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 9 µ m
THE PERFECT “STORM”
THE PERFECT “STORM” Lumen: 5.5 µ m Distance from alveolus: 0.5 µ m
THE PERFECT “STORM” Lumen: 5.5 µ m Distance from alveolus: 0.5 µ m
THE PERFECT “STORM”
HLA ANTIBODIES & TRALI ANTIBODY-DEPENDENT MODEL Class II HLA antibody or Fc γ R Class I HLA antibody
HLA ANTIBODIES & TRALI ANTIBODY-INDEPENDENT MODEL (2 hit theory) 1 st EVENT (1 ST HIT) Recipient predisposing clinical condition resulting in the sequestration of primed neutrophils in the lungs (cytokines promote priming and adherence of neutrophils). 2 nd EVENT (2 ND HIT) Transfusion of blood product(s) carrying a biological substance able to activate primed neutrophils (i.e. leukocyte antibodies, DAMPs, LysoPC, etc.)
HOW CAN HLA ANTIBODIES BE DETECTED IN THE LABORATORY?
HLA ANTIBODY DETECTION SOLID PHASE ANTIBODY LUMINEX SOLID PHASE SCREENING ANTIBODY SCREEN ASSAY ELISA-BASED ANTIBODY SCREENING ™DONORSCREEN HLA ASSAY ™DONORSCREEN HLA ASSAY
LUMINEX SCREENING
ELISA SCREENING INCUBATION WASH INCUBATION WASH DETECTION INCUBATION STOP
HLA ANTIBODY DETECTION SOLID PHASE ANTIBODY LUMINEX SOLID PHASE SCREENING ANTIBODY SCREEN ASSAY ELISA-BASED ANTIBODY SCREENING ™DONORSCREEN HLA ASSAY ™DONORSCREEN HLA ASSAY
RHODE ISLAND BLOOD CENTER EXPERIENCE
TRALI MITIGATION TIMELINE AABB Standard 5.4.1.2 to be ABC releases statement to implemented encourage considering TRALI reduction strategies First AABB bulletin on TRALI ~1998 - 2008 - 2002 2004 2006 2016 2002 present Luminex ELISA CDC Solid Phase (DonorScreen HLA) Screening
THE RIBC EXPERIENCE 0-20(0.5%) RIBC Donor Population Age groups High volume plasma donors >60 21-40 36,952 previously pregnant female 21% 22% 41-60 56.5% Data Range: 2008 to April 2015
THE RIBC EXPERIENCE 40000 36952 30000 TOTAL NEGATIVE 23823 20000 POSITIVE 13129 10000 (35.5%) 0 FEMALE BLOOD DONORS Data Range: 2008 to April 2015
THE RIBC EXPERIENCE Negative >60 41-60 (17.3%) (59.3%) Positive 21-40 (23%) 0-20 High volume plasma donors 36,952 previously pregnant female (0.4%) 23, 823 negative for HLA antibodies 13,129 positive for HLA antibodies Data Range: 2008 to April 2015
THE RIBC EXPERIENCE Negative 41-60 >60 (36.9%) (28.8%) Positive 21-40 (36.5%) 0-20 (28%) 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 Donor age is NOT a factor; number of pregnancies may be more relevant 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.
CONCLUSION Mitigation proves to be effective in reducing TRALI occurrence An action plan must be in place by October 1 st , 2016
CONCLUSION Mitigation proves to be effective in reducing TRALI occurrence An action plan must be in place by October 1 st , 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)
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