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    Managing Blood Bank Challenges in Multiple Myeloma

    Multiple myeloma and its treatments can create unique challenges when patients need blood. One common therapy, daratumumab (Darzalex), interferes with blood compatibility testing, often delaying transfusions. This article explains how multiple myeloma is diagnosed, how daratumumab affects blood matching, and what patients can do to help ensure safe, timely care.

    Michele Palermo, MLS(ASCP), CLT(NYSED)
    Managing Blood Bank Challenges in Multiple Myeloma

    What Is Multiple Myeloma?

    Multiple Myeloma, also called Kahler’s disease, is a rare cancer of the plasma cells. Plasma cells are a type of white blood cell found in the bone marrow. Plasma cells are responsible for producing immunoglobulins. Immunoglobulin allows your body to fight off pathogens efficiently.

    How is Multiple Myeloma Diagnosed

    On the CBC, you may see low red blood cell counts, along with red cells that are different in size or shape. These changes show up in the red cell indices (indicator): MCV, MCH, MCHC, and RDW. White blood cells may also be lower than normal, depending on how the disease is affecting the bone marrow. It might also be caught in a metabolic panel. A common blood test ordered by providers which looks at your liver, kidneys, metabolism and chemical balance. In multiple myeloma a key clue is a high total protein level. If that happens, a follow-up test might show an abnormal protein called an M-protein, which is linked to multiple myeloma. Sometimes, a urine test is done as well, which may detect Bence Jones proteins, another sign of the disease.

    Once caught in blood work imaging such as MRI and X rays may be used to look for bone damage. Bone marrow aspiration or a biopsy are typically used for confirmatory testing. They will look for the myeloma cells directly and use cytogenetics to confirm the disease.

    Why These Proteins Matter

    • They can coat the surface of blood cells, making it harder for the cells to do their job.
    • They can make the plasma “thicker”, which puts extra strain on the heart and kidneys.
    • They may interact with medications or natural compounds in the body, which can cause unusual test results or side effects.

    What Is Daratumumab/Darzalex (Dara)?

    Daratumumab is a medication used for multiple myeloma that works by attaching to CD38 proteins on red blood cells. You can think of CD markers (cluster of differentiation markers) as protein name tags. The binding of CD38 kills myeloma cells by encouraging the immune system to destroy them. The drug also enhances other immune cells' ability to fight the cancerous cells.

    What complication is often seen with Dara?

    Patients taking Dara often show falsely positive results on antibody screening and antibody identification panels. The pattern shows “panagglutination”, meaning all cells show up positive. This can hide antibodies that could be dangerous. Many blood banks are not equipped to work up Dara patients to completion. This forces many blood banks to ask for extra tubes to send out to reference labs for a Dithiothreitol assay (DTT). Results may take a day to several days to receive back.

    Why Is This Test Ordered?

    A DTT assay denatures (changes) an antigen called CD38 on red blood cells. This prevents Dara from binding to CD38, allowing hidden antibodies to be exposed.

    How Should You Prepare for the Test?

    This test requires no special preparation by the patient. A healthcare member will draw the quantity of tubes that the reference lab requires for a DTT test at a later time than your original sample.

    How does this affect time and blood availability?

    DTT testing requires more time for safe blood to be received by patients. This is due to extended workup requirements, such as send-out tests and finding safe units. The test also removes the antibody Kell from red blood cells, meaning that there is still the potential for it to hide. Blood for these patients will require Kell antigen-negative units and a full crossmatch, which takes additional time. Should any other antibody be found, the rarity will determine if the unit needs to be sourced and how long it might take to receive. These units will have further testing before they can be fully crossmatched to the patient.

    What do the results mean?

    If the reference lab informs the blood bank that no additional antibodies were found, the blood bank will do a full crossmatch. Kell-negative blood will be given to prevent a potential reaction and lower the risk of future transfusions. If the results show other antibodies hiding due to Dara, the blood bank will give units negative for the antigens found, along with Kell-negative units.

    What can be done to speed up care?

    A patient who has a history of Dara within the last six months should mention the use of this drug to any Physician they see, especially emergency room staff.

    Any blood transfusion history from other hospitals or centers should also be disclosed.

    This information should be communicated to the blood bank as soon as possible to prevent drawn-out workups and also allow for proper coordination to be made with reference laboratories.

    Patients who have had a Type and Screen done before starting Dara, with no recent blood transfusions or pregnancies, help to ease concerns. Depending on the severity of your situation, this may allow you to receive blood sooner than a patient without a history.

    Questions to Ask Your Provider

    • How may Dara affect my care?
    • If going for an operation, how might this affect my pre-admission testing sample per hospital policy?
    • Would a Type and Screen before starting Dara be an option for me?

    Final Takeaway

    Daratumumab/ Darzalex(Dara) is a drug commonly used for Multiple Myeloma, a rare cancer that affects plasma cells. Dara works by binding to the CD38 antigen. Patients on Dara often show false-positive screens and antibody identifications. This can hide antibodies underneath that could be dangerous. A send-out test called the Dithiothreitol assay (DTT) helps to denature the CD38 antigen, revealing hidden antibodies. The additional testing can add several hours or days to finding blood for a multiple myeloma patient.

    Sources:

    Cancer Research UK. "Myeloma (multiple myeloma)."

    American Cancer Society. "What Is Multiple Myeloma?"

    Darzalex HCP. "Mechanism of Action of Daratumumab (DARZALEX®)."

    Fay, P. J., & Glanville, A. R. "Managing CD38 interference in pretransfusion testing." Transfusion, 2018; 58(6):1350–1357.

    This information is not a substitute for, nor does it replace professional medical advice, diagnosis, or treatment. If you have any concerns or questions about your health, you should always consult with a healthcare professional.