dxy

The two types of PRP available are methylene blue and lighttreated FFP (MBFFP) and solvent detergent-treated FFP (SDFFP). Each type has certain potential drawbacks that may influence the clinical decision on which to use (see Section 3). Furthermore, even PRP may transmit hepatitis A virus (HAV) or parvovirus B19.

Blood group status (see Table I). Group O FFP should only be given to group O patients. For patients of group A, B, or AB, FFP of the patient’s ABO group should be the first choice. If this is not possible, FFP of a different group may be acceptable if it does not possess ‘high-titre’ anti-A or anti-B activity (grade B recommendation, level III evidence).

Infants or neonates who are not group O may be particularly susceptible to haemolysis from group O FFP because of the relatively high volumes required (grade B recommendation, level III evidence).

Handling of FFP, cryoprecipitate and cryosupernatant

Procedures for thawing any of these products must be designed to avoid bacterial contamination.

After thawing, and when FVIII replacement is not required, FFP and cryosupernatant may be stored at 4 C in an approved blood storage refrigerator before administration to the patient, so long as the infusion is completed within 24 h of thawing (grade B recommendation, level III evidence).

Purpose of this guideline

The purpose of this guideline is to assist clinical decisions about the transfusion of FFP. Many of the conventional and widely taught indications for the transfusion of FFP are not supported by reliable evidence of clinical benefit. The largest avoidable risk to patients from transfusion is probably due to the transfusion of FFP for inappropriate or unproven clinical indications (Cohen, 1993). These guidelines are targeted to all clinical staff involved in acute care including clinical haematologists, paediatricians, surgeons, anaesthetists, blood transfusion practitioners, biomedical scientists, and nurses including ward and theatre staff.

Methods

These guidelines are based on MedLine literature searches using appropriate keywords (including: plasma, plasma + randomized, plasma + trial, plasma + therapy, plasma + liver, plasma + cardiac surgery, plasma + surgical bleeding, plasma + thawing and plasma + storage). All these searches were repeated substituting either cryoprecipitate or cryosupernatant for plasma. A draft of the systematic review (Stanworth et al, 2004) was also consulted. Existing guidelines were also reviewed, including that by the College of American Pathologists(1994) and several published by the BCSH (1988, 1990a,b, 1992, 1994, 1998, 1999, 2003, 2004). Grading of evidence and strength of recommendations used originated from the US Agency for Health Care Policy and Research (see Appendix A).

1. Introduction

1.1. Historical and current use of FFP

Fresh-frozen plasma has been available since 1941 and was initially often used as volume replacement. With the availability of albumin and hydroxyethyl starch, and a better understanding that FFP is contraindicated for volume expansion, it is now usually used in cases of excessive bleeding or to prevent bleeding in those patients with abnormal coagulation tests that are undergoing an invasive procedure. Its use has been extended to patients with a coagulopathy but who are not bleeding (for instance, in the ICU).

The use of FFP in hospital practice has risen by over 20% in the past few years, 5Æ9% in the past year, and concern has been raised about the appropriateness of its clinical use. The UK Transfusion Services issued 365 547 units of FFP and 94 114 units of cryoprecipitate in 1999–2000; 374 760 units of FFP and 95 456 units of cryoprecipitate in 2000–2001; and 385 236 units of FFP and 88 253 units of cryoprecipitate in 2001–2002 [Serious Hazards of Transfusion (SHOT), 2001, 2002, 2003]. The UK Census of 2001 revealed a total population of 58 789 194.

Indications for appropriate use of FFP, as then perceived, were last published by the BCSH in 1992. Three audits in London and Oxford between 1993 and 2000 identified that 34% of transfusions were for reasons outside those guidelines (Eagleton et al, 2000). A similar unpublished audit, with comparable results, was conducted in the Wessex Region in 1998, and Stainsby and Burrowes-King (2001) have described the first phase of a national audit in England as showing a disappointing level of implementation of policies and strategies for the use of plasma components. Despite strict policies for release of FFP from blood banks, inappropriate use (19% in Oxford, and 15% in Southampton in 2000) remains a concern (O’Shaughnessy, 2000).

1.2. The problems of variant Creutzfeldt–Jakob disease (vCJD) and the use of non-UK plasma (see the vCJD position statement in the document library of the UK Blood Services; http://www.transfusionguidelines.org.uk)

In 1996, the first cases of vCJD, a new and rapidly progressive spongiform encephalopathy, were described (Will et al, 1996). At that time, it was noted to be unique to the UK and followed the epidemic of bovine spongiform encephalopathy (BSE) that affected 200 000 cattle and resulted in the slaughter of 750 000 animals. By 1 December 2003, there were 143 cases of definite or probable vCJD. It is untreatable and universally fatal within months of the first appearance of symptoms, although there is considerable interest in the first two cases that have been treated with pentosan polysulphate (Dyer, 2003). The vCJD prion shows affinity for lymphoid tissue and has been demonstrated in the tonsillar tissue of affected individuals and in the appendix of an asymptomatic patient, months before obvious onset of disease (Hilton et al, 2002). Animal experiments have demonstrated infectivity of both plasma and buffy coat as well as whole blood in transferring the infective prion agent (Houston et al, 2000; Hunter et al, 2002). This evidence, along with studies showing that B lymphocytes appeared to be necessary for the transfer of prions from the periphery to the brain, resulted in the universal leucocyte depletion of blood components in the UK, completed in November 1999 (Det Norske Veritas, 1999; Murphy, 1999).

Subsequent analysis on the distribution of normal cellular prion (PrPc) has shown that plasma is a major source (68%) with only 26% present on platelets and the remainder on red cells and leucocytes (MacGregor et al, 1999). As the mechanism of infection appears to involve the alteration of the normal cellular PrPcto PrPsc, and as exclusion of UK donors for all products is neither feasible nor acceptable, it seemed prudent to exclude UK plasma for fractionation whilst still accepting UK donors for cellular products and individual units of FFP (Turner & Ironside, 1998). It is for these reasons that plasma for the production of ‘batch products’ in the UK has been sourced from the USA and Germany since 1998.