dxy

9.3. Complications associated with leucocyte depletion

There are few reports of complications. Those relating to ‘red eyes’ in the USA (a form of allergic conjunctivitis) were reported after red cells were given using one type of leuco-filter from one particular batch. Hypotension has occurred after bedside filtration of cellular products in patients on angiotensin converting enzyme inhibitors, but has not been a problem with prestorage filtration because bradykinin is rapidly degraded in normal plasma. Although bedside filtration is no longer performed in the UK, this is a reminder to report any complication, including red eye syndrome, to the SHOT scheme (Williamson, 2001).

9.4. Infection

The freezing process inactivates bacteria. Bacterial contamination and growth, with endotoxin production, prior to freezing is unlikely, and has not been reported in the UK in the past 5 years (Sazama, 1994; SHOT, 2001, 2002, 2003). The removal of cellular components also removes cell-associated bacteria, most protozoa (except Tryponasoma cruzi) and cell-associated viruses. Thus, transmission of malaria, cytomegalovirus and human T-lymphotropic virus have not been reported with FFP.

However, freezing does not remove free viruses such as hepatitis A, B and C, human immunodeficiency virus (HIV) 1 + 2, and parvovirus B19 (Pamphilon, 2000). Taking into account the exclusion of first-time donors for FFP production and HCV genome testing (Garwood et al, 2003; R. Eglin & K. Davison, personal communication), the estimated residual risk that a unit of FFP might contain the following viruses is: 1Æ0 in 10 million for HIV 1 + 2; 0Æ2 in 10 million for hepatitis C, and 0Æ83 in 10 million for hepatitis B.

Nevertheless, vaccination for hepatitis A and for hepatitis B should be considered for patients who are transfused frequently. Note, the vaccine for hepatitis A is not licensed for children younger than 2 years old.

Recommendation
Patients likely to receive multiple units of FFP, such as those with a congenital coagulopathy, should be considered for vaccination against hepatitis A and B (grade C recommendation, level IV evidence).

9.5. Graft versus host disease (GvHD)

There have been no case reports of FFP-associated GvHD. FFP does not need to be irradiated.

9.6. VTE

See Section 3.2.3 (VTE associated with use of SDFFP in plasma exchange for TTP).

9.7. Reporting of adverse reactions

As both SDFFP and MBFFP are new products to the UK, it is important to report unexpected problems. For SDFFP the ‘Yellow Card’ system of the Medicines Control Agency for drug reactions applies. Adverse reactions to MBFFP should be discussed immediately with the supplying blood centre, and adverse reactions to either MBFFP or SDFFP, as well as to cryoprecipitate and cryosupernatant, should be reported to the SHOT office (details in Appendix B).

10. Clinical indications for the use of FFP, cryoprecipitate and cryosupernatant

10.1. Single factor de?ciencies

Fresh-frozen plasma should only be used to replace single inherited clotting factor de?ciencies for which no virus-safe fractionated product is available. Currently, this only applies to FV. FFP should also be used, rather than FXI concentrate, in patients with congenital FXI de?ciency where there is concern about the potential thrombogenicity of FXI, for example, during the peripartum period (see recommendation in Section 3.2.3). More details about individual clotting factor concentrates and their application are available in the United Kingdom Haemophilia Centre Directors’ Organisation (1997, 2003). PRP is recommended for children born after 1 January 1996, and there is a case for considering PRP (Section 3) for patients of all ages.

10.2. Multiple coagulation factor de?ciencies

Fresh-frozen plasma is indicated when there are multi-factor de?ciencies associated with severe bleeding and or DIC, as indicated in the following paragraphs.

10.3. Hypo?brinogenaemia

The most common use for cryoprecipitate is to enhance ?brinogen levels in dys?brinogenaemia and the acquired hypo?brinogenaemia seen in massive transfusion and DIC. Treatment is usually indicated if plasma ?brinogen is less than 1 g/l, although there is no absolute threshold value for diagnosing clinically signi?cant hypo?brinogenaemia. Results of ?brinogen assays vary according to the method used. A pathogen reduced ?brinogen concentrate of higher purity is under development but not yet available.

10.4. DIC (see Section 10.9.2)

Disseminated intravascular coagulation occurs when septicaemia, massive blood loss, severe vessel injury or toxins (such as snake venom, amniotic ?uid, pancreatic enzymes) trigger the haemostatic mechanism. This may be clinically compensated and only demonstrable by laboratory tests. However, a ‘trigger’ may cause decompensation, resulting in overt microvascular bleeding as well as microangiopathic thrombosis. All coagulation factors are depleted, but particularly ?brinogen and FV, FVIII and FXIII.

Treating the underlying cause is the cornerstone of managing DIC. Although transfusion support may be needed, there is no consensus regarding optimal treatment. If the patient is bleeding, a combination of FFP, platelets and cryoprecipitate is indicated. However, if there is no bleeding, blood products are not indicated, whatever the results of the laboratory tests, and there is no evidence for prophylaxis with platelets or plasma (Levi & ten Cate, 1999).

10.5. TTP (Machin, 1984; BCSH, 2003)

Most patients with TTP have normal or near-normal clotting tests, although in a few patients late ?ndings may be similar to those found in DIC – low platelet count, abnormal PT and activated partial thromboplastin time (APTT). Neurological abnormalities develop late, and indicate serious deterioration requiring prompt intervention. Furlan et al (1998) demonstrated that most patients are de?cient in an active metalloproteinase enzyme resulting in the accumulation of HMW-VWF, which leads to excess platelet activation and consumption.

The mainstay of treatment of acute TTP is daily plasma exchange (Evans et al, 1999). Prior to its institution mortality rates were in excess of 90%. With plasma infusion alone mortality rates improved to 37% and plasma exchange improved mortality further to 22%. All forms of FFP contain the missing enzyme, but FFP lacking HMW-VWF may be preferred, namely SDFFP (Harrison et al, 1996) or cryosupernatant (cryo-poor FFP). This is based on a study using historical controls (Rock et al, 1996), is currently the subject of a Canadian randomized trial of cryosupernatant versus SD FFP, but is in contrast to a report by Zeigler et al (2001).

Methylene blue and light-treated FFP is also ef?cacious in this setting, but may require more plasma exchange procedures (De la Rubia et al, 2001). Although no randomized studies have been carried out to compare SD and MB products in this scenario, De la Rubia et al (2001) stated that MBFFP was less ef?cacious than standard FFP (grade C recommendation, level III evidence). SDFFP has been associated with the development of VTE when used as the plasma exchange medium in TTP. MB cryosupernatant may be more effective than standard FFP in the treatment of TTP (grade C recommendation, level III evidence), but at the time of writing is not routinely available in the UK.