Blood Donors with a Positive Direct Antiglobulin Test Are at Increased Risk for Hematologic Malignancies and Cancer in General.
Authors: Rottenberg Yakir , Yahalom Vered , Shinar Eilat , Adler Bella , Paltiel Ora 
Published: October 2019

Abstract
Positive direct antiglobulin tests (DAT) may be non-specific or associated with auto-antibodies and malignancies, including multiple myeloma and lymphoproliferative disorders. Screening blood donations for DAT is not routinely performed. Furthermore, it is unknown whether a positive DAT in healthy donors is associated with an increased risk of malignancy. All blood donations at MDA National Blood Services in Israel undergo Autocontrol (AC) testing using automated blood grouping equipment (Autogrouper© 1986–2000, and Olympus PK7200© from 2000-present). AC-positive donations are tested for DAT using tubes and/or Diamed gel cards with anti-IgG, anti-C3 and anti-IgG/C3. Donors with positive DAT tests were identified from 1999–2003 and matched in a 1:4 ratio to DAT-negative donors for sex, year of donation and age (by 5 year categories). Cancer incidence was ascertained through July 30, 2006 via the Israel Cancer Registry. We compared the incidence of all cancers, hematopoietic, and solid tumors among DAT+ and DAT– donors. We also compared cancer rates in DAT+ donors with the expected rates in the general Israeli population, controlling for age, sex and ethnicity.
Results: The final study population included 586 DAT+ and 2344 DAT– donors. In both groups 62.6% were males, and the mean age of the DAT+ donors was 34.5 (range: 17–67) compared to 32.0 (11–74) years in DAT– donors. Malignancies occurred in 17 (2.9%) of the DAT+ and 27 (1.2%) of the DAT– donors during the follow-up period; of these, three donors in the DAT+ group were diagnosed with hematopoietic cancer within 12 months of their donation (Hodgkin lymphoma within 2 months, non-Hodgkin lymphoma within 4 months and multiple myeloma within 8 months). Even after excluding these early cases and with a mean follow up of 66 months (range: 14–91 months), the relative risk (RR) of developing cancer was 2.14 (95% confidence interval (CI): 1.13–4.10) comparing donors with positive DAT to those with negative DAT, while the RR for hematopoietic cancer was 8.3 (95% CI: 1.5–43.2). Comparing DAT+ blood donors with the general population, the standardized incidence ratios (observed/expected cases) were elevated at 2.11 (95% CI: 1.15–3.54, p=0.016) for all malignancies and 8.03 (95% CI: 2.2–20.6, p=0.003) for hematologic malignancies, while they were not increased in the DAT negative group. Among DAT+ donors, the most frequent malignancies were lymphoma, multiple myeloma, thyroid, prostate and gastrointestinal tumors (2 cases in each category).
Conclusion: There is evidence of a significantly increased risk of cancer, especially hematologic malignancies, among blood donors with a positive DAT, within a short follow-up period. A positive direct antiglobulin test thus appears to be a risk marker for malignancy. Further studies are necessary to confirm these findings, assess their significance, and determine whether the DAT would be a useful aid to early detection of cancer in healthy populations.