14. Blood Component Therapy

CHAPTER 14. Blood Component Therapy

Nancy L. Trick, RN, CRNI®





Blood Storage and Preservation, 243


Immunohematology, 244


Preparation and Clinical Application of Blood Components, 245


Administration of Blood Components, 248


Blood Component Therapy in Severe Sepsis and Septic Shock, 249


Special Equipment, 249


Adverse Effects, 254


Autologous Blood Transfusion, 260


Summary, 261


This chapter provides a foundation on which to construct a broader understanding of the more encompassing subject of transfusion therapy. The topics addressed here are not intended to be all-inclusive of the discipline of transfusion therapy, nor are they offered as a “how to” manual. They are intended to establish a firm theoretical footing and a practical framework on which the practitioner may build.

It was fewer than 200 years ago that James Blundell performed the first blood transfusion to save a life. Since then, because of the incredible advances in knowledge and technology that have been made in blood group identification, collection, fractionation, storage, and transmissible disease testing, transfusion medicine has evolved into a specialty of its own. This specialty has made advances in new surgical procedures possible and has supported the ever-changing approaches to cancer chemotherapy.

Blood component therapy has advanced so far so fast and is so common in today’s medicine that there could be a tendency to approach this familiar therapy with some complacency. Therefore it should be remembered that blood infusion is a “living transplant” that carries with it significant risks, only a few of which are avoidable. Consequently, this effective and readily accessible therapy should be used prudently; the potential benefit should always outweigh the potential for harm. Furthermore, it is the practitioner’s duty in transfusion therapy to be knowledgeable in the application of this therapy and to be familiar with its possible untoward effects and their appropriate interventions.


DONOR TESTING


The American Red Cross began testing for syphilis in the United States in 1948, and since 1985 has been testing for HIV/AIDS. All blood donated for the purpose of homologous transfusion must be subjected to a number of tests (Table 14-1).






























































TABLE 14-1 Testing of Donor Blood
HBV, hepatitis B virus; RBC, red blood cell.
No longer required but included by many centers.
Test To determine
ABO—forward typing Presence of antigen A or B on RBC
ABO—reverse typing Presence of antibody A or antibody B in plasma
Rh typing:
With anti-D sera Presence of D antigen on RBC
With anti-D sera or with indirectantiglobulin test Presence of weak D antigen
Screen for unexpected antibodies Presence of antibodies other than anti-A and anti-B
Screen for transmissible disease:
Serologic test for syphilis Treponema infection
Hepatitis B surface antigen Infectivity for hepatitis B
Hepatitis C (anti-HCV) Infectivity for hepatitis C
Hepatitis B core antibody May indicate HBV carrier
Alanine aminotransferase Indicates liver damage
Human immunodeficiency virus (HIV):
Enzyme-linked immunosorbent assay Presence of antibody to HIV-1 and HIV-2
HIV antigen Presence of antibody to HIV virus
Human T-cell leukemia/lymphoma virus I (HTLV-I) Presence of antibody to HTLV-I/II


ABO AND RH TYPING


ABO forward typing is the process in which red blood cells are mixed with a known antibody (anti-A or anti-B). This process identifies the antigens present on the red blood cells by the visually apparent agglutination of the cells when an antibody combines with the corresponding antigen (e.g., anti-A with antigen A).

ABO reverse typing tests serum for the presence of predicted ABO antibodies by adding red blood cells of a known ABO type.

The Rh factor is the red cell antigen D. Rh typing is accomplished by testing red cells against anti-D serum. If agglutination occurs, the red cells possess the D antigen and the blood is Rh positive. Some people demonstrate a weak expression of the D antigen (formerly referred to as D U). In the past, laboratory testing to identify this weak D antigen included the indirect antiglobulin test. However, that test is no longer necessary in most cases because licensed anti-D reagents are sufficiently potent to identify patients with a weak expression of the D antigen as Rh positive. These individuals are considered Rh positive as donors and recipients.

Additional testing for red cell antigens is not recommended or encouraged by the AABB, formerly known as the American Association of Blood Banks.


SCREENING FOR UNEXPECTED ANTIBODIES


Unexpected antibodies are those other than anti-A or anti-B. Many blood banks screen all donated units for clinically significant antibodies rather than limiting their search to the donor group most likely to harbor them. The most likely donors of blood with unexpected antibodies are those with a history of pregnancy or previous transfusion. In general, clinically significant antibodies are those known to have caused hemolytic disease of the newborn, a frank hemolytic transfusion reaction, or unacceptably short survival of transfused red blood cells (Roback et al, 2008).


SCREENING FOR TRANSMISSIBLE DISEASE


All donor blood must be tested to detect units that might transmit disease (Klein and Anstee, 2005). Components and whole blood units must not be used for transfusion unless all tests are nonreactive, are negative, or have values within normal limits.




• Test for syphilis using a serological test as required by the U.S. Food and Drug Administration (FDA).


• Test for the presence of the hepatitis B surface antigen to identify hepatitis B infectivity.


• Test for the presence of the antibody for hepatitis C virus (HCV).


• Test for the presence of the hepatitis B core antibody. This component of the hepatitis B virus (HBV) testing may indicate an HBV carrier state.


• Alanine aminotransaminase (ALT) is a serum enzyme that, if elevated, can signal liver malfunction. This test is no longer required by the AABB, but many blood centers still perform it.


• Test for the presence of the antibody to human immunodeficiency viruses 1 and 2 (anti–HIV-1/2). A positive result using the standard screening methods necessitates a repeat standard screen and then a confirming screen using a more specific assay. In addition to this enzyme-linked immunosorbent assay (ELISA) to detect antibody, all blood must be tested for the presence of HIV (HIV-1 antigen test).


• Test for the presence of the antibody to the human T-cell lymphotropic viruses 1 and 2 (HTLS-1/2). (See Adverse Effects later in this chapter.)


Donor screening


Donors are required to answer questions that may have a bearing on the safety of their blood. For example, donors with a history of intravenous drug abuse are routinely deferred. Since November 1999, the FDA has requested the blood industry to defer potential donors who had lived in European countries with reported or suspected cases of bovine spongiform encephalopathy (BSE), the “mad cow disease,” and who therefore might be carriers of the BSE agent.


Donor lists


Blood collection centers must keep current a list of deferred donors and use it to make sure that they do not collect blood from anyone on the list. Donated blood must be quarantined until it is tested and shown to be free of infectious agents. To ensure a safe blood supply, blood collection centers must investigate manufacturing problems, correct all deficiencies, and notify the FDA when product deviations occur in distributed products.


BLOOD STORAGE AND PRESERVATION


Because blood is a living tissue at the time of its harvest from a donor and because it must remain healthy during its storage, substances are added to meet two conditions necessary for successful shelf life:




1. A food source must be provided to maintain adequate nutrition to the stored cells.


2. Anticoagulation must be achieved to ensure that the blood remains in its liquid cellular state for the duration of the storage period.

Several anticoagulants-preservatives are available from which to choose. All of them provide the aforementioned necessary conditions for shelf life, but they differ in the length of storage time that they provide (Table 14-2).




















TABLE 14-2 Anticoagulants-Preservatives
Anticoagulant-Preservative Composition Shelf life provided (days)
CPD Citrate, phosphate, and dextrose 21
CPDA-1 CPD plus adenine 35
Additive systems CPD plus various preservative combinations 35–42

CPD (citrate-phosphate-dextrose) and CPDA-1 (citrate-phosphate-dextrose-adenine) differ in composition by just one substance—adenine. However, the addition of adenine extends the shelf life by 14 days and is of great significance to a blood transfusion service whose concern revolves around adequate blood reserves and their ability to supply upon demand. CPDA-1 is considered the anticoagulant-preservative of choice for whole blood and is also used when the donated unit may be processed into separate components.

The additive solutions, commonly called adenine-saline, are approved by the FDA for the extended storage of red blood cells. These solutions differ in composition by manufacturer. However, there is a limited menu from which these compounds are made. They contain various combinations of 0.9% sodium chloride, adenine, dextrose, phosphate, citrate, and mannitol. These additives allow red cells to be stored for up to 42 days. The additive solutions, which are secondary or “add-on” solutions, are used only with red cells that were harvested in a primary anticoagulant-preservative such as CPD. The red cells are then separated and mixed with the additive solutions.


ANTICOAGULANTS AND PRESERVATIVES


The following is a brief summary of the substances that preserve blood:




Citrate: Sodium citrate by itself, or sometimes in combination with citric acid, achieves anticoagulation by inhibiting several calcium-dependent steps in the coagulation cascade. It also slows the process of glycolysis, which is the conversion of glucose to lactic acid and adenosine triphosphate (ATP) through various metabolic pathways (Embden-Meyerhof, Krebs cycle, and the electron transport system). Slowing glycolysis allows adequate amounts of ATP to continue to be produced and the limited supply of sugar in the stored cells to be preserved.


Phosphate: Inorganic phosphate acts as a buffer that helps maintain the pH.


Dextrose: When sugars were first investigated as possible participants in blood preservation, red blood cells were thought to be impermeable to them. Therefore it was theorized that sugar would act as a colloid to protect the cells against hemolysis. It was soon recognized that red blood cells are permeable to dextrose and that this was an excellent food source for the stored cells (Klein and Anstee, 2005). Dextrose is a deterrent to hemolysis, but not because of a colloidal action. It supplies the food from which ATP, the principal intracellular energy-storage compound, is formed. Adequate supplies of ATP are necessary for the continued integrity of the cell.


Adenine: Although other factors appear to be involved, the ATP content of stored red blood cells generally can be equated with their viability (i.e., their capacity to survive in the recipient’s bloodstream after transfusion). In the 1950s, it was shown that the ATP content of stored cells could be restored by adding adenosine, which consists of adenine and the five-carbon sugar ribose. However, because of its toxicity, adenosine was never used in transfusion practice. Later it was discovered that adding adenine by itself accomplishes the same positive result of restoring ATP levels in stored red cells (Klein and Anstee, 2005).


Mannitol: Mannitol, which appears to reduce hemolysis by its effect as an osmotic stabilizer, is found in at least one of the additive systems.


REJUVENATION OF RED CELLS


Red cells that have been stored up to 3 days beyond their expiration dates can be incubated (at 37° C for 1 hour) in FDA-approved solutions containing inosine, pyruvate, phosphate, adenine, and sometimes glucose. This incubation will increase the cellular levels of ATP and 2,3-diphosphoglycerate (2,3-DPG). These rejuvenated cells may be washed and used within 24 hours, or they may be glycerolized and frozen for extended storage (Roback et al, 2008).


IMMUNOHEMATOLOGY


Immunology is the scientific discipline that deals with the immune system and immune response (antibody response to antigenic stimulus). Immunohematology narrows the view of immunology to focus specifically on the antigens and antibodies of the blood.

The antigens of the blood, called agglutinogens, are found as integrated parts of the red cell membrane, as components of the white cells, and as soluble substances in the plasma. The largest group of agglutinogens, which numbers more than 400 belonging to 24 known systems, is associated with red cells.

The first set of red cell antigens discovered, those of the ABO system, was identified by Landsteiner at the turn of the twentieth century. The ABO system is the most important of the known antigen systems and is the foundation for determining compatibilities in transfusion therapy.


THE ABO SYSTEM


There are four blood types in the ABO system: A, B, AB, and O. The name of the blood type is determined by the name of the antigen on the red cell. The type of antigen present on the red cell is an inherited characteristic; the A and B genes are equally dominant, and the O gene is recessive (Table 14-3).


































TABLE 14-3 ABO Blood Groups
Possible genotypes Phenotype Blood group Red blood cell antigen Plasma antibody
OO O O Neither A nor B A and B
AA or AO A A A B
BB or BO B B B A
AB AB AB A and B Neither A nor B

The A and B genes dictate the presence of A and B antigenic determinant sites, respectively. Although the O gene is inactive and does not code for any of the erythrocyte alloantigens, blood group O erythrocytes do exhibit an antigenic glycoprotein on their surface—the H antigen. This glycoprotein is not the product of the O gene, as evidenced by its presence on red blood cells of all types.

The relationship between the A, B, and H antigens can be explained as follows. During the synthesis of the blood group molecules, the H antigen is synthesized first; thus the H antigen is present on all red cells. If the A gene is present, it will code for a transferase (enzyme), which will facilitate the attachment of the sugar N-acetylgalactosamine to the H antigen. This chemical complex is the antigenic determinant for blood group A. Similarly, the B gene will code for a different transferase that will allow for the attachment of an alternate sugar group, d-galactose, which will complete the antigenic determinant for blood type B. Group O individuals do not possess either enzyme system, and thus group O erythrocytes possess only the unmodified H antigen on their surface (Smith, 2001 and Roback et al, 2008). The antibodies of the ABO system occur naturally (i.e., without direct antigen stimulation) and are called isohemagglutinins. They are complete, and in the presence of red cells that exhibit the corresponding antigen; they can cause agglutination in a 0.9% sodium chloride medium. The antibody that agglutinates type A is called antibody A (anti-A), and the corresponding antibody for antigen B is called antibody B (anti-B).

This adversarial relationship between antigen and the corresponding antibody is the basis for understanding compatibilities within the ABO system. The antigens are located on the cells, and the antibodies reside in the plasma. If a unit of red cells is to be administered it should be thought of as an antigen and should be given only to a recipient who does not exhibit the corresponding antibody. Conversely, plasma should not be given to a recipient who possesses the corresponding red cell antigen (Table 14-4).















































































TABLE 14-4 Summary of Compatibilities
Component Compatibilities
Whole blood Give type-specific blood only
Packed red cells (stored, washed, or frozen/washed) Donor Recipient
O O, A, B, AB
A A, AB
B B, AB
AB AB
Fresh-frozen plasma Donor Recipient

O O

A A, O

B B, O

AB AB, B, A, O
Platelets RBC: ABO and Rh compatible preferred

Donor Recipient

O O, A, B, AB

A A, AB

B B, AB

AB AB
Cryoprecipitate Plasma: ABO compatible preferred

Donor Recipient

O O

A A, O

B B, O

AB AB, B, A, O


THE RH SYSTEM


The Rh system is complex and extensive. Because nearly 50 Rh antigens have been identified, a complete discussion of this system is not included here. Sufficient for the topic of routine transfusion therapy are the unmodified terms of Rh+ (Rh positive) and Rh− (Rh negative), which respectively refer to the presence or absence of the red cell antigen D.

The blood recipient who carries antigen D (Rh positive) may receive products that are either Rh+ or Rh−. However, a recipient who is Rh negative should receive only blood products that are Rh negative. This is especially true for Rh-negative women of childbearing age who might become sensitized to the D antigen, which could raise the potential for complications in subsequent pregnancies.


THE HLA SYSTEM


The HLA blood grouping system consists of a series of highly immunogenic antigens that can be found predominantly on the cells of the leukocyte family. These antigens exist on the surface of the lymphocytes, granulocytes, monocytes, and platelets. Although the HLA antigens and their precipitated antibodies are best known for their role in transplantation rejection, they also contribute to several of the complications of transfusion therapy, including the following:




• Febrile nonhemolytic reaction (FNH)


• Immune-mediated platelet refractoriness


• Transfusion-related acute lung injury (TRALI)


• Transfusion-associated graft-versus-host disease (TA-GVHD)


PREPARATION AND CLINICAL APPLICATION OF BLOOD COMPONENTS



WHOLE BLOOD


Whole blood requires no processing beyond collection into an anticoagulated closed collection system and testing. It is stored at 1° to 6° C with the satellite pack attached. If packed cells are needed at any time during the shelf life of the blood, this satellite pack will allow for their separation within a closed system. However, because whole blood transfusions are rarely used except to treat massive blood loss, most homologous donations are not stored as whole blood but are separated into components soon after donation. Autologous donations, which are planned to be transfused back to the donor within the shelf life period for refrigerated blood, are stored whole. These units are often given as whole blood. They can be spun down and given as packed cells if the donor-recipient does not need or cannot tolerate the additional volume that the plasma represents.

Clinical applications for the administration of whole blood include the following:




• When increased oxygen-carrying capacity and volume expansion are needed


• When active bleeding has resulted in a 25% to 30% blood volume loss


• When exchange transfusion is performed

Although whole blood may be appropriate for the preceding clinical situations, it is not always readily available. Therefore the use of packed red cells in combination with asanguineous solutions has become the standard when replacement therapy is needed in surgery or trauma cases (Klein, Spahn, and Carson, 2007 and Roback et al, 2008).


PACKED RED BLOOD CELLS


Packed red blood cells are prepared by separating the plasma from the cellular portion of a unit of whole blood. This can be done any time before the expiration date. Cells can be separated from plasma by centrifuge, which causes a rapid separation, or by sedimentation, in which cells will settle to the bottom of an upright container and the plasma will concentrate on top. Once separation has occurred, 200 to 250 mL of plasma can be manually expressed into the attached satellite bag.

The shelf life of a unit of packed red blood cells (PRBCs) is the same as that for the unit of whole blood from which it was obtained, but it can be extended if an additive system is mixed with the cells at the time of their separation (see previous discussion under Anticoagulants and Preservatives). These additive solutions, which must be added within 72 hours of the blood donation, extend the shelf life of the packed cells from 35 to 42 days.

PRBCs are used for routine blood replacement during surgery and to increase the oxygen-carrying capacity (i.e., the red blood cell mass) in patients with symptomatic anemia that cannot be treated with pharmaceuticals.


MODIFIED PACKED RED BLOOD CELLS



0.9% sodium chloride–washed red blood cells


The 0.9% sodium chloride washing of red blood cells (RBCs) is carried out in the blood bank using automated or semiautomated equipment. The washed cells are suspended in sterile 0.9% sodium chloride solution. The processed product has a hematocrit of 70% to 80%. This process removes platelets and cellular debris, diminishes plasma to trace levels, and reduces the number of leukocytes. It should be noted that the leukocytes are not eliminated, so this component does contain viable lymphocytes and it can precipitate the graft-versus-host response. Stored packed cells may be washed at any time during the shelf life. However, because the washing is performed in an open system, their shelf life at 1° to 6° C is only 24 hours after washing. This limited shelf life is imposed because of concerns for bacterial contamination; washed red cells are not considered free from the risk of disease transmission.

Washed packed cells are used for patients with recurrent or severe allergic reactions thought to be related to one or more plasma proteins and for neonatal and intrauterine transfusions.


Frozen-deglycerolized packed cells


Two decades ago, there were many reasons for freezing blood, but they have diminished over time because of improved technologies. Today, blood is frozen for one reason: long-term storage. For autologous blood, this extended storage capacity means that blood can be stored well beyond the 42-day shelf life afforded by refrigeration. This permits scheduling of elective surgical procedures well in advance and allows the donation of enough blood to provide for the safety of autologous transfusion.

In addition to its application in autologous transfusion, blood is frozen to maintain stores of rare blood types. AABB’s Standards for Blood Banks and Transfusion Services allows frozen blood intended for routine transfusion to be stored for up to 10 years (AABB, 2008). A policy should be developed if rare frozen units are to be retained beyond this time.

Blood that is to be frozen may be collected in CPD or CPDA-1 solutions and stored as whole blood. It can also be stored as packed cells with or without an additive system. Most often, blood is glycerolized and frozen within the first 6 days after donation. Glycerol is added to the cells before freezing because it is a cryoprotective agent that prevents cell dehydration and mechanical damage from ice formation. Although the first 6 days after donation is the usual window in which to freeze blood, red cells nearing the end of their shelf life may be rejuvenated for up to 3 days after expiration and then frozen. PRBCs preserved in adenine-saline solutions may be frozen up to 42 days after donation. These options help eliminate unnecessary waste of valuable blood stores. Frozen blood is maintained at −65° C or colder (Roback et al, 2008).

When a unit of frozen blood is needed, it is first thawed in a water bath (37° C) or a dry warmer (37° C). It is then washed to remove the glycerol, which is hypertonic to the blood. The washing process used to deglycerolize red cells is the same as that used to process washed red cells.

As with 0.9% sodium chloride–washed packed cells, there are concerns for bacterial contamination with frozen-deglycerolized cells. This product must be infused within 24 hours of processing. Also, as is true with washed packed cells, frozen-deglycerolized cells are not considered free from the risk of disease transmission. Clinical applications for frozen-deglycerolized red blood cells are the same as those for washed PRBCs.


Leukocyte-filtered red blood cells


Leukocyte-filtered RBCs, also known as leukocyte-reduced RBCs, are indicated for patients who have experienced repeated febrile nonhemolytic reactions associated with the transfusion of red cells or platelets (see discussion under Adverse Effects: Acute Effects). They should also be used as prophylaxis against alloimmunization in selected patients who are expected to receive long-term blood component therapy and for recipients who are at risk for post-transfusion cytomegalovirus (CMV) infection.

Leukocyte-reduced packed cells can be prepared in the blood bank by centrifugation and filtration and by automated 0.9% sodium chloride washing of liquid or previously frozen blood. In the past, frozen and washed packed cells, which have a 95% to 99% reduction in leukocytes, were considered the components of choice when white blood cell reduction was indicated. However, the newer generations of leukocyte filters, which are more efficient in terms of leukocyte reduction and less costly, have made leukocyte-filtered components the products of choice. The cells may be filtered during the initial processing of red cells before storage or during transfusion using an in-line filter (Dzik et al., 2000, Nordmeyer, Forestner, and Wall, 2007 and Roback et al, 2008). The AABB Technical Manual states that in all clinical applications of leukocyte-reduced products, prestorage leukocyte-filtered components are recommended over those that are filtered during transfusion (Dzik et al., 2000, Nordmeyer, Forestner, and Wall, 2007 and Roback et al, 2008).

Clinical applications for leukocyte-reduced red blood cells include the following:




• Patients with repeated febrile nonhemolytic transfusion reactions


• Patients at risk for HLA alloimmunization who may face hemotherapy


• Patients at risk for post-transfusion CMV infections


GRANULOCYTES


Granulocytes are usually prepared by leukopheresis. This blood component also contains other leukocytes, platelets, and some red cells in 200 to 300 mL of plasma. They should be transfused as soon as possible after collection but may be stored at 20° to 24° C without agitation for up to 24 hours (Roback et al, 2008).

The use of granulocyte transfusion in adults is rare. When this therapy is used, the recipient is usually severely neutropenic with documented infection that is unresponsive to aggressive antibiotic therapy. The candidate for granulocyte transfusion should meet the following three conditions:




1. Neutropenia (granulocyte count less than 500/μL)


2. Fever for 24 to 48 hours, unresponsive to appropriate antibiotic therapy, or bacterial sepsis unresponsive to antibiotics or other modes of therapy


3. Myeloid hypoplasia

In the pediatric population, granulocyte transfusion has been used in conjunction with antibiotic therapy for severe bacterial neonatal sepsis. Although controversy surrounds this choice of therapy, there appear to be clinical situations in which granulocyte transfusion can supplement antibiotics. The AABB (Roback et al, 2008) states that pediatric candidates for granulocyte transfusion are infants with all of the following conditions:




• Strong evidence of bacterial septicemia


• An absolute neutrophil count below 3000/μL


• A diminished marrow storage pool

Granulocytes should come from CMV-negative donors because they cannot be given though a leukocyte filter to reduce the risk of CMV transmission. Granulocytes should also be irradiated to reduce the risk of GVHD.


FRESH-FROZEN PLASMA


Fresh-frozen plasma (FFP) is prepared by removing the plasma from a unit of whole blood and freezing it within 6 hours of collection. The storage time for FFP is 1 year at 18° C or colder. This component, if kept frozen and then thawed in a warm water bath (30° to 37° C) just before use, is an excellent source of all clotting factors, including the labile factors V and VIII and fibrinogen. The activity of these labile factors is lost when plasma is stored in the nonfrozen state (Roback et al, 2008).

FFP is indicated when clotting factors are needed for which a concentrate is not available, in the presence of severe liver disease where limited synthesis of plasma coagulation factors may be suspected, and when needed to counteract the effects of warfarin therapy (Box 14-1).

Box 14-1
CLINICAL APPLICATIONS FOR FRESH-FROZEN PLASMA







• For patients with active bleeding who have multiple coagulation factor deficiencies secondary to liver disease


• For patients with disseminated intravascular coagulation and evidence of demonstrated dilutional coagulopathy from large-volume replacement


• For patients with congenital factor deficiencies for which there are no concentrates (e.g., factors V and XI)


• For warfarin reversal


PLATELET CONCENTRATES


Platelet concentrates can be prepared by two methods: as single units from multiple donors or as multiple units from a single donor.


Multiple donors, single units


To prepare a single unit of platelet concentrate from multiple donors, a donated unit of whole blood that is less than 6 hours old and stored at room temperature is centrifuged to isolate the platelet-rich plasma. The platelet-rich plasma is then centrifuged at 20° C to separate the platelet concentrate from the now platelet-poor plasma. Fifty to seventy milliliters of plasma are allowed to remain with the platelet concentrate. After this second centrifugation, that which remains is a single unit of random-donor platelet suspended in plasma. The plasma will ensure that the platelets are kept at a pH of 6 or higher to maintain their viability during the 5-day storage period at 20° to 24° C.


Single donor, multiple units


Plateletpheresis is the harvesting of multiple units of platelets from a single volunteer donor. The quantity taken from a single donor is equal to approximately 6 units of random-donor platelets. The platelets are harvested by automated machines called cell separators. These separators isolate the blood component to be harvested as a concentrate, and those components not needed are returned to the donor.

Although plateletpheresis is an efficient way to obtain platelets, there are two reasons why this method is not used exclusively. First, there are several risks to the donor, including allergic reactions, chills, syncope, and citrate toxicity. The citrate toxicity is related to the anticoagulation of the donor blood, which is necessary before the blood is processed through the cell separator (Klein and Anstee, 2005). This anticoagulation, in varying amounts, is ultimately infused along with the returned components to the donor. The second reason that plateletpheresis is limited in its use is concern over its cost-versus-benefit ratio.

Single-donor platelets were traditionally used for patients who needed repeated platelet infusions and were at risk for alloimmunization to foreign leukocyte antigens (HLAs) present on leukocytes and platelets. Laboratory leukoreduction has made significant improvements in reducing the risk of alloimmunization.

Refractoriness is the state of being inadequately responsive to platelet transfusions. This occurs in about 20% to 70% of multitransfused thrombocytopenic patients and is more likely to be seen in patients being treated for malignant hematopoietic disorders (Roback et al, 2008).

There are both nonimmune reasons and immune-response causes for refractoriness. Some of the nonimmune causes of platelet refractoriness are active bleeding, sepsis, splenomegaly, disseminated intravascular coagulation (DIC), and antibiotic therapy. Of the possible immune-response causes, the presence of antibodies in the recipient to multiple HLAs is the most common precipitating factor. As explained earlier, alloimmunization to HLA is a direct result from previous exposure to white blood cells through transfusions. Therefore it has been recommended that all blood components containing white blood cells that are to be used for recipients requiring long-term transfusion support should be leukocyte reduced by filtration (Dzik et al, 2000). This would limit exposure to foreign HLAs and reduce the risk for alloimmunization and the majority of immune-response refractoriness. When these antibodies are known to be present, one approach is to transfuse multiunit platelets from a single donor.

The most suitable single-donor platelet preparation in cases of known HLA sensitization is the HLA-matched product, obtained by plateletpheresis from a volunteer donor who is HLA-matched to the recipient. Although this is a limited match (the donor and recipient have only some HLA antigens in common), this product is the most appropriate for the patient who has demonstrated unresponsiveness to platelet concentrates. HLA-matched platelets should be irradiated to prevent TA-GVHD (see Adverse Effects later in this chapter).

In addition to the HLA-matching approach to providing platelets in refractoriness, a second option is pretransfusion platelet crossmatching. This approach is predictive and can therefore avoid subsequent platelet transfusion failures. However, platelet crossmatching is not without shortcomings. When 70% or more of the donors are reactive to the recipient, finding enough compatible donors can be a problem (Roback et al, 2008).


CRYOPRECIPITATE (CRYOPRECIPITATED ANTIHEMOPHILIC FACTOR)


Cryoprecipitate is used to treat hypofibrinogenemia and factor XIII deficiency. Cryoprecipitated antihemophilic factor is prepared by slowly thawing a unit of FFP at 4° to 6° C and then recovering the cold precipitated protein by centrifugation. Once harvested, cryoprecipitate can be refrozen at −18° C or colder and stored for 1 year. This component is a rich source of the entire factor VIII complex, factor XIII, fibronectin, and fibrinogen—and it is the only source of concentrated fibrinogen (Table 14-5) (Box 14-2).
















TABLE 14-5 Factor VIII Complex
Factor Activity
VIII:C Procoagulant
VIII:Ag Immune reactant antigen
VIII:vWF von Willebrand’s factor: required for normal platelet function

Box 14-2
MAJOR INHERITED COAGULOPATHIES




HEMOPHILIA A (CLASSIC HEMOPHILIA)


This gender-linked inherited disorder is manifested in males but is transmitted by female carriers. The clotting factor deficiency in classic hemophilia is factor VIII:C. Commercial factor VIII concentrates provide factor VIII:C. In the past, cryoprecipitate was used to treat this deficiency. Today, it is used only if commercial virus-inactivated concentrates are unavailable.


VON WILLEBRAND’S DISEASE


This condition, the most common of the inherited coagulopathies (Table 14-6), is not gender linked and affects both sexes. All three of the measurable activities of the factor VIII complex are deficient in von Willebrand’s disease. However, it is the deficiency of factor VIII:vWF that is responsible for the capillary defect seen in this coagulopathy. von Willebrand’s factor is necessary for normal platelet function, and thus a diminished level of this factor will result in platelet dysfunction characterized by capillary defect.






















TABLE 14-6 Inherited Coagulopathies
Type Also known as Factor deficiency
Hemophilia A Classic hemophilia VIII:C
Hemophilia B Christmas disease IX
von Willebrand’s disease Vascular hemophilia or angiohemophilia VIII:CVIII:Ag


VIII:vWF

Mild cases of von Willebrand’s disease can be treated with DDAVP (desmopressin acetate), which is a synthetic analog of vasopressin. DDAVP appears to cause the release of endogenous stores of high-molecular-weight von Willebrand’s factor from the vascular subendothelium.

More severe cases of this disease are treated with virus-inactivated commercially prepared factor VIII concentrates. Although not all commercial concentrates contain therapeutic levels of vWF, there are a limited number that meet this need. If the appropriate commercially prepared product is unavailable, severe cases may be treated with cryoprecipitate or fresh-frozen plasma. In this situation, cryoprecipitate would be the component of choice because of its higher concentration of vWF.


HYPOFIBRINOGENEMIA


This deficiency may be inherited or acquired as part of the disseminated intravascular coagulation (DIC) syndrome. Cryoprecipitate is the only source currently available with concentrated fibrinogen.


FACTOR XIII DEFICIENCY


This clotting factor is also called the fibrin stabilizing factor. A deficiency of this factor leads to bleeding, poor wound healing, and an increased incidence of spontaneous abortion. Intravenous supplementation of factor XIII is accomplished by the use of cryoprecipitate.


ADMINISTRATION OF BLOOD COMPONENTS


Administering a blood component is the last step in the process of matching a donor component with a recipient. Remembering that the most common causes of fatal transfusion reactions are improperly labeled blood samples, mislabeled component units, and misidentified recipients, it is clear that most fatal transfusion errors are clerical rather than laboratory failures. The transfusionist is the last person in the administration process with the opportunity to note a clerical error. Therefore the transfusionist should be attentive to every detail of the administration procedure and guard against the relaxed approach that so often accompanies familiarity.

Policies and procedures for the administration of blood components vary greatly among providers of this therapy, but their purpose, which is to ensure precision and safety, is universal (Box 14-3). Therefore those who administer transfusion therapy should be knowledgeable of policy and adhere strictly to the procedures embraced by their particular organization or home care provider.

Box 14-3
BASIC GUIDELINES FOR BLOOD ADMINISTRATION







• Gloves should be worn when handling blood products.


• Blood should not be out of controlled refrigeration for longer than 30 minutes before being initiated as a transfusion.


• Blood should not be stored in non–blood bank refrigerators because they are subject to vast fluctuations in temperature.


• No intravenous solution other than 0.9% sodium chloride should be added to or administered simultaneously with blood.


• A blood administration set should not be affixed (“piggy-backed”) into a main line that has been used for any solution other than 0.9% sodium chloride.


• All blood components must be filtered using in-line or add-on filters that are appropriate for the component or specifically requested by a physician’s order.


• A new administration set and filter should be used for each transfusion. A blood filter should not be used for more than 4 hours.

Table 14-7 presents a detailed summary of blood components, including their preparation, indications for use, blood type compatibility, administration, and special considerations.



















TABLE 14-7 Summary of Blood Components
CMV, cytomegalovirus; DIC, disseminated intravascular coagulation; GVHD, graft-versus-host disease; Hct, hematocrit; Hgb, hemoglobin; IM, intramuscular; ITP, idiopathic thrombocytopenia; IV, intravenous; WBCs, white blood cells.
Component Preparation/ composition Use/Indications ABO/Rh compatibility Administration Special consideration
Whole blood


RBCs


WBCs


Plasma


Platelets


(WBCs, platelets, and some clotting factors not viable after 24 hr of storage)



Increase RBC mass


Increase volume

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