Allogeneic Blood Products

The term allogeneic refers to blood products manufactured from blood donations from healthy subjects (blood donors) which are intended for transfusion to different subjects (blood recipients). In the past these products were called "homologous", but the current preferred term is allogeneic, in order to be consistent with solid organ transplantation terminology. Other names used regionally to describe these products are; "regular blood", "shelf blood" or "banked blood".

The term Blood Product, then, is an all embracing term used to describe any end-product produced from human blood. First, there is whole blood, which is collected into a solution that functions both to anticoagulate and preserve the red blood cells. These are simple solutions containing citric acid to chelate calcium and, therefore, prevent activation of the coagulation system and glucose to allow red cells to metabolize during in vitro storage (e.g., citrate-phosphate-dextrose or CPD). Adenine may also be present (CPD-A1), which improves red blood cell adenosine triphosphate (ATP) levels. Anticoagulated whole blood is collected into, stored in, and transfused from, its primary container. Although whole blood was commonly used prior to the 1970s, this has diminished over the past decades. The two remaining clinical situations where whole blood is still preferentially requested for transfusion are patients with trauma requiring multiple transfusions and cardiac surgery, particularly pediatric cardiac surgery. This is because it has been suggested that 'fresh' whole blood (less than 48 hours old) may be preferable to correct any coagulopathy which may develop in these patients . However, the practical logistics of having fresh whole blood routinely available makes this difficult to achieve in practice.

Second, most whole blood donations are further processed by centrifugation into a number of blood components. Each whole blood donation is capable of producing up to five different components, but commonly, either red blood cells and plasma, or red cells, plasma and platelets are produced. Further processing of a unit of plasma can produce a unit of cryoprecipitate and a cryosupernatent, the latter known as cryo poor plasma. Some fibrin glue preparations are similar to cryoprecipitate, except that the process may be modified to enhance fibrinogen yields (see Chapter 23). In practice, almost all allogeneic whole blood donations are processed into at least two components, such as a red cell concentrate and plasma. The red cell concentrate can be stored in the anticoagulant plasma alone (CPD red blood cells; CPD-A1 red blood cells), or a crystalline solution can be added, which contains glucose and stabilizers to maintain the quality of red cells during the storage period (Adsol®, Nutricell®, or Optisol®). The maximum duration of storage for red cells (at 1-6°C) under such circumstances is currently 42 days (Chapter 27). Much of the plasma produced from the whole blood dona tions is shipped to fractionation plants for further manufacture into blood derivatives. Some of the plasma, however, is retained in blood centers in the frozen state and used for clinical transfusion purposes (see Chapter 29).

A single unit of platelets may also be produced from each blood donation. Although the terminology is confusing, a platelet unit derived from a whole blood donation is commonly known as a random donor platelet. A separate type of blood component is an apheresis blood component. Several different types of apheresis components are available but the most important is the platelet apheresis product, commonly known as single donor platelets. As indicated above, a unit of random donor platelets is also derived from a "single donation" and hence the terminology is confusing (Chapter 28). Other allogeneic apheresis products may be more widely available in the future, as a 'double unit' of red cells, or combinations of platelets and red cells, or red cells and plasma, may be obtained from a single donor using these devices. It is anticipated that many such products will be approved for use by late 1999. The hallmark of a blood component is that is derived from a single donation. Each such donation has a unique identification (unit number or lot number).

Third, there are blood products known as blood derivatives. These are manufactured from a plasma pool usually containing between 5,000 and 20,000 donations. This plasma pool constitutes a new lot number, composed of the individual lot numbers of each donation which makes up the pool. All blood derivatives in current use are acellular products. Derivatives in common use are 5% or 25% albumin, immunoglobulins, and the plasma derived coagulation factor concentrates. Since blood derivatives are produced from such a large number of blood donations, there is always the ongoing concern that new viruses from apparently health donor(s), may enter each pool and potentially infect a large number of recipients. This was responsible for the spread of hepatitis in the 1970s and, subsequently, human immunodeficiency virus (HIV-1) in the 1980s in the hemophilic population. Blood derivatives are routinely subjected to a variety of processing steps. Some of these steps are intentionally performed to destroy viruses, which is called viral attenuation. Use of at least two different types of viral attenuation processes is now common in order to optimize the destruction of viruses. Examples of these processes are pasteurization i.e., heating to 60° C for ten hours; various separation steps, e.g., gel filtration or micro-filtration, and chemical treatments such as solvent detergent exposure. In spite of the clear effectiveness of these viral attenuation processes, there is still the potential for some viruses to be resistant to these steps and result in the infection of blood transfusion recipients.

The last type of allogeneic blood product is stem cell products. Stem cells can now be collected from a number of sources, other than the traditional bone marrow, such as peripheral blood or umbilical cord blood. Allogeneic stem cell products are always derived from a single donor, but multiple donations may be required if peripheral blood is the source. Since stem cells are generally transfused in specialized transplant units, they will not be described further and the reader is referred to the Clinical Handbook of Bone Marrow Transplantation for further information on these products and associated technology. These products are illustrated in Figure 2.1.

The physical state of blood products during storage varies with the product type. Red cells and platelets are typically stored in the liquid state. Plasma and cryoprecipitate are stored in the frozen state. Certain blood products are manufactured and stored in the lyophilized state; examples are some immunoglobulin preparations and coagulation factor concentrates. However, red cells (or less commonly platelets) may also be stored in the frozen state using cryoprotective agents; and certain blood derivatives, such as one preparation of immunoglobulin and all albumin preparations, are stored in the liquid state. All products are transfused as a liquid product, either after thawing of frozen products or reconstitution of lyophilized products. This accounts for the delay in availability since it takes between 15-30 minutes to either thaw frozen products, or to reconstitute lyophilized products prior to transfusion. This is shown in Table 2.1.

The allogeneic blood supply in the United States, much of Europe and Japan is predominantly collected from what are known as 'volunteer blood donors'. These donors donate for altruistic reasons and do not receive any remuneration or reward of a material monetary value. Platelet pheresis donors in some centers receive a token remuneration. However, much of the plasma collected for fractionation comes from paid donors. A different type of volunteer blood donor is known as a directed donor, and the donation as a 'directed donation'. Directed donor blood products are allogeneic blood products which meet all the requirements for

Source:

Products:

Healthy Humans Donors

Donation ( = individual lot #)

Whole blood (single donation)

Blood components (single donation)

Blood Derivatives

donations)

Stem Cells

(single/multiple donations)

Red Blood Cells

-plasma ^ cryoprecipitate; cryo poor plasma -platelets

-apheresis components Albumin

Immunoglobulins Coagulation Factors

Bone Marrow Peripheral Blood Umbilical Cord Fetal Hepatocytes

Physical State

Liquid (e.g., red cells, platelets) Frozen (e.g., plasma) Lyophilized (e.g., derivatives)

Table 2.1. Some properties of allogeneic blood products in common use

Product Physical Approx. Storage Shelf

State Volume (mls) Temperature Life

Whole blood in CPD

Whole blood in CPD-A1

Red Blood Cells in CPD

Red Blood Cells in CPD-A1

Red Blood Cells in Preservative

Random Donor Platelets (RDP)

Single Donor Platelets (SDP)

Fresh Frozen Plasma

Liquid Liquid Liquid Liquid Liquid

Liquid

Liquid Frozen

180-350

Cryoprecipitate Frozen 5-15

Vial of Lyophilized 10-20

Coagulation

Factor

21 days 35 days 21 days 35 days 42 days

1 year

1 year

Refrigeration 1 year

Comments

Hematocrit approx. 35

Hematocrit approx. 35

Hematocrit < 70

Hematocrit

Hematocrit 50-60; little plasma

4-10 units pooled into a single container

Equivalent to 6-8 units of RDP

15-30 minutes to thaw

Thawed, then pooled

Reconstituted with diluent, then transfused

CPD = Citrate - Phosphate - Dextrose

CPD-A1 = Citrate - Phosphate - Dextrose - Adenine a standard allogeneic blood product. However, they differ in that the intended recipient is identified at the time of donation. The practice of directed blood donation is often performed in the context of donating blood for a relative or friend in anticipation of surgery or cancer chemotherapy. Directed donations are generally neither encouraged nor discouraged by blood collection facilities. There is no evidence that they are any more safe (i.e., less likely to transmit viral infections)

than the non-directed volunteer blood supply. On the contrary, since many directed donors are first time donors, there is a higher prevalence of viral disease markers, raising concern regarding a possible increased risk. Directed donor blood may be transfused to a recipient other than the intended recipient, if the latter does not require transfusion, a practice "called crossover".

All allogeneic blood donations are routinely tested for syphilis and viral disease markers as shown in Table 2.2.

Table 2.2. Testing of blood donations for microbial diseases

Test Year Initiated

Serological Test for Syphilis 1949

Hepatitis B Surface Antigen (HBs As) 1972

Antibody to HIV-1 1985

Antibody to Core Antigen of Hepatitis B (Anti HBc) 1986

* Alanine Aminotransferase (ALT) 1986

Antibody to HCV

Generation I 1990

Generation II 1992

P24 Antigen of HIV-1 1996

Nucleic Acid Testing for HCV, and HIV-1 1999

* No longer routinely required

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