ANTIBODY PRODUCTION ANTIBODY PRODUCTION 5/20/2015 IMPLICATION OF HLA ANTIBODIES & TRALI MITIGATION PROGRAM

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Roxanne Sutton
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1 IMPLICATION OF HLA ANTIBODIES & TRALI MITIGATION PROGRAM Massimo Mangiola, Ph.D. Director, Special Services Rhode Island Blood Center LEARN Webinars: Management of TRALI May 21, :00 3:30 pm (EDT) ANTIBODY PRODUCTION ANTIBODY PRODUCTION 1

2 ANTIBODY PRODUCTION ANTIBODY RESPONSE ANTIBODY RESPONSE 2

3 ANTIBODY CLASSES ANTIBODY CLASSES ANTIBODY CLASSES 3

4 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? 4

5 WHAT IS NON-SELF ON A HLA MOLECULE? WHAT IS NON-SELF? HOW IS NON-SELF ON A HLA MOLECULE RECOGNIZED? 5

6 HOW IS NON-SELF ON A HLA MOLECULE RECOGNIZED? ANTIBODY ½ LIFE PREGNANCY ANTIBODY 6

7 HOW CAN HLA ANTIBODIES CAUSES TRALI? 7

8 THE PERFECT STORM THE PERFECT STORM About 9mm THE PERFECT STORM 8

9 THE PERFECT STORM Lumen: 5.5 mm Distance from alveolus: 0.5 mm THE PERFECT STORM Lumen: 5.5 mm Distance from alveolus: 0.5 mm THE PERFECT STORM 9

10 HLA ANTIBODIES & TRALI ANTIBODY-DEPENDENT MODEL Class I HLA antibody Class II HLA antibody or FcgR 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? 10

lungs (cytokines promote priming and adherence of neutrophils).

DONORSCREEN HLA ASSAY DONORSCREEN HLA ASSAY LUMINEX SCREENING

11 HLA ANTIBODY DETECTION LUMINEX SOLID PHASE SOLID PHASE ANTIBODY 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 11

12 HLA ANTIBODY DETECTION LUMINEX SOLID PHASE SOLID PHASE ANTIBODY SCREENING ANTIBODY SCREEN ASSAY ELISA-BASED ANTIBODY SCREENING DONORSCREEN HLA ASSAY DONORSCREEN HLA ASSAY RHODE ISLAND BLOOD CENTER EXPERIENCE 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) 12

releases statement to encourage considering TRALI reduction strategies First AABB bulletin on TRALI AABB Standard 5.4.1.

THE RIBC EXPERIENCE RIBC Donor Population Age groups High volume plasma donors 36,952 previously pregnant female >60 21% 0-20(0.5%) 21-40 22% 41-60 56.

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

5% Data Range: 2008 to April 2015 THE RIBC EXPERIENCE 40000 36952 30000 TOTAL 20000 23823 NEGATIVE POSITIVE 10000 13129 (35.

THE RIBC EXPERIENCE Negative 41-60 (36.9%) >60 (28.8%) Positive High volume plasma donors Rate of positive donors Normalized data by age group 21-40 (36.

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

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

15 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, :00 3:30 pm (EDT) 15

Because age of donor does not seems to be a factor, changes in recruitment strategies may not help in decreasing the positive rate.

Evaluation of the Patient with Suspected Platelet Refractory State

$Evaluation of the Patient with Suspected Platelet Refractory State$ Evaluation of the Patient with Suspected Platelet Refractory State NOTE: While evaluating the patient for suspected immune refractory state provide ABO matched platelets if available. 1. Determine if the