Jeffrey McCullough - Transfusion Medicine

Several platelet concentrates are usually pooled to provide an adequate dose for most patients (see Chapter 10). For some patients, the volume of plasma in the final pooled component is too large, and plasma must be removed prior to transfusion. This involves another centrifugation step after the platelets have been pooled that causes a loss of 15% to as much as 55% of the platelets [90, 91].

The leukocyte content of the platelet concentrates is an important issue (see Chapters 10, 11, and 16). The conditions used to centrifuge WB influence the leukocyte content of the platelet concentrate, but most platelet concentrates contain 10 8or more leukocytes. Filters are available that remove most of the leukocytes in the platelet concentrate. The filters can be used at the bedside, or preferably before the platelets are stored. All platelets should be leukodepleted.

Filters are available for leukodepletion of platelets, as well as red cells. This is necessary if it is hoped to prevent alloimmunization or cytomegalovirus transmission in patients receiving platelet transfusion [53]. The platelet filters result in a loss of about 20–25% of the platelets and have a rate of failure in achieving fewer than 5 × 10 6leukocytes of about 5–7% [53].

Granulocytes for transfusion are prepared by cytapheresis (see Chapter 6). Some investigators have prepared granulocytes from fresh WB by sedimentation with hydroxyethyl starch to obtain doses of 0.25 × 10 9. This is below the 1–3 × 10 9desired for transfusion even to a neonate [92]. The possibility of obtaining granulocytes from units of WB is usually raised in a crisis; the blood bank often does not have procedures to prepare the cells, and it is not possible logistically to test the blood for transmissible disease. Thus, preparation of granulocytes from units of fresh WB is not recommended.

The techniques and clinical indications for irradiating blood components are described in Chapter 10.

Hematopoietic stem cells are being obtained from bone marrow, peripheral blood, and cord blood. Collection of marrow and umbilical cord blood is described in Chapter 19and peripheral blood stem cells in Chapter 6. Stem cells from these different sources are undergoing an increasing variety of cellular engineering methods that produce new blood components with exciting therapeutic potential.

Procedures for the fractionation of plasma were developed during the 1940s in response to World War II (see Chapter 1). A large pool of plasma, often up to 10,000 L or 50,000 donor units, is processed using cold ethanol fractionation. In cold ethanol, different plasma proteins have different solubilities, which allow their separation. This large‐scale separation and manufacturing process results in the isolation of several proteins from plasma that are prepared for therapeutic use. These are called “plasma derivatives” ( Table 5.10). The major derivatives have been albumin, immune serum, immune globulin, and coagulation factor VIII concentrate. Until the late 1980s, techniques were not available to sterilize some blood derivatives after manufacture. Thus, because of the large number of units of donor plasma in each pool, the chance of contamination of the pool with viruses (i.e., hepatitis and HIV) was high and the risk for disease transmission from these nonsterilized blood derivatives was high (see Chapter 17). This risk was accentuated because much of the plasma that serves as the raw material for the manufacture of blood derivatives was obtained from paid donors, a group known to provide blood with an increased likelihood of transmitting disease [93, 94]. Initially, only albumin and immune globulin carried no risk for disease transmission—albumin because it was sterilized by heating, and immune globulin because none of the known infectious agents was contained in that fraction prepared from the plasma. Because of the recognition of the high risk for disease transmission by coagulation factor concentrates, methods were developed to sterilize them [95, 96].

Concerns arose about the possible transfusion transmission of the agent responsible for variant Creutzfeldt–Jakob disease because this infectivity is not inactivated by most conventional methods. Fortunately, it appears that the prions associated with variant Creutzfeldt–Jakob disease do not partition with the therapeutic proteins during plasma fractionation [97, 98].

Although coagulation factor concentrates were known to transmit hepatitis when they first became available, the risk has been reduced over the years by improvements to the donor history, the addition of laboratory tests for transmissible agents, and the introduction in the mid‐1980s of methods to treat the concentrates to separate and inactivate viruses [95, 96, 99]. The major methods of viral inactivation for plasma‐derived concentrates are: (a) dry heating, in which the sealed final vial is heated between 80°C and 100°C; (b) pasteurization, in which the concentrate is heated to 60°C while still in solution before lyophilization; (c) vapor heating, in which the lyophilized powder is exposed to steam before bottling; and (d) solvent–detergent (SD) treatment, in which the organic solvent tri‐ n ‐butyl‐phosphate and the detergent Tween 80 or Triton X‐100 are added at intermediate processing steps. Currently, the SD method is most commonly used. The pasteurization and vapor heating methods result in substantial loss of factor VIII activity [99, 100].

Table 5.10 Plasma‐derivative products.

Source : From information provided by the Plasma Protein Therapeutics Association; and modified from Burnouf T. Transfus Med Rev 2007; 21(2):101–117.

Each of these methods uses a different strategy of viral inactivation. There are differing amounts of data about the effectiveness of these viral inactivation methods, because not all of their products have been subjected to randomized controlled trials. In general, it appears that the methods are effective in inactivating virus with a lipid envelope, but infections with nonlipid envelope viruses, such as parvovirus B19 [101] and hepatitis A [102], have been reported.