Should donor sex influence blood transfusion practices?

Sick or injured men who receive blood transfusions may be more likely to die if their donor was a woman who has been pregnant in the past, a new study suggests. 

The reasons are unclear, and the study wasn’t focused on explaining them, but senior author Rutger Middelburg of Leiden University Medical Centre in The Netherlands and colleagues write in JAMA that it is possible antibodies women develop during pregnancy to protect their growing baby might later trigger dangerous reactions in some male recipients of blood from previously pregnant donors. 

“During pregnancy, the mother is exposed to her child’s blood, and can, therefore, develop antibodies that she will have for life, which will be carried in her donated blood,” said Dr Henrik Bjursten a researcher at Lund University and Skane University Hospital in Sweden who was not involved in the study. 

“These antibodies can be one explanation for the finding,” Bjursten said by email. “But no definitive mechanism has been found.” 

The study team examined data on 31,118 patients who received a total of 59,320 red blood cell transfusions at six Dutch hospitals from 2005 to 2015. The majority of the blood donors were men; just 6 per cent were women who had been pregnant in the past, and another 6 per cent were women without a history of pregnancy. 

Overall, 3,969 blood recipients, or 13 per cent, died during the study. 

When men got transfusions from previously pregnant female donors, the mortality rate was 101 fatalities for every 1,000 recipients per year, compared to 80 fatalities per 1,000 recipients with male donors and 78 per 1,000 recipients with never-pregnant female donors, the study found. 

Women did not appear to have an increased risk of death when they received blood from a previously pregnant female donor, however. 

Research to date on sex-mismatched blood donations has been inconclusive, and the current findings would need to be verified in other patient populations before considering any changes to current transfusion practices that do not consider sex in matching donors with recipients, said Gustaf Edgren, a researcher at the Karolinska Institute in Stockholm who was not involved in the study. 

“The largest study to date with almost a million patients did not find an association between donor sex and patient survival,” Edgren said by e-mail. “Another fairly large Canadian study did find such an association, but neither of these studies did look specifically at donor pregnancy status.” 

The most common cause of death in the study was what is known as transfusion-related acute lung injury, which has been linked to transfusions from female donors with a history of pregnancy. 

For female recipients of blood transfusions, mortality rates were 74 deaths for every 1,000 patients per year with a previously pregnant female donor and 62 deaths with a male donor. 

One limitation of the study is that the difference in mortality rates for male recipients with previously pregnant female donors was only statistically meaningful for men age 50 or younger, the authors note. Researchers also lacked data on the pregnancy history for some female donors in the study. 

Even so, the results add to research suggesting that there may be some unknown harms associated with blood transfusions, said Dr Fred Buckhold, a researcher at Saint Louis University School of Medicine who was not involved in the study. 

Under current transfusion practices, however, it is not possible for doctors and patients to know the sex of donors, Buckhold said by e-mail. Transfusions are not risk free, and patients should get them only when necessary, he added. 

“It is clear in the US that blood transfusions are overused and there is often a mentality of, ‘we might as well fill up the tank’ for an anaemic patient,” Buckhold said. “While that concept is good in theory, it is becoming clear that there are clear harms that need to be considered fully.” 

Still, there is not enough evidence yet to warrant changes in transfusion practices based on the sex of donors and recipients, said Dr Ritchard Cable of the American Red Cross in Farmington, Connecticut, who co-wrote an editorial accompanying the study. 

“No change in transfusion practices is needed now,” Cable said by e-mail. “Rather, efforts to restudy the findings in different populations and with different methods should be undertaken.”