4/11/2025
PITTSBURGH – Traumatically injured women are considerably less likely to receive whole blood transfusions within the first four hours of injury compared to men, despite whole blood being associated with reduced mortality in both women and men, according to new research led by University of Pittsburgh School of Medicine scientists.
The findings were published in advance of a special issue of the journal Transfusion and point to the urgent need to better understand the underlying reasons for the sex-based disparity in providing the potentially life-saving whole blood to anyone who would benefit.
“We want medicine to be equitable,” said lead author Skye Clayton, clinical research coordinator in Pitt’s Trauma and Transfusion Medicine Research Center (TTMRC), who also works as an emergency medical technician. “Seeing these disparities that women are at increased risk of not receiving life-saving treatment was really disappointing.”
Significant blood loss is the leading cause of preventable trauma-related deaths, with an estimated 30,000 people dying each year in the U.S. because of untimely or inadequate care of bleeding. Pitt and UPMC are leading multiple national and international studies intended to improve this care.
Clayton and the research team gathered information from an American College of Surgeons database on almost 41,000 females and 116,000 males who had been traumatically injured between 2020 and 2022 and received at least one liter of low-titer O whole blood (LTOWB) within the first four hours of hospital admission. This type of blood is donated by a person with type O blood – commonly referred to as a “universal donor” – and has low-levels of antibodies against type A or B blood.
Among traumatically injured people, females younger than 50 received LTOWB 40% less often compared to males of similar age and females 50 and older received it 20% less often than their male counterparts. This finding held after adjusting for injury severity.
“Interestingly, in both men and women, the use of whole blood is associated with better outcomes,” said senior author Philip Spinella, M.D., professor of surgery and critical care medicine at Pitt and co-director of the TTRMC. “When whole blood was used there was a 20% to 25% reduced risk of mortality. The magnitude of these results is hard to ignore and consistent with findings in other studies.”
Clayton and Spinella are unsure why women were less likely to be given whole blood, but suspect that younger women and girls are the least likely to be given it because of their potential to later become pregnant. The majority of LTOWB available for trauma resuscitation is positive for the RhD antigen. If someone who is negative for this antigen receives positive blood, then they may make antibodies against it. This is very unlikely to affect them during trauma or throughout their lives. But if a female who makes these antibodies after a blood transfusion goes on to become pregnant and their fetus is positive for the antigens, then the mother’s antibodies may attack the fetus’s blood, which can be life-threatening to the unborn baby.
The risk of fetal death is estimated to be very low—at about 0.3%—as a result of advances in pregnancy and fetal medicine that will continue to improve and further reduce this risk. With appropriate care, this condition is treatable during pregnancy, resulting in a healthy baby. Spinella believes that lack of knowledge about the low risk and advances in care have led to the persistence of clinicians not giving whole blood to younger females out of fear it will affect a future fetus.
“You can’t go on to become pregnant and have a baby if you are dead,” Spinella said.
Spinella’s colleague, Mark Yazer, M.D., professor of pathology at Pitt, is co-senior author on a companion study published online a few weeks ago that will also be in the special issue of Transfusion.
Yazer worked with colleagues at the University of Colorado Anschutz Medical Campus, including co-senior author Steven Schauer, D.O., to look at females specifically of child-bearing potential between ages 15 to 50 recorded in the American College of Surgeons trauma database. They found that the males were nearly twice as likely to receive LTOWB compared to females of child-bearing potential.
The team noted that although several surveys have shown that females of childbearing potential would generally accept receiving RhD-positive LTOWB, despite the small chance that it could lead to complications with future pregnancies, only about half of the clinical institutions surveyed have policies permitting the use of RhD-positive LTOWB in this population.
“This research builds on several years of work that Dr. Spinella and I, along with our colleagues at Pitt, Colorado and others nationwide, have been doing,” Yazer said. “Historically the transfusion community has feared giving RhD-positive blood to women of childbearing potential whose RhD-type was either negative or unknown during their trauma resuscitation because of the risk it potentially poses to future pregnancies. However, this risk is now highly manageable with heightened awareness of this problem and with modern treatments during pregnancy. We need to recalibrate the risk-benefit formula for giving RhD-positive LTOWB to traumatically injured women when RhD-negative isn’t available and save more lives.”
Additional authors of Clayton and Spinella’s manuscript can be found in the Transfusion manuscript.
Additional authors of Yazer and Schauer’s study can be found in the Transfusion manuscript.
Neither study received outside funding.
PHOTO DETAILS: (click images for high-res versions)
Right photo
CAPTION: Skye Clayton, clinical research coordinator in the University of Pittsburgh Trauma and Transfusion Medicine Research Center
CREDIT: Skye Clayton
Left photo
CAPTION: Philip Spinella, M.D., professor of surgery and critical care medicine and co-director of the University of Pittsburgh Trauma and Transfusion Medicine Research Center
CREDIT: Philip Spinella