Blood Banking¹¹

Although traditional allogenic donation methods still predominate, increasing use is being made of red cell apheresis technology (about 10% of all units donated), by which red cells are separated from the blood at the time of collection, with everything else returned to circulation. This allows collection of about two transfusable units during a single donation. Autologous blood collection, in which the donor is also the intended recipient, peaked in the early 1990s and continues to decline.¹¹

Red blood cell (RBC) storage methods aim to ensure viability of at least 75% of the cells 24 hours after infusion.¹² Blood collection bags contain an anticoagulant preservative of citrate, phosphate, dextrose, and adenine (CPDA-1), ensuring a shelf life of 35 days and hematocrit of 70 to 80% for PRBCs. Additive solutions (Adsol, Nutricel, Optisol) provide additional nutrients, extending maximum storage to 42 days and lowering viscosity, which makes infusion easier.¹³

Storage, however, impairs red cell function.¹⁴ Stored blood initially delivers oxygen to the tissues less efficiently. Although PRBCs are maintained at 1 to 6° C, cell metabolism continues, and changes occur. These changes are collectively referred to as the “storage lesion.”¹⁴ Documented alterations are numerous and include a decrease in both pH and the level of 2,3-diphosphoglycerate (2,3-DPG). In addition, the deformability of stored RBCs changes over time, making them more spherical and rigid, increasing resistance to capillary flow. After infusion, however, many of these changes are readily reversed. The decrease in 2,3-DPG, for example, results in a left shift in the Hgb-oxygen dissociation curve, but 2,3-DPG levels begin to recover within minutes and are fully restored within 24 hours.¹⁵ Further complicating the issue, the relationship between overall oxygen transport and oxygen delivery to tissues is complex. Depletion of S-nitrosohemoglobin during storage, for example, alters oxygen-dependent regulation of microcirculatory blood flow (“hypoxic vasodilation”).¹⁶ Research and debate are ongoing with regard to whether and when these and other changes are clinically significant, and how they might be addressed.^17–20

Additional well-established changes in stored blood include cell leakage of potassium, although the amount (approximately 6 mEq/U) is readily tolerated by most otherwise healthy patients. PRBCs contain essentially no functional platelets or granulocytes.²¹

Blood Typing

The appropriate ordering of blood bank products and services is facilitated by a basic understanding of compatibility testing, which identifies clinically significant blood antigens and antibodies.

When a clinician anticipates that transfusion might be indicated, a type and screen is often ordered. A blood specimen from the patient is then sent for the following tests: ABO grouping, Rh typing, and an antibody screen for unexpected antibodies (non-ABO/Rh antibodies). Completion of these steps speeds the delivery of crossmatched blood if it is subsequently required.

Identified RBC antigens include the ABO and related carbohydrate antigens (H, P, I, and Lewis), the 48 Rh system antigens, and more than 200 non-ABO/Rh antigens. ABO incompatibility results in acute hemolysis, the most serious transfusion reaction.

ABO grouping requires that the recipient’s red cells be tested with anti-A and anti-B serum and that his or her serum be tested with A and B red cells. At about 6 months of age, patients form antibodies against the A and B antigens they lack. Those with type AB blood form no ABO group antibodies. Patients with type O have antibodies against both. The major clinically significant Rh antigen is the D antigen. Rh typing is usually done by adding a commercial reagent (anti-D) to recipient RBCs.¹²

The antibody screen identifies unexpected antibodies in the patient’s serum. These result from prior exposure to foreign RBC antigens during allogenic transfusion or pregnancy. The antibody screen entails mixing commercial RBC reagents (mixtures of red cells expressing clinically significant antigens) with the patient’s serum. The incidence of these unexpected antibodies in the general population is low (<1-2%), but a positive screen prompts further compatibility testing, which can take hours to days. When transfusion is delayed by a positive antibody screen in a critically ill patient, clinicians should communicate directly with the blood bank to determine the best course of action. Although ABO compatibility is mandatory in all patients, non-ABO antigens are very unlikely to cause immediate intravascular hemolysis.15,21,22 Administering blood that is not completely crossmatched is therefore an option if the need is emergent.

The type and screen allows for quicker selection of appropriate banked blood for complete crossmatch if a transfusion is later ordered.

When a unit of blood is ordered for transfusion, a crossmatch is done. In an ideal situation, blood identical to the patient’s own ABO and Rh group is used. Local blood supplies, however, might dictate that a nonidentical but compatible unit be used. Patients with blood group AB (who lack anti-A and anti-B antigens), for example, are “universal recipients”—they can receive blood from any of the ABO groups. Type O blood (lacking the A and B antigens), also known as “universal donor” blood, conversely, can be given to anyone. Rh compatibility is also important. Rh sensitization can occur in Rh-negative patients exposed to Rh-positive blood, and this sensitization in turn can result in hemolytic disease of the newborn with subsequent pregnancies.

The traditional crossmatch requires mixing recipient serum with donor RBCs and observing for agglutination as a final compatibility test before transfusion. If the antibody screen is negative, an “immediate spin crossmatch” at room temperature serves as a final check for ABO incompatibility. A “complete crossmatch” is generally done before transfusion if the antibody screen is positive. This requires incubation to 37° C and the addition of antihuman globulin (Coombs’ reagent) to promote agglutination.¹³ Many blood banks also substitute a “computer crossmatch” for patients whose blood has been tested at least twice within their system. Decisions about which method is used, however, are generally made by the blood bank, not the clinician.

Special Clinical Circumstances

To select the most appropriate blood products in the emergency setting, clinicians should consider the patient’s hemodynamic stability, the likelihood of ongoing hemorrhage, and the amount of time available to intervene. When time is short, waiting for fully crossmatched blood may result in a dangerous delay, and alternatives should be considered. When the clinician anticipates large and ongoing blood losses, complications resulting from massive transfusion are a concern as well.

Massive Transfusion

Massive transfusion has no formal definition. Administration of at least 10 units of RBCs in 24 hours is a commonly used cutoff.²⁵ Although patients receiving any amount of blood are susceptible to a variety of infectious, physiologic, and immunologic insults, this section will discuss those uniquely associated with massive transfusion.

Some of these complications are well understood and easily managed. Hypothermia is common in these patients, and can reduce clotting factor activity.²⁶ Warmed intravenous fluids, blood warmers, and warming lights and blankets are often needed. Frequent laboratory testing will identify electrolyte disturbances (low magnesium and calcium, and both high and low potassium), which are in general treated in a standard fashion by replenishing deficits, or administering calcium for hyperkalemia. Acidosis is a common finding with massive hemorrhage but can also be caused by hypoperfusion, and the contribution of transfused blood to acidosis is felt to be variable. Citrate from banked blood, for example, is metabolized in the liver to bicarbonate, which can sometimes result in metabolic alkalosis. With rapid infusion or reduced hepatic function, however, this pathway can be overwhelmed, and the net effect of infusing large amounts of citrate can be worsening metabolic acidosis. A rational response to metabolic acidosis is to optimize oxygen delivery and ventilation. Administering sodium bicarbonate may be considered in severe cases, but the benefits are less certain.²⁷

Patients receiving massive transfusion are also prone to coagulopathy and thrombocytopenia. Consumption and dilution of clotting factors and platelets occur in these patients owing to ongoing hemorrhage, fluid boluses, and transfusion of PRBCs. This undoubtedly plays a role in the coagulopathy of trauma, but recent research asserts that coagulopathy often occurs in massive trauma even before these mechanisms have taken effect.28–30 A number of reports (none of them from randomized prospective trials) have stated that a more proactive approach to administering plasma and platelets in massive transfusion is associated with better outcomes.^31–43 In response, many institutions have adopted massive transfusion protocols that call for plasma (and often platelets) to be given in a 1 : 1 ratio with RBCs.⁴⁴ When set ratios are not used, clinical assessment and judgment often augment laboratory values such as international normalized ratio (INR), partial thromboplastin time (PTT), and fibrinogen and platelet counts because there is no direct evidence supporting any particular threshold for platelet or coagulation factor replacement in patients with severe hemorrhage.⁷ Commonly recommended goals in this setting would be to consider maintaining an INR below 1.5, a fibrinogen level greater than 1 to 2 g/L, and platelet count above 50,000 to 100,000/µL.^7,45

Administration

Decision-Making

In considering the use of blood component therapy, the patient’s age, severity of symptoms, cause of the deficit, underlying medical condition, ability to compensate for decreased oxygen-carrying capacity, and tissue oxygen requirements are all important. Clinical evaluation, including appearance (pallor, diaphoresis), mentation (alert, confused), heart rate, blood pressure, and the nature of the bleeding (active, controlled, uncontrolled), can be supplemented by laboratory evaluation.

A review of relevant literature supports the recent trend toward more conservative red cell transfusion triggers but also highlights the need for further investigation.⁴⁶ The same can be said for FFP and other blood components.^47,48 Benefits of transfusion have been difficult to prove,⁹ and the list of known and suspected associated risks is long and growing.⁴⁹