Blood Donor Sex Could Play a Crucial Role in Transfusions Practices
Transfusions from females to males may be associated with increased risk for all-cause mortality, compared with such transfusions to females or with transfusions from women who have never been pregnant to recipients of either sex, according to a new study from the Netherlands.
Senior author Rutger Middelburg of Leiden University Medical Center in The Netherlands and colleagues write in JAMA that it’s 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.
Transfusion of red blood cells is among the most commonly performed procedures in hospitals. Transfusion-related acute lung injury is the most common cause of transfusion-related deaths and has been shown to be associated with transfusions from female donors, specifically from those with a history of pregnancy.
“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 wasn’t 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 analysis included data from 31,118 patients from six major Dutch hospitals who received 59,320 red blood cell transfusions exclusively from one of three types of donors — 88% men, 6% previously pregnant women and 6% never-pregnant women — from May 30, 2005, to Sept. 1, 2015.
All-cause mortality during follow-up served as the main outcome. Researchers compared outcomes following red blood cell transfusions from ever-pregnant or never-pregnant women, with transfusions from male donors.
Researchers reported 3,969 deaths — for a 13% mortality rate — among the entire cohort.
Male recipients of red blood cell transfusions had higher all-cause mortality rates per 1,000 person-years when they had an ever-pregnant vs. male donor. This risk increased among men aged 18 to 50 years.
However, the difference in risk was not statistically significant when researchers compared male recipients with never-pregnant vs. male donors.
Among female recipients of red blood transfusions, mortality rates did not significantly differ with ever-pregnant vs. male donors, nor with never-pregnant vs. male donors.
“We found transfusion of red blood cells from previously pregnant donors to be associated with about 1.5 times increased mortality of male recipients younger than 50 years, compared with transfusion of red blood cells from male donors,” Middelburg said. “The risk remained increased for many years after transfusion. No such increase was observed for female recipients or for male recipients over 50 years.”
Henrik Bjursten, a professor in the department of cardiothoracic surgery, anesthesia and intensive care at Lund University/Skane University Hospital in Stockholm, who assisted in the study, said that male-to-female and vice versa transfusions are not likely to have good outcomes. He added that the possible mechanism behind this is not clear and that needs to be found out. He explained that his own experience with cardiac surgery patients who received blood from the opposite sex has been similar as this study concludes. He noted that if there is actual harm, we cannot conduct human clinical trials where one group is given a sex mismatched blood transfusion – that would be unethical.
One of the reasons why men do not respond well to blood of women who have been pregnant could be some immune factor that the women develop in their blood. This immune factor could be making the male recipient’s body reject the donated red blood cells especially among younger males.
Until a smaller study on sex mismatches by the same Dutch team six years ago, no one had thought to look at the pregnancy history of red blood cell donors, says Rutger Middelburg, an epidemiologist with Sanquin Research in the Netherlands, who helped lead that pilot work and the study published Tuesday. The differences in mortality are difficult to detect unless researchers know what to look for, Middelburg wrote via e-mail. “Even now, we find that in our data set simply looking at all patients can dilute the effect to the level where it becomes undetectable,” he added. “We had to specifically look at the right patient group.” He does not know why the team saw a survival difference only in younger men.
The data was not perfect, Middelburg says. The team examined records of patients who had received transfusions years earlier, and the researchers did not know the pregnancy status of all the women donors. The researchers disqualified data from patients who received blood from both men and women—and because men can donate blood more often than women, the pool was already skewed male, he notes. Women who had been pregnant at any point accounted for just 6 percent of the donors the team studied, although the association was still statistically valid. “We are very confident of our results,” Middelburg says.
He is continuing his research, and now hopes to get additional funding. “My priorities would be [to] look into more detailed pregnancy histories and causes of death,” he says, “but much other relevant research could still be done with sufficient resources.”
