april 2007 1 the american red cross experience with trali richard j benjamin md phd chief medical...
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1April 2007
The American Red Cross experience with TRALI
Richard J Benjamin MD PhD
Chief Medical Officer
American Red Cross, Biomedical Headquarters
Washington DC
2April 2007
Suspected TRALI Fatalities (2003-2005):
72 reported Fatalities (2003-2005)
0
5
10
15
20
25
30
35
2003 2004 2005
Calender Year
Rep
ort
ed
Fati
lite
s
Eder et al Transfusion 47(4):599-607;2007
3April 2007
Independent Review of TRALI Fatalities:
probableTRALI
unrelated
05
1015
20
25
30
35
40
No Ab detected
Female donorwith Ab
Association with leukocyte antibodiesP <0.0012- test
Rec
ipie
nt F
atal
ities
Eder et al Transfusion 47(4):599-607;2007
4April 2007
Probable TRALI by Implicated Component:
0
5
10
15
20
25
Don
or
Fata
litie
s
No AbdetectedFemale donorwith Ab
Eder et al Transfusion 47(4):599-607;2007
5April 2007
Rate of Probable TRALI Fatality
per 106 Distributed Units
Fatality is correlated with female plasma exposure
Proportion 48% 35% 48% 48% 48%female donors
0
1
2
3
4
5
6
plas
ma
aph.
plts
RB
C
WB
-plts
Cry
oppt
Do
no
r fa
tali
ties
(per
106 p
rod
uct
s)
0
50
100
150
200
250
300
350
Vo
lum
e o
f p
lasm
a (m
l)O.R.12.5*
O.R. 7.9*
* P<0.001
6April 2007
Strategies to Reduce TRALI
Appropriate use of Blood products
Selective use of Male products
Donor history of transfusion or pregnancy
Testing for HLA and HNA antibodies
Others Pool & store platelets Platelet additive solutions Solvent detergent plasma
7April 2007
Plasma Production in the ARC System (2005)
0
500,000
1,000,000
1,500,000
2,000,000
2,500,000
3,000,000
3,500,000
FemaleMale
8April 2007
Red Cross Pilot Program
ARC instituted a pilot program in 3 of 10 divisions to produce predominantly male plasma frozen within 24 hours (FP24) on October 1st 2006.
Program assessed the manufacturing issues, not the clinical efficacy.
Products were temporarily labeled with gender at collection and triaged on receipt at manufacturing.
Process instituted as a business practice final product was not labeled customers were not notified used female AB plasma as needed.
9April 2007
DallasTucsonMobileBirminghamWichitaOaklandLos AngelesLittle RockTulsaPortlandBoiseBoisePortlandBoiseBoiseSt LouisOmahaMadisonSt PaulPeoriaNashvilleLouisvilleAlantaCharlotteNorfolkColumbiaRoanokeJohnstownColumbusFt WayneLansingToledoDetroitFarmingtonBaltimoreClevelandPhiladelphiaWilkes-BarreDedhamRochesterAREA SC SE NA NC WAmerican Red CrossBlood Service Regions%San Juan
DallasTucsonMobileBirminghamWichitaOaklandLos AngelesLittle RockTulsaPortlandBoiseBoisePortlandBoiseBoiseSt LouisOmahaMadisonSt PaulPeoriaNashvilleLouisvilleAlantaCharlotteNorfolkColumbiaRoanokeJohnstownColumbusFt WayneLansingToledoDetroitFarmingtonBaltimoreClevelandPhiladelphiaWilkes-BarreDedhamRochesterAREA SC SE NA NC WAmerican Red CrossBlood Service Regions%San Juan
Tucson Birmingham
Oakland
Los Angeles
Little Rock
Portland Boise
St Louis
Omaha
Madison
St Paul
Nashville
Louisville
Atlanta
Charlotte
Columbia
Roanoke
JohnstownColumbus
Ft Wayne
Lansing
Toledo
Detroit
Farmington
Baltimore
Cleveland
Philadelphia
Dedham
West Henrietta
San Juan
Tulsa
Wichita
Mobile
Peoria
Wilkes-Barre
Norfolk
Male Predominant 24-hour Plasma Pilot: December 2006
99.3% male
95.2% male
98.0% male
97.6% male
Overall 72.7% FP24 Male
10April 2007
FFP (<8 hrs), FP24 (<24 hrs), and Cryo Poor Plasma Selective use of male products achieving >95% male plasma
distributions by November 2007Longer term goal is 100% male plasmaLeeway reserved to ensure availability Currently collect enough AB plasma to ensure 92% Male Will need to move to >80% FP24 (<24 hrs) FFP (<8 hours) will become a specialty product Final Product will not be labeled with Donor Gender
Apheresis Plasma (Auto-C, excluding concurrent) Donor history + Testing (details still under evaluation) by
November 2007
Apheresis Platelets and Concurrent Plasma Donor history + Testing (details still under evaluation) by
November 2008
Overview of Red Cross Approach
95%
5%
Shar
e of
tran
sfus
able
pl
asm
a di
strib
utio
ns
11April 2007
Overview: Impact on Customers
73%
27%
FY02 FY07(YTD)
55%45%
FY08
FFP FP24
To achieve 95% male distributions and maintain fill rates, the American Red Cross will need to substantially increase the proportion of FP24 distributed (from 45% today). Specific messaging to Hospitals is being developed to notify and educate customers.
12April 2007
0
50,000
100,000
150,000
200,000
250,000
Male
Female
60% 67% 90% 53% 67% 63%
Approach to Apheresis Products (in development)
Proportion of Male Apheresis Donors
13April 2007
Approach to Apheresis Products (in development)
Prestorage pooled whole blood-derived platelets are being developed as an alternative
We assume that we must test, though donor history may play a role
REDS II LAPS alloantibody data needed to define who should be screened What is the prevalence in untransfused males?
If a significant proportion of untransfused males harbor antibodies, will this necessitate universal testing?
What is the incremental prevalence with transfusion? What is the incremental prevalence with pregnancy?
14April 2007
Issues Regarding Testing for Alloantibodies
No FDA licensed assays for donor screening
No suitable technology for routine Human Neutrophil Antibody (HNA) screening
U.S. manufacturers are developing automated HLA class I and class II antibody screening technologies
Uncertainties remain What is the appropriate screening strategy? How do we define a clinically relevant positive test? What is the appropriate donor deferral? Are product recalls and withdrawals appropriate?
15April 2007
Summary
Prudent measures to reduce patient exposure to alloantibodies may markedly reduce risk.
Availability issues with AB plasma and apheresis platelets argue against product gender labeling and the use of only male plasma-rich products.
Uncertainty regarding the etiology of TRALI, the lack of available antibody screening technology and a poor understanding of the role of specific antibodies prevents and argues against universal history and/or antibody screening at this time.