Does Transfusion of Red Blood Cells Impact Germline Genetic Test Results?

Abstract

Purpose: molecular testing is often indicated for recently transfused patients. However, there are no guidelines regarding the potential interference from donor DNA or whether it is necessary to wait for a period of time post-transfusion prior to genetic testing. While the majority of patients are transfused in the non-trauma setting using leukoreduced (LR) red blood cell products, the degree of leukoreduction varies among centers and is not universally practiced.

Methods: whole blood units collected from anonymous donors were used in an in vitro transfusion model. One unit was split: half being leukoreduced simulating a leukopenic recipient and half left untreated. Donors were simulated by leukoreduced, partially leukoreduced (PLR), or non-leukoreduced units, transfused in 2, 5, or 16 unit equivalents. DNA from the combinations were subjected to short tandem repeat (STR) analysis for chimerism detection.

Results: donor DNA was not detectable in any of the LR combinations, but detected in the PLR combinations, ranging from 0.1 to 1.5% donor DNA in the immunocompetent recipient and 6.3-27.8% in the leukopenic recipient. Non-LR donor DNA was also detected (13-95%).

Conclusion: donor-derived DNA from leukoreduced blood products is unlikely to interfere with the interpretation of germline genetic testing in immunocompetent recipients but may interfere in immunocompromised recipients.

Keywords: genetic testing; interference; leukoreduction; transfusion; transfusion-associated microchimerism.

Figure 1

Three whole blood units, representing donors, are shown as red cylinders; the units were processed as leukoreduced (LR), partially leukoreduced (PLR), or nonleukoreduced (NLR), with the residual white blood cell (WBC) counts indicated. A fourth unit was split into 2 aliquots to represent a leukopenic and an immunocompetent recipient (black boxes at top and bottom). Arrows with numbers depict the quantity of donor blood mixed with 10 mL of recipient to simulate transfusion, then chimerism studies were performed. Each “donor” and “recipient” was also tested without mixing (blue arrows with “X”) to identify informative short tandem repeat (STR) markers.