfusion decision making.

Pharmacology

PRBCs are administered through a filter and an intravenous (IV) line or intraosseous (IO) line, along with normal saline. No other in-line solutions should be utilized, unless approved for this purpose. For example, combining calcium containing fluids, such as lactated Ringers solution, with PRBCs can cause clotting in the line as the calcium binds with the citrate which is added to the PRBCs to act as an anticoagulant. Of note, this concern for clotting was mostly established in laboratory studies, and over the last 20 years there is anesthesiology literature that suggests that this clotting is not seen in clinical practice given the rapidity of administration and the PRBC to lactated Ringers ratios used. Nonetheless, no large study has demonstrated the safety of this practice, and therefore it is not routinely recommended. Dextrose containing fluids should also be avoided because the PRBCs may take up the dextrose, which causes osmotic shifts that can lead to cell lysis. Likewise, medications should not be added or pushed through the blood component transfusion line. There is growing literature demonstrating that some medications may be compatible with PRBC administration, and local guidelines or clinical pharmacist input is prudent if medication administration is necessary through the same line as a PRBC transfusion.

Devices and Techniques

Urgent or emergent transfusion requires flow rates faster than gravity can provide. An administration set with an in-line pump that is squeezed by hand is the simplest method to speed infusion. Pressure bags and rapid infusion devices are commercially available for clinical scenarios that require infusion of units of PRBCs within a matter a minutes. With high-pressure infusion, large-bore catheters are recommended so that hemolysis is prevented, however the literature supporting this recommendation is sparse.

Whole Blood

Reports on the successful use of FWB in military field hospitals have been published. In civilian practice in the United States, however, it has generally been unavailable and rarely used. The military experience with using whole blood dates back to World War I where type-specific, crossmatched blood was used in combat. This was almost 25 years before Rh typing was developed. The use of citrate phosphate dextrose (CPD) or citrate phosphate double dextrose (CP2D) can allow for safe preservation of SWB for 21 days at 1°C to 6°C. The use of citrate phosphate dextrose adenine (CPDA-1) at 1°C to 6°C can increase storage time to 35 days. Owing to time dependent degradation of clotting factors and platelets, whole blood older than 2 weeks may require the addition of fresher whole blood or supplemental platelets to avoid contributing to coagulopathy.

When PRBCs, plasma, and platelet transfusions in the 1 : 1 : 1 ratio are used, the mixture is significantly more diluted than when SWB is transfused. Average hematocrit and platelet count in 1 : 1 : 1 mixtures were 29% and 90 K/μl, respectively, when compared to 35% to 38% and 150 to 200 K/μl with SWB. Coagulation factors were also higher in SWB transfusions.

Current studies show that the use of SWB results in outcomes at least as good as component (RBC + plasma + platelet) therapy in hemorrhaging patients. We recommend the use of whole blood when available. Although the shelf-life of whole blood is shorter than component therapy, it can still be cost-effective owing to the higher cost of separating blood into components. The argument for using SWB early in the resuscitation process can be summarized as follows: ^,

SWB provides a physiologic balance of blood components that are simultaneously transfused.
A smaller volume of anticoagulant/preservative solution is transfused with SWB.
Platelet function in SWB may be significantly enhanced compared to component therapy.
Higher levels of hemostatic factors are delivered with SWB.
Fibrinogen delivery is higher when utilizing SWB, as FFP does not deliver significant amounts of fibrinogen.
Hemolytic transfusion reaction rate in SWB is low (about 1 : 120,000), therefore transfusions are generally safe and confer fewer donor exposures compared with component therapy, such as 1 : 1 : 1 protocols.
Administration of all components together in one unit can improve the time to complete a transfusion.
Errors associated with transfusion of type-specific blood can be minimized.

One potential complication from the lack of Rh typing in LTOWB, is the possibility of isoimmunization causing hemolytic disease of the newborn. Premenopausal women who receive LTOWB are potential candidates for anti-D immunoglobulin (Rhogam) and consultation with obstetrics.

Autotransfusion may also be used in the emergency setting in the event of severe chest trauma. A large retrospective trial showed it to be both safe and effective. Autotransfusion is the process of giving a patient back his or her own blood that has been collected from an uncontaminated active bleeding site. This is most frequently done using blood from the thorax after trauma. This strategy has numerous advantages—immediate availability, blood compatibility, elimination of donor to patient disease transmission, lower risk of circulatory overload, and fewer direct complications related to the transfusion itself, such as hyperkalemia, hypothermia, hypocalcemia, or metabolic acidosis. It is also more acceptable to patients whose religious convictions prohibit non-autologous transfusions. It is impractical in some settings owing to a relatively limited number of appropriate trauma patients, specific training required to operate the equipment, and time required for equipment setup.

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