New Study Suggests Donor Sex Does Not Significantly Affect Transfusion Recipient Survival

New research suggests that the sex of a blood donor does not have a significant overall effect on the survival of red blood cell transfusion recipients. A team of investigators led by the Ottawa Hospital in Canada published the findings Thursday in the New England Journal of Medicine.

Since the National Heart, Lung and Blood Institute identified the possible impact blood donor sex on recipient survival as a research priority in 2015, some studies have suggested that sex-related differences like hormone levels might affect recipient survival. However, observational evidence about whether donor sex affects recipient outcomes is conflicting.

In this double-blind, randomized trial, investigators randomized 8,719 patients undergoing RBC transfusion to receive RBC units from either male donors or female donors in a 60:40 ratio. A total of 5,190 patients were assigned to the male donor group while 3,529 were assigned to the female donor group. The primary outcome was survival, measured from the date of randomization to the date of death or the end of the trial follow-up period. The mean follow-up was 11.2 months, and the maximum follow-up was 29 months.

During the study period, 1,141 patients in the female donor group and 1,712 patients in the male donor group died. The unadjusted hazard ratio for death was 0.97 (95% confidence interval [CI], 0.90 to 1.05), and the adjusted hazard ratio was 0.98 (95% CI, 0.91 to 1.06). The findings corroborate a 2022 natural experiment in Sweden, which found that donor sex and parity were not associated with increased 2-year mortality risk in RBC transfusion recipients.

The trial also included secondary outcomes, but investigators observed no between-group differences in the secondary outcomes (except for a higher incidence of MRSA infection in the female donor group). While investigators observed subgroup effects in the recipient-sex subgroup and in the subgroup of recipients of RBC units from donors 20 to 29.9 years of age, they believe the inconsistency of the point estimates across groups and the multiplicity of analyses increases the risk that those findings were due to chance.

According to the researchers, the trial is notable for its innovative approach. The team estimated that using typical trial methods, this trial would have cost $9 million. (Its actual cost was $300,000.) Their approach involved enrolling every adult patient at the Ottawa Hospital who might need a transfusion, randomizing them to receive male or female blood, and then collecting data from existing hospital databases and provincial registries.

As male and female blood were considered equivalent treatments, patients did not need to provide written consent to join the trial, but patients were given the option to opt out after the first transfusion. Using this approach, the team was able to enroll the participants within two years.