Providing Best Matched Blood by James AuBuchon

Providing the Best-Matched BloodThe Present and the Future

James P. AuBuchon, MD, FCAP, FRCP(Edin)President & CEO

Professor of Medicine and of Laboratory MedicineUniversity of Washington

Blood Bank of HawaiiTransfusion Medicine Symposium

August 6, 2016

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

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!

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)

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 identificationUnit screening Unit typingCrossmatching


I II III

III + + + - + - -

I - - + - + - +

II + + - + - + -




- -

- - +

- - +

+

Panagglutinin?Alloantibody “underneath”?


I II III

III + + + - + - -

I - - + - + - +

II + + - + - + -




- -

- 3+

- - 2+

1+

Multiple specificities?

1+

Preventing Alloimmunization

Who?- All patients- Women of child-bearing potential- Chronically transfused patients- “Responders”- WAIHA patients

How?- Pathogen inactivation (?)- Prospective matching

- Limited- Extensive- “Complete”

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

Drawing courtesy of Suzanne Lentzsch, Columbia University

Multiple Myeloma Plasma Cell

CD38

CD38

Daratumumab (Darzelex™)

Monoclonal Antibody Immunotherapy

NK Cell

CD38

Reagent red cell

Anti-CD38 in patient serum

YAnti-IgG YPositive Ab Screen

“Panagglutinin”but negative DAT

Monoclonal Antibody ImmunotherapyComplications…

About one-third of myeloma patients require RBC transfusions

CD38

Reagent red cell


Monoclonal Antibody ImmunotherapyCounteracting the complications…

Cord red cell

Schmidt AE et al. Transfusion 2015;55:2292-3.

CD38

Reagent red cell


Monoclonal Antibody ImmunotherapyY

Anti-idiotype antibody


Y

Anti-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.

CD38

Reagent red cell



DTT

DTT

DTT

Chapuy CI et al. Transfusion 2015;55:1545-54.

CD38

Reagent red cell



K kKpa

Kpb

Jsa

Jsb

Lua

Lub

DoaDob

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.

Monoclonal Antibody ImmunotherapyAvoiding the complications…

Before therapy:Document lack of antibodiesPhenotype/Genotype

Panagglutinin but negative DAT:Check historyDemonstrate causeProvide matched RBCs

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

One Approach to GenotypingBioArray – Since 2006

Donors: Group O A B≥ 10 donations 8 4

Phenotyping: C/c, E/e automated

Self-identified African-AmericanGenotyping: R1R1, R2R2, RoRo, rr

15,000+ phenotyped donors (35 antigens)

Research Institute USN contract for genotyping research Rotary grant IRL

Passing Along the Information

O negDonor genotyped as C-E-K-Fy(a-b-)Jk(a-b+)

BPAC: November, 2014FDA: February, 2015 (must request variance)

Two separate donations genotyped

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

Providing the Best-Matched BloodThe 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.

Health & Medicine

Providing Best Matched Blood by James AuBuchon