Gadi_edit.qxp 12/2/09 16:24 Page 86
Transfusion
involve diverting the collected blood to a temporary storage container therapeutic dose of whole-blood-derived platelets. This system provides
where detection and/or inactivation procedures are conducted before the leukocyte-reduced platelets that are bacteria-tested via a highly sensitive
blood or its components are stored in their final storage containers. The culture technique that detects over 99% of bacterial infection.
50
safety of blood supplies has been significantly improved in some
countries by the selection of non-remunerated voluntary donors who are A third approach is to inactivate and/or remove pathogens in
at low risk of TTIs.
36
contaminated units of donated blood or blood products.
3,27,51
Although
the acceptable ‘log reduction’ number for a given organism is not
Epidemiological control and other prevention techniques, while carefully standardised, experience suggests that fewer than four log reductions
implemented in developed countries, may be problematic (if not absent) may be insufficient and greater than six log reductions sufficient.
27
A
in many developing countries. This may be due to a high number of target to reduce the infectious titres of pathogens by five logs in blood
misinformed donors and poor staff training in donor management.
37
and blood components has been set by the US Food and Drug
Administration (FDA).
52
The challenge of pathogen inactivation in blood
is to reduce the level of pathogen infectivity without significantly
compromising the key essential cellular or protein components or
introducing some new toxicity, carcinogenicity or teratogenicity.
27
More than two-thirds of the world does
not have access to safe blood.
Solvent detergent (SD) treatment has been successfully applied with
pooled plasma during the last 20 years. The solvent detergent destroys
‘enveloped’ viruses including HIV-1, HIV-2, HCV, HBV and HTLV-I/II. It
does not destroy ‘non-enveloped’ viruses such as parvovirus and the
hepatitis A virus. The detergents need to be removed by either oil
Even in cases where the donors belong to a low-risk blood donor group, extraction or chromatographic adsorption. In addition to being ineffective
the rates of seroprevalence for pathogens may be high in pathogen- against non-enveloped viruses, SD plasma has been implicated in patient
endemic areas.
38
death and has caused at least 16 deaths due to SD plasma-induced blood
clots.
53
SD treatment also results in some loss of crucial plasma proteins:
Detection relies on identifying the pathogens in blood as a way to avoid α2-antiplasmin and protein-S. These concerns, along with economic
the use of contaminated units. Technologies use nucleic acid factors, resulted in the removal of SD plasma from the US market. SD
amplification testing (NAT), bacterial culture, bacterial fluorescent probes plasma is still used widely in Europe. Due to the above concerns, and the
and serological and biochemical tests to detect pathogen proliferation. need to effectively remove the detergents used from the plasma and
HBV, HCV, HIV, parvovirus B19, HTLV I/II and Treponema palladium are plasma components (a burdensome and expensive procedure), the
regularly being tested for in donated blood units in developed effectiveness and safety of SD treatment on a routine basis in developing
countries.
39–42
Other pathogen screening conducted on an ‘as-needed’ countries is questionable.
basis are cytomegalovirus, malaria and Trypanosoma cruzi.
10
The
introduction of NAT systems for the detection of viral genomes has Other inactivation procedures, such as pasteurisation and dry-heat
significantly reduced contamination frequency.
41
An example of this application, are effective in inactivating ‘enveloped’ and ‘non-enveloped’
reduction is the residual risk of post-transfusion hepatitis reduction to as viruses (e.g. HAV and the B19 virus).
54
These procedures are used for
low as one in 100,000.
43
isolated blood proteins, such as albumin or clotting factors. Since protein
denaturation occurs, stabilisers need to be introduced (and later
Detection procedures have their own difficulties. One of these is the removed), making these procedures expensive and cumbersome, and
documented problem of determining the existence of contaminated under some conditions they do not achieve complete viral inactivation.
27
blood during the pre-seroconversion period of infection. Highly sensitive
detection tests, such as individual or mini-pool NAT, reduce but do not Most other inactivation approaches use chemicals that target the nucleic
eliminate this period of potential infectivity.
44,45
The amount of time and acids of pathogens.
27
The blood products that the chemicals are added to
the high cost required for such testing make single-unit NAT testing on a are then subjected to ultraviolet (UV) radiation. It causes the compounds
large scale infeasible. to link to the pathogen’s nucleic acids, preventing their replication.
Methylene blue-light treatment of single-donor plasma units has a
Other detection methods that require seroconversion do not have the similarly long track record to pooled SD-treated plasma. This method is
sensitivity to determine the presence of HIV or HCV during the pre- less documented and also has a greater affect on coagulation factors.
3
seroconversion stage of viral infections. In countries where the endemic
rates of many pathogens are high, the residual risk of TTI, in spite of Psoralen light-treated plasma has recently been introduced to Europe. The
careful blood screening, is still high (e.g. Brazil).
46
method of riboflavin light treatment of plasma is still being developed.
Some reduction of coagulation factor activity occurs and the removal of
Bacterial contamination, which occurs in platelet concentrates, is excess compounds and by-products is needed to avoid potential toxicity.
screened by using the most sensitive method available, which has a Psoralen and riboflavin light treatment for platelets have been approved
sensitivity of less than 40% due to the low numbers of bacteria during for use in Europe and for clinical trials in the US. Photochemical treatments
the initial contamination periods.
47
More sensitive detection methods are affect platelet activity.
55
Pathogen reduction of RBCs with other
constantly being developed and improved.
48,49
In 2005, the US-based Pall compounds, such as frale (S-303) or inactine (PEN110), has so far resulted
Corporation developed the first technology allowing a transfusion-ready in the formation of auto-antibodies, and until the immunoreactivity and
86 EUROPEAN HAEMATOLOGY
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