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.