Original Investigation 

June 13, 2022

Mortality Among Patients Undergoing Blood Transfusion in Relation to Donor Sex and Parity: A Natural Experiment

Jingcheng Zhao, Arvid Sjölander, Gustaf Edgren

JAMA Intern Med. 2022;182(7):747-756.

doi:10.1001/jamainternmed.2022.2115

Key Points

Question  Does blood donor sex or parity affect mortality of patients undergoing transfusion?

Findings  In this nationwide cohort study involving a natural experiment of 368 778 patients undergoing red blood cell transfusion, the 2-year survival differences comparing transfusions from female and parous donors with male donors were both not statistically significant at −0.1% and 0.3%, respectively. Receiving blood from female donors was associated with an increased risk of additional transfusions owing to female donors having lower hemoglobin counts.

Meaning  Patients undergoing transfusion with blood from female or parous donors did not have a higher mortality compared with patients undergoing transfusion with blood from male donors; however, female blood units tended to have lower hemoglobin content.

Abstract

Importance  Prior evidence suggests that plasma and platelet transfusions from female and parous donors are associated with adverse clinical outcomes, which has led to the predominant use of male donors for plasma and platelets in many countries. However, studies on red blood cell transfusions have been conflicting.

Objective  To determine whether blood donor sex and parity affect mortality of patients undergoing transfusion with red blood cells.

Design, Setting, and Participants  This cohort study used nationwide blood bank and health register data in Sweden and involved a natural experiment created by donor sex and parity being concealed and randomly allocated. Patients were included if they were 18 to 90 years old, did not have a history of blood transfusion, and received a transfusion between January 1, 2010, and December 31, 2017. Patients were followed up from their first red blood cell transfusion until death, emigration, or end of study (June 30, 2018). Data analysis was performed between June 15 and December 15, 2021.

Exposures  (1) Female vs male donors and (2) parous or nonparous female vs male donors.

Main Outcomes and Measures  Overall survival up to 2 years estimated using inverse probability–weighted Kaplan-Meier estimates and relative risk for additional transfusions within 24 hours.

Results  Among the 368 778 included patients (mean [SD] age, 66.3 [17.7] years; 57.3% female), 2-year survival differences comparing red blood cell transfusions from female and parous donors to male donors were −0.1% (95% CI, −1.3% to 1.1%) and 0.3% (95% CI, −0.6% to 1.2%), respectively. No statistically significant survival differences were observed regardless of patient sex or age. Median (IQR) hemoglobin counts for female donors (13.5 [13.0-14.0] g/dL) were lower than for male donors (14.9 [14.4-15.5] g/dL). Red blood cell transfusions from female donors were associated with a relative risk of 1.12 (95% CI, 1.08-1.17) for additional transfusions within 24 hours but not after adjusting for donor hemoglobin counts (relative risk, 1.03; 95% CI, 0.98-1.08). Pretransfusion patient characteristics were naturally distributed as-if randomized.

Conclusions and Relevance  In this nationwide cohort study involving a natural experiment, after accounting for the lower hemoglobin values in blood from female donors, patients undergoing transfusion with blood from female or parous donors did not have higher 2-year mortality compared with recipients of blood from male donors.