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IMPLICATION OF HLA ANTIBODIES & TRALI MITIGATION PROGRAM
Massimo Mangiola, Ph.D. Director, Special Services Rhode Island Blood Center
LEARN Webinars: Management of TRALI June 23, 2015 2:00 – 3:30 pm (EDT)
ANTIBODY PRODUCTION
ANTIBODY PRODUCTION
ANTIBODY PRODUCTION
ANTIBODY RESPONSE
ANTIBODY RESPONSE
ANTIBODY CLASSES
ANTIBODY CLASSES
ANTIBODY CLASSES
WHAT TRIGGERS THE IMMUNE SYSTEM TO
GENERATE HLA ANTIBODIES ?
WHAT CAN INDUCE ANTIBODY PRODUCTION ?
TRANSPLANT
TRANSFUSION
PREGNANCY
WHAT IS NON-SELF ON A HLA MOLECULE ?
WHAT IS NON-SELF ON A HLA MOLECULE ?
WHAT IS NON-SELF ?
HOW IS NON-SELF ON A HLA MOLECULE RECOGNIZED ?
HOW IS NON-SELF ON A HLA MOLECULE RECOGNIZED ?
ANTIBODY ½ LIFE
PREGNANCY ANTIBODY
HOW CAN HLA ANTIBODIES
CAUSES TRALI ?
THE PERFECT “STORM”
THE PERFECT “STORM”
About 9µm
THE PERFECT “STORM”
THE PERFECT “STORM”
Lumen: 5.5 µm Distance from alveolus: 0.5 µm
THE PERFECT “STORM”
Lumen: 5.5 µm Distance from alveolus: 0.5 µm
THE PERFECT “STORM”
HLA ANTIBODIES & TRALI
Class I HLA antibody
ANTIBODY-DEPENDENT MODEL Class II HLA antibody or FcγR
HLA ANTIBODIES & TRALI
1st EVENT (1ST HIT)
Recipient predisposing clinical condition resulting in the sequestration of primed neutrophils in the lungs (cytokines promote priming and adherence of neutrophils).
2nd EVENT (2ND HIT)
Transfusion of blood product(s) carrying a biological substance able to activate primed neutrophils (i.e. leukocyte antibodies, DAMPs, LysoPC, etc.)
ANTIBODY-INDEPENDENT MODEL (2 hit theory)
HOW CAN HLA ANTIBODIES BE
DETECTED IN THE LABORATORY?
HLA ANTIBODY DETECTION
™DONORSCREEN HLA ASSAY
™DONORSCREEN HLA ASSAY
ANTIBODY SCREEN ASSAY
SOLID PHASE ANTIBODY SCREENING
LUMINEX SOLID PHASE
ELISA-BASED ANTIBODY SCREENING
LUMINEX SCREENING
ELISA SCREENING
INCUBATION WASH INCUBATION WASH
INCUBATION STOP
DETECTION
HLA ANTIBODY DETECTION
™DONORSCREEN HLA ASSAY
™DONORSCREEN HLA ASSAY
ANTIBODY SCREEN ASSAY
SOLID PHASE ANTIBODY SCREENING
LUMINEX SOLID PHASE
ELISA-BASED ANTIBODY SCREENING
RHODE ISLAND BLOOD CENTER EXPERIENCE
TRALI MITIGATION TIMELINE
CDC Screening
Luminex Solid Phase
ELISA (DonorScreen HLA)
ABC releases statement to encourage considering TRALI reduction strategies First AABB bulletin on TRALI
~1998 -2002 2002 2004 2006 2008 -
present 2016
AABB Standard 5.4.1.2 to be implemented
0-20(0.5%)
21-40 22%
41-60 56.5%
>60 21%
THE RIBC EXPERIENCE
RIBC Donor Population Age groups High volume plasma donors 36,952 previously pregnant female
Data Range: 2008 to April 2015
THE RIBC EXPERIENCE
0
10000
20000
30000
40000
FEMALE BLOOD DONORS
36952
23823
13129 (35.5%)
TOTALNEGATIVEPOSITIVE
Data Range: 2008 to April 2015
0-20 (0.4%)
Positive
Negative
41-60 (59.3%)
>60 (17.3%)
21-40 (23%)
THE RIBC EXPERIENCE
High volume plasma donors 36,952 previously pregnant female 23, 823 negative for HLA antibodies 13,129 positive for HLA antibodies
Data Range: 2008 to April 2015
0-20 (28%)
21-40 (36.5%)
41-60 (36.9%) >60
(28.8%)
Positive
Negative
THE RIBC EXPERIENCE
High volume plasma donors Rate of positive donors Normalized data by age group
Data Range: 2008 to April 2015
SUMMARY
TRALI is the leading cause of transfusion-related fatalities
HLA antibodies can induce TRALI in sensitized recipients
HLA pregnancy antibodies can disappear overtime
HLA antibodies detection can be done by Luminex or ELISA solid phase
RIBC TRALI Mitigation program started around 1998. Since then, only ~400 TRALI investigation have been done. Of these, only 5% had HLA antibodies in the donor sample and just a handful of cases may be due to reverse-TRALI.
Donor age is NOT a factor; number of pregnancies may be more relevant
CONCLUSION
Mitigation proves to be effective in reducing TRALI occurrence
An action plan must be in place by October 1st, 2016
CONCLUSION
Mitigation proves to be effective in reducing TRALI occurrence
An action plan must be in place by October 1st, 2016
CONCLUSION
Should positive donors be re-screened and when ?
If a donor is still positive after re-screen, should testing be repeated ? testing frequency ? for how long to re-test ? Because age of donor does not seems to be a factor, changes in recruitment strategies may not help in decreasing the positive rate.
Can PAS help us in re-entry of some aphaeresis donor ?
How do we establish which donor to re-entry with PAS ?
Should we consider transfusion risk ?
What about HNA antibody screening ?
What else ?
LEARN Webinars: Management of TRALI May 21, 2015 2:00 – 3:30 pm (EDT)
