IMPLICATION OF HLA ANTIBODIES & TRALI MITIGATION PROGRAM

Transcription

1 IMPLICATION OF HLA ANTIBODIES & TRALI MITIGATION PROGRAM LEARN Webinars: Management of TRALI June 23, :00 3:30 pm (EDT) Massimo Mangiola, Ph.D. Director, Special Services Rhode Island Blood Center

2 ANTIBODY PRODUCTION

3 ANTIBODY PRODUCTION

4 ANTIBODY PRODUCTION

5 ANTIBODY RESPONSE

6 ANTIBODY RESPONSE

7 ANTIBODY CLASSES

8 ANTIBODY CLASSES

9 ANTIBODY CLASSES

10 WHAT TRIGGERS THE IMMUNE SYSTEM TO GENERATE HLA ANTIBODIES?

11 WHAT CAN INDUCE ANTIBODY PRODUCTION? TRANSPLANT TRANSFUSION PREGNANCY

12 WHAT IS NON-SELF ON A HLA MOLECULE?

13 WHAT IS NON-SELF ON A HLA MOLECULE?

14 WHAT IS NON-SELF?

15 HOW IS NON-SELF ON A HLA MOLECULE RECOGNIZED?

16 HOW IS NON-SELF ON A HLA MOLECULE RECOGNIZED?

17 ANTIBODY ½ LIFE

18 PREGNANCY ANTIBODY

19 HOW CAN HLA ANTIBODIES CAUSES TRALI?

20

21

22 THE PERFECT STORM

23 THE PERFECT STORM About 9µm

24 THE PERFECT STORM

25 THE PERFECT STORM Lumen: 5.5 µm Distance from alveolus: 0.5 µm

26 THE PERFECT STORM Lumen: 5.5 µm Distance from alveolus: 0.5 µm

27 THE PERFECT STORM

28 HLA ANTIBODIES & TRALI ANTIBODY-DEPENDENT MODEL Class I HLA antibody Class II HLA antibody or FcγR

29 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.)

30 HOW CAN HLA ANTIBODIES BE DETECTED IN THE LABORATORY?

31 HLA ANTIBODY DETECTION LUMINEX SOLID PHASE SOLID PHASE ANTIBODY SCREENING ANTIBODY SCREEN ASSAY ELISA-BASED ANTIBODY SCREENING DONORSCREEN HLA ASSAY DONORSCREEN HLA ASSAY

32 LUMINEX SCREENING

33 ELISA SCREENING INCUBATION WASH INCUBATION WASH DETECTION INCUBATION STOP

34 HLA ANTIBODY DETECTION LUMINEX SOLID PHASE SOLID PHASE ANTIBODY SCREENING ANTIBODY SCREEN ASSAY ELISA-BASED ANTIBODY SCREENING DONORSCREEN HLA ASSAY DONORSCREEN HLA ASSAY

35 RHODE ISLAND BLOOD CENTER EXPERIENCE

36 TRALI MITIGATION TIMELINE ABC releases statement to encourage considering TRALI reduction strategies First AABB bulletin on TRALI AABB Standard to be implemented ~ present 2016 CDC Screening Luminex Solid Phase ELISA (DonorScreen HLA)

37 THE RIBC EXPERIENCE RIBC Donor Population Age groups High volume plasma donors 36,952 previously pregnant female >60 21% 0-20(0.5%) % % Data Range: 2008 to April 2015

38 THE RIBC EXPERIENCE TOTAL NEGATIVE POSITIVE (35.5%) 0 FEMALE BLOOD DONORS Data Range: 2008 to April 2015

39 THE RIBC EXPERIENCE Negative Positive High volume plasma donors 36,952 previously pregnant female 23, 823 negative for HLA antibodies 13,129 positive for HLA antibodies (59.3%) (23%) >60 (17.3%) 0-20 (0.4%) Data Range: 2008 to April 2015

40 THE RIBC EXPERIENCE Negative (36.9%) >60 (28.8%) Positive High volume plasma donors Rate of positive donors Normalized data by age group (36.5%) 0-20 (28%) Data Range: 2008 to April 2015

41 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 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.

42 CONCLUSION Mitigation proves to be effective in reducing TRALI occurrence An action plan must be in place by October 1 st, 2016

43 CONCLUSION Mitigation proves to be effective in reducing TRALI occurrence An action plan must be in place by October 1 st, 2016

44 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?

45 LEARN Webinars: Management of TRALI May 21, :00 3:30 pm (EDT)