In the JournalsPerspective

Donor sex, prior pregnancy not linked to mortality risk among transfusion recipients

Red blood cell transfusions from female, previously pregnant or sex-discordant donors did not appear to increase risk for mortality among transfusion recipients, according to results of a retrospective study published in JAMA.

“NHLBI is charged with conducting and supporting research that improves the blood supply and outcomes in transfused recipients,” Simone Glynn, MD, MPH, chief of the blood epidemiology and clinical therapeutics branch at NHLBI, said in a press release. “The results are reassuring in that the survival of patients who got transfused with red blood cells does not appear to be associated with whether the blood they received was donated by a man, by a woman who had been pregnant — or by one who had not. That’s important to know.”

Previous studies of whether blood donor age, sex and pregnancy history affect mortality of transfusion recipients have yielded conflicting results. Plasma transfusions from women with a history of pregnancy contain antibodies the women develop when exposed to fetal blood, and this plasma has been linked to incidence of transfusion-related acute lung injury.

In this retrospective study, Glynn and colleagues analyzed transfusion recipients from three separate cohorts: Kaiser Permanente Northern California (KPNC; n = 34,662; mean age, 69 years; 54% women), Recipient Epidemiology and Donor Evaluation Study-III (REDS-III; n = 93,724; mean age, 61 years; 52% women), and Scandinavian Donations and Transfusions database (SCANDAT; n = 918,996; mean age, 72 years; 57% women).

In the KPNC cohort, 9% of transfusions were from previously pregnant women, 39% were from female donors and 44% were from sex-discordant donors. These percentages appeared higher in the REDS-III (18% previously pregnant; 43% women; 49% sex discordant) and SCANDAT (25% parous; 41% women; 50% sex discordant) cohorts.

Median number of red blood cell transfusions per patient was three (interquartile range [IQR], 2-5) in the KPNC and SCANDAT cohorts and two (IQR, 0-2) in the REDS-III cohort.

Results showed 3,217 in-hospital deaths in the KPNC cohort, 8,519 in the REDS-III cohort, and 198,537 in the SCANDAT cohort.

Stratified Cox regression models showed no statistically significant associations between in-hospital mortality and transfusions from:

  • female donors (KPNC: HR = 0.99; 95% CI, 0.96-1.03; REDS-III: HR = 1; 95% CI, 0.99-1.01; SCANDAT: HR = 1; 95% CI, 0.99-1);
  • previously pregnant or parous donors (KPNC: HR = 1; 95% CI, 1-1.01; REDS-III: HR = 1.01; 95% CI, 0.98-1.03; SCANDAT: HR = 1; 95% CI, 1-1.01); and
  • PAGE BREAK
  • sex-discordant donors (KPNC: HR = 1.02; 95% CI, 0.99-1.05; REDS-III: HR = 0.99; 95% CI, 0.98-1; SCANDAT: HR = 1; 95% CI, 0.99-1).

The retrospective nature of the analysis, as well as a lack of data on adverse events or longer hospital stays, served as the study’s main limitations.

“We proactively address potential risks to the blood supply, and we take this seriously,” Gustaf Edgren, MD, PhD, senior researcher in the department of medicine, Solna, at Karolinska Institute in Stockholm, said in a press release. “Transfusions are very common procedures, and our findings ensure that the current practice is safe and doesn’t need to be changed.” – by John DeRosier

Disclosures: Glynn and Edgren report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Red blood cell transfusions from female, previously pregnant or sex-discordant donors did not appear to increase risk for mortality among transfusion recipients, according to results of a retrospective study published in JAMA.

“NHLBI is charged with conducting and supporting research that improves the blood supply and outcomes in transfused recipients,” Simone Glynn, MD, MPH, chief of the blood epidemiology and clinical therapeutics branch at NHLBI, said in a press release. “The results are reassuring in that the survival of patients who got transfused with red blood cells does not appear to be associated with whether the blood they received was donated by a man, by a woman who had been pregnant — or by one who had not. That’s important to know.”

Previous studies of whether blood donor age, sex and pregnancy history affect mortality of transfusion recipients have yielded conflicting results. Plasma transfusions from women with a history of pregnancy contain antibodies the women develop when exposed to fetal blood, and this plasma has been linked to incidence of transfusion-related acute lung injury.

In this retrospective study, Glynn and colleagues analyzed transfusion recipients from three separate cohorts: Kaiser Permanente Northern California (KPNC; n = 34,662; mean age, 69 years; 54% women), Recipient Epidemiology and Donor Evaluation Study-III (REDS-III; n = 93,724; mean age, 61 years; 52% women), and Scandinavian Donations and Transfusions database (SCANDAT; n = 918,996; mean age, 72 years; 57% women).

In the KPNC cohort, 9% of transfusions were from previously pregnant women, 39% were from female donors and 44% were from sex-discordant donors. These percentages appeared higher in the REDS-III (18% previously pregnant; 43% women; 49% sex discordant) and SCANDAT (25% parous; 41% women; 50% sex discordant) cohorts.

Median number of red blood cell transfusions per patient was three (interquartile range [IQR], 2-5) in the KPNC and SCANDAT cohorts and two (IQR, 0-2) in the REDS-III cohort.

Results showed 3,217 in-hospital deaths in the KPNC cohort, 8,519 in the REDS-III cohort, and 198,537 in the SCANDAT cohort.

Stratified Cox regression models showed no statistically significant associations between in-hospital mortality and transfusions from:

  • female donors (KPNC: HR = 0.99; 95% CI, 0.96-1.03; REDS-III: HR = 1; 95% CI, 0.99-1.01; SCANDAT: HR = 1; 95% CI, 0.99-1);
  • previously pregnant or parous donors (KPNC: HR = 1; 95% CI, 1-1.01; REDS-III: HR = 1.01; 95% CI, 0.98-1.03; SCANDAT: HR = 1; 95% CI, 1-1.01); and
  • PAGE BREAK
  • sex-discordant donors (KPNC: HR = 1.02; 95% CI, 0.99-1.05; REDS-III: HR = 0.99; 95% CI, 0.98-1; SCANDAT: HR = 1; 95% CI, 0.99-1).

The retrospective nature of the analysis, as well as a lack of data on adverse events or longer hospital stays, served as the study’s main limitations.

“We proactively address potential risks to the blood supply, and we take this seriously,” Gustaf Edgren, MD, PhD, senior researcher in the department of medicine, Solna, at Karolinska Institute in Stockholm, said in a press release. “Transfusions are very common procedures, and our findings ensure that the current practice is safe and doesn’t need to be changed.” – by John DeRosier

Disclosures: Glynn and Edgren report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Rutger Middelburg

    Rutger Middelburg

    The results from this paper are in stark contrast with those from two of our previous studies and several publications from other authors. As Edgren and colleagues correctly noted, this could be due to differences between patient or donor populations or blood banking practices, or methodological differences between the studies.

    Differences in populations and banking practices clearly exist. For example, donors are much younger in the United States, where high school and college blood drives are common. Also, prevalence of many diseases differs widely among countries. It has been suggested that patients with cardiovascular disease, which is relatively common in the United States, are insensitive to the negative effects of blood from previously pregnant donors. Further, the investigated patient population consists only of transfusion recipients, which creates a strong selection bias. Because of the much more liberal transfusion policies in both the United States and Scandinavia, patients will be transfused with diagnoses that would not have resulted in a transfusion in the Netherlands.

    There are also major differences in blood product preparation techniques. In the United States, the standard method is the “soft spin,” whereas in Europe it’s the “hard spin,” which could lead to a completely different composition of the red cell pellet, including how many and which types of leukocytes end up polluting that pellet.

    All these differences could provide important clues about the biological mechanism behind the association we have repeatedly observed.

    Differences in methodology also are plentiful, but difficult to fully appreciate in a short text. One major difference is that Edgren and colleagues focused their primary analyses on in-hospital mortality, which covers a very short time span. We previously observed a difference in mortality that kept growing for at least 3 years. Also, the methods used to correct for confounding by number of transfusions are not entirely clear from the short text that is allowed in a JAMA publication, but it appears these could leave room for residual confounding. Similarly, the very short description of the imputation model seems to suggest this method could introduce random noise, which would result in effect dilution.

    Finally, in both our previous studies we analysed a “single transfusion cohort,” which cannot suffer from confounding by number of transfusions. We could therefore present a Kaplan-Meier survival graph, which suggested one in 16 men aged younger than 50 years who receives a single transfusion with blood from a previously pregnant female donor will die within 3 years, whereas he would not have had he received that transfusion from a male donor. Although Edgren and colleagues analyse a single transfusion cohort, they do not present such an insightful Kaplan-Meier graph.

    Edgren and colleagues did some great work that raises important new suggestions for future lines of research. However, these results should not detract from the problem we observe in several other countries, including the Netherlands. Further research should aim to elucidate the biological mechanism, which would allow a much more targeted approach to increasing the safety of transfusion recipients. Currently, our best options seem to be matching transfusions by sex of the donor and recipient or permanently deferring all previously pregnant donors. Both of these are logistically demanding, and information that would allow for more targeted approaches is clearly needed.

    • Rutger Middelburg , PhD
    • Leiden University Medical Center

    Disclosures: Middelburg reports no relevant financial disclosures.