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    1 ISBT Immunohematology WP Case Study201601 FINAL

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    Inmunohematogia

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    1 ISBT Immunohematology WP Case Study201601 FINAL

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    Inmunohematogia

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    1-ISBT-Immunohematology-WP-Case-Study201601-FINAL

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    Inmunohematogia

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    2 views20 pages

    1 ISBT Immunohematology WP Case Study201601 FINAL

    Uploaded by

    angel alex g
    Inmunohematogia

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 20

    Immunohematology Case Studies

    2016 - 01

    Sofia Lejon Crottet, PhD


    Swiss National Immunohematology
    Reference Laboratory
    Interregional Blood Transfusion SRC Ltd.
    [email protected]
    Clinical History

    • 74 year old male with multiple myeloma


    undergoing a treatment with Daratumumab
    (DARA)
    • Admitted to the hospital with anemia, three units
    of blood needed
    Immunohematology Laboratory
    History

    • In December of 2015
    • Negative antibody screen
    • DAT negative
    • Extended genotype (KEL, JK, FY, MNS,
    CO, YT, LU, DO)
    Current Sample Presentation Data

    ABO/Rh: O, D+ C+ c+ E- e+
    DAT: negative

    Antibody Screen Method: IAT in Gel Antiglobulin


    (ID Gel AHG) card with six test cells in LISS, four
    untreated and two cells treated with papain (Bio-
    Rad) were used simultaneously

    Antibody Screen Results:


    all four untreated test cells were weakly reactive,
    while the papain cells showed a very weak reactivity
    Current Sample Presentation Data

    Antibody Identification Method:


    IAT in ID Gel AHG card with eight untreated test
    cells (in-house) in LISS (ID/IAT) and IAT in natural
    card with papain treated cells (in-house) in LISS
    (papain/IAT)

    Antibody Identification Preliminary Results:


    all cells reacted weakly positive in ID/IAT, whereas
    only three out of eight papain treated cells reacted
    very weakly with the patient plasma
    Question

    1) What could be the cause of the panreactivity


    seen in ID/IAT?
    Challenge with the Current
    Presentation

    The clue to this case is the treatment with DARA.


    DARA is an IgG1k human monoclonal antibody
    targeting the cell-surface protein CD38. It is in
    clinical development for the treatment of multiple
    myeloma (MM). MM cells have a high expression of
    CD38 making it an interesting therapeutic target.
    However, CD38 is also expressed at low levels on
    red blood cells (RBC). The anti-CD38 (DARA) found
    in the patients plasma/serum is what is causing the
    panreactivity as it binds to CD38 on the test cells.
    In-house Panel Results

    Nr. D C c E e Cw K k Fya Fyb Jka Jkb Lea Leb P1 M N S s ID/IAT papain


    1 + + 0 0 + 0 0 + 0 w 0 + + 0 + + + + 0 w 0
    2 + 0 + + 0 0 + + + 0 + 0 0 + + + + + + w 0
    3 + + 0 0 + + 0 + 0 + 0 + 0 w + 0 + 0 + w 0
    4 0 0 + 0 + 0 0 + + 0 0 + 0 0 + + 0 0 + w -/+
    5 0 + + 0 + 0 0 + + 0 + + 0 + + 0 + 0 + w 0
    6 0 0 + + + 0 0 + 0 + + 0 0 + 0 + + + 0 w 0
    7 0 0 + 0 + 0 0 + + + + 0 0 + + + + + + w -/+
    8 0 0 + 0 + 0 + + 0 + + + 0 + 0 + 0 0 + w -/+
    Interim Antibody Identification
    Possible Answers and Next Steps

    Due to the presence of CD38 on the test cells DARA


    will interfere with the antibody screening, antibody
    identification as well as the crossmatch. DARA
    bound to the test cells will thus mask detection of
    potential allo-antibodies to erythroid antigens.

    DARA will however not interfere with the standard


    identification of ABO/RhD antigens. This is not true
    for the RhD testing at antiglobulin phase.
    Question

    2) What would be the next step?


    Further Work

    In order to eliminate the interference of anti-CD38


    test cells can be treated with trypsin or dithiothreitol
    (DTT).

    Reduction or elimination of reactivity due to anti-


    CD38 is achieved by enzymatic digestion by trypsin
    or disulfide bond reduction by DTT, with trypsin
    treatment less efficient than DTT treatment.
    Further Testing Results and
    Interpretations

    Nr. D C c E e Cw K k Fya Fyb Jka Jkb Lea Leb P1 M N S s trypsin DTT


    1 + + 0 0 + 0 0 + 0 w 0 + + 0 + + + + 0 0 0
    2 + 0 + + 0 0 + + + 0 + 0 0 + + + + + + 0 0
    3 + + 0 0 + + 0 + 0 + 0 + 0 w + 0 + 0 + 0 0
    4 0 0 + 0 + 0 0 + + 0 0 + 0 0 + + 0 0 + 0 0
    5 0 + + 0 + 0 0 + + 0 + + 0 + + 0 + 0 + 0 0
    6 0 0 + + + 0 0 + 0 + + 0 0 + 0 + + + 0 0 0
    7 0 0 + 0 + 0 0 + + + + 0 0 + + + + + + 0 0
    8 0 0 + 0 + 0 + + 0 + + + 0 + 0 + 0 0 + 0 0
    Question

    3) Which blood group antigens are completely or


    partially destroyed by trypsin and/or DTT?
    Further Testing Results and
    Interpretations

    Trypsin, which is an endopeptidase belonging to the


    family of serine proteases, cleaves peptide chains
    mainly at the carboxyl side of the amino acids lysine
    or arginine, except when either is followed by a
    proline.

    It is important to remember that blood group


    antigens Ch, Rg, Yka, Kna, McCa, and partially JMH,
    and antigens in the GE, LU, MN blood group
    systems are destroyed by trypsin.
    Further Testing Results and
    Interpretations
    DTT, which is a reducing agent, acts on CD38 by
    disrupting the extracellular disulfide bonds.

    DTT also destroys blood group antigens, such as


    Raph and JMH, and antigens in the KEL, KN, LW,
    LU, YT, DO and IN blood group systems.

    Papain, which is a cysteine protease enzyme, will


    also have a proteolytic activity on CD38.

    Antigen typed cord cells have been reported to be


    useful in ruling out antibodies to high prevalence
    antigens
    Question

    4) What could be done in order to reduce the risk


    of an alloimmunization?
    Genotyping Results

    Since certain blood group antigens are destroyed


    when the test cells are treated with trypsin or DTT, it
    is recommended to pheno- or genotype the patient
    (if possible before treatment with DARA). In that
    way, the patients can be transfused with
    phenosimilar blood units without time delay and the
    risk of alloimmunization is reduced.
    Summary and Conclusions

    • DARA interferes with the antibody screening, causing


    an panreactivity that can mask clinically significant allo-
    antibodies
    • The interference can be eliminated by treating the test
    cells with trypsin or DTT
    • Detection of clinically significant antibodies like anti-K
    and anti-Yta is not feasible when using DTT treated test
    cells
    • Transfusion of ABO/RhD and K compatible blood units
    is recommended
    • Knowledge of patient red cell antigen types that are
    destroyed by DTT or trypsin may also be important in
    future transfusion therapy
    Lessons Learned by the Case

    The information that the patient is undergoing a


    Daratumumab therapy is essential for a correct and
    rapid pretransfusion workup.

    An antibody screen and an extended genotype


    before the first Daratumumab distribution will
    contribute to a blood product distribution without
    time delay.
    References

    1. Chapuy CI, Nicholson RT, Aguad MD, et al. Resolving the


    daratumumab interference with blood compatibility testing.
    Transfusion. 2015;55(6Pt2):1545-1554.
    2. Oostendorp M, Lammerts van Bueren JJ, Doshi P, et al. When
    blood transfusion medicine becomes complicated due to
    interference by monoclonal antibody therapy. Transfusion.
    2015;55(6Pt2):1555-62.

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