Two case reports involving therapeutic monoclonal anti‐CD47 (Hu5F9‐G4), it's effect on compatibility testing and subsequent selection of components for transfusion

A stressful predicament for blood bankers!

“…One of the more notable results of the serology is the enormous plasma titres of anti‐CD47 detectable. Titres > 16 000 have been previously reported, and in the two cases reported by Reyland et al, the titres in both instances are >65 000, making it impossible to elucidate underlying potentially clinically significant alloantibodies as the anti‐CD47 titres are so high. In addition, not surprisingly with plasma titres so high is the fact that the antibody levels cannot be significantly reduced with auto‐ or alloadsorption approaches to allow for alloantibody detection using polyclonal antihuman globulin (AHG) sera.…”

“…When anti‐CD47 is administered to certain cancer patients, it is given at very high dosage, which creates huge problems for transfusion services during their serologic evaluations related to type and screen and provision of compatible blood . In the paper by Reyland et al, in this issue of Transfusion Medicine , the authors present two case studies of patients who are receiving anti‐CD47. These cases confirm a previous report of the type of problems that arise in a transfusion service or reference laboratory when faced with patients being administered this drug.…”

“…Second is that the direct antiglobulin test (DAT) in these patients receiving anti‐CD47 can be negative, yet high titres of anti‐CD47 can be found in eluates. This is a result of the high antigen site density of CD47 on the RBCs coupled with the high titre of circulating antibody resulting in the “blockade” of the antigen sites and a false‐negative DAT, also known as prozone effect …”

“…An approach that uses a combination of alloadsorption and Gamma‐clone AHG could work. That is, using a multiple alloadsorption strategy to decrease the titre of >16 000 to 65 000 down to perhaps 512, as indicated in Reyland et al, may allow for antibody investigation using the Gamma‐clone AHG. IAT results that would then be negative with Gamma‐clone AHG for the anti‐CD47 would still allow for the Gamma‐clone to react with other IgG subclass alloantibodies that could be underlying the anti‐CD47.…”

“…IAT results that would then be negative with Gamma‐clone AHG for the anti‐CD47 would still allow for the Gamma‐clone to react with other IgG subclass alloantibodies that could be underlying the anti‐CD47. With more immunotherapeutic antibodies that can react with RBCs coming into the clinic, a consistent strategy must be implemented by transfusion services and reference laboratories . One needs to make sure that a diagnosis and drug history is obtained on admission of patients requiring type and screen or crossmatch.…”