Association of Blood Transfusion From Female Donors With and Without a History of Pregnancy With Mortality Among Male and Female Transfusion Recipients

Abstract

Importance: Transfusion of red blood cells from female donors has been associated with increased mortality in male recipients.

Objective: To quantify the association between red blood cell transfusion from female donors with and without a history of pregnancy and mortality of red blood cell recipients.

Design, setting, and participants: Retrospective cohort study of first-time transfusion recipients at 6 major Dutch hospitals enrolled from May 30, 2005, to September 1, 2015; the final follow-up date was September 1, 2015. The primary analysis was the no-donor-mixture cohort (ie, either all red blood cell transfusions exclusively from male donors, or all exclusively from female donors without a history of pregnancy, or all exclusively from female donors with a history of pregnancy). The association between mortality and exposure to transfusions from ever-pregnant or never-pregnant female donors was analyzed using life tables and time-varying Cox proportional hazards models.

Exposures: Red blood cell transfusions from ever-pregnant or never-pregnant female donors, compared with red blood cell transfusions from male donors.

Main outcomes and measures: All-cause mortality during follow-up.

Results: The cohort for the primary analyses consisted of 31 118 patients (median age, 65 [interquartile range, 42-77] years; 52% female) who received 59 320 red blood cell transfusions exclusively from 1 of 3 types of donors (88% male; 6% ever-pregnant female; and 6% never-pregnant female). The number of deaths in this cohort was 3969 (13% mortality). For male recipients of red blood cell transfusions, all-cause mortality rates after a red blood cell transfusion from an ever-pregnant female donor vs male donor were 101 vs 80 deaths per 1000 person-years (time-dependent "per transfusion" hazard ratio [HR] for death, 1.13 [95% CI, 1.01-1.26]). For receipt of transfusion from a never-pregnant female donor vs male donor, mortality rates were 78 vs 80 deaths per 1000 person-years (HR, 0.93 [95% CI, 0.81-1.06]). Among female recipients of red blood cell transfusions, mortality rates for an ever-pregnant female donor vs male donor were 74 vs 62 per 1000 person-years (HR, 0.99 [95% CI, 0.87 to 1.13]); for a never-pregnant female donor vs male donor, mortality rates were 74 vs 62 per 1000 person-years (HR, 1.01 [95% CI, 0.88-1.15]).

Conclusions and relevance: Among patients who received red blood cell transfusions, receipt of a transfusion from an ever-pregnant female donor, compared with a male donor, was associated with increased all-cause mortality among male recipients but not among female recipients. Transfusions from never-pregnant female donors were not associated with increased mortality among male or female recipients. Further research is needed to replicate these findings, determine their clinical significance, and identify the underlying mechanism.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Zwaginga reported receiving a speaking fee from Vifor Pharma and serving on the advisory councils of Novartis and Amgen Science. No other authors reported disclosures.

Figures

Figure.. Cumulative Incidence of Death According to Sex of the Transfusion Recipient and Sex and Pregnancy History of the Donor in the Single-Transfusion Cohort

The single-transfusion cohort consists of all the follow-up time during which patients had received only a single transfusion. Follow-up time was censored at the time this inclusion criterion was violated. Median follow-up for male recipients of red blood cell transfusions exposed to male donors, 16 (interquartile range [IQR], 1-780) days; to female ever-pregnant donors, 12 (IQR, 1-567) days; and to female never-pregnant donors, 14 (IQR, 1-563) days. Median follow-up for female recipients of red blood cell transfusions exposed to male donors, 24 (IQR, 1-846) days; to female ever-pregnant donors, 21 (IQR, 1-584) days; to female never-pregnant donors, 17 (IQR, 1-640) days.