The impact of medication on blood transfusion testing has been highlighted in the case of daratumumab, a monoclonal antibody used in the treatment of multiple myeloma. Blood transfusion involves the transfer of healthy donor blood to a recipient through intravenous venipuncture. Donor blood is typically separated into components such as packed red blood cells, platelets, plasma, and white blood cells, which are then used as therapeutic requirements for patients. However, when whole blood is used, it can only be used as autologous blood for the same patient.

Donors must meet certain criteria established by AABB to ensure the safety and security of blood collection, including screening for diseases such as HIV, hepatitis C virus, and hepatitis B virus, as well as drugs that may interfere with transfusion testing. Patients must also undergo pre-transfusion testing to ensure the compatibility and absence of alloantibodies. When substantial alloantibodies are present, further testing is necessary to determine the appropriate blood group for the patient.

Multiple myeloma is a condition marked by the accumulation of malignant plasma cells in the bone marrow. While the cause is unknown, exposure to radiation, toxins, and chromosomal abnormalities may contribute to the development of myeloma cells. Symptoms of MM include hypercalcemia, anemia, renal impairment, and bony pain, and may be diagnosed through tests such as CBC and biochemistry tests, serum electrophoresis, and immunofixation. While a cure for MM has not been discovered, chemotherapy and stem cell transplantation can induce remission.

Daratumumab is a monoclonal antibody that targets CD38, which is highly expressed in MM cells. It induces ADCC, CDC, ADCP, and apoptosis in MM cells and has become an effective treatment for the condition. However, it interferes with antibody identification and cross-matching based on indirect antiglobulin tests (IAT).

The use of Daratumumab in patients has led to unnecessary testing and delays in blood delivery due to the antibody's interference. Interference with alloantibody recognition can cause severe reactions, raising concerns about transfusion safety, particularly in emergency situations. Research has demonstrated several methods to reduce Daratumumab interference in pre-transfusion testing.

One method involves using red blood cells (RBCs) with degraded or missing CD38 antigens for pre-transfusion testing. Studies have shown that CD38 can be denatured using a reducing agent like dithiothreitol (DTT) or cleaved from the cell surface using trypsin. This interference can be resolved by blocking the binding of Daratumumab to CD38 on reagent RBCs through various methods, such as using F(ab)2 fragments of Daratumumab or anti-CD38 monoclonal antibodies.

Another approach involves using reagent cells lacking CD38 antigens or cord blood cells with little or no CD38 on their surface. This method has proven successful in screening patients' plasma and avoiding interference.

Lastly, prior to IAT testing, anti-CD38 antibody neutralization in patient plasma samples can be utilized. The use of an anti-idiotype antibody and recombinant soluble CD38 extracellular domain protein can effectively inhibit interference by Daratumumab and similar antibodies.

Clinicians caring for patients receiving Daratumumab should notify the blood bank of the patient's use. These methods can aid in reducing interference and ensuring transfusion safety.

In the future, monoclonal antibody therapy will be increasingly popular. An example of this is Daratumumab, which highlights the importance of recognizing potential therapeutic agent interferences with pre-transfusion testing. It is crucial to develop appropriate methodologies to overcome these obstacles while maintaining good communication between the blood bank and the physician to ensure the patient's safety.

As the clinical use of Daratumumab increases, new ways are being developed to resolve the pre-transfusion test interference. It is essential for clinical providers and physicians to be aware of Daratumumab interference and contact a blood bank before starting therapy to conduct a baseline screen and test for the patient's phenotype. Additionally, they should set up a process to avoid Daratumumab interference if necessary. AABB has released a bulletin with guidance to aid transfusion services in dealing with Daratumumab interference.

References:

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3. Nedumcheril, M. T., DeSimone, R. A., Racine-Brzostek, S. E., Chaekal, O. K., & Vasovic, L. V. (2021). Overcoming Drug Interference in Transfusion Testing: A Spotlight on Daratumumab. Journal of Blood Medicine, Volume 12, 327–336. https://doi.org/10.2147/jbm.s213510

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1. Sullivan et al. (2017) conducted a study on the impact of daratumumab, an anti-CD38 monoclonal antibody, on red blood cells. They found that the use of the drug led to loss of CD38 on the surface of these cells.

2. Berthelier et al. (2000) investigated the conformational changes in human CD38 induced by ligands. Their study sheds light on the molecular mechanisms behind the effects of such molecules.

3. Chapuy et al. (2015) reported on the interference of daratumumab in blood compatibility testing. Their findings have important implications for the safe and effective use of this drug in clinical practice.

4. Schmidt et al. (2015) proposed an alternative method to dithiothreitol treatment for antibody screening in patients receiving daratumumab. This could provide a more reliable way to assess blood compatibility in affected patients.

5. Selleng et al. (2018) explored the use of F(ab')2 fragments to overcome the interference of daratumumab in transfusion tests. This offers a promising strategy to mitigate the effects of the drug in clinical settings.

6. Chinoca Ziza et al. (2019) proposed a blockage monoclonal antibody protocol as an alternative strategy to avoid anti-CD38 interference in immunohematological testing. Their study demonstrates the feasibility of this approach in real-world clinical settings.

7. Oostendorp et al. (2015) discussed the challenges associated with the use of monoclonal antibody therapy in blood transfusion medicine. They highlight the need for careful consideration of the implications of these treatments on patient safety and care.

The task at hand involves minimizing the interference caused by anti-CD38 during serologic testing. This is discussed in detail in the AABB Association Bulletin #16-02, which was published in 2016. You can refer to this bulletin for more information, as it is publicly available through the following link: http://www.aabb.org/programs/publications/bulletins/Documents/ab16-02.pdf. This link was accessed on May 3rd, 2021.