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1. Providing the Best-Matched Blood
The Present and the Future
James P. AuBuchon, MD, FCAP, FRCP(Edin)
President & CEO
Professor of Medicine and of Laboratory Medicine
University of Washington
Blood Bank of Hawaii
Transfusion Medicine Symposium
August 6, 2016

2. Disclosures
• I have no financial relationships
related to this presentation.
• I will not be speaking about any
specific commercial product,
device, or medication.
• I will not be speaking of any off
label use of medications or devices

3. The Evolution of Matching
ABO
Rh: D, C, c, E, e …
M, N, S, s, P, I, Jka
, Jkb
, Fya
,
Fyb
, Doa
, Dob
, Wra
, K, k, V, VS,
Goa
and over 200 others!

4. What Does Matching Mean to You?
Alloimmunized patient
- for current and past specificities
- acknowledgement of “responder” status (?)
Inability to perform an antibody screen or crossmatch
- e.g., panagglutinin
Chronically transfused patients (prospective matching)

5. Finding Those Who Need a Better Match
I II III
III + + + - + - -
I - - + - + - +
II + + - + - + -
Reagent Cells' Phenotypes Reactions
I.S. 37C AHGJkaKeEcCD
Antibody Screen for red cell alloantibodies
- - -
- - +
- - -
Antibody identification
Unit screening  Unit typing
Crossmatching

6. Finding Those Who Need a Better Match
I II III
III + + + - + - -
I - - + - + - +
II + + - + - + -
Reagent Cells' Phenotypes Reactions
I.S. 37C AHGJkaKeEcCD
Antibody Screen for red cell alloantibodies
- -
- - +
- - +
+
Panagglutinin?
Alloantibody “underneath”?

7. Finding Those Who Need a Better Match
I II III
III + + + - + - -
I - - + - + - +
II + + - + - + -
Reagent Cells' Phenotypes Reactions
I.S. 37C AHGJkaKeEcCD
Antibody Screen for red cell alloantibodies
- -
- 3+
- - 2+
1+
Multiple specificities?
1+

8. Preventing Alloimmunization
Who?
- All patients
- Women of child-bearing potential
- Chronically transfused patients
- “Responders”
- WAIHA patients
How?
- Pathogen inactivation (?)
- Prospective matching
- Limited
- Extensive
- “Complete”

9. Who Needs Prevention?
Transfused Sickle Cell Disease Patients
Alloimmunization
58%
15%
62% with “unexplained” Rh Abs
 delayed reactions in one-third
Chou ST et al. Blood 2013; 122:1062-71.
Phenotypically and racially matched donor
insufficient to prevent alloimmunization.
High-resolution genotyping:
87% of patients had Rh variants

10. Drawing courtesy of Suzanne Lentzsch, Columbia University
Multiple Myeloma Plasma Cell
CD38
CD38
Daratumumab
(Darzelex™)
Monoclonal Antibody Immunotherapy
NK Cell

11. CD38
Reagent red cell
Anti-CD38 in
patient serum
Y
Anti-IgG
Y
Positive Ab Screen
“Panagglutinin”
but negative DAT
Monoclonal Antibody Immunotherapy
Complications…
About one-third of myeloma
patients require RBC transfusions

12. CD38
Reagent red cell
Anti-CD38 in
patient serum
Monoclonal Antibody Immunotherapy
Counteracting the complications…
Cord red cell
Schmidt AE et al. Transfusion 2015;55:2292-3.

13. CD38
Reagent red cell
Anti-CD38 in
patient serum
Monoclonal Antibody Immunotherapy
YAnti-idiotype antibody
Anti-CD38 in
patient serum
YAnti-idiotype antibody
Counteracting the complications…
Oostendorp M et al. Transfusion 2015;55:155-62.
Lokhorst HM et al. ASCO Meeting Abstr 2013;31(15 Suppl):8512.

14. CD38
Reagent red cell
Anti-CD38 in
patient serum
Monoclonal Antibody Immunotherapy
Counteracting the complications…
DTT
DTT
DTT
Chapuy CI et al. Transfusion 2015;55:1545-54.

15. CD38
Reagent red cell
Anti-CD38 in
patient serum
Monoclonal Antibody Immunotherapy
Counteracting the complications…
K k
Kpa
Kpb
Jsa
Jsb
Lua
Lub
Doa
Dob
Yta
Ytb
DTT
DTT  Impaired ability to detect antibodies with Kell,
Dombrock, Lutheran or Cartwright specificity
Provide units matched for (at least) K
Chapuy CI et al. Transfusion 2015;55:1545-54.

16. Monoclonal Antibody Immunotherapy
Avoiding the complications…
Before therapy:
Document lack of antibodies
Phenotype/Genotype
Panagglutinin but negative DAT:
Check history
Demonstrate cause
Provide matched RBCs

17. Wilkinson K et al. Transfusion 2012:52; 381-8.
Is Matching Feasible?
ABO, D, C, c, E, e, K + Fya
, Fyb
+ Jka
, Jkb
, S, s
Of 70 SCD pts:
from 10,000 donors

18. One Approach to Genotyping
BioArray – Since 2006
Donors: Group O  A  B
≥ 10 donations  8  4
Phenotyping: C/c, E/e
automated
Self-identified African-American
Genotyping: R1R1, R2R2, RoRo, rr
15,000+ phenotyped donors (35 antigens)
Research Institute  USN contract for genotyping research  Rotary grant  IRL

19. Passing Along the Information
O neg
Donor genotyped as
C-E-K-Fy(a-b-)Jk(a-b+)
BPAC: November, 2014
FDA: February, 2015
(must request variance)
Two separate donations genotyped

20. Serving 90 hospitals with over 300,000 blood components annually.

21. Providing the Best-Matched Blood
The Present and the Future
Objectives
Identify two antibody workup situations in which red cell genotyping
should be considered.
Name two patient populations that would benefit from prospective
phenotype/genotype matched red cells.