Biomedical Excellence for Safer Transfusion

Press Release

20 July 2016 17:00 EDT

Oxford, UK -  Interference of New Drugs in Compatibility Testing for Blood Transfusion

The BEST Collaborative has drawn attention to the issue that novel drugs may have important yet underappreciated clinical consequences for patients requiring blood transfusion in Correspondence to the New England Journal of Medicine (N Eng J Med 375;3 July 21, 2016 LINK). Interference with routine methods for compatibility testing for blood transfusion puts patients at risk of delays in providing compatible blood. Even if laboratory methods are developed to circumvent the drug-related artefacts, it will take time to establish them in general laboratories.

Daratumumab (“DARA,” a monoclonal anti-CD38 manufactured by Janssen, Inc.), recently FDA-approved as a multiple myeloma therapy, was used as an illustrative case. Once enrollment in the phase I/II trial began, study sites quickly observed that DARA consistently interferes with routine blood compatibility testing. Standard serological methods to eliminate panreactive antibodies failed to resolve the DARA interference, at times delaying needed blood transfusions to DARA-treated patients. It was eventually shown that DARA in patient plasma directly binds to CD38 on reagent red blood cells used in the blood bank, causing the false positive antibody screens. A dithiothreitol (DTT)-based method to eliminate the interference was discovered in an investigator-initiated study,1 and later validated to be both effective and widely generalisable in a multicenter international study performed by BEST2; both studies were sponsored by Janssen.

The BEST Collaborative proposes that there is a pressing need to actively investigate whether new drugs interfere with routine blood bank testing. Investigations should be performed early during drug development, certainly during Phase I studies in healthy volunteers, and if interference with compatibility tests is found it should be clearly drawn to the attention of clinicians and blood banks with advice about how to overcome the interference.

1. Chapuy CI, Nicholson RT, Aguad MD, et al. Resolving the daratumumab interference with blood compatibility testing. Transfusion. 2015;55(6pt2):1545-1554. doi:10.1111/trf.13069.
2. Chapuy CI, Aguad MD, Nicholson RT, et al for the BEST Collaborative. International validation of a dithiothreitol (DTT)-based method to resolve the Daratumumab interference with blood compatibility testing. Transfusion (in press).

About the BEST Collaborative:

The Biomedical Excellence for Safer Transfusion (BEST) Collaborative ( is an international research organization that explores ways to improve transfusion-related services through standardization of analytic techniques, development of new procedures, systematic review of evidence, and execution of clinical and laboratory studies. BEST currently operates in teams covering 4 areas: Conventional Blood Components, Clinical Transfusion Studies, Cellular Therapy, and Donor Studies. BEST has 42 scientific members, 9 manufacturing and 16 blood service supporting members from 22 countries representing a diversity of interests and high levels of accomplishment. The supporting members of BEST span a broad range of the companies and blood suppliers engaged with blood collection, distribution and transfusion worldwide. BEST has published 97 peer reviewed papers and has 34 studies currently open.


Michael Murphy, MD; Chair of the BEST Collaborative, in Oxford, UK: +44 1865 447902
Eileen Selogie, MT(ASCP)SBB; Executive Director of the BEST Collaborative: +1 310 497 6469 x2