Jeffrey McCullough - Transfusion Medicine

It appears that febrile nonhemolytic transfusion reactions are caused not only by leukocyte antigen–antibody reactions but also by the cytokines produced by leukocytes in the transfused blood component (see Chapter 16). This would be more effectively prevented if the leukocytes were removed immediately after the blood was collected, avoiding the formation of cytokines. This is referred to as “prestorage” leukodepletion. Filtering the red cells at the bedside at the time of transfusion has the advantage of not requiring a separate blood bank inventory, but the disadvantage of allowing cytokines to accumulate during blood storage, thus being less effective in preventing febrile transfusion reactions (see Chapter 16). Also, bedside filtration is not as effective in removing leukocytes as filtration in the laboratory under standardized conditions and with a good quality‐control program [53]. Because the leukocyte content of the depleted units is very low, the usual methods for leukocyte counting are not accurate [53–55]. The Nageotte chamber and flow cytometry are used for this quality‐control testing [53, 55].

Table 5.8 Established or potential adverse effects of leukocytes in blood components.

HTLV‐I, human T‐lymphotropic virus I.

FFP is plasma separated from WB and placed at −18°C or lower within 8 hours of collection [24]. Fresh plasma may be frozen by placing it in a liquid freezing bath composed of ethanol and dry ice, or between blocks of dry ice, or in a mechanical or a blast freezer. The unit of FFP has a volume of about 200–250 mL and contains all of the coagulation factors present in fresh blood. FFP can also be produced as a by‐product of plateletpheresis, and this may result in a unit of FFP with a volume of about 500 mL, often called “jumbo” units of FFP. These can be stored or separated into two separate products. The electrolyte composition of FFP is that of freshly collected blood and the anticoagulant solution. FFP is not considered to contain red cells, and so is usually administered without regard to Rh type. However, there have been occasional rare reports suggesting that units of FFP contain a small amount of red cell stroma that can cause immunization to red cells [56]. Because it contains ABO antibodies, the plasma must be compatible with the recipient’s red cells. The number of leukocytes in FFP depends on the centrifugation procedures used for preparation.

FFP is stored at −18°C or below and can be stored for up to 1 year after the unit of blood was collected. Although there is no defined lower temperature for FFP storage, freezers capable of maintaining very low temperatures, such as −65°C, are not usually used for storage of FFP because these freezers are expensive to operate and there is no reason to keep the FFP that cold.

Twenty‐four‐hour frozen plasma (FP24) is plasma frozen more than 8 and less than 24 hours after collection. It contains normal amounts of factor V but only an average amount of about 55–75% of factor VIII [31]. Despite this lower coagulation factor VIII level, 24‐hour frozen plasma (FP24) is often used interchangeably with FFP (see Chapter 10).

FFP and FP24 are usually thawed in a 37°C water bath in an overwrap. However, it takes about 15–20 minutes to thaw one or two units, and someone must occasionally manipulate the unit to speed thawing by breaking up the pieces of ice. This time requirement is a substantial difficulty when FFP is needed for actively bleeding patients. Several approaches have been used, including larger water baths and water baths with agitating trays so that staff members do not need to manipulate the units. Another more promising approach is the use of microwave ovens for thawing FFP [57, 58]. The concern with microwave thawing has been the uneven energy distribution within the unit of FFP and resulting “hot spots” and damage to proteins. As microwave devices have improved, it appears that these problems have been overcome. After thawing, FFP or FP24 can be relabeled as thawed plasma (TP) and stored for up to 5 days at 1–6°C. Upon thawing, factor VIII and protein C levels are lower in FP24 than FFP, but there are adequate coagulation factor activities to maintain hemostatic effectiveness [59]. By day 5, factor V levels are about 60% and factor VIII levels 40–70%. Thus, as a source of coagulation factor replacement, it is best to use the TP within 24–48 hours. Five‐day storage makes it possible to maintain a stock supply of TP for emergency use in massive transfusion or urgent correction of warfarin therapy (see Chapters 10and 11).

Plasma from a unit of WB can be removed at any time during the storage period of the WB unit or up to 5 days after the unit outdates. This plasma can be stored for up to 5 years at −18°C or lower. Because it was not frozen within 8 hours after the WB was collected, plasma is not a satisfactory source of coagulation factors V and VIII. Although other coagulation factors are present because the plasma is removed from the WB after several days of storage, the electrolyte concentrations of the plasma will reflect those of stored WB. Liquid plasma is becoming more common because it has a longer shelf life compared with TP. It does not need to be thawed and is used as a “bridge” to TP for initial treatment in massively hemorrhaging protocols [60].

Coagulation factor VIII is a cold insoluble protein [61]. Pool and Shannon [62] took advantage of this to develop a method to recover most of the factor VIII from a unit of WB in a concentrated form. Cryoprecipitate is the cold insoluble portion of FFP that has been thawed between 1°C and 6°C. The cold insoluble material is separated from the thawed plasma at 1–6°C immediately and refrozen within 1 hour. Although there are no specific requirements for the volume of a unit of cryoprecipitate, it is usually 5 mL or more, but less than 10 mL. The cryoprecipitate units must contain at least 80 units of factor VIII and 150 mg of fibrinogen [24]. Cryoprecipitate is not a suitable source of coagulation factors II, V, VII, IX, X, XI, and XII [63]. Several factors influence the content of factor VIII in cryoprecipitate, including the blood group of the donor (group A is higher than group O), the anticoagulant (CPD is higher than acid–citrate–dextrose), the age of the plasma when frozen, and the speed of thawing the FFP [64]. Cryoprecipitate also contains fibrinogen and von Willebrand factor, and with the availability of coagulation factor concentrates these are the primary uses of cryoprecipitate. Each bag of cryoprecipitate contains about 250 mg of fibrinogen [63]. Cryoprecipitate is stored at −18°C or below and can be kept for up to 1 year.

Cryoprecipitate is thawed at 37°C, usually in a water bath. Care must be taken to ensure that the water bath is not contaminated and that the bags of cryoprecipitate are placed inside another bag (overwrap) to minimize the chance of contamination. When using cryoprecipitate, it is customary to pool several bags so that only one container is sent to the patient care area for transfusion. Some blood centers pool several bags of cryoprecipitate before freezing them; this is more convenient for the transfusion service because it eliminates the need to pool individual bags of cryoprecipitate after they are thawed. After thawing, the cryoprecipitate must be maintained at room temperature to avoid reprecipitation of factor VIII.