dxy

The risk of vCJD transmission by blood or blood products could be considerable. Fifteen people who later developed vCJD may have donated blood in the UK. In December 2003, the UK Department of Health reported the first case of possible transmission of vCJD by transfusion (Pincock, 2004). In 2002, the UK Departments of Health issued a recommendation that FFP for neonates and children born after 1 January 1996 be sourced from areas where BSE and vCJD are of low endemicity. Children born since this date and living in the UK have benefited from regulations enacted by the Food Standards Agency affecting meat quality, which keep infected material out of the human food supply. These are the Specified Bovine Materials Ban and the Over Thirty Months rule. Both rules have been enhanced progressively since 1996 (Food Standards Agency, 2003). The effect of these bans has reduced the risk of such children contracting vCJD from their diet to levels which may well be lower than the risk of them contracting vCJD from transfused blood donated by UK donors who – although showing no signs of vCJD – may be incubating it. This position will remain until there is more accurate data indicating the scale of the vCJD epidemic in UK adults.

Although sourcing materials for FFP production from donors residing in areas where BSE and vCJD are of low endemicity may introduce other risks (e.g. if prevalence of transfusion-transmissable diseases caused by known organisms is relatively high) most of these diseases can be effectively eliminated from plasma by pathogen reduction procedures. Although these procedures do not inactivate prions, by applying them to imported plasma the overall risks of transmitting infection (including vCJD) from treated products will be mitigated. At present two procedures are currently licensed to reduce pathogens in FFP; MBFFP (as currently applied by the UKBTS), and SDFFP (available commercially – ‘Octaplas’). Because a methylene-blue/light process has been developed within the UKBTS, limited supplies of FFP of UK origin and treated this way are already available. Plans are nearing completion for the UKBTS to provide MBFFP sourced from male donors in the United States. From 1998, Octaplas for use in the UK has been sourced by the manufacturer, Octapharma, from donors in the United States.

Arguably, PRFFP sourced from non-UK untransfused male donors should be used wherever possible (see Sections 1.3 and 9.2 on the choice of untransfused men as donors). There are obvious difficulties in establishing a year of patient birth after which only the microbiologically safest available FFP must be used, especially if many patients (such as adults) are excluded. Although extending the use of PRP sourced from non-UK donors to all recipients deserves careful consideration, the main constraint at present is cost. The following guidelines preclude neither the use of non-PRFFP from UK donors, nor the use of PRP for older patients, although no specific conditions are identified for the latter option. As many elderly UK patients will have been exposed to BSE in their diet, the only justification for the use of PRP in adults would be a reduction in the risk of pathogen transmission. This is already low for FFP from UK donors (see Section 9.4).

These issues emphasize the need to ensure that all blood products are prescribed only when appropriate.

1.3. The problems of transfusion-related acute lung injury (TRALI) and the use of plasma from male donors (see Section 9.2)

Transfusion-related acute lung injury is significantly but not solely associated with the presence of leucocyte alloantibodies in donor plasma. Such antibodies are found most frequently in women after pregnancy, and are not present in plasma from men unless they have been transfused. Even then, such antibodies seem less active than those found in women who have been pregnant. Restricting the source of plasma for FFP production to men seems likely to reduce the incidence of TRALI.

2. Specifications, preparation, storage and handling of FFP and cryoprecipitate

2.1. FFP

In the UK, FFP is produced from donations by previously tested donors, either of whole blood, which undergoes hard centrifugation, or by aphaeresis. The current guidelines (United Kingdom Blood Transfusion Services/National Institute for Biological Standards and Control, 2002) give the quality monitoring requirements, including the degree of platelet and leucocyte depletion, and specify that FFP should be rapidly frozen to a temperature that will maintain the activity of labile coagulation factors. Donations from first-time donors are not used to produce FFP.

♦ FFP prepared from units of whole blood and from plasmaphaeresis may differ only in the quantity of plasma in the pack. The volume may vary between 180 and 400 ml. Procedures for thawing FFP must be designed to avoid bacterial contamination (see Section 6.1).

♦ Collected plasma is frozen rapidly to )30 C, the recommended temperature for storage. The interval between collection and storage is no longer defined in the guidelines (United Kingdom Blood Transfusion Services/National Institute for Biological Standards and Control, 2002), provided the specification is achieved.

♦ When frozen, the plastic packs containing the FFP become relatively brittle and must be handled with care. Vulnerable parts of the pack include the stumps of the entry lines, which can break off if knocked.

♦ Immediately after being thawed, the standard FFP must have at least 70 IU/ml of FVIII in at least 75% of the packs. This requirement has been reduced for PRP (see Section 3, and Table III).

♦ Packs should be inspected immediately before infusion and rejected, or referred for further opinion, if there is any unexpected appearance such as flocculation or discolouration, or apparent leaks when the pack is put under pressure. Other details of the quality monitoring required are available elsewhere (United Kingdom Blood Transfusion Services/National Institute for Biological Standards and Control, 2002).

Recommendation
Fresh-frozen plasma prepared from units of whole blood and from plasmaphaeresis are therapeutically equivalent in terms of haemostasis and side-effect profile (grade A recommendation, level I evidence).