High-frequency whole blood donation and its impact on mortality: Evidence from a data linkage study in Australia.

Background: Previous reports suggest that blood donors have a lower mortality risk, which may partially reflect the "healthy donor effect" (HDE). HDE arises in donors due to selection bias and confounding if not appropriately addressed.

Study design and methods: Using the Sax Institute's 45 and Up Study data linked with blood donation history, we used a "5-year exposure window" method to select donors into regular high-frequency whole blood (WB)donors (at least two donations per exposure year) and low-frequency donors (remaining donors) with an active donation career of 5 years. To further reduce the confounding, we used statistical approaches like the inverse probability weighted (IPW) marginal structural model and the doubly robust targeted minimum loss-based estimator (TMLE), which incorporated machine learning algorithms and time-varying analyses.

Results: We selected 4750 (64.7%) low-frequency and 2588 (35.3%) high-frequency donors in the analyses. A total of 69 (1.5%) from the low-frequency and 45 (1.7%) donors from the regular high-frequency group died during the 7-year follow-up period. We did not find any statistically significant association between regular high-frequency blood donation and mortality (IPW RR = 0.98 95% CI 0.68, 1.28). TMLE model also showed similar results to IPW (RR = 0.97 95% CI 0.80, 1.16). Time-varying TMLE did not find any significant association between high-frequency donation and all-cause mortality either (RR = 0.98 95% 0.74, 1.29).

Conclusions: We did not find a significant association between regular high-frequency WB donation and all-cause mortality when appropriate methods were employed to minimize the HDE.