ISSUE SUMMARY
Issue: FDA seeks to be advised
whether available scientific data support the development of FDA policies on
methods to reduce the incidence of TRALI
In part due to increased recognition of the syndrome by transfusing clinicians, TRALI deaths reported to FDA have risen over the past several years and now represent the leading cause of transfusion-associated mortality. An average of 24 annual TRALI deaths was reported in the two year period between October, 2003 and September 2005. Thirty-five TRALI deaths were reported to FDA in calendar year 2006, and accounted for 50.7% of all reported transfusion-related fatalities. TRALI-related morbidity is substantially higher with a per-transfusion incidence estimated at 1/2500 to 1/5000. Due to the difficulty in establishing a definitive diagnosis, it is not known how many deaths may occur each year in which TRALI is a contributing factor. All transfusable blood components (and rarely IGIV) have been implicated in TRALI, however plasma and single donor platelet products account for the majority of cases.
Discussion:
Despite the association of prior pregnancy with HLA and
other leukocyte antibodies, there are practical difficulties in screening female
donors for prior pregnancy. This is due to the potential sensitivities of
asking donors about previous miscarriage or abortion, and the wide range of possible
responses, including uncertainty about a prior pregnancy. The AABB has recently
recommended that to reduce the incidence of TRALI, member blood establishments should
minimize the use of high plasma volume components from donors known to have
anti-leukocyte antibodies, or known to be at risk of leukocyte
allo-immunization. The target date for voluntary implementation of these
recommendations is November 2007.
The preferential use of male plasma
in the US has been regarded as generally feasible from a plasma supply
perspective, although conversion to a 100% male plasma supply may be
problematic in situations where a need exists for large volumes of AB plasma, or
during periods of localized plasma shortage. Avoidance of plasma for
transfusion collected from previously transfused persons (who may also be
allo-immunized to leukocyte antibodies), or from persons found to have
circulating anti-leukocyte antibodies through the use of screening tests might
also be considered, although there are no clinical data to support these
interventions.
Whole blood donation in the
The AABB has also recommended that
interventions be considered to reduce TRALI incidence among recipients of
Platelets, Pheresis by November 2008. Specific interventions to be considered
were not described. Reduction of
TRALI associated with single
donor platelet units is challenging,
both from a platelet supply perspective, and due to the fact that laboratory
assays for the detection of leukocyte antibodies or other possible etiologic
moieties in blood are not widely available for use in donor screening.
The overall supply of single donor
platelets in the
Relevance of Assays for
Anti-Neutrophil and Anti-HLA Antibodies
Evidence to date including both
case reports and experimental animal studies indicate that NSA are found in
less than 1% of donors, and may have a high degree of association with TRALI,
as well as with other forms of transfusion reactions. Research assays for NSA
exist, but have to date only been implemented in small academic donation
settings to characterize female donors of AB plasma and Platelets, Pheresis. Similarly, donors with anti-HLA antibodies
have also been implicated in TRALI. While HLA Class I and Class II antibody tests
are widely available, the background prevalence levels in donors are higher,
and the implication of HLA antibodies in TRALI causation is weaker.
Use of Plasma Transfusion in
the
FDA has licensed Fresh Frozen
Plasma (FFP) and several forms of plasma components containing reduced amounts of
labile coagulation factors. Only FFP is
indicated for replacement of the labile factors V and VIII. Otherwise, the indications for use are identical
and include:
Practice guidelines currently do
not exist for some of the major uses of plasma transfusion therapy in the
1. Do current scientific
data support the concept that the following interventions will reduce the
incidence of TRALI?
a.
Use of predominantly
male plasma for transfusion.
b.
Non-use of plasma for
transfusion from donors with a history of prior transfusion
c.
Selective donor
screening for anti-neutrophil or anti-HLA antibodies
2. Based upon
available data, please comment on the effect on the
a.
Use of predominantly male
plasma for transfusion
b.
Non-use of plasma for
transfusion from donors with a history of prior transfusion
c.
Selective donor
screening for anti-neutrophil or anti-HLA antibodies
References:
1.
Densmore TL, Goodnough LT, Ali S, et al.
Prevalence of HLA sensitization in female apheresis donors. Transfusion
1999;39:103-6.
2.
Kleinman S, Caulfield
T, Chan P, et al. Toward an understanding of transfusion-related acute lung
injury: Statement of a consensus panel. Transfusion 2004;44:1774-89.
3.
US Department of
Health and Human Services. The 2005 nationwide blood collection and utilization
survey report.
4.
Chapman CE, Williamson
LM, Cohen H, et al. The impact of using male donor plasma on hemovigilance
reports of transfusion-related acute lung injury (TRALI) in the
5.
Transfusion-related
acute lung injury. Association
Bulletin #06-07 (November 6, 2006).
6.
Eder A, Heron R, Strupp A et al. TRALI
surveillance (2002-2005) and the potential impact of the selective use of
plasma from male donors in the American Red Cross. Transfusion 2007 in press.